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17996053 | The training in specific communication skills during medical school is based on the notion that independent of the physician's medical knowledge, the practice of communication skills will have a significant impact upon the character and quality of the consultation. The reason for consulting the doctor may be concerns about more than symptom-related distress . In some studies, successful levels of communication skills have been linked to students' diagnostic efficiency, patient stress, patient compliance, medical errors, general outcome, outcome in chronic disorders, and patient and physician satisfaction . However, the intermediate variable between communication skills and such outcome measures, the content of a consultation in a general practice setting, has still not been sufficiently explored. One way to explore these issues is to observe students or physicians in their interaction with patients in a clinical setting. In this regard, one basic methodological problem should be addressed. Should one employ a standardized patient (i.e. an actor in a constructed but typical patient setting) or many different patients? This study design has adopted the first option so all interviewers attending the study could be compared in their skills, but the generalization of the findings may be limited to the specific case being played by the actor, even if the case in its relative complexity is fairly representative of patients in general practice. Findings indicate that a significant case-by-student interaction between communication skills and decision making exists and that individuals' communication skills vary systematically with specific cases . The length of the test being observed may also influence the results. A 15-minute consultation, ordinary in a general practice setting and part of the present study design, has been found to be too short to assess generalizable interviewing skills . Concerning background variables, we would presume that female and older students will develop communication skills promoting psychosocial issues more easily and more effectively than males and younger students. The sample has to be viewed as an "availability" sample, and we cannot know for sure how representative the attendees were of the national student population. The data from our survey sample showed that the gender proportion among the final-year students in spring 2004 (N = 320) was 65% females (N = 208, ratio 0.65, CI 95% 0.60 – 0.70); in the observational sample (N = 111 of the same 320), the gender proportion of females was 70% (N = 78, ratio 0.70, CI 95% 0.61 – 0.78). Mean age among the 320 was 27,3 (CI 95% 26,9 – 27,7) years, among the 111 27,8 (CI 95% 27,2 – 28,4). When we compared the scores on a self-report questionnaire assessing their self evaluation of communication skills (Oslo Inventory of Self-reported Communication Skills – OSISCS), the participants in the survey study yielded approximately the same mean score (3,75 +0 .46 on a 1–5 scale) one year earlier (when they were in their 5 th year of medical school; medical school in Norway lasts for six years) as the 111 attendees (3,51 +0 .34) with minor variance between genders . With overlapping confidence intervals regarding gender and age and close to similar scores on self-reported skills, none of these differences should be viewed as significant. Thus we presume that we have achieved a fairly representative sample. Since the construction of the content scale was not based upon psychometric properties, we found it most reasonable to look at the face validity. The 15 consultation content items (Table 1 ) were divided into three Content indices: The Somatic Index comprising the two diagnostic items (myomas and anemia) together with the five illness items (numbers 3 – 7). Due to very low internal consistency (Cronbach's α = 0.26), the two diagnostic items were excluded and with the five illness items left constituting the Illness index (1), alpha increased to 0.44. The Concern Index (2) comprised two items related to the patient's concern about possible cancer (numbers 8 – 9, α = 0.53), and the Psychosocial Index (3) comprised the six psychosocial items (numbers 10 – 15, α = 0.46). We also constructed a fourth index called The Informing/planning Index (4) by combining two items (item 6 – treatment planning and item 9 – information, α = 0.72) from the Maastricht History and Advice Checklist (MAAS) . This index covered the action taken by the student at the end of the consultation. MAAS items were scored on a 0–5 scale, yielding a median of 3,0. A cut off >3 was used to demonstrate presence of the item during the consultation. Inter-rater reliability between the MAAS raters was (ICC(1.1)) = 0.69. The Arizona Communication Interview Rating Scale (ACIR) consists of 14 items (Table 2 ) all with a scale from 1 (least) to 5 (best) . Three trained raters scored the videotapes and one separate rater scored 2/3 of them in order to check the inter-rater reliability (not the same as above). The Intra-class correlation coefficient between raters was similar to that between the MAAS raters ICC(1.1) = 0.69. The overall ACIR mean was 3,10 (0.69). The psychometric properties of ACIR have been found satisfactory in an earlier study . A Principal Component Analysis with a Varimax rotation yielded a typical one-factor solution, so the overall mean was used in all analyses. The internal consistency of ACIR in our sample was 0.91 (Cronbach's α). As one way of validating ACIR, we correlated ACIR-mean against the MAAS-mean (without the two items constituting the Informing/planning index being used as a content index) giving a value of Pearson's r = 0.61. The question of tautology may be raised as the rating of the ACIR items could be influenced by how the content items were rated and vice versa, even if separate raters were used. We, therefore, wished to control for this possibility using a special procedure. When carefully scrutinizing the ACIR items one by one, we categorized them as content-related and non-content-related. Items number 3, 4, 5, 6, 8, 10 and 11 were considered non-content-related. This categorization, which of course may be disputed, is highly consonant with the separation of ACIR items performed in a previous study by Aspegren et al. . This group of items (numbers 5, 6, 8, 10, and 11, Cronbach's α = 0.86) was viewed as more typical for civil social conversation, i.e. not strictly related to a specific medical context. The mean of these non-content related items could be used as a substitute for the ordinary overall ACIR-mean in the multiple analyses to test for possible differences in association with our outcome variables (Content indices). In four linear regression analyses, the four consultation Content indices (Illness, Psychosocial, Concern, and Informing/planning) were used as dependent variables and the overall ACIR-mean as the independent variable with gender and age as control variables. The level of communication skills had a significant impact upon the Psychosocial, the Concern and the Informing/planning indices, controlled for gender and age, yielding standardized Beta-values of 0.45 for the concern index (explaining 19% of the variance), .34 for the Informing/planning index (11%), and 0.29 for the psychosocial index (8%). The Illness index had no significant relationship to level of communication skills (Table 5 ). When substituting the overall ACIR-mean with the ACIR non-content-related mean, no deviating associations were detected (Beta-values deviating at a maximum of 0.02). When exploring characteristics for the eight sub-groups derived from combinations of the dichotomized Illness, Psychological/concerns, and the Informing/planning part-counts, overall ACIR-mean was significantly higher in those with high score (above median) on all three indices (Illness, Psychosocial/concern, and Informing/planning) compared with those having low score on all three or high on the Illness but low on the two others (F = 4,60, p = 0.001). Gender and age did not vary between the eight sub-groups. One of the main findings in this study is that the level of communication skills was significantly related to the total content index, especially to the Psychosocial, the Concerns, and the Informing/planning indices, but not to the Illness index, controlled for gender and age. As shown in Table 5 , the strongest relationship was with the Concern index, while the Informing/planning and Psychosocial indices yielded somewhat weaker relationships. This implies that the higher the level of communication skills, the more adequately addressed was the content of the consultation related to the patient's possible stressors; i.e. her fear of having the cancer from which her mother may have died 10 years earlier, responsibility for her children, the divorce she had been through, and the burden of moving to a new place, a.o. The students with the higher level of communication skills were also more able to perform adequate informing/planning procedures at the end of the consultation. These results were supported by the fact that students scoring high on all three dichotomized indices (the Illness, the Psychosocial/Concerns, and Informing/planning) had significantly higher levels of communication skills than those scoring low on all three indices, as well as those with high score on the Illness, but low scores on the other two indices. No variation in gender and age characterized these sub groups, showing that it was the level of communication skills that mattered. The risk of tautology when exploring associations between phenomena with instruments possibly covering some of the same issues has been considered and attended to by testing any possible difference when using the overall mean in contrast to the no-content-related mean of ACIR. When no such difference existed, it is reasonable to presume that the relationship we have found between communication skills and the content indices in this specific consultation was real and not confounded by lack of construct validity for the two instruments. The finding that there was no significant relationship between a high level of communication skills and a high count on the Illness index is important. This may be due to a low variance in the Illness index, but this does not coincide with Table 3 . Another interpretation of this finding, therefore, may be that the somatic content of this particular consultation (the diagnoses of possible myomas and anemia as well as the subjective complaints) depends more on biomedical knowledge than the communication skills themselves and that the presence of these symptoms was not related to psychosocial aspects. Along the same line, we found that those who scored high on the Illness index but low on the Psychosocial and Informing/planning indices had a significantly lower level of communication skills compared with those with high scores on all three indices. This supports the view that graduate students who are very competent in evaluating somatic complaints nevertheless may fail to identify important psychosocial stressors and concerns, in this case due to the lack of communication skills. We know that these issues are important both for patient compliance and satisfaction as well as for the further course and outcome of many somatic disorders . In order to obtain valuable information on the emotional burdens of patients who may be less willing than the "patient" in this study to disclose such issues, the need for specific communication skills is obvious. In a study by Pfeiffer et al. , a decrease in students' communication skills was found through the last part of medical school, after an initial increase, especially their skills in obtaining an adequate social history. One interpretation offered was that this can be due to a medical culture which de-emphasizes communication skills in favor of somatic knowledge. This can also be a possible explanation of our findings. Therefore it is important to identify factors that may enhance as well as hamper the development of communication skills among medical students. This study has shown that the level of communication skills and the content of the consultation with regard to psychosocial issues, patient concerns and the informing and planning procedures (with a representative patient in a general practice setting) among graduate medical students are significantly correlated. On the other hand, no such relationship between communication skills and the somatic/illness content of the consultation was detected. Even if the students attending this study had good biomedical knowledge on this specific case, they may have overlooked important psychosocial stressors as well as the patient's concerns, and may have lacked the necessary skills to conclude this single patient consultation in a fruitful way. In this light, medical schools and researchers, utilizing a broader spectrum of patient stories, should continue to identify factors that promote as well as inhibit medical students' learning of communication skills. | Other | biomedical | en | 0.999996 |
18298853 | Oral lesions are well-documented clinical features in patients with Crohn's disease (CD) . The spectrum of these lesions described so far in the medical and dental literature is quite large and includes oral ulceration, labial, buccal and gingival swelling, buccal abscesses, mucosal inflammatory hyperplasia, mucosal tags and fissuring, gingivitis, granulomatous inflammation of minor salivary glands, granulomatous cheilitis , candidiasis, angular cheilitis, lichen planus, pyostomatitis vegetans, lymphadenopathy, perioral erythema, orofacial granulomatosis, midline lip fissuring, cobblestone appearance of the mucosa, and dental caries. The prevalence of oral lesions in newly diagnosed patients has been estimated to be up to 48% . The patient was a man aged 25. He was a smoker (20 cigarettes per day) since the age of 19. His symptoms started on June 1998 at the age of 24, with chronic diarrhea not accompanied by mucus or blood in the stools, abdominal pain, fever, or loss of weight. Two years previously on June 1996, he had noticed a slight swelling of the lower lip which contrasted with the previously normal appearance of his mouth . He consulted a specialist in oral medicine, who performed a lip biopsy. The histology of the specimen (13 × 7 × 7 mm) showed a multilayer squamous epithelium covering the tissue specimen, scattered clusters of lymphocytes and histiocytes resembling non-caseating granulomas, as well as infiltration of the small vessel walls of the underlying connective tissue by monocytes . The diagnosis was compatible with granulomatous cheilitis. Colonoscopy performed in 1998 revealed large ulcers in the terminal ileum and caecum. Enteroclysis confirmed the involvement of the terminal ileum in a total length of 50 cm. Administration of methylprednisolone, mesalazine and cholestyramine, resulted in prompt improvement of clinical symptoms and laboratory abnormalities. Orofacial granulomatosis is a term generally used to describe swelling of the orofacial area, mainly the lips, secondary to an underlying granulomatous inflammatory process. It is a heterogeneous clinical condition that presents with chronic swelling of the oral or facial tissues due to granulomatous inflammation. Granulomatous cheilitis is a very rare disorder of unknown etiology, characterised by recurrent swelling of the labial tissues. The typical histological picture is the formation of scattered aggregates of non-caseating granulomas and epithelioid histiocytes. Melkersson-Rosenthal syndrome (a triad of orofacial swelling, facial paralysis and a fissured tongue) is one manifestation of orofacial granulomatosis, which more commonly presents as granulomatous cheilitis alone . Most reported cases of orofacial granulomatosis have been in adults and some in adolescents. Orofacial granulomatosis in the paediatric population may be an initial manifestation of CD. The interesting points regarding the clinical manifestations and the course of our patient were the fact that granulomatous cheilitis preceded the diagnosis of CD by two years, the fact that the enlargement of the lower lip occurred in parallel with the clinical exacerbations of CD and that the administration of corticosteroids resulted not only in improvement of bowel symptoms but also in diminishment of the size of the lip swelling. Another point of interest was the fact that granulomatous cheilitis was the only extraintestinal manifestation in our patient, a fact not mentioned in other descriptions. The etiology of this lesion is unknown although various factors including levels of vitamins and trace elements, other nutritional components, and certainly the underlying inflammatory bowel disease could be involved. Mycobacterium paratuberculosis has not been found to be implicated in the pathogenesis of orofacial granulomatosis or oral CD as was suggested previously. In the absence of mechanical irritation or other mucosal disease, the oral lesions in CD could be attributed to the inflammatory bowel disease itself. It is of interest that patients with oral lesions have a significantly higher proportion of involvement of the upper gastrointestinal tract (esophagus) with CD . This case emphasizes the fact that orofacial granulomatosis may be misdiagnosed since its clinical manifestations may be independent of or even precede the appearance of CD. Thus, patients with possible granulomatus cheilitis should be carefully asked about the presence of gastrointestinal symptoms. Those with suspicious symptoms should have a careful gastrointestinal evaluation, including enteroclysis or imaging capsule as well as complete gastrointestinal endoscopic examination. Once granulomatus cheilitis is diagnosed the patient should be followed up carefully and investigated for CD when gastrointestinal symptoms develop . However, not all authors agree completely with this assumption. Van der Waal et al found a low chance of developing CD in their patients with granulomatus cheilitis and thus they suggest that patients with a negative history of gastrointestinal complaints should not be exposed to routine investigations of the gastrointestinal tract . | Review | biomedical | en | 0.999997 |
18718001 | A forty five year old lady presented with chronic dull aching pain with gradually increasing lump in the epigastric and pelvic region since 3 years. A well defined, firm mass of about 20 × 20 centimeters was palpable in epigastrium extending more on right hypochondrium, probably arising from left lobe of liver. A similar mass was palpable in the hypogastrium while multiple small nodular masses palpable in the right iliac fossa and lumbar region. Detailed inquest revealed a 5 year old incidence of blunt abdominal trauma, while working in her farm. The ultrasonography and CT scan showed multiple thin walled cysts of varying size involving left lobe of liver, peritoneal cavity, omentum and mesentery. Cysts showing internal septae and peripheral tiny calcific foci were also seen extending into pelvis around uterus, adnexae and retro-uterine cervical region, markedly compressing distal descending colon, sigmoid colon and rectum. Ileal loops were compressed and displaced superiorly. Serology for hydatid cyst disease was positive with ELISA test. Two courses of 4 weeks of Albendazole (15 mg/kg/day) were given with the interval of 1 month. The follow up after 1 month did not show any decrease in the size of the cysts and decision of laparotomy was taken. Peritoneal cavity was crammed with cysts ranging from 1 to 12 centimeters . Omentum was studded with cysts which was incised and cysts were picked up . A superficial cyst found in the left lobe of liver was opened with small incision and the hydatid fluid and daughter cysts were drained. After the excision of germinal membrane the cavity was masupialized. Later, the pelvic cavity was exposed and cysts adherent to adnexa, uterus, broad ligament, urinary bladder and rectum were removed. More than 250 cysts of different sizes were removed from the abdomen . Patient died of anaphylactic shock within few hours of operation. | Clinical case | clinical | en | 0.999996 |
18822182 | Diseases of the heart valves cut across all age groups, race and geographic locations to form a significant cause of morbidity and mortality. These deformities may be congenital or acquired, as a result of developmental, post-inflammatory and degenerative changes. In our country, owing to high prevalence of rheumatic heart disease , the etiology in most valvular dysfunctions (stenosis and/or regurgitation) is attributed to rheumatic heart disease, unless proved otherwise. This is largely true in most instances, but there do exist occasions, where a "rheumatic "assumption is erroneous. We present a rare case of inflammatory pseudotumor, manifesting as a granulomatous valvulitis, producing chronic mitral and aortic regurgitation in a 62 years old lady. A 62-year-old woman presented to our Cardiovascular & Thoracic Center with complaints of breathlessness and palpitation. The dyspnea (grade II), present for the past eight years, had progressed in six months to grades III/IV. She had had past hospital admissions for similar complaints. A secundum atrial septal defect had been closed in the year 1990. She was advised valve replacement for rheumatic valvular heart disease. Routine hematological and biochemical investigations had been normal. Two-dimensional echocardiography showed severe mitral and moderate aortic, regurgitation. The pulmonary arterial pressure was 80 mm Hg. She was taken up for mitral and aortic valve replacements. The anterior mitral leaflet was thick and fleshy while the posterior leaflet was thin. There was no significant sub-valvular pathology. The anterior leaflet and the medial scallop of the posterior leaflet were excised and the valve was replaced by Carbomedics mechanical valve (27 mm). The right and non-coronary cusps of the aortic valve showed similar thickening. The cusps were excised and the valve replaced by a St. Jude's mechanical valve (19 mm). During surgery, there was inadvertent tear of the superior caval vein, which was sutured and the patient was put on ventilator support. She expired eight hours after surgery. On gross examination, the anterior leaflet , at its basal, commissural aspects was nodular and firm. The remaining leaflet was mildly thickened with rolling of the free margin. The tendinous chords were discrete, but moderately thickened. The right and non-coronary cusps were markedly thickened and firm; the left cusp looked normal . The thickened portions of both valves had a homogeneous, creamy cut surface. No thrombi were identified on gross. On histology, these valves revealed extensive polymorphic inflammatory infiltrate in their entire thickness with associated vascularization and minimal collagenization. There were plasma cells, lymphocytes, histiocytes and clusters of multinucleated giant cells , with few eosinophils and neutrophils. Interestingly, there were total seven foci of central ill-defined necroses, accompanied by nuclear debris and neutrophils ; these were surrounded by a vague palisade of histiocytes and giant cells. Stains for microorganisms, including fungi and acid fast bacilli, were negative. Since no obvious vegetations were formed, we entertained a possibility of Q fever endocarditis, but the organism ( Coxiella burnetii ) could not be demonstrated on immunohistochemistry or in-situ hydridization. We designated this lesion initially as idiopathic granulomatous valvulitis, but on the basis of exclusion, a diagnosis of valvular inflammatory pseudotumor was finally made. Immunohistochemistry confirmed the polyclonality of the inflammatory cells; myofibroblastic cells were not identified. In the partial chest autopsy that was subsequently performed, similar inflammatory cells were identified at the anterior mitral annulus and in the walls of the right and non-coronary sinuses of Valsalva. There was no involvement of the preserved posterior mitral leaflet or the ascending aorta. Our patient, a woman in her early sixties, had long-standing mitral and aortic regurgitation. She had had secundum atrial septal defect, patched at the age of 45 years. This type of defect is known to coexist with mitral valvular disease, especially rheumatic . However, review of the valvular morphology at operation and the subsequent valvectomy, did not suggest a rheumatic etiology. More interesting was the presence of inflammation that produced a tumorous expansion of the leaflet/cusps or an "inflammatory pseudotumor". Such inflammatory pseudotumors (IPT) or inflammatory myofibroblastic tumors (IMT), apart from the lungs, are also described in other organs, but occurrence in the heart is rare. Since its first description in 1975 , fewer than 30 cases of cardiac IMT have been described . By and large, the tumors have manifested mainly in children as inflow or outflow obstructions due to a propensity to involve the chambers . The present case is the eleventh case to be reported in adults . Apart from cardiac symptoms, our patient did not have any other constitutional symptoms, seen with IPTs . The IMT are considered as quasineoplastic lesions composed of inflammatory cells and myofibroblasts. In one subset of IMT, there is a profusion of inflammatory cells, secondary to infective or non-infective immune reactions, while the other group (considered neoplastic) is composed of myofibroblastic proliferation . We saw a predominance of inflammatory cells, including multinucleated giant cells in the excised mitral and aortic valves; the entire tissue had been processed. Hence we have preferred to use the term IPT. So far only nine patients have had involvement of the atrioventricular or the arterial valves with or without concomitant chamber involvement . It is interesting to note that lesions which tended to infiltrate the entire thickness of the valve leaflet/cusp were predominantly inflammatory while those having a polypoidal configuration were rich in spindled cells . No organisms were identified by special stains performed for bacteria, Mycobacteria and fungi. Assuming that there was a subtle underlying mitral valvulopathy due to the defect in the inter-atrial septum, we thought that a strong contender for producing valvulitis is chronic Q fever, where endocarditis accounts for 60 to 70% of the cases . The patients are often afebrile, and interestingly, vegetations are absent or small . However, Coxiella burnetii was not detected. One must also bear in mind other rarer causes of granulomatous valvulitis such as rheumatoid arthritis , Wegener's granulomatosis , and large vessel vasculitides . Our patient did not have any manifestations, suggestive of the aforementioned diseases. | Clinical case | biomedical | en | 0.999995 |
19523243 | Malignant transformation of mature cystic teratoma (MCT) is a rare complication occurring in approximately 1–3% of patients who have mature cystic teratoma . Although any of the constituent tissues of a teratoma has the potential to undergo malignant transformation, squamous cell carcinoma is the most commonly associated malignancy . Other reported malignancies arising in MCT include carcinoid tumor, adenocarcinoma, basal cell carcinoma, adenosquamous carcinoma, thyroid carcinoma, sebaceous carcinoma, malignant melanoma, sarcoma and neuroectodermal tumor . Primary renal carcinoid tumor is a low grade malignancy with neuroendocrine differentiation, and was first described by Resnick et al in 1966 . Since then less than 100 cases of primary renal carcinoid tumor have appeared in the international medical literature, and are often associated with horseshoe kidney (18–26%), renal teratoma (15%) and polycystic kidney disease (2%) . Primary carcinoid tumor arising within mature cystic teratoma of the kidney is rare. Only seven cases of primary carcinoid tumor arising in mature cystic teratoma of the kidney have been reported in the world medical literature to date , since the association was first described in 1976 by Kojiro et al . The simultaneous occurrence of mature cystic teratoma and adenocarcinoma in the kidney is also rare . To the best of our knowledge, the synchronous presentation in the same kidney of mature cystic teratoma, carcinoid tumor and adenocarcinoma has never been reported in the world medical literature. We present a unique and first case of a 50-year-old female with both primary carcinoid tumor and primary moderately differentiated adenocarcinoma simultaneously arising within mature cystic teratoma of horseshoe kidney. Additionally, we review the world medical literature and discuss the extreme rarity of this combination of primary tumors in the kidney and the probable common histogenesis of these synchronous neoplasms in horseshoe kidney. The patient was a 50-year-old female who presented with a 3-months history of progressive chronic low back and right hip pain. She had no symptoms of carcinoid syndrome. She had no previous history of malignancy, chemotherapy or radiotherapy. General physical exam was unremarkable. Chest radiographs and electrocardiogram were within normal limits. Her routine hemogram, urine and blood biochemical analyses were within normal ranges. A lumbar spine X-ray, done to workup her complaint of low back pain, accidentally found a large (1.9 cm) calcification overlying the lower pole of the right kidney . Subsequent computed tomography (CT) and magnetic resonance imaging (MRI) scans of abdomen and pelvis revealed horseshoe shaped kidney and a large (10.5 × 7.8 cm) multiseptated cystic lesion immediately anterior to the right renal pelvis with central calcification (1.9 cm) and peripheral enhancement , which was interpreted radiologically as a Bosniak category IV renal lesion with a 90% chance of malignancy. No additional lesions were identified in the brain, gastrointestinal tract, liver, spleen, pancreas, bladder, uterus, ovaries and bones on additional MRI scans of the abdomen, brain, chest and pelvis, and positron emission tomography (PET) scan. This excluded the possibility of other primary malignancies metastatic to the right kidney. Her serum levels of alpha-fetoprotein (α-FP), beta-subunit of human chorionic gonadotropin (β-hCG), carbohydrate antigen (CA) 19-9, CA72-4, CA125, carcinoembryonic antigen (CEA), chromogranin and serotonin were within normal ranges. Her urinary 5-hydroxyindoleacetic acid (5-HIAA) level was also within normal range. In view of the high concern for primary malignancy in this Bosniak category IV right renal lesion, the patient elected to undergo right partial nephrectomy for definitive surgical treatment. After the peritoneal cavity was surgically opened, a thorough inspection and palpation of the peritoneal cavity was performed which revealed no ascitic fluid, adhesions, or other evidence of metastatic disease or non-renal primary malignancy. The entire right renal tumor was surgically resected with an excellent margin of 0.5 cm of normal parenchyma surrounding the entire cyst wall, and the tumor was entirely confined to the kidney. No other lesions were present in the adjacent renal parenchyma. The postoperative period was uneventful and the patient was discharged four days after surgery. Additional sections were used to perform immunohistochemical studies using an avidin-biotin peroxidase technique with hematoxylin counterstain. The antibodies used in this study included the following; alpha-methylacyl-coenzyme A-racemase (AMACR/P504S) [1:100, Ventana Medical Systems Inc, Tucson, Arizona], calretinin (1:100, Becton Dickinson, San Jose, California, USA), carbonic anhydrase IX (CA-IX, 1:200, DakoCytomation, Carpinteria, California, USA), CD10 (1:200, Ventana), CD56 (1:200, DakoCytomation), CD99 (1:100, Ventana), CDX2 (1:100, Ventana), chromogranin (1:200, Signet Pathology Systems Inc, Dedham, Massachusetts, USA), cytokeratin 7 (CK7, 1:200, Ventana), cytokeratin 20 (CK20, 1:200, DakoCytomation), pancytokeratin cocktail (AE1-AE3, 1:500, DakoCytomation; CAM 5.2, 1:50, Becton Dickinson; MNF116, 1:50, DakoCytomation; and UCD/PR-10.11, 1:25, Zymed, San Francisco, California), smooth muscle actin (SMA, 1:200, DakoCytomation), synaptophysin (1:100, DakoCytomation), and thyroid transcription factor-1 (TTF-1, 1:250, Ventana). Appropriate tissue sections that had been shown to be positive or negative for each marker were used as controls. Slides stained omitting the primary antibody were also used as negative controls. We analyzed the intensity and immunoreactivity of the immunostained sections. The intensity was graded qualitatively as weak, moderate, or strong on the basis of the brown color produced by the 3, 3'-diaminobenzidine chromogen. Diffuse and intense brown staining of the cytoplasmic or nuclear surfaces, as appropriate for each stain, was interpreted as strong staining intensity. Moderate intensity staining was characterized as non-diffuse but intense staining pattern, whereas weak intensity had a non-diffuse and non-intense staining pattern. Immunoreactivity was quantitatively estimated by the percentage of positive cells per representative section. Immunoreactivity was graded as 1+, 2+, and 3+, corresponding to less than 25%, between 25% and 50%, and greater than 50% of neoplastic cells showing positive staining per representative section, respectively. Grossly, the partial nephrectomy specimen revealed an encapsulated multiloculated gray-tan tumor (9.7 × 7.4 × 7.8 cm). The interface between tumor and uninvolved kidney was sharp. Sectioning of the tumor revealed circumscribed complex solid and multiloculated cystic lesion with large area of calcification (1.7 cm). The largest cyst measured up to 1.4 cm, and the cysts were filled with yellow-tan gelatinous material. The wall of the cysts showed focal thickened firm and hard calcified areas. The tumor was confined to the kidney and was at least 0.5 cm from the nearest stapled resection margin. There was no gross evidence of extension of the tumor into the renal pelvis, renal vein, renal artery, ureter, renal sinus, renal capsule, or perinephric adipose tissue. The entire tumor was submitted for histological examination. The histological examination revealed three components. The first component was multilocular cystic spaces lined by mucinous columnar enteric-type or colonic-like epithelium and ciliated epithelium , and containing fragments of smooth muscle in the wall. These findings in the first component represent a mature cystic teratoma . The predominant teratomatous element in the first component was mucinous columnar enteric-type or colonic-like epithelium , followed by ciliated epithelium , and smooth muscle . The second and third components of the tumor make up the solid parts of the tumor. The second component of the tumor showed tightly-packed back-to-back highly atypical infiltrating glands composed of cohesive pleomorphic epithelioid cells with adjacent necrosis . The tumor cells were large with abundant eosinophilic cytoplasm, enlarged nuclei with contour irregularities, and occasional prominent nucleoli . Mitotic figures were readily identified. There was no evidence of lymphovascular invasion. These features of the second component represent an invasive moderately differentiated adenocarcinoma . The carcinoid tumor and adenocarcinoma components were found adjacent and closely apposed to each other, with or without a clear transition zone. The third component showed proliferating trabecular and anastomosing ribbon-like nests of monotonous small round cells with fine granular "salt-and-pepper" chromatin pattern , and peripheral palisading . Mitotic figures were not identified. There was no evidence of lymphovascular invasion. These features of the third component represent a carcinoid tumor . The carcinoid tumor and adenocarcinoma components were found underneath and closely apposed to the epithelial lining of the teratomatous cysts, and focally invading teratomatous smooth muscle wall . All surgical resection margins were free of the three components of the tumor. Alpha-methylacyl-coenzyme A-racemase (AMACR/P504S), calretinin, CD10 and thyroid transcription factor-1 (TTF-1) did not stain any of the three components of the tumor. The teratomatous cysts were lined by ciliated epithelium (strong and diffuse cytoplasmic labeling for cytokeratin 7 and pancytokeratin) and mucinous columnar enteric-type or colonic-like epithelium , but were negative for calretinin (a mesothelial marker). Additionally, the teratomatous cyst wall was strongly and diffusely immunoreactive (3+, cytoplasmic staining) for smooth muscle actin ; and weakly and focally immunoreactive (1+, cytoplasmic staining) for carbonic anhydrase IX (CA-IX), CD99, chromogranin and synaptophysin. The carcinoid tumor and adenocarcinoma components were found adjacent and closely apposed to each other , with the adenocarcinoma component in right upper part of figure being strongly and diffusely immunoreactive (3+, cytoplasmic staining) for CK7 whilst the carcinoid tumor component in left lower part of figure being negative for CK7 . The adenocarcinoma component was strongly and diffusely immunoreactive (3+, cytoplasmic staining) for CK7 and pancytokeratin; weakly and focally immunoreactive (1+, cytoplasmic staining) for CD56 and synaptophysin; and negative for CA-IX, CD99, CDX2, chromogranin, CK20 and SMA. The carcinoid tumor component was strongly and diffusely immunoreactive (3+, cytoplasmic staining) for CD56 , chromogranin and synaptophysin ; weakly and focally immunoreactive (1+, cytoplasmic staining) for pancytokeratin ; and negative for CA-IX, CD99, CDX2, CK7, CK20 and SMA. On the basis of the above histopathological and immunohistochemical features, a definitive diagnosis of synchronous primary carcinoid tumor and primary moderately differentiated adenocarcinoma arising within mature cystic teratoma of horseshoe kidney was rendered. This tumor could not be staged since no relevant staging system exists for synchronous primary carcinoid tumor and primary moderately differentiated adenocarcinoma of kidney. Her postsurgery serum levels of alpha-fetoprotein (α-FP), beta-subunit of human chorionic gonadotropin (β-hCG), carbohydrate antigen (CA) 19-9, CA 72-4, CA 125, carcinoembryonic antigen (CEA), chromogranin and serotonin continued to remain within normal ranges. Her postsurgery urinary 5-HIAA level also continued to remain within normal range. Additionally, postsurgery whole body somatostatin receptor scintigraphy with octreotide performed was negative, hence confirming the carcinoid tumor as originating primarily in the resected renal tumor (rather than elsewhere with metastasis to the kidney) and the absence of metastases from the resected renal carcinoid tumor. Hence, the partial nephrectomy with complete resection of the tumor was considered adequate conservative clinical management. She received no adjuvant therapy. Two follow-up CT and MRI scans of the brain, abdomen, chest and pelvis, and PET scans performed at 3-month intervals after surgery revealed no lesions. The patient herein presented is alive with no evidence of local recurrence or metastatic disease, six months postoperatively, and regular periodic follow-up with interval CT, MRI and PET imaging studies, and octreotide scintigraphy is planned. Mature cystic teratomas may consist of a wide variety of ectodermal, mesodermal, and endodermal tissues, and hence the possibility of additional neoplasms occurring in teratomas, though rare, can at least be anticipated. It is not surprising that squamous cell carcinoma leads the list of secondary neoplasms arising in teratomas, because many mature cystic teratomas contain large amounts of squamous epithelium . In second place among secondary neoplasms in mature cystic teratomas, carcinoid tumor and adenocarcinoma are said to be of equal frequency, but the former is reported to be increasing in frequency . Hence, adenocarcinoma or carcinoid tumor arising from mature cystic teratoma of kidney is an uncommon occurrence . The simultaneous occurrence of mature cystic teratoma and adenocarcinoma in the same kidney is rare , and so is the simultaneous occurrence of mature cystic teratoma and carcinoid tumor in the same kidney . Similarly, the simultaneous occurrence of carcinoid tumor and adenocarcinoma in the same kidney is rare. To the best of our knowledge, the synchronous presentation in the same kidney of these three neoplasms (mature cystic teratoma, carcinoid tumor and adenocarcinoma) has never been reported in the world medical literature. We have presented a unique and first case of a 50-year-old female with both carcinoid tumor and adenocarcinoma simultaneously arising within mature cystic teratoma of horseshoe kidney. We discuss below the extreme rarity of this combination of three primary tumors in the kidney and the probable common histogenesis of these three synchronous neoplasms in horseshoe kidney. Carcinoid tumors are characteristically low grade malignant tumors with neuroendocrine differentiation that have been described in several locations, including the gastrointestinal, respiratory, hepatobiliary, and genitourinary systems. Carcinoid tumors most commonly occur in the gastrointestinal tract (74%) and bronchial system of the lungs (25%) . In less than 1% of cases these tumors have been reported in the genitourinary system. Carcinoid tumors arising in the genitourinary system are rare, but have been reported in the ovary, testes, kidney and prostate . Primary renal carcinoid tumor is the second most prevalent genitourinary carcinoid tumor in each sex, following testicular carcinoids in males and ovarian carcinoids in females . Primary renal carcinoid tumors are among the most unusual of all renal neoplasms, since neuroendocrine cells are not found within normal renal parenchyma. Primary renal carcinoid tumors have been reported in the literature primarily as case reports (as in the case herein presented), with the three largest series to date consisting of 5 , 6 , and 21 patients. Primary carcinoid tumor of the kidney was first described by Resnick et al. in 1966 , and since then fewer than 100 cases of primary renal carcinoid tumor have appeared in the international medical literature . Primary renal carcinoid tumors have been reported to arise most commonly in the setting of acquired and congenital renal abnormalities (as in the case herein presented), such as horseshoe kidney (18–26%) , renal teratoma or teratoid malformation (15%) , and polycystic kidney disease (2%) . The age range for reported cases of primary renal carcinoid tumor is 12 to 78 years, but most patients present in the fourth to seventh decades of life and there is no gender predilection . A recent review of 56 primary renal carcinoid tumors reported in the literature up to December 2005 by Romero et al. observed that the median patient age was 49 years. Romero et al. further reported that horseshoe kidneys were present in 17.8% of patients (as in the case herein presented), incidental diagnosis was made in 28.6% of patients (as in the case herein presented), and metastases were present in 45.6% of patients at initial diagnosis. They also observed that the significant adverse prognostic factors include age greater than 40 years, tumor size greater than 4 cm, purely solid tumors on cut surface, mitotic rate higher than 1 per 10 high power fields, metastasis at initial diagnosis and tumors extending through the renal capsule . The largest series of primary renal carcinoid tumors reported to date consisting of 21 patients by Hansel et al. observed that the mean patient age was 52 years. As in the case herein presented, Hansel et al. further reported that horseshoe kidneys were present in 19% of patients, and calcifications were present in 23.8% of cases of primary renal carcinoid tumor. They concluded that primary renal carcinoid tumor was morphologically and immunohistochemically similar to carcinoid tumors present at other anatomic sites, and that patients frequently presented with regional lymph node metastases and may progress to distant organ metastases, but usually have a prolonged clinical course despite widely metastatic disease . Complete surgical resection is the main treatment modality for primary renal carcinoid tumors and can be curative for localized disease (as in the case herein presented), and long-term follow-up of patients is recommended since metastases have occurred as late as seven years after the primary diagnosis . Primary carcinoid tumors of the kidney are rare , and primary carcinoid tumor arising within horseshoe kidneys and mature teratomas of the kidney are even rarer. Less than 100 cases of carcinoid tumor of the kidney have been reported in the international medical literature , including 18 cases arising in horseshoe kidneys and seven cases arising within mature cystic teratomas . A recent review by Armah and Parwani identified that only seven cases of primary carcinoid tumor arising in mature cystic teratoma of kidney have been reported in the world medical literature to date , since the association was first described in 1976 by Kojiro et al . Primary carcinoid tumor arising in a mature teratoma of the kidney is over-represented in patients with congenital developmental renal defects such as horseshoe kidney, with one out of the seven cases (15%) of primary carcinoid tumor arising in mature cystic teratoma occurring in a horseshoe kidney . Epidemiologically, primary carcinoid tumor arising within mature cystic teratoma of the kidney occurred predominantly in the fourth to seventh decades of life (mean age of 41.4 years), except one case occurring at age 23, and showed no sex predilection . An incidental diagnosis was made in 28.6% of cases, and clinically apparent carcinoid syndrome was absent in all the seven reviewed cases of primary carcinoid tumor arising within mature cystic teratoma of the kidney (as in the case herein presented), likely reflecting their hindgut origin and the breakdown of their secreted biologically active hormones in the liver before reaching the systemic arterial circulation. Armah and Parwani further observed that primary carcinoid tumor arising within mature cystic teratoma of the kidney were morphologically similar to carcinoid tumors present in normal kidneys and at other anatomic sites, and that surgery was curative with no additional treatment required, and no local recurrences and metastases occurred in all seven cases reviewed , as in the case herein presented. Immunohistochemically, synaptophysin, chromogranin and neuron specific enolase were the most valuable markers for the diagnosis of primary carcinoid tumor arising within mature teratoma of the kidney , as in the case herein presented. Despite the absence of long term follow-up data for some of the seven cases reviewed, the biologic behavior and prognosis of primary carcinoid tumor arising within mature teratoma of the kidney appeared excellent , as in the case herein presented. Recent studies comparing the prognosis of carcinoid tumors arising within teratomatous and normal kidneys have reported contradictory findings . Four studies have reported better prognosis for carcinoid tumor arising within teratomatous kidneys compared to those arising within normal kidneys . However, a recent review of renal carcinoid tumors revealed that neither renal teratoma nor horseshoe kidneys derived carcinoid tumors were associated with a better prognosis than carcinoid tumors originating in normal kidneys . Hence, although definitive conclusions cannot be drawn from such a small set of studies and patients without systematic long term 5-year follow-up, the ultimate biologic behavior of primary carcinoid tumor arising within mature teratoma of the kidney and horseshoe kidneys may be excellent, and may be better than that for carcinoid tumors arising in normal kidneys and non-renal locations . We were not able to find any reported case of simultaneous occurrence of mature cystic teratoma, carcinoid tumor and adenocarcinoma in the same kidney, in our literature search. We have herein described a case of coexistent mature cystic teratoma, carcinoid tumor and adenocarcinoma in a horseshoe kidney in a 50-year-old female. The age of the case herein presented is close to the mean and/or median age of both previously reported patients with carcinoid tumor arising within normal kidneys (49–52 years) and carcinoid tumor arising within teratomatous kidneys (41.4 years) . The strong expression of three neuroendocrine markers (CD56, chromogranin and synaptophysin) and the absence of expression of two epithelial markers (CK7 and CK20), exclude the possibility of invasive urothelial carcinoma arising from the renal pelvis in the case herein presented. Most urothelial carcinomas have the immunoprofile of CK7+/CK20+ or CK7+/CK20- . In contrast, most carcinoid tumors arising from the digestive tract or of hindgut origin have the pattern CK7-/CK20- , as in the case herein presented. Therefore, it is most likely that the carcinoid tumor in the present case arose outside the urothelial epithelium of the renal pelvis. Carcinoid tumors are thought to arise from enterochromaffin cells or amine precursor uptake and decarboxylation (APUD) cells, and are widely distributed throughout the body. In the urogenital tract, APUD cells have been described in the urinary bladder (especially in the neck and trigone), the urethra, the prostate, and the renal pelvis, but not in the renal parenchyma . In contrast, paraganglionic tissue is present in fetal or adult renal hilum . Although primary renal carcinoid tumors, as in the case herein presented, exhibit morphologic and immunohistochemical features consistent with a hindgut neuroendocrine phenotype , the precise histogenesis of renal carcinoid tumors is uncertain and is a matter for continuing speculation. Multiple published reports support the notion that renal carcinoid tumors are derived from interspersed neuroendocrine cells associated with acquired and congenital renal abnormalities such as teratomas and horseshoe kidneys . Carcinoid tumors occurring in renal teratomas are thought to be derived from neuroendocrine cells of the gastrointestinal and respiratory epithelium, which are components of these teratomatous lesions . Two main hypotheses have been proposed for the coexistence of congenital and acquired renal abnormalities (such as horseshoe kidney and mature cystic teratoma) and secondary malignancies (such as carcinoid tumor and adenocarcinoma in the case herein presented) in the kidney. The most popular hypothesis, the totipotent cell hypothesis, states that primary renal carcinoid tumor arise from totipotential primitive stem cells capable of neuroendocrine, mesenchymal and epithelial differentiation . Although conclusive evidence for this theory is lacking at present, one renal carcinoid tumor has been shown to share some genetic aberrations with renal cell carcinomas, indicating a common genetic event in the tumorigenesis for these two entities . Furthermore, this hypothesis of derivation from a multipotent stem cell is most consistent with the occurrence of neuroendocrine tumor in conjunction with epithelial malignancies, which might express markers of both components, as in the case herein presented. The less popular hypothesis states that the coexistence of carcinoid tumors (and other secondary malignancies such as adenocarcinoma in the case herein presented) with congenital and acquired renal abnormalities (such as horseshoe kidney and mature cystic teratoma) are due to hyperplasia of interspersed neuroendocrine cells within metaplastic or teratomatous epithelium in horseshoe kidneys; or nests of misplaced progenitor cells developing into teratomatous intestinal or respiratory epithelia in renal teratomas, might serve as a nidus for renal carcinoid tumors and adenocarcinoma. Cases of renal carcinoid tumor arising in association with renal teratoma and/or horseshoe kidneys lend weight to this hypothesis . The relative risk of renal carcinoid tumors in patients with horseshoe kidneys has been calculated at between 62 and 85 . Horseshoe kidneys have been proposed to be the result of teratogenic factors, which may also account for the increased risk of malignant tumors in horseshoe kidneys . The high association of carcinoid tumors with horseshoe kidneys is likely due to predisposing embryological factors or teratogenic events involving the abnormal migration of posterior nephrogenic cells in utero , which coalesce to form the isthmus of horseshoe kidneys . Additionally, this hypothesis is supported by the common occurrence of renal carcinoid tumors in the isthmus of teratomatous and horseshoe kidneys , as in the case herein presented with an additional adenocarcinoma. Applying this hypothesis to the case herein presented, the carcinoid tumor and adenocarcinoma would represent secondary tumors derived from foci of neuroendocrine and epithelial differentiation in the mature cystic teratoma of the horseshoe kidney. This hypothesis suggests that renal carcinoid tumors bearing no relationship to congenital and acquired renal abnormalities might arise directly from neuroendocrine cells situated in the renal pelvic urothelium . From the above discussion, the direct supporting experimental and clinical evidence for these two hypotheses of histogenesis for multiple malignancies arising within teratomatous and horseshoe kidneys is inconclusive, and the exact mechanism is not well understood. As with all malignancies, the pathway for carcinogenesis is likely to be complex and multifactorial. Further studies would be required in order to elucidate the precise histogenesis for multiple secondary neoplasms arising within teratomatous and horseshoe kidneys. Synchronous primary carcinoid tumor and primary adenocarcinoma arising within mature teratoma of horseshoe kidney is a unique occurrence. This is the first reported case to our knowledge of mature cystic teratoma coexisting with carcinoid tumor and adenocarinoma in the same kidney. This unique case report emphasizes the need for thorough sectioning and entire submission for histologic evaluation of mature cystic teratomas since multiple additional histogenetically distinct small neoplasms occurring in a mature cystic teratoma could easily be missed through incomplete sectioning and histologic evaluation, potentially compromising patient care. Although longterm follow-up was lacking in the case herein presented, this unique occurrence of three neoplasms in horseshoe kidney was not associated with local recurrence and metastasis, was surgically curable, and had a rather favorable prognosis. | Clinical case | biomedical | en | 0.999998 |
19918501 | Autoimmune hemolytic anemia is occasionally reported in patients with other autoimmune illnesses, most commonly systemic lupus erythematosis, rheumatoid arthritis, scleroderma, and ulcerative colitis . There are at least 10 case reports of autoimmune hemolytic anemia associated with hyperthyroidism , and 1 report of autoimmune hemolytic anemia associated with reactive arthritis . However, a Medline search reveals no previous reports of concurrent reactive arthritis, hyperthyroidism, and autoimmune hemolytic anemia. We report the case of a 40-year-old man who developed severe warm autoimmune hemolytic anemia while under treatment for both Graves’ disease and reactive arthritis. Our subject’s mother and possibly his maternal grandmother also had autoimmune hemolytic anemia, which raises the possibility of hereditary autoimmune hemolytic anemia, a rarely reported condition . A 40-year-old Caucasian American man with reactive arthritis, Graves’ disease, type 2 diabetes mellitus, mitral valve prolapse, and Gilbert’s disease was admitted with one month of progressive jaundice, fatigue, lightheadedness, and exertional dyspnea. He also described dark urine (“the color of raspberry iced tea”) and dark brown to black stools. He denied fevers or chills, but gave a long history of night sweats and occasional diarrhea, which he ascribed to his medications. He had no history of blood transfusions, prior hepatitis, alcohol use, intravenous drug use, or tattoos, and he did not use herbal medications or supplements. He had recently come to Cleveland to help care for his father, who had stage IV colon cancer. His mother had been diagnosed with autoimmune hemolytic anemia at the age of 40; she was treated with corticosteroids and eventually required splenectomy. His maternal grandmother also had anemia and jaundice, although the patient was not aware of the cause. His medications were etanercept, metformin, pioglitazone, methimazole, niacin, and aspirin. He had stopped the pioglitazone and metformin more than one month prior to admission (before the onset of jaundice) on the advice of an endocrinologist. He had been diagnosed with reactive arthritis about 10 years before admission, and had been treated with etanercept for the previous 8 years. His Graves’ disease had been diagnosed 18 months before admission, and treated over that time with methimazole. Physical examination revealed a calm, well-nourished man with scleral icterus and generalized jaundice. Blood pressure was 130/76, heart rate 102/min., respiratory rate 16/min, temperature 97.7F. There was no cervical, supraclavicular, epitrochlear, axillary, or inguinal lymphadenopathy. The thyroid gland was not enlarged or tender, and there was no proptosis, lid-lag, or tremor. The lungs were clear and the heart rhythm was regular without murmur, click, or gallop. The abdomen was soft and non-tender, with the liver edge palpable 2 cm below the right costal margin; the spleen was not palpable. A vesiculobullous rash was seen on the plantar aspect of the right foot. Laboratory tests were significant for hemoglobin 5.8 g/dL, hematocrit 18.7%, MCV 107.5, platelet count 231,000, WBC count 9,800, reticulocyte count 23.4%, Bilirubin 13.6 (direct 0.6), LDH 369, and haptoglobin <6. Hepatitis A, B, and C serologies, antinuclear antibody, antimicrosomal antibody, D-dimer, cold agglutinins, cryoglobulins, and HIV test were negative. The fibrinogen was normal at 342. The INR was 0.8 and the partial thromboplastin time was 26.4. The peripheral smear showed spherocytes and bite cells, with no schistocytes, helmet cells, spur cells, sickle cells, or teardrop cells. The differential was 54.1% neutrophils, 35.6% lymphocytes, 8.3% monocytes, 1.7% eosinophils, and 0.3% basophils. Direct antiglobulin test (DAT) was + for anti IgG and negative for anti-C3. The indirect antiglobulin test was negative. The G6PD level was normal. TSH was 1.067. In this case, the elevated LDH and indirect bilirubin, low haptoglobin, and high reticulocyte count all were consistent with hemolysis. There was no fever, leukocytosis, or pertinent travel history to suggest malaria or babesiosis, and there was no evidence of spider or insect bites. The patient did not have a history of chronic anemia, which was against the diagnosis of hereditary spherocytosis. The normal fibrinogen, negative D-dimer, and absence of schistocytes on peripheral smear ruled out a microangiopathic process. A normal G6PD level, obtained after the acute phase of the illness, eliminated G6PD deficiency as a possibility. The DAT revealed an anti-IgG antibody on the RBC’s, consistent with either a warm autoimmune hemolytic anemia (WAIHA) or a drug-induced hemolytic anemia (DIHA). There are 4 case reports of metformin-induced hemolytic anemia , but our patient had stopped metformin at least a month before his symptoms developed, so this was very unlikely. There is one reported case of a patient with rheumatoid arthritis who developed cold agglutinin disease during etanercept treatment , but cold agglutinin disease is associated with IgM antibodies and typically causes only mild hemolysis. Our patient’s cold agglutinin screen was negative. None of his other medications have been reported to cause hemolytic anemia. The leading diagnosis was therefore WAIHA. Most cases of WAIHA are idiopathic, but secondary causes can include viral infections, autoimmune disorders (particularly SLE, RA, UC, and scleroderma), immune system malignancies (most commonly CLL), AIDS and other immunodeficiency disorders, and various non-lymphoid neoplasms. The work-up for secondary causes was negative with the exception of the CT scan findings of thymus enlargement, mild splenomegaly, and multiple sub-centimeter (ranging 5 to 9 mm) hypodensities in the liver and kidney of uncertain significance. WAIHA often precedes the development of lymphoid malignancies, sometimes by several months; a repeat CT scan is planned in 2-3 months to reassess the abnormalities. Graves’ disease is associated in some patients with autoimmune dysfunction of multiple organs, including pernicious anemia, type 1 diabetes mellitus, autoimmune adrenal insufficiency, vitiligo, systemic sclerosis, myasthenia gravis, Sjogren’s syndrome, systemic lupus erythematosis, and rheumatoid arthritis. Multiple cases of autoimmune hemolytic anemia associated with hyperthyroidism have been reported. In Graves’ disease, IgG type autoantibodies bind to the thyroid cell and activate the thyroid stimulating hormone receptor, which increases thyroid metabolic activity. In one case of hyperthyroidism with AIHA, treatment of hyperthyroidism with propylthiouracil not only restored euthyroidism but ameliorated the hemolytic anemia as well, without use of corticosteroids or blood transfusions . The authors speculate that the hyperdynamic circulatory state in hyperthyroidism might accelerate hemolysis in antibody-coated red blood cells. Thomson et al. describe a patient who developed Graves’ disease during long-term immunosuppressive therapy for acquired autoimmune hemolytic anemia . Thomson’s conclusion was that the IgG type immunoglobulins that cause Graves’ disease can develop even in the setting of long-term immunosuppressive treatment. At the time he developed WAIHA, our patient was clinically and chemically euthyroid after 18 months of propylthiouracil treatment. He had also been on immunosuppressive treatment with the tumor necrosis factor-inhibitor etanercept for several years, with good control of his reactive arthritis symptoms. The WAIHA seems not to have developed in response to a flare-up of either condition. Reactive arthritis occurs after primary extraarticular infections, either enteric or sexually transmitted, and is characterized by the presence of bacterial antigen and/or viable but non-culturable bacteria that persist within the joint. HLA-B27 is present in 70-80% of patients with reactive arthritis, and HLA-B27 increases the risk of reactive arthritis by 25-fold. Although there are a number of known bacterial triggers for development of reactive arthritis, the precise mechanism of the pathologic host response is unknown. Possibilities include an HLA-B27 autoantigen, cellular uptake of causative organisms, toll-like receptors, and chemokine involvement . Graves’ disease has been associated with a variety of infectious agents, including Yersinia enterocolitica , which is also one of the bacteria known to cause reactive arthritis . Yersinia enterocolitica has not, however, been reported as a cause of WAIHA. We were unable to find any prior case reports of concurrent reactive arthritis and Graves disease. There is one report of a 30-year-old man in Papua New Guinea who developed severe hemolytic anemia (Hb 2.8) in the setting of reactive arthritis with urethritis, conjunctivitis, and keratoderma blenorrhagica . Although a DAT was not reported, the author argued that the hemolysis was autoimmune because malaria and hypersplenism were excluded, and the anemia resolved with methotrexate and prednisolone treatment. There are only a few case reports of hereditary autoimmune hemolytic anemia . The paucity of reports and the sporadic pattern of involvement suggests that familial occurrence of AIHA is likely to be coincidental, although the sharing of HLA antigens 1 and 8 in a report of two affected sisters might argue for a genetic susceptibility in some cases . It has been postulated that autoimmune diseases are a “mosaic” of genetic, immune, hormonal, and environmental factors. Genetic causes may include human leukocyte antigen (HLA) genes, non-HLA immune-regulatory or tissue-specific genes, and genetically-determined selective IgA deficiency . Environmental factors may include infection, with Yersinia as a possibility, or the use of medications including long-term cytokine suppression with etanercept. A combination of genetic and environmental factors might have contributed to this patient’s development of multiple autoimmune diseases. We report the first case of concurrent reactive arthritis, Graves’ disease, and autoimmune hemolytic anemia. Yersinia enterocolitica infection could theoretically cause both reactive arthritis and Graves’ disease, although we cannot prove this connection in our patient’s case. It is not clear whether the autoimmune hemolysis was coincidental or related to an underlying condition that predisposed this patient to multiple autoimmune diseases. The family history of autoimmune hemolysis suggests the possibility of an inherited predisposition. | Clinical case | biomedical | en | 0.999999 |
20454696 | Achromatopsia is a congenital autosomal recessive cone disorder with a prevalence of 1 in 30,000 individuals . The clinical features include low visual acuity, nystagmus, photophobia, severe color vision defects, and no recordable or only residual cone function on electroretinography (ERG) with normal rod functions. Fundoscopy is usually normal, although macular pigmentary changes and atrophy have been described in the literature . ACHM is characterized by progressive cone loss, which has been described in a large proportion of patients in terms of the worsening of the macular appearance and deterioration of the central vision irrespective of the genetic cause . It has been reported that the use of red contact lenses or red tinted glasses can alleviate photophobia in patients with ACHM or cone dystrophy . To date, ACHM has been described as being caused by mutations in four genes: cyclic nucleotide-gated channel alpha-3 ( CNGA3), cyclic nucleotide-gated channel beta-3 (CNGB3), guanine nucleotide-binding protein, alpha-transducing activity polypeptide 2 (GNAT2), and phosphodiesterase 6C ( PDE6C) . The proteins encoded by these four genes are specifically expressed in cone photoreceptor cells, where they have been shown to be involved in the cone phototransduction cascade. CNGA3 encodes the α-subunit and CNGB3 the β-subunit of the cyclic nucleotide-gated (CNG) channel that has a central function in signal transduction of the visual pathway . 25% of all ACHM patients carry mutations in CNGA3 , and 45%–50% carry CNGB3 mutations, whereas only a few families have been reported to have GNAT2 or PDE6C mutations . Mutations in CNGA3 , CNGB3, and PDE6C have also been associated with cone dystrophy in a small proportion of patients . For family RP26, blood samples were collected from 16 individuals (four affected and 12 healthy individuals) from a six generation pedigree . For family RP44, blood samples were collected from eight individuals (two affected and six normal individuals) from a four-generation pedigree . DNA isolation was performed as described previously . All the affected members of family RP26 (IV-1, V-2, V-3, VI-2), and seven individuals of family RP44 (healthy individuals III-2, IV-2, IV-4, IV-6, IV-7 and affected individuals IV-1 and IV-3) were genotyped using the Affymetrix 10K single nucleotide polymorphism (SNP) array containing 10,204 SNPs (Affymetrix, Santa Clara, CA). Multipoint parametric linkage analysis of the SNP array data of both families was performed using the GeneHunter program in the EasyLinkage software package (version 5.02) . Fine-mapping of the region on chromosome 2q11.2 with the highest logarithm (base 10) of odds (LOD) score in family RP26 was conducted using microsatellite markers that were amplified by the polymerase chain reaction (PCR) under standard conditions. Haplotypes were constructed based upon the size of the alleles of the microsatellites. The positions of the microsatellite markers were derived from the Marshfield map. Two-point parametric LOD scores for the microsatellite markers were calculated using the SuperLink program (version 1.6) in the EasyLinkage software package . The sequencing primers for the candidate genes CNGA3 and CNGB3 have been described before . For family RP26, the seven coding exons of the CNGA3 gene were sequenced in one affected individual (V-2) along with a control sample, and for family RP44, all 18 coding exons of the CNGB3 gene were sequenced in individual IV-1 as well as a control sample. The amplified PCR products were separated on agarose gel and purified with a Nucleospin DNA extraction kit (Nucleospin Extract II, Macherey-Nagel GmbH and Co, Germany). Purified products were directly sequenced using the corresponding primers and dye-termination chemistry . Segregation of the CNGA3 mutation in family RP26, and analysis of the mutation in 22 unrelated probands with autosomal recessive retinal dystrophies and 150 ethnically-matched control individuals, was performed via allele-specific PCR . For this purpose, three primers were designed; a forward wild type (5′-AAA GGT GGG CAC AAA CTA CCC AGA AGT GAG G-3′), forward mutant (5′-AAA GGT GGG CAC AAA CTA CCC AGA AGT GAG T-3′) and a common reverse primer (5′-AAT GGC AAA GTA GAT GCA GGC ATT CCA GTG G-3′). DNA was amplified using 0.5 mM dNTPs, 1.5 mM MgCl 2 , 0.3 μM of each forward and reverse primer, and 2.5 U Taq polymerase. The thermal cycling conditions were as follows: initial denaturation at 95 °C for 5 min, followed by 35 cycles at 95 °C for 30 s, 60 °C for 30 s, and 72 °C for 30 s, with a final extension cycle at 72 °C for 6 min. Due to the specific genetic defect that was identified, the affected members of family RP26 were clinically revisited and a detailed clinical examination was performed to confirm the status of the disease in the family. Fundoscopy and electroretinogram (ERG) data were obtained for both families. Visual acuity tests were performed for the affected individuals (IV-1, V-2, and VI-2) of family RP26, and they were also subjected to color differentiation tests using the standard Ishihara plates. Family RP44 could not be revisited for the visual acuity test, but a detailed clinical history was documented from the proband (IV-1) of the family. The affected members of family RP26 were also given pink glasses to use for the alleviation of photophobia. In family RP26, whole-genome SNP array analysis revealed a homozygous interval of 9.1 Mb at 2q11.2 between SNP rs718159 and rs1375002 in all the affected members, with a multi-point LOD score of 3.81 at theta 0. Confirmation and refinement of this region was performed by analyzing microsatellite markers between flanking SNPs rs718159 and rs1375002 . As a result, the critical region for the underlying defect was refined from the initial 9.1 Mb to 7.2 Mb, flanked by markers rs718159 and D2S2229 . This region contains the CNGA3 gene, which has previously been implicated in ACHM and cone dystrophy . In family RP44, homozygosity was observed at nine different chromosomal regions in both affected members (IV-1, IV-3), with a LOD score of 1.22 at theta 0, whereas the unaffected individuals III-2, IV-2, IV-4, IV-6, and IV-7 were heterozygous in these regions. The CNGB3 gene, which has also previously been shown to be involved in ACHM and cone dystrophy, resides in one of these regions on chromosome 8q21.3 . Sequencing of all the coding exons of the CNGB3 gene in the proband of family RP44 resulted in the identification of a novel mutation, a one nucleotide deletion at position 1825 in exon 16 of the gene c.1825delG; Figure 3A ), which results in a frameshift and premature termination of the protein (p.V609WfsX9). Segregation analysis in the family revealed that the two affected individuals, IV-1 and IV-3, are homozygous for the mutation, while four healthy persons (III-2, IV-2, IV-4, IV-7) are heterozygous carriers, and two healthy persons (IV-5, IV-6) are homozygous for the wild type allele . The c.1825delG mutation was not identified in 44 probands with retinal dystrophies. As it has previously been reported that mutations in CNGA3 and CNGB3 are associated with cone dysfunction , the clinical status of the affected individuals from both families was re-evaluated. The affected individuals of family RP26 (IV-1 and VI-2), who were aged 35 and 11 years, respectively, at the time of fundoscopy, showed a normal macular region. However, one affected individual from each family (RP26_V-2 [age 14 years] and RP44_IV-1 [age 19 years]) showed the beginning of a Bull’s eye maculopathy , and revealed some residual cone responses on the photopic ERG on the 30 Hz flicker stimulation , showing that the disease is progressive in these patients. The affected individuals from family RP26 had congenital nystagmus, photophobia and were color blind. In addition, the affected individuals (IV-1, V-2, and VI-2) had low visual acuity of 20/200, 20/400, and 20/200, respectively. Members of family RP44 could not be revisited for the visual acuity test because they live in a very remote rural area. In this family, a detailed telephone interview with both affected members IV-1 and IV-3 revealed that they also had congenital nystagmus. In addition, they had photophobia along with low visual acuity and were found to be color blind, thereby confirming the molecular diagnosis of ACHM. There are six cyclic nucleotide gated (CNG) channels present in mammals, and these are divided in two subfamilies, the A subunits (CNGA1–4) and the B subunits (CNGB1 and CNGB3). The CNGA3 and CNGB3 channels play a critical role in cone-mediated vision, which is required for central and color vision, as well as visual acuity. CNGA3 and CNGB3 encode the cone CNG channel subunits that are able to form heterotetramers , although CNGA3 subunits may also form homotetramers . Mutations in these two genes have been shown to result in different forms of ACHM and cone dystrophy . In CNGA3 , the p.R274S mutation is located in a conserved region , which is part of the fourth transmembrane helix (S4) . The arginine residue at this position is conserved among the CNG alpha subunits of rods (CNGA1) and olfactory neurons (CNGA2), Shaker K + channels and HCN channels . Mutations in the S4 domain have been shown to cause failure in cellular channel processing. Mutant channel proteins are not glycosylated, and do not reach the surface plasma membrane; they remain trapped in the endoplasmic reticulum, and are most likely misfolded . The c.1825delG mutation in exon 16 of CNGB3 should in theory give rise to nonsense-mediated decay of the mutant RNA, and can, therefore, be considered a loss-of-function mutation. In case there is residual CNGB3 mRNA, the predicted truncated protein (p.V609WfsX9) lacks the conserved cyclic nucleotide-monophosphate (cNMP) domain. The cNMP domain is the binding site for cyclic nucleotides, and is involved in the cyclic nucleotide mediated activation of the protein. It is hypothesized that both putative effects of this variant will lead to the loss-of-function of CNGB3. Identification of causative mutations aided in the correct diagnosis of ACHM in these two Pakistani families, which had previously been diagnosed to suffer from retinal dystrophy. After the correct re-diagnosis of the disease, the use of pink glasses reduced the photophobia to some extent in the affected individuals of family RP26. Due to the use of these dark colored pink glasses, the light exposure was reduced, resulting in increased scotopic vision that helped the patients to see objects at a distance, even during the day time. In this study, we report the first genetic screening and use of dark glasses as supportive therapy for ACHM in Pakistan, a disease that is often misdiagnosed. | Review | biomedical | en | 0.999996 |
20602800 | Her initial set of cardiac enzymes, complete blood count (CBC), basic metabolic panel (BMP) and urine analysis were normal. She was admitted with diagnosis of unstable angina. Treatment with heparin, eptifibatide and nitroglycerine was begun. Her repeat EKG on 09/07/09 showed ST depressions in the inferior leads, repeat cardiac enzymes were normal, however her chest pain continued to persist. 2D Echocardiogram (ECHO) on 09/07/09 revealed ejection fraction (EF) of 65%, without any pericardial effusion. Chest pain continued to persist, became hypotensive and oliguric, blood pressure medications were with held. Repeat CBC and BMP revealed elevated WBC 15,800/μl and hemoglobin of 9.4 gm/dl. Serum creatinine changed from 1.13 to 3.01 and blood urea nitrogen increased from 29 to 53. Urine analysis revealed 15-20 white blood cells per high power field (HPF), positive leukocyte esterase and nitrite, 5-10 red blood cells per HPF. In view of leucocytosis, increased renal parameters and pyuria septic shock secondary to urinary tract infection was considered and transferred to Intensive care unit (ICU). After fluid resuscitation, broad spectrum antibiotics were intiated. On 09/09/09 in ICU the patient was in distress and continued to have chest pain. Vital signs were significant for pulse rate 90/min, regular, BP 70 mmHg, RR of 22/min, SpO2 95%. Auscultation of heart and lungs was unremarkable. Central venous pressure was 15 cm of water. Intravenous vasopressor therapy was intiated. As her chest pain continued to persist, a non-contrast computerized tomography (CT) of the chest was done which revealed hemorrhagic pericardial effusion with lead perforation of the right atrium which was subsequently confirmed by 2D ECHO Imaging studies including chest x-rays, 2D/3D ECHO and CT scan have been utilized to diagnose the atrial perforation. The superiority of the either CT scan or ECHO has to be further studied . In this case the suspicious chest x-ray after the placement of the central line lead to the further investigations. Persisting chest pain without elevation of troponins and hemodynamic instability with elevated JVD raised the suspicion pericardial tamponade. CT scan of the chest confirmed the hemorrhagic pericardial effusion along with the exact position of the right atrial lead. 2D ECHO with multiple projections further confirmed the effusion. During the surgery the lead was noted to perforate the right atrium and it was retrieved and the perforated atrial wall was repaired. | Other | biomedical | en | 0.999996 |
20704700 | Ticlopidine is a thienopyridine derivative with platelet inhibitor capability. It acts by inhibiting the platelet aggregation induced by adenosine diphosphate and by blocking the membrane receptors of fibrinogen. It is used to prevent thrombosis in patients with cerebrovascular or coronary artery disease. Two randomized clinical studies proved the drug's efficacy versus placebo and aspirin in reducing the risk of transient ischemic attack and stroke in patients with a history of cerebrovascular events. Because of its adverse effects, the use of this drug is reserved for patients in whom aspirin is contraindicated, not tolerated, or when treatment with aspirin fails. The most common side effects are mild and transitory: diarrhea, dyspepsia, nausea and rashes. More serious, but less frequent, adverse effects are hematological dyscrasia (particularly agranulocytosis, aplastic anemia, neutropenia, pancytopenia, thrombocytopenia and thrombotic thrombocytopenia purpura) and cholestatic hepatitis. However, to our knowledge, there are only a few published reports of the simultaneous occurrence of hematological and hepatic toxicity induced by ticlopidine. We report a case of agranulocytosis associated with cholestatic hepatitis related to the use of ticlopidine. A 70-year-old Caucasian woman was admitted to our Rehabilitation Ward (San Paolo Hospital, Milan) because of gait ataxia after right bulbar stroke, which occurred 10 days previously. Her medical history pointed out hypertension and hypercholesterolemia. She had no prior history with regard to hematological or liver diseases, alcohol abuse or blood transfusion. Her habitual medications were aspirin 100 mg/day, atorvastatin 20 mg/day and amlodipine 5 mg/day. Immediately after her stroke, she discontinued aspirin and started therapy with ticlopidine 250 mg twice daily. Upon admission, her blood tests were normal. About four weeks later, she developed agranulocytosis. Her white blood count was 2600 cells/μL , neutrophil count was 100 cells/μL , and liver function tests revealed a mixed cholestasis and hepatocellular injury. She had no fever and she was asymptomatic. She had elevated levels of alanine aminotransferase (560 U/L, reference range 5 to 41 U/L), of aspartate aminotransferase (551 U/L, reference range 5 to 41 U/L), of γ-glutamyl transpeptidase (449 U/L, reference range 11 to 50 U/L), of alkaline phosphatase (821 U/L, reference range 98 to 279 U/L). Total and direct bilirubin and the coagulation tests were normal. | Review | biomedical | en | 0.999996 |
20860812 | She was comatose and had a fever (39.1°C). The Glasgow coma score (GCS) was 7: eye opening, verbal response and motor response were 1, 2 and 4, respectively. Meningismus was present. Her eyeballs deviated to the left; the pupils were equal and normally reactive to light. The deep tendon reflexes were normal, with no pathological reflex. As she had frequently experienced generalized seizures with hypoventilation, the patient received mechanical ventilation. Intravenous sedation (midazolam) was started. The white cell count was 18200/μL and the C-reactive protein concentration was elevated (13.5 mg/dL). Other blood cell counts and the results of routine biochemical analysis were normal. Cranial T2-weighted magnetic resonance imaging showed bilateral regions of increased signal intensity in the hippocampus and amygdaloid body, the insular, medial temporal and medial frontal lobes . A lumbar puncture on day one showed 321 white cells/mm 3 (93% lymphocytes, 7% polyneutrophils), 1 red cell/mm 3 , a protein concentration of 66 mg/dL and a glucose concentration of 74 mg/dL. Real-time PCR amplification of HSV-1 in cerebrospinal fluid (CSF) was positive (38,000 copies/mL). HSV-1 immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies were not detected in the CSF. In the serum, HSV-1 IgM antibodies were absent and the HSV-1 IgG antibody titer was 26.3. HSVE was diagnosed. Cranial computed tomography (CT) performed on day five showed hemorrhagic foci in the left amygdaloid body and low-intensity bilateral lesions in the frontal and temporal lobes. We performed repeated lumbar punctures in order to evaluate the disease severity and the responses to these treatments because a reduced consciousness level and cranial neuroimaging abnormalities persisted. CSF analysis performed on day seven showed 188 lymphocytes/mm 3 , 38 red cells/mm 3 , a glucose concentration of 72 mg/dL and increased titers of HSV-1 IgM and IgG antibodies (3.08 and 6.17, respectively). During her hospitalization, she did not experience any intermittent or persistent hypertension. Intravenous heparin (12,000 U/day) was started and the dose was adjusted according to the activated partial thromboplastin time for about a month (maximal dose of heparin, 20,400 U/day). CSF analysis on day 39 showed 6 lymphocytes/mm 3 , 52 red cells/mm 3 and a glucose concentration of 78 mg/dL; the titers of HSV-1 IgM and IgG antibodies were 1.34 and greater than 12.8, respectively. Cranial CT on day 54 showed that the subarachnoid and intracranial bleeding had disappeared. Enhanced CT angiography demonstrated an avascular area in the left temporal lobe but no other arterial or venous abnormalities, such as aneurysm formation or irregular vascular distribution, were evident (data not shown). PCR has become the standard diagnostic test for HSVE. However, intrathecal antibody measurements are still of value, with an estimated specificity of 80% or 95% . Real-time PCR is a recent modification of conventional PCR for HSV. The relation between the results of PCR and intrathecal antibody levels remains poorly understood. This issue has been addressed by one study but real-time PCR and measurement of antibody titers were performed in many patients at different times . Intrathecal viral genomes on PCR and increased intrathecal HSV antibodies have been detected within five days and after seven days from the onset of neurologic symptoms, respectively. Our study found that the results of real-time HSV PCR were positive three days after the onset of central nervous symptoms, without intrathecally synthesized specific HSV antibodies. Intracerebral hematoma is rarely associated with HSVE and only 14 cases have so far been reported. To the best of our knowledge, this is the first report to document a case of HSVE associated with subarachnoid bleeding. Obvious abnormalities of major cerebral vascular arteries, such as aneurysm formation and an irregular distribution of the anterior, middle and posterior cerebral arteries, were not evident which suggests that the subarachnoid bleeding was directly attributed to HSVE. HSV causes a necrotizing vasculopathy ascribed to cortical and subcortical intense hemorrhagic necrosis and perivascular cuffing in the medial temporal and orbitofrontal regions and CSF analysis often demonstrates the presence of red cells. In gyri located near the CSF, diffuse necrotizing angiitis of venules and capillaries induced by intense inflammatory necrotizing vasculopathy can cause vessel wall necrosis and subsequent bleeding, leading to hematogenous spread into the CSF space. Subarachnoid bleeding in our patient may have been caused by red-cell diapedesis from the hemorrhagic necrotizing amygdaloid body into the adjacent CSF spaces, resulting in 'subarachnoid bleeding with intraventricular extension'. Coagulopathy or hepatocellular damage with a consequent insufficient production of clotting factors can complicate severe HSV infections and may potentially cause bleeding. | Clinical case | biomedical | en | 0.999998 |
21113305 | The surgical management of GORD sometimes fails,whether performed as an open procedure or laparoscopically, and may require a reoperation for optimal results . Amongst the various mechanisms of failure, migration of the stomach into potential spaces such as in paraoesophageal herniation is a serious and important complication as the diagnosis may be significantly delayed resulting in an increase in morbidity and mortality of the affected patients [ 5 – 7 ]. In this report, we describe a case of migration of the stomach into a congenital postdiaphragmatic space following laparoscopic Nissen Fundoplication. She then continued to be hypoxic and hypotensive and a chest X-ray revealed a right sided pneumothorax which was managed with a right chest drain. Serial arterial blood gas samples did not reveal any acid-base disturbances at this stage. A gastrografin swallow ruled out any perforation in the oesophagus and was otherwise nonspecific. After a short period of noninvasive ventilation, she remained hypoxic and was consequently intubated. A second chest drain was inserted on the left side due to worsening bilateral pleural effusions on a subsequent chest X-ray. A repeat OGD revealed a normal GOJ with a rotated and distended stomach but there was no evidence of gastric outlet obstruction. As the patient continued to deteriorate, a computerised tomography (CT) scan was done which confirmed herniation of the stomach into a congenital postdiaphragmatic space. At exploratory laparotomy, the anterior wall of the stomach was noted to be herniating into a congenital space behind the diaphragm pushing the liver and the inferior vena cava anteriorly. There was no evidence of a gastric volvulus. Following the retrieval of the herniating segment, the wrap was noted to be congested with an area of ischaemia which recovered promptly following reduction and no resection was necessary. The wrap was undone revealing a defect in the anterior wall of the stomach. The margins of the defect, which were of doubtful viability, were trimmed and the defect was closed with nonabsorbable sutures and covered with omentum. The stomach was then fixed to the anterior abdominal wall with nonabsorbable sutures. No defect was noted in the diaphragm where three hiatal interrupted nonabsorbable sutures, which were placed during the previous fundoplication and were noted with a normal length of abdominal oesophagus. Although migration of Nissen fundoplication wraps has been previously described [ 5 – 7 ], there are no reports of migration into congenital spaces including congenital post diaphragmatic spaces in the literature. It is timely to raise awareness of this potentially serious complication and carefully present the associated clinical features . In our case, it is possible that the creation of pneumoperitoneum resulted in a residual pocket of gas within the space exposing it as a potential herniating space postoperatively. A further possibility is that a tight GOJ after fundoplication might have induced acute gastric dilatation and herniation. It is notable that the patient did not have specific symptoms apart from reflux to account for the presence of this congenital space. As described earlier, our patient presented with nonspecific clinical signs including hypoxia, hypotension, pyrexia, vomiting, a unilateral pneumothorax, and bilateral pleural effusions. Some of her nonspecific symptoms could be explained in the context of systemic inflammatory response syndrome. Worsening of her clinical condition despite aggressive conservative treatment in ICU was a prompt for further investigations and subsequent surgical intervention. Anterior gastropexy was considered to be the most appropriate surgical intervention in the context of the life-threatening clinical presentation. The retention of an adequate length of abdominal oesophagus with an intact oesophageal hiatus repaired by three nonabsorbable sutures could explain the resolution of reflux symptoms after a long period of followup. | Review | biomedical | en | 0.999997 |
21734923 | Les tumeurs neuro-ectodermiques primitives appartiennent à la famille des tumeurs sarcomateuses d’Ewing qui dérivent toutes de la même cellule souches . Les cellules de la crête neurale sont soupconnées d’être à l’origine de ces tumeurs. Les sites de prédilections de ces sarcomes sont: la région paravertébrale, la paroi thoracique et les extrémités distales. Plus rarement, ils se développent aux dépens du poumon, de l’utérus, des ovaires, des voies urinaires, du myocarde, de la glande parotide et du rein . Le diagnostic positif des tumeurs neuro-ectodermiques primitives nécessite la contribution de l’histopathologie, de l’immunohistochimie et de la cytogénétique. Il s’agit d’un homme de 30 ans, sans antécédents particuliers, se plaignant de douleurs épigastriques évoluant depuis un mois dans un contexte d’apyrexie et de conservation de l’état général, sans vomissement ni hémorragie digestive extériorisée. L’examen clinique a objectivé une masse épigastrique de 9 cm de grand axe fixée au plan profond mobile par rapport au plan superficiel et indolore. La fibroscopie oesogastroduodénale a révélé la présence d’une ulcération antropylorique de la face antérieure de 2 cm de grand axe. L’échographie abdominale a montré l’existence d’une masse tissulaire de 10 cm de grand axe, présentant des végétations endokystiques et se développant au dépend de l’estomac sans ascite et sans image de métastase hépatique. La Tomodensitométrie (TDM) abdominale a confirmé ces données, et a visualisé la tumeur kystique avec sa composante tissulaire périphérique rehaussée par le produit de contraste . Le rétablissement de la continuité a été réalisé au moyen d’une anastomose oeso-jéjunale sur anse en Y. Les suites opératoires ont été simples avec reprise de l’alimentation au 5 ème jour. L’examen anatomopathologique de la tumeur trouvait des massifs de petites cellules contenant des tâches noirâtres, des nucléoles arrondis et ovales, un cytoplasme éosinophile et des mitoses fréquentes. Ces cellules présentaient une discrète différentiation en rosette et un stroma de nature desmoplastique. Les ganglions n’étaient pas envahis. L’immunomarquage par les anticorps anticytokératine, antichromagranine, antidésmine et antisynaptophysine était négatif. En revanche, celui par l’anticorps anti-CD99 (Mic2) était fortement positif. Il s’agissait donc, d’une localisation gastrique d’une tumeur neuroectodérmique primitive périphérique. Le geste chirurgical étant jugé curatif, le complément chimiothérapique n’a pas été indiqué. Au recul de six mois, le contrôbiologique et scanographique n’a pas objectivé de récidive. En janvier 2000, l’OMS a classé Les pPNET comme appartenant au groupe des tumeurs neuroépithéliales embryonnaires c’est-à-dire développées à partir de cellules germinales du tube neural . Ces tumeurs représentent moins de 1 % de tous les sarcomes. Elles prédominent avant l’âge de 35 ans (75 % des cas) avec un pic de fréquence entre 15 et 20 ans. Neuf cas sur dix sont de race blanche avec une légère prédominance masculine, mais aucun facteur favorisant n’est retrouvé . La localisation thoracique est la plus fréquente (44%) suivie des pPNET abdominopelviens (26%) puis des extrémités (20 %) et enfin de la tête (6 %) . A notre connaissance, notre cas serait le 3ème cas de pPNET gastrique décrit chez l’adulte . Les signes cliniques manquent de spécificité. La douleur abdominale ainsi que la présence d’une masse abdominale et d’une fièvre sont les symptô les plus fréquents. La biologie est également non spécifique. Les examens radiologiques explorent la tumeur et recherchent les métastases, localisées par ordre de fréquence aux poumons (50 %), os (25 %), moelle (20 %), foie et cerveau , jugeant ainsi de la résécabilité de la tumeur primitive. D’un point de vue anatomopathologie, la tumeur est multilobulaire, molle, friable. Elle est en général blanchâtre avec de larges plages de nécroses, des formations kystiques et des hémorragies intratumorales . D’un point de vue microscopique, les cellules tumorales sont rondes, avec un noyau arrondi. La membrane nucléaire est bien distincte, avec une chromatine fine et parfois un ou deux petits nucléoles. Les mitoses sont plus ou moins fréquentes. En général on note la présence de grains de glycogène intracytoplasmiques. La présence de rosettes ou pseudo-rosettes caractérise plus précisément les PNET. La plupart du temps, ces tumeurs surexpriment un antigène déterminé par le gène MIC2 désigné sous le nom de CD99. Elles surexpriment d’autre part une autre protéine appelée FLI1 issue de la translocation entre le chromosome 22 et le chromosome 11. | Study | biomedical | fr | 0.999998 |
21849070 | Pancoast syndrome is most commonly associated with a primary lung carcinoma and rarely with metastatic malignancies and certain infections, including mucormycosis. It is characterized by Horner syndrome, shoulder pain radiating down the arm, compression of the brachial blood vessels, and, in long-standing cases, atrophy of the arm and hand muscles. Pulmonary mucormycosis usually occurs in the setting of hematological malignancies. The typical presentation is a patient with neutropenic fever, pulmonary infiltrates, and a clinical course that worsens despite antibiotics. We present a case of pulmonary mucormycosis associated with postchemotherapy neutropenia in a patient with acute myeloid leukemia. His course was fulminating, leading to chest wall invasion, brachial plexopathy, and Horner syndrome. A 51-year-old Caucasian man was hospitalized for the management of a relapse of acute myeloid leukemia. He had hyperleukocytosis and complained of mild shortness of breath and generalized weakness. He denied cough, fevers or chills, hemoptysis, or orthopnea. He had smoked 39 pack years. His significant medical history began six months prior to admission, when his condition was diagnosed as acute myelomonocytic leukemia. He had been treated with cytarabine and daunorubicin followed by high-dose cytarabine. Shortly after admission, he required urgent leukopheresis because of worsening hyperleukocytosis and acute respiratory failure. He recovered and had further chemotherapy with clofarabine and cytarabine. Eighteen days after admission, he was neutropenic and febrile. He developed left axillary burning pain, which evolved in a matter of hours to numbness of his arm. Soon afterward, weakness started in his hand and later moved proximally up his arm. At that time, he had a temperature of 38°C, a respiratory rate of 20 breaths per minute, a heart rate of 133 beats per minute, blood pressure of 117/77 mm Hg, and an oxygen saturation of 94% on 50% venturi mask. He was dyspneic and a chest examination revealed signs of lung consolidation in the left upper and left lower lobes. A chest radiograph revealed elevation of the left hemidiaphragm, alveolar and interstitial opacities of the left upper lobe and lower lobe with air bronchograms, and blunting of the costophrenic angle. He was started on broad-spectrum antibiotics and voriconazole prophylaxis. A physical examination revealed edema of the skin over the anterior left chest wall but no erythema, scaling, or discrete skin lesions. In a matter of hours, the numbness spread from a T1 distribution to a C8 distribution. The following day, his left arm was plegic with the exception of trace movement of the deltoid muscle. He was anesthetic to all sensory modalities in the left arm as well as areflexic. He also developed a left Horner syndrome. Further swelling developed in his left arm and anterosuperior chest with fullness in the supraclavicular fossa. Doppler ultrasound showed occlusion of his left distal subclavian, axillary, and brachial arteries and deep vein thrombosis of his left internal jugular, subclavian, and axillary veins. Heparin was started for his thrombosis, but soon after he had mild hemoptysis. A chest computed tomography scan showed extensive edematous changes of the left chest wall and axilla along with left pleural effusion and pulmonary parenchymal consolidation. A bronchoscopy that revealed a blood clot in the left upper lobe bronchus without endobronchial lesions was performed. Six days after the onset of numbness, a palpable purpuric plaque developed over his left chest and progressed to a 2 cm black eschar. A punch biopsy of the plaque was performed. With failure to respond with broad spectrum antibiotics (which included vancomycin, imipenem, voriconazole and acyclovir), liposomal amphotericin B 5 mg/kg per day was added empirically to his regimen. A histological evaluation of skin biopsy showed abundant angiocentric and angioinvasive ribbon-like hyphae with irregular nonparallel contours, occasional right-angle branching, and rare septae . Cultures from both skin and bronchoalveolar lavage confirmed a diagnosis of mucormycosis by a Rhizopus species. Twenty-four hours later, he developed respiratory distress, shock, and multiorgan failure resulting in death. An autopsy was declined by his next of kin. Pulmonary mucormycosis occurs with inhalation of spores into the bronchioles and alveoli, usually resulting in a rapidly progressive pneumonia or endobronchial disease. Symptoms are typically nonspecific and may include fever, dyspnea, cough, and chest pain . The infection can spread to contiguous organs or disseminate hematogenously. Of particular interest to our case is the overwhelming speed with which the process extended from the lung parenchyma to the surrounding structures (tissue, nerves, vessels, and skin). The progression of symptoms suggests that the lower brachial plexus trunk became ischemic initially and that the rest of the plexus followed as the lesion extended from the lung to the surrounding tissues. Mucor is known to locally invade nerves, most often in rhinocerebral disease. Common clinical findings include rhinitis, periorbital and facial swelling, mucosal necrosis, ophthalmoplegia, multiple cranial nerve palsies, facial pain, and headache . Whereas stroke from rhinocerebral mucormycosis causing occlusion of the cavernous portion of the internal carotid is well documented , involvement of the brachial vascular and nervous plexus is a very unusual presentation. Three reports document mucormycosis presenting as a Pancoast syndrome . Notably, two had diabetes (both survived) as their only risk factor and one had acute lymphoblastic leukemia (died). Pancoast syndrome is characterized by Horner syndrome (ptosis, miosis, hemianhidrosis, and enophthalmos), shoulder pain radiating toward the axilla or ulnar aspect of the arm, compression of the brachial blood vessels, and atrophy of the arm and hand muscles. This syndrome is most commonly caused by a bronchogenic carcinoma in the superior sulcus of the lung with destructive lesions of the thoracic inlet and invasion of the brachial plexus and cervicothoracic sympathetic chain. Other causes include metastatic neoplasms and infections. In a recent review of 31 patients with infectious causes of Pancoast syndrome, five were immunocompromised (acute myelogenous leukemia, acute lymphoblastic leukemia, and postchemotherapy), and all had opportunistic organisms ( Aspergillus spp., mucor, nocardia, and Pseudoallescheria boydii ) . In contrast, only one of the 26 immunocompetent patients had an opportunistic organism. In immunocompromised patients, it can be challenging to distinguish pulmonary disease caused by mucormycosis from that caused by aspergillosis. The concomitant presence of sinusitis or a history of voriconazole prophylaxis may suggest mucormycosis . Of note, our patient received voriconazole prophylaxis. The radiographic presentation of pulmonary mucormycosis can be diverse, and there are no pathognomonic radiographic features. In a review of imaging findings in 32 cases of mucormycosis, two thirds of the patients had consolidation as a main finding . Other radiographic manifestations include cavitation, mass-like lesions, widened mediastinum, an "air crescent sign", "halo sign", pleural effusion, and fistula to the chest wall . Chamilos and colleagues , in a retrospective chart review, found that multiple nodules (at least 10) and the presence of pleural effusion were more often found in mucormycosis than in aspergillosis. Definitive diagnosis of mucormycosis often evades initial noninvasive techniques such as sputum and blood cultures. The organism may be recovered by bronchoscopy with bronchoalveolar lavage or transbronchial lung biopsy. However, because of the focal distribution of the disease, transthoracic computed tomography-guided needle biopsy or open lung biopsy may be required to make the diagnosis in pulmonary disease . Histology is characterized by infarction and necrosis of tissue which results from an invasion of the vasculature by hyphae. The fungus can also be associated with neural, vascular, and cutaneous invasion, as in our patient. The fungus is usually recognized by broad, irregular, nonseptate, right-angled, branching hyphae and is demonstrated by hematoxylin and eosin and specialized fungal stains. In contrast, Aspergillus hyphae are narrow with septate branches at 45° angles. As with other fungal diseases, mucorales rarely grow by culture. | Clinical case | biomedical | en | 0.999996 |
22242023 | Venous thromboembolism (VTE) remains one of the main direct causes of maternal mortality in developed countries [ 1 – 4 ], largely due to pulmonary thromboembolism (PE) [ 5 – 7 ] which is responsible for around 20% of maternal deaths . Epidemiologic studies estimate the annual frequency of deep venous thrombosis (DVT) in the general population to be from 0.16‰ to 1‰ , of which 2% are pregnancy related . There is an increased risk of thromboembolic event, either DVT or PE, during pregnancy and puerperium , and it has been estimated that the risk of VTE is 10-fold higher [ 11 – 15 ], reaching up to 2‰ . Established risk factors for VTE during pregnancy include maternal age , obesity (body mass index (BMI) >30) , preeclampsia/hypertension, parity ≥3 , previous VTE or congenital or acquired thrombophilia , smoking, diabetes , multiple gestation , black race , and anaemia. During the labour there are other factors : type of delivery (with 3–6-fold higher risk for cesarean versus vaginal delivery, higher for emergency cesarean , and mid-cavity instrumental delivery) , prolonged labour >12 hours , immobility; major abdominal surgery for >30 minutes during pregnancy or puerperium , preterm delivery , excessive blood loss (>1 litre), or blood transfusion. In the postpartum period, other factors may be added as dehydration, immobility, and anaemia . Table 2 shows the characteristics of the deliveries and the associated thromboembolism risk factors. Cesareans were almost always at term, with only 12.7% preterm, while 73.6% were emergency cesareans, an added thrombosis risk factor. The most frequent anesthesia was locoregional (88.3%). Other potential thrombosis factors (due to the possible underlying disease) were placental abruption (2.2%) and intrauterine growth retardation (IUGR) (8.5%). In the present study, only placental abruption and gestational age (preterm) were significantly related to PE ( P < 0.005). There was only one PE case. This case was in a 25-year-old nulliparous woman assigned to group B with a BMI of 29.5 and no family history of thrombosis; her smoking habit of <10 cigarettes/day was the only risk factor during pregnancy. She was hospitalized in week 32 with placental abruption symptoms and underwent emergency cesarean with locoregional anesthesia. At this time two other risk factors were added up: emergency cesarean section and vaginal bleeding. The fetus was delivered alive with appropriate weight for gestational age. The mother presented with moderate anemia that required intravenous iron treatment. On the first postoperative day, before beginning the thrombophylaxis with bemiparin, she reported difficulty in breathing and pain in right costodiaphragmatic recess. PE was diagnosed after clinical examination, elevated D-dimer, and complementary tests: perfusion lung scintigraphy (PE in lateral and medial segments of medial lobe of right lung) and bilateral lower limb Doppler's ultrasound examination (normal). Consequently, a therapeutic LMWH regimen was started instead of the thromboprophylaxis regimen and was subsequently replaced with oral anticoagulant therapy. A hypercoagulation test at 6 months ruled out thrombophilias. Some authors have recommended the postcesarean use of LMWH only when there is an additional risk factor or in cases of emergency cesarean . However, we agree with the recommendations of several clinical practice guidelines , which have recommended that the threshold for prescribing thromboprophylaxis should be lower in the postnatal period than that in the antenatal period since the risk of developing VTE per day is higher and the duration of exposure shorter. Even some of them recommend that all women, who have had an emergency caesarean section or an elective cesarean section and have one or more additional risk factors for VTE, should receive thromboprophylaxis with LMWH for seven days. We agree with the recommendations of recent clinical practice guidelines ; and although, a cost-effectiveness analysis was not completed specifically for this population subgroup, the cost-effectiveness model for medical patients indicates that prophylaxis with LMWH is cost effective for patients at increased risk. In our investigation, bemiparin 3500 once daily during five days has been sufficient to prevent thromboembolic events, so health costs are lower (two days less than recommended in the clinical practice guideline) , although clotting factors may take a few more days to normalize. | Study | biomedical | en | 0.999996 |
22335966 | Cluster headache (CH) is defined as a paroxysmal, strictly unilateral and very severe headache . It is seen very rarely with a prevalence of less than 0.1% . Ptosis, miosis, lacrimation, conjunctival injection, rhinorrhea and nasal congestion are autonomic symptoms, which usually accompany retro-orbital pain. CH can be categorized into episodic and chronic forms. Various treatment modalities have been tried in both the prevention and treatment of CH . The intranasal application of 10% lidocaine to the nasal mucosa corresponding to the sphenopalatine fossa has proved effective . However, the mechanism of lidocaine in treating the headache is unknown. Here, we report a male patient suffering from CH and severe ptosis that immediately resolved with intranasal lidocaine application and discuss the possible mechanism of lidocaine in treating CH. A 22-year-old Turkish man presented with a five-year history of intermittent daily headache centered on the left retro-orbital and orbital side. The pain was unilateral with a side shift only within the same bout. He experienced four to twenty attacks a week from the beginning of the bout, which resulted in severe social agitation. The attacks started abruptly and usually peaked within five minutes, without any aura or precipitating factors, and lasted 30 minutes to 120 minutes. He suffered from rhinorrhea, lacrimation and ptosis during the headaches, without any noted nausea, vomiting or photophobia. He had previously used several daily medications unsuccessfully, such as verapamil 160 mg thrice daily, naproxen 500 mg thrice daily, ibuprofen 600 mg thrice daily, dexketoprofen trometamol 25 mg twice daily, indomethacin 25 mg thrice daily, loratadine 5 mg daily and prednisolone 60 mg daily. Both general and neurological examinations between attacks and hematological-biochemical screenings were normal. He had neither significant past medical history nor family history of headache. On the day of a severe headache, an ophthalmological examination of our patient revealed lacrimation, conjunctival injection and ptosis without miosis. We measured both his pupils as 3.5 mm, with normal pupillary reactions to both light and near stimulation. As attacks occurred without significant periods of remission, we diagnosed our patient with chronic CH. We applied a cotton tip with 2 mL of lidocaine hydrochloride and epinephrine (Jetocaine, 20 mg lidocaine/0.025 mg epinephrine) into the left nostril for 10 minutes. The ptosis responded to the treatment and the intensity of his headache decreased. The magnetic resonance (MR) images of his brain and orbit and MR angiography of his brain and carotid artery were within normal limits. In 12 months of follow-up, he had six to ten attacks a week accompanied by autonomic symptoms, which resolved with intranasal lidocaine application. CH is a type of primary headache characterized by severe, unilateral trigeminal pain with cranial parasympathetic autonomic symptoms involving oculocephalic functions . The estimated prevalence is less than one in 1,000 in the general population and the disease affects men with a sex ratio between two point five and seven point five to one . The diagnostic criteria of the International Headache Society allow for the distinction of two main CH subtypes, namely an episodic form and a chronic form . In the episodic form, attacks occur daily for some weeks followed by a period of remission. In the chronic form, attacks occur without significant periods of remission. Practitioners have used lidocaine as an acute treatment option for many types of headache by suppository, intramuscular, intravenous and nasal routes. Lidocaine 4% application in the sphenopalatine fossa may offer the fastest relief of any known agent . The sphenopalatine ganglion (SPG) resides just posterior to and immediately above the posterior tip of the middle turbinate, beneath the nasal mucosa at a depth of 1 mm to 9 mm. Intranasal lidocaine is administered with the patient supine, with the tip of the nose pointed vertically, and the head turned slightly toward the side of the block. A cotton-tipped applicator saturated with 4% lidocaine is inserted intranasally and applied to the lateral posterior wall of the nasal cavity. The application of lidocaine to the area corresponding to the sphenopalatine fossa has been shown to be effective at extinguishing pain attacks in patients with CH. Robbins reported the clinical features and results of the treatment of 30 patients with CH who had tried 4% lidocaine solution as a nasal spray to abort the attacks. Of these 30 patients, 27% of the patients reported moderate relief, 27% obtained mild relief and 46% found no relief from the lidocaine. Costa et al . conducted a placebo-controlled study in nine CH patients on the effect of a 1 mL solution of 10% lidocaine applied during nitroglycerine-precipitated CH attacks, applying a cotton swab intranasally on both sides in the area of the sphenopalatine fossa under anterior rhinoscopy. In all treated patients, the pain disappeared on average within 37 minutes of lidocaine application. It has been demonstrated that nasal congestion, rhinorrhea, lacrimation and photophobia generally disappear with pain, while conjunctival injection, miosis and ptosis are resolved later . In our case, following intranasal lidocaine application, pain ceased first and then ptosis resolved, as described in the literature. We encountered no complications in our case and, to date, there is no reported toxicity in the literature. The mechanism for lidocaine in treating CH is unknown. Lidocaine provides its anesthetic effect as a sodium pump inhibitor. It is hypothesized that lidocaine provides local anesthesia, blocking neural transmission of the SPG, which may be important in CH pathophysiology . The SPG is a complex region, including sensory fibers that contribute to the trigeminal nerve, as well as both parasympathetic and sympathetic fibers. Therefore, intranasal lidocaine may produce both sensory and parasympathetic nerve blockade. However, the mechanisms by which these blockages occur are not clear. | Clinical case | biomedical | en | 0.999997 |
22802895 | Glomus tumor (GT), also termed tumor of Popoff, or Barre-Masson syndrome, is an extremely rare benign lesion composed of rounded uniform cells often arranged in a brick-work-like manner. They are intimately associated with the vascular structures . At one time, this tumor was considered to derive from the neuromyoarterial glomus, a neurovascular structure . At present, however, it is believed that the tumor arises from the modified smooth muscle cell. Outside the bone, the glomus tumors with cellular atypia (so-called symplastic glomus tumors) and malignant glomus tumors have been described both of which are exceedingly rare . In 1812, Wood made the first clinical description of a GT; he described it as a “painful cutaneous tubercle” . In 1924, Masson published its first comprehensive pathologic description . These tumors typically present as a painful, firm, purplish, solitary, subcutaneous nodule. Tumor size is generally reported to be small, rarely bigger than 1 cm . When the tumors are located at the lower extremity, the average tumor size is more than 2 cm, in contrast to those tumors located in typical locations (fingers). Symptoms include intense burning pain at the tumor size, which occurs spontaneously or is precipitated by temperature changes or touch. A fear of using the lower extremity may cause severe limb atrophy, extremity vasomotor disturbances or flexion restrictions . | Clinical case | clinical | en | 0.999998 |
22937298 | Calcium is not only an important component of bone, it also plays a key role in generating action potentials. As a result, hypocalcaemia increases excitability of nerve and muscle cells, leading to cramps and, in severe cases, tetany. Serum calcium levels are hormonally controlled, mainly by parathyroid hormone and vitamin D. The latter is to a small extent attained from food, but the majority is formed in sun-exposed skin. The risk for deficiency is increased in dark-skinned people living at higher latitudes. We describe a case of a dark-skinned patient with extreme hypocalcaemia, caused by an unusual disorder in calcium metabolism. An 18-year-old negroid woman presented at the emergency department with progressive cramps in both hands for two days. She was born in Jamaica and had moved to The Netherlands eight months prior to presentation. She had no relevant medical history and did not use any medication. On physical examination, we found her fingers to be cramped with Trousseau's sign positive. No other abnormalities were observed. Laboratory analysis showed severe hypocalcaemia (1.17 mmol/L; reference value 2.10–2.50) and hyperphosphataemia (2.0 mmol/L; 0.7–1.4) with normal blood levels of albumin (36 g/L; 35–50), creatinin (61 μ mol/L; 50–90), and alkaline phosphatase (96 U/L; 0–120). Magnesium was slightly decreased (0.6 mmol/L; 0.7–1.0). Electrocardiography showed normal QTc time, but flattened ST segments, consistent with hypocalcaemia. As could be expected in a dark-skinned person in Dutch autumn, the 25OHD level was low (31 nmol/L; 50–280). However, this minor deficiency was an unlikely explanation for the severe calcium depletion. 1,25-(OH) 2 -vitamin D was low normal (69 pmol/L; 48–161). Instead, the combination of hypocalcaemia and hyperphosphataemia was considered more consistent with hypoparathyroidism, a diagnosis supported by urine analysis, showing a low excretion of both calcium (0.8 mmol/day; 2.5–7.5) and phosphate (5 mmol/day; 10–50). Unexpectedly, parathyroid hormone (PTH) was increased (22.1 pmol/L; 1.3–6.9), rendering the possibility of pseudohypoparathyroidism (PHP). To confirm this diagnosis, an Ellsworth-Howard test was performed, measuring urinary phosphate excretion after administration of a high dose of synthetic PTH. In our patient, phosphate excretion only increased fivefold, where a 100-fold increase is regarded as normal, supporting the diagnosis PHP. No other hormonal imbalances were found. Although the normal alkaline phosphatase level suggested no PTH-induced increase in bone resorption, densitometry was performed to assess bone mineral density, revealing normal values of the lumbar spine ( T = +0.2) and hips ( T = +1.4). Different types of PHP, each with specific features, have been described ( Table 1 ). The best known type of PHP is type 1a, where biochemical disruptions are combined with a phenotype called Albright's hereditary osteodystrophy (AHO), including short stature, round face, brachymetacarpia, and subcutaneous ossifications . The origin of PTH resistance accounts for the differences between the types. The GNAS1 gene, encoding the PTH receptor, can either be mutated (PHP type 1a and pseudo-PHP) or its methylation can be altered (PHP type 1b). In most target tissues both maternal and paternal alleles are transcriptionally active. However, in the proximal tubulus only the maternal allele is read. Thus, changes in the paternal GNAS1 allele do not lead to electrolyte imbalances . In our patient, who presented with biochemical abnormalities and a normal phenotype, the most likely diagnosis is PHP type 1b, a methylation defect of the maternal GNAS1 gene. This is supported by the fact that a mutation in GNAS1 could not be demonstrated. However, type 2 PHP, where the problem originates from the signaling cascade of PTH, cannot be ruled out. Since all types of PHP are congenital and the patient did not experience any symptoms during the first 18 years of her life, we believe moving to The Netherlands aggravated her hypocalcaemia. Possibly, the lack of sunshine in Dutch winter resulted in decreased vitamin D levels, lowering calcium levels even further. Strangely, even with low 25OHD levels and a PTH resistant kidney, calcitriol levels were within the normal range. Adaptation might have occurred by augmenting the normal activation of 25OHD in other tissues. We assume that vitamin D levels were significantly higher when living in a sunnier climate. | Clinical case | biomedical | en | 0.999998 |
23243539 | Hemangiomas are benign vascular lesions that are most common in infancy and childhood. The tumor occurs frequently in head and neck. One third of these lesions will present at birth. Besides, 20% of hemangiomas are multiple. Hemangiomas of the tympanic membrane and/or external auditory canal are rare entities, with 16 previous case reports in the literature. It is a benign vascular tumor. It generally occurs in males in the sixth decade of life. It appears as a small vascular lesion interesting the deep posterior bony external auditory canal and/or the posterior superior tympanic membrane. The first two cases of hemangioma of the tympanic membrane and posterior external ear canal were reported by Freedman et al. in 1972 . Balkany et al. in 1978 reported the first case of capillary hemangioma exclusively envolving the tympanic membrane . In 1982, there was proposed a hemangiomas classification that divides these lesions in two histological categories: cavernous and capillary. The cavernous hemangioma is characterized by large cavernous vascular space lined by endothelium. Capillary hemangioma is made up of small vessel of capillary caliber. It is lobulated and lacks a capsule. In 1990, one case of mixed hemangioma (cavernous/capillary) has been described . Pathologic examination revealed a well-defined proliferation of dilated tortuous vascular structures, closely adhering to each other, filled by erythrocytes in the lumen. They varied in size and were delimited by a single layer of flat endothelial cells. Superficially, the lesion was lined by hyperkeratotic squamous epithelium. These features were consistent with a cavernous hemangioma . The postoperative course was uneventful, and conductive hearing loss disappeared. There has been no recurrence for 1 year postoperatively. All authors, except Magliulo, exclude the involvement of middle ear or mastoid. In fact, in no case histological examination after the surgical procedure showed involvement of the middle ear and/or mastoid. Even in the case described by Magliulo, hemangioma interested in full-thickness the tympanic membrane in correspondence of the handle of the hammer but without signs of erosion or pathology of the same . In the light of the lack of aggressiveness of the disease, while in the past it tended to increase the area of excision and then use a myringoplasty, if not even to a exploratory mastoidectomy, the most recent reports indicate the simple excision technique of choice with respect to medial layers of the tympanic membrane. Recurrence of hemangioma has been reported only in one case and was related to inadequate surgical excision . | Review | biomedical | en | 0.999998 |
23710383 | Drug-induced immune hemolytic anemia (DIIHA) is a serious condition that can be a rare side effect of commonly used over-the-counter medications. The incidence of DIIHA is estimated to be 1 per million of the population. While no explicit data exist regarding the incidence of ibuprofen induced hemolysis, various case series have found that NSAIDs compromise less than 15% of cases; the majority of cases are caused by beta-lactamase antibiotics (e.g., cephalosporins and penicillins). Timely recognition of this condition along with discontinuation of the offending agent is paramount in treating its potentially fatal complications [ 1 – 3 ]. A 36-year-old healthy caucasian female presented to the emergency department complaining of 1-day duration of shortness of breath. The only medication that she was taking was ibuprofen, which she started to take twice daily one week before presentation for tension headaches. The patient was found to have regular sinus tachycardia of 127 beats per minute. Subsequent physical examination revealed jugular venous distention and pale mucous membranes with no jaundice, lymphadenopathy, or organomegaly. No obvious source of bleeding was identified. Upon initial workup, she was found to be severely anemic with a hemoglobin of 4.9 (normal range 12–15 g/dL), hematocrit of 14.2 (normal range 36%–47%), MCV 98.8 (normal range 80–100 fL), and RDW of 24.6 (normal range 11%–14.5%). Anemia workup was initiated and was significant for an elevated lactate dehydrogenase (LDH) 435 (normal range 135–214 IU/L), reticulocytosis 23.2 (normal range 0.5%–2.8%), and decreased haptoglobin <6 (normal range 36–195 mg/dL). Stool test for occult blood was negative. Type and screen were positive for antibodies and Direct Antiglobulin Test (DAT) was reactive with anti-IgG and anti-C3 antibodies. Coombs test elution was also found to be positive. Biochemical tests except for bilirubin 2.7 (normal range 0.0–1.0 mg/dL) were unremarkable. The patient's peripheral blood smear demonstrated an abundance of spherocytes and polychromasia . No abnormalities were noted among white blood cells and platelets. Antinuclear antibodies (dsDNA, Chromatin, Ribosomal P, SS/A, SS/B, Sm, SmRNP, RNP, Scl 70, Jo 1, and Centromere B), rheumatoid factor (RF) and CT scan of chest, abdomen, and pelvis were all negative as part of the workup for autoimmune hemolytic anemia. Drug-induced immune hemolytic anemia (DIIHA) is a rare condition, affecting approximately 1 per million of the population. As a comparison, drug-induced thrombocytopenia and neutropenia have an incidence of 10–18 cases per million and 2–15 cases per million, respectively . DIIHA can be further classified by dividing the drug into whether or not antibodies to the drug are present: drug dependent (DDAB) and drug independent (DIAB). DDAB shows activity only in the presence of the drug; DIAB has activity in the absence of drug . Most cases of DIIHA are caused by DDABs. Usually direct antigen testing (DAT), which is also known as the direct Coombs test, is used to diagnose DIIHA . In this test washed RBCs are mixed with antiserum or monoclonal antibodies prepared against IgG and a third component of complement C3d . It is positive almost in all cases of DIIHA, although some rare cases of negative DAT can be occasionally seen . If DAT is positive, then elution test should be performed to characterize antibodies. In case of DDAB elution test is negative since drug is not present in vitro testing. DIIHA is less frequently mediated by DIAB which is almost identical to warm autoimmune hemolytic anemia (WAIHA). In this case both DAT and elution are positive. The only way to differentiate between DIAB and WAIHA is to stop the causative agent and observe the hematologic response . Usually it takes a few weeks to reach hematological remission, meanwhile serological remission (when Combs test becomes negative) might take a few months . Treatment of DDAB is discontinuation of an offending drug. In the case of DIAB, steroids should be also added besides culprit drug discontinuation . The main diagnostic entities to be considered in the differential diagnosis of drug-induced immune hemolytic anemia (DIIHA) include different causes of warm autoimmune hemolytic anemia (WAIHA), since they are characterized by IgG antibodies that react with red blood cell antigens at body temperatures. The main causes of WAIHA are idiopathic WAIHA, autoimmune and connective tissue diseases (especially systemic lupus erythematosus, scleroderma, dermatomyositis, ulcerative colitis, and rheumatoid arthritis), lymphoma, chronic lymphocytic leukemia, and prior organ transplantation [ 8 – 13 ]. DIIHA is most commonly confused with idiopathic WAIHA, which is more common . An elution test can be useful in differentiating DIIHA from WAIHA. In the case of WAIHA, both DAT and elution tests are positive. In rare cases of DDAB and in almost all cases of DIAB, the elution test can be positive too. In this scenario the only way to confirm the diagnosis of DIIHA is documentation of complete hematologic and serologic recovery after discontinuing the offending medicine . | Review | biomedical | en | 0.999997 |
24711821 | Basal cell adenoma (BCA) is a benign salivary gland tumor that most frequently arises in the parotid gland and is characterized by the basaloid appearance of the tumor cells and the absence of the myxochondroid stromal component present in pleomorphic adenoma. BCA accounts for 1–3% of all salivary gland tumors and is included as a separate salivary gland tumor in the 1991 World Health Organization classification . Of 13749 primary epithelial salivary gland tumors, 160 cases of BCA were registered at the Armed Forces Institute of Pathology (AFIP) in 1991. The main locations are the parotid gland (75%) and the minor salivary glands of the upper lip (20%) . Here, we report a rare case of BCA arising in the minor salivary gland of the upper lip. The patient was a 59-year-old Japanese man who visited the Division of Oral and Maxillofacial Surgery, Ebina General Hospital, in December 2012, with a chief complaint of a mass in the upper lip, which had increased in size over several years. A mobile, elastic, and relatively soft mass without tenderness was palpable in the upper lip. The mucosa in the upper lip covering the mass was normal. The patient had no relevant medical history. The mass in the upper lip region measured 1.0 × 1.0 cm . The clinical diagnosis was suspected to be pleomorphic adenoma arising in the minor salivary gland of the upper lip. Histopathologically, the tumor was encapsulated by fibrous connective tissue and demarcated from the surrounding tissues ( Figure 3(a) ). It consisted of monomorphic epithelial cells with a trabecular or tubular pattern (Figures 3(b) and 3(c) ). The solid nests were composed of almost uniform epithelial cells that were columnar or cuboidal in shape with scanty eosinophilic cytoplasm and round to ovoid nuclei. The stroma surrounding the epithelial tumor nests was composed of thin fibrous tissue and was well demarcated from the solid nests (Figures 3(a) and 3(b) ). Further analysis showed a glandular structure containing a mucinous substance that was positive in Periodic Acid-Schiff (PAS) staining ( Figure 4(a) ) and deposition of abundant PAS-positive basal lamina material within and around the tumor nests ( Figure 4(b) ). The incidence of BCA is low, accounting for 1 to 3% of all salivary gland tumors, with a peak in the seventh decade of life . The main locations are the parotid gland (75%) and the minor salivary glands of the upper lip (20%) . Fantasia and Neville have reported 50 cases of BCA arising in the upper lip in the minor salivary gland . Mucoceles most commonly involve the lower lips of young patients (second and third decades), whereas the BCA typically occurs in older patients (mean age: 61 years) and usually involves the upper lip . Histopathologically, BCAs are benign tumors composed of relatively isomorphic basaloid cells, a conspicuous basal cell layer, and distinctive basement membrane-like material. Most are well circumscribed and encapsulated, although a multinodular microscopic pattern may be found in any of the subtypes. BCAs lack the characteristic myxochondroid matrix found in pleomorphic adenoma . BCAs are classified based on their morphologic pattern into four subtypes: solid, trabecular, tubular, and membranous , with the solid variant being the most common. The tumor in our case had a predominant tubular-trabecular pattern composed of islands of tumor cells with a hyperchromatic, palisaded, and peripheral layer of cells . The initial clinical diagnosis was suspected to be pleomorphic adenoma in the minor salivary gland in the upper lip. In such cases, immunohistochemistry is needed for differential diagnosis to exclude mucocele, malignant lymphoma, lymphangioma, hemangioma, adenocystic carcinoma (ACC), and basal cell adenocarcinoma (BCAC). Hiranuma et al. also suggested that a mixed tumor should be considered in differential diagnosis for BCA. Important distinguishing features of BCAs include an absence of histologically recognizable myoepithelial cells and a sharp demarcation between the epithelium and stroma. The stroma in a BCA tends to be scanty and thereis an absence of the myxoid or chondroids elements that are present in pleomorphic adenoma. BCA has sometimes been mistaken for ACC. Jung et al. reported that, compared to BCA without capsular invasion, the BCACs and BCAs with capsular invasion were more likely to be larger and have solid or cribriform patterns and most BCACs and BCAs exhibited nuclear beta-catenin expression, and beta-catenin, CK5/6, CD117, and S-100 protein were helpful for differentiating basal cell neoplasms from ACC. BCAs with capsular invasion shared several pathological features with BCACs, including a large size and frequent cribriform patterns but the malignant potential of these tumors seems highly limited and should be reexamined. Jung et al. also reported that beta-catenin immunostaining may aid the differential diagnosis between basal cell neoplasms and ACCs. Final diagnosis is difficult based on imaging and clinical findings alone. Thus, total excision and immunohistochemistry including Ki-67 labeling and beta-catenin should be performed to make a definite diagnosis. The recurrence rate is 25% for the membranous variant of BCA and malignant transformation of BCA has been reported . Therefore, it is necessary to perform complete tumor excision. This approach was used in our case and the postoperative course was uneventful 12 months after surgery with no recurrence. | Clinical case | biomedical | en | 0.999995 |
24716095 | Deep venous thromboses (DVTs) and pulmonary embolisms (PEs), commonly described together as venous thromboembolisms (VTEs), are important complications in hospitalized patients. DVTs commonly occur in the deep veins of the lower leg or the proximal veins of the iliofemoral segment and rarely occur in the inferior vena cava (IVC) [ 2 – 5 ]. Some case reports and reviews of IVC thrombosis currently exist; however, little information has been published regarding its morphology. We present three cases of IVC thrombosis, with each showing a different morphology. A 60-year-old man underwent surgical resection for cholangiocarcinoma and was referred to our department because of an IVC thrombus detected on contrast-enhanced abdominal computed tomography (CT), four days later. The patient did not have a family history of VTEs or sudden and/or premature deaths. Prior to his diagnosis, he had not complained of chest pain, dyspnea, or lower back pain. His physical examination showed a regular pulse rate of 96 beats/min, a blood pressure of 106/69 mmHg, and a low-grade temperature of 37.8°C. Auscultation failed to detect any obvious murmur or rales, and peripheral leg edema was not observed. Laboratory tests revealed an increased D-dimer concentration (12.8 μ g/mL) and a slightly decreased concentration of antithrombin (55%) and protein C (62%). The patient was also negative for the presence of antinuclear antibody, lupus anticoagulant, and cardiolipin antibody; his protein S concentration was normal. Contrast-enhanced abdominal CT demonstrated the presence of a mural thrombus adhered to the vessel wall in the infrarenal IVC ( Figure 1(a) ); interruption or hypoplasia of the IVC was not observed. We initially administered anticoagulant therapy with unfractionated heparin and antithrombin to minimize the possibility of bleeding complications. However, the IVC thrombus was found to increase in size, five days later ( Figure 1(b) ). Thus, we switched to an anticoagulant therapy involving warfarin and fondaparinux sodium, and the IVC thrombosis shrank significantly during the following month of treatment ( Figure 1(c) ); the patient was then discharged. A 40-year-old woman presented with a uterine cervical adenocarcinoma with metastasis to the liver, right kidney, pelvis, and sacral bone. She was referred to our department because an IVC thrombus was detected on contrast-enhanced abdominal CT. The patient's family history was unremarkable, but she did present with lower back pain and severe, bilateral leg edema. A physical examination showed a regular pulse rate of 91 beats/min, blood pressure of 132/90 mmHg, and a normal temperature of 35.9°C. Upon auscultation, the patient did not demonstrate any obvious murmur or rales. Her laboratory tests revealed severe anemia (hemoglobin level, 6.8 g/dL) and an increased D-dimer concentration (32.4 μ g/mL). Contrast-enhanced CT demonstrated a massive, floating thrombus, approximately 18 × 20 mm in size, extending from the right common iliac vein to the infrarenal IVC (Figures 2(a) and 2(b) ); an intra-arterial thrombus occluding a right lower lobe pulmonary artery was also noted ( Figure 2(c) ). We considered the patient to have a high risk of recurrent PE, but administration of an effective and safe anticoagulant therapy was difficult due to her severe anemia. Thus, an IVC filter was implanted. Although PEs were successfully prevented, she succumbed to the uterine cervical adenocarcinoma approximately 1 month later. A 37-year-old man with a liver abscess was referred to our department for management after the implantation of an IVC filter. The patient's family history was unremarkable, and the patient had not complained of chest pain, dyspnea, or lower back pain. His physical examination showed a regular pulse rate of 80 beats/min, blood pressure of 90/50 mmHg, and a normal temperature of 36.8°C. The patient did not demonstrate any obvious murmur or rales, but his laboratory tests revealed an increased D-dimer concentration (3.6 μ g/mL); the patient did not show any findings suggestive of congenital thrombotic disease. Contrast-enhanced CT and catheter-based venography demonstrated a small, polyp-like thrombus at the site of the infrarenal IVC , in absence of any IVC malformation. The patient was administered an anticoagulant therapy involving unfractionated heparin, and the IVC thrombus was completely resolved approximately 2 weeks later. He was discharged after removal of the filter. IVC thrombosis is a rare but significant complication in hospitalized patients. According to a report from the United States, DVTs occur in 0.85% of hospitalized patients and 1.25% of these patients have IVC thrombosis. PEs occurred in 12% of the patients with IVC thrombosis, in the absence of DVTs at other sites . However, relevant information regarding IVC thrombosis, especially about its morphology, remains scarce. In this report, our findings indicate that IVC thromboses can show at least three morphologies, that is, mural, floating, and small, polyp-like thromboses; this has not been reported previously. The clinical significance of the morphological characteristics of IVC thrombi could not be clarified based on the reported cases. However, we speculate that the floating and polyp-like thrombi may be more likely to cause PEs than the mural type because the risk of PE has been reported to be also higher in patients with free-floating thrombi in the lower-extremity deep veins . Further studies in more patients are required to verify or refute this suggestion. The classical physical signs of IVC thrombosis include bilateral leg swelling and dilated superficial abdominal wall collateral veins ; another sign preceding the development of these signs is lower back pain . However, two of the present cases did not have significant clinical signs or symptoms, and the IVC thromboses were only incidentally diagnosed when the patients underwent contrast-enhanced CT. The etiology of DVTs includes long-haul flights, pregnancy, prolonged immobility, cancer, obesity, oral contraceptive use, thrombophilia, a history of VTE, and the presence of varicose veins . IVC thromboses have also been reported to be frequently associated with cancer . Furthermore, extensive venous thromboses are frequently seen in postmortem liver abscesses , and IVC thromboses have been occasionally reported in patients with liver abscesses . Thus, physicians should keep in mind that such patients may have IVC thromboses as well as lower-extremity vein thromboses, even if they are asymptomatic. | Study | biomedical | en | 0.999996 |
24891960 | Vascular tumors in the oral region have been traditionally described as hamartomas or malformations rather than as true neoplasms. Stout stated that a vascular tumor, in contrast to a hamartoma, contained more endothelial cells than was necessary to line the lumina. Clinically, vascular lesions have a tumor-like appearance, due to endothelial proliferation in vessels and enlargement of vessels with secondary reactive change . Intravascular papillary endothelial hyperplasia (IPEH) is a benign, nonspecific, vascular lesion consisting of reactive proliferation of the endothelial cells that arise in organizing thrombus . It comprises approximately 2% of the vascular tumors of the skin and subcutaneous tissue . A 40-year-old female patient reported with a complaint of pain and increased swelling on the right side of the face of 1-week duration. The swelling was first noticed by the patient on the right cheek region 4 years back and was not associated with any trauma or chronic irritation. The swelling had gradually increased in size and was asymptomatic until a week before reporting to us during which the patient claimed that the swelling exhibited rapid increase in size and was associated with continuous moderate pain which aggravated on manipulation. No meal time variation in size of swelling was noted and patient did not give history of dryness of mouth. The patient's medical history was otherwise noncontributory. Clinical examination revealed a solitary diffuse extraoral swelling on the right cheek, measuring about 2 × 2 cm. The skin overlying the swelling was normal with no secondary changes. On palpation, the swelling was tender, with no local rise in temperature, soft to firm in consistency, and lobulated with a smaller hard nodule palpable at the inferior portion of the swelling . The swelling was nonfluctuant, nonreducible, noncompressible, and nonpulsatile. The swelling was not fixed to any underlying or overlying structures and was freely mobile. There were no signs of altered sensations in the area involved. Intraorally a mild fullness of the right buccal mucosa was noted with no secondary changes with similar palpatory findings as performed extraorally . Right submandibular incision measuring about 6 cm in length was marked to gain access to the masseteric area. Local anesthesia with adrenaline was infiltrated at the incision site. After the initial skin incision, parotidomasseteric fascia was then incised to gain access to the lesion within masseter muscle; care was taken not to involve any branches of facial nerve and blunt dissection was used. Once the masseter muscle was accessed, it was explored using blunt dissection and the masses of the lesion were localized. The lesion was found to have feeding blood vessels which were ligated before excision. The surgical site was checked for any residual bleeding keeping in mind the suspected nature of lesion. Upon achieving hemostasis, the surgical site was irrigated with povidone iodine solution and saline; suturing was done in layers using 3-0 vicryl and 4-0 prolene sutures . In 1922, Ewing described a rare and obscure intravascular endothelioma in the corpus cavernosum. He also described some cases of encapsulated, slow growing, subcutaneous tumors with abundant endothelial cells occurring in dilated varicose veins with previously obstructed circulation. These tumors grew in broad papillary masses formed by enlarged cells with hyperchromatic nuclei. In 1923, Pierre Masson first described an intravascular papillary proliferation formed within the lumen of inflamed hemorrhoidal plexus in a man which he believed was a neoplastic lesion and which he called Hémangioendothéliome végétant intravasculaire. Henschen described similar changes in nasal and laryngeal vessels which he considered to be a reactive phenomenon . Various terminologies have been put forth by different authors for this lesion including papillary fibroendothelioma and intravascular endothelioma, papillary proliferation of the endothelium, papillary endothelioma, Hémangioendothéliome végétant intravasculaire, L'endovasculite proliférante trombopoiétique, intravenous atypical vascular proliferation, intravascular angiomatosis, intravascular papillary endothelial hyperplasia, Masson's vegetant intravascular hemangioendothelioma, Masson's pseudoangiosarcoma, intravascular endothelial hyperplasia, Masson's lesion, and papillary endothelial hyperplasia . The most accepted term being intravascular papillary endothelial hyperplasia (IPEH) was first used by Clearkin and Enzinger as quoted by Johraku et al. . The pathogenesis of IPEH is poorly understood. One possible mechanism is a benign neoplastic process involving endothelial cell proliferation and papillary formation in the vascular lumen that undergoes degeneration and necrosis in the manner of a red infract. Alternative mechanisms include a benign endothelial proliferation arising from a thrombus as a variant of angiolymphoid hyperplasia with eosinophilia, a reactive process of endothelial cells induced by blood stasis and perivascular inflammation, and a pseudotumoral lesion caused by endothelial proliferation with papillary formation proceeded by an accumulation of thrombotic material, which serves to facilitate development of the lesion . IPEH can have varied appearance on imaging studies depending on the degree of thrombosis. In our patient, concentric calicifications were noted initially on conventional and digital radiographs. Performing an ultrasonographic study elucidated a well-defined cyst-like lesion located within the masseter. Color Doppler sonography revealed that the lesion lacked any obvious vascularity. Advanced imaging like CT and MRI enabled us to further identify the exact plane in which the lesion and associated calcific foci were located. The Hounsfield value of 100 HU and the isointense appearance on T2-weighted MRI indicated that the lesion was solid and not cystic. The lesion was also shown to have continuation with the right masseter muscle on CT and fatty infiltration of masseter on MRI which explains the difficulty in resecting the tumor mass alone. Areas of microcalcification have been noted in IPEH lesions. The presence of calcification is said to be typical in IPEH and the involved vessels may either be occluded or patent . Phleboliths, however, are also common in patients with hemangiomas. Likewise, calcification can occur in hematomas and tumors, and they can follow necrosis of soft tissues. Moreover, on angiography, IPEH can manifest as either a vascular or avascular mass. MRI is usually superior as the initial diagnostic test for vascular malformations, and further investigations are usually not necessary in low-flow lesions. The CT, MRI, and angiographic patterns of IPEH can all simulate other benign (e.g., hemangioma) and malignant (e.g., angiosarcoma) conditions. Histopathologically, in cases of IPEH associated with thrombi, an organizing thrombus is observed in an expanded blood vessel. The endothelial cells proliferated in a papillary pattern towards the lumen of the enlarged blood vessel from the area of the organizing thrombus. The structure of papillary proliferation was covered with no more than 2 layers of endothelial cells, and no atypia or mitotic activity was seen around the cores of fibrous connective tissue, which were frequently hyalinized and hypocellular . Histological differential diagnosis of IPEH includes angiosarcoma, hemangioma, mucocele, intravenous, pyogenic granuloma, Kaposi sarcoma, spindle cell hemangioendothelioma, malignant endovascular papillary angioendothelioma or Dabska's tumor, and intravascular endothelioma . Salyer and Salyer as referred by Robertson and Hernández, described the features which distinguish this lesion from angiosarcoma. (1) The lesions are well circumscribed and have a predominately intra- vascular location. (2) Extravascular lesions are associated with hematomas. (3) Rare but normal mitotic figures occur. (4) There is a lack of cellular atypia. (5) There are no necrotic areas. (6) Cells do not invade the perivascular space. (7) Solid areas exist with or without vascular differentiation. (8) Papillary fronds are one or two cells thick. (9) Papillary structures are mainly supported by a core of thrombotic material . Constantino et al. as alluded by Robertson and Hernández hypothesized the stages through which the lesion progresses into 4 stages: the process probably starts with a recently formed thrombus and early endothelial proliferation occurs. Later, papillary projections develop when endothelial cells cover the irregular surface of the thrombus. In the more advanced stage, thrombotic material is slowly resorbed and papillary projections become smaller. At an end stage, the thrombotic material is completely resorbed and only a nodule composed of endothelial cells remains . Sarode et al. cited various treatment modalities, most cases are cured by simple total excision with healthy margins. Cohen et al. used sclerotherapy (intralesional injection of a sclerosing agent “sodium tetradecyl sulfate”, causing compression and fibrosis of the blood vessels) followed by surgery with good esthetic results and minimal intra-operative bleeding. Endoscopic surgery has been used to treat an extensive IPEH of the sinonasal cavity. Noninvasively IPEH has been successfully treated by the beta-adrenergic antagonist nebivolol . | Review | biomedical | en | 0.999997 |
24895698 | In 2009, a new strain of swine-originated influenza A (H1N1) caused the first pandemic of the 21st century. 1 Clinical manifestations of influenza A (H1N1) pdm09 infection ranged from mild symptoms to severe illness and death. Most patients with severe or fatal disease were reported to have underlying medical conditions, including chronic lung disease, diabetes, cardiovascular disease, neurological disease, and pregnancy; 2 – 4 nevertheless, some individuals developed neurological complications without having underlying comorbidity. In fact, neurological complications associated with either vaccination or infection events are well described in influenza. 5 – 7 We conducted systematic searches in Ovid, Medline, EMBASE, and PubMed databases using the keywords “neurological complications of Influenza AH1N1” or “post-vaccine Influenza AH1N1” to identify published papers on this topic. Two clinical neurologists (C.G. and D.-A.A.) performed a full-text review of the papers and extracted all relevant data. Inclusion criteria for this review included studies reporting basic clinical data on influenza-related neurologically defined events, laboratory data confirming influenza A (H1N1) pdm09 infection and at least age-group information (adults versus pediatrics), because in most cases, a precise age was missing. In those cases reporting the age, pediatric patients were considered as <16 years old, both for infection and post-vaccine events. Only papers written in English, Spanish, German, French, Portuguese, and Italian were included. Those papers written in other languages or poorly written because of lacking relevant clinical and epidemiological data were excluded. Additionally, two adult patients with acute disseminated encephalomyelitis (ADEM) post-influenza A H1N1 vaccination studied at a Mexican neurological care center are reported. Post-vaccine-related neurological complications were observed in 287 patients. From these, 54 were male and 14 female, and there was no information on gender for the remaining patients (219). Mean age was 30·16 ± 25 years. Neurological complications consisted mainly of Guillain-Barré syndrome (GBS) or, polyneuropathy (125), seizures (23), acute disseminated encephalomyelitis (ADEM) (20), encephalopathy-encephalitis (41), stroke (7), transverse myelitis (3), and others (68). All patients survived and permanent sequelae were reported in 2 (0·69%). CSF-cytochemical characteristics showed 23·55 ± 31·8 cell/μl, 88 ± 28·8 mg/dl of glucose, and 45·97 ± 23·7 mg/dl of protein. While few reports and series provided a neuroimaging pattern, demyelinating lesions were predominant in this group. Infection-related neurological complications were observed in 1349 patients. Mean age was 12·75 ± 14·6 years. Two hundred and ninety-four were male and 196 female; there was no gender information on the 855 remaining patients. One-thousand two hundred and fifty-six patients (93%) were pediatric and 93 were adults. Forty-nine patients showed previous co-morbidity, mostly previous neurologic disease such as anoxo-ischemic cerebral sequelae, febrile seizures, and myasthenia. In this group, 60 patients (4·7%) died and 52 (30·1%) developed permanent sequelae. CSF-cytochemical characteristics were 67·99 ± 253·5-cells/μl, 63·62 ± 27·5 mg/dl of glucose, and 118·75 ± 381·3 mg/dl of proteins. In 49 patients, previous co-morbidity factors such as obesity, asthma, or other chronic diseases were present. A wide spectrum of neurological complications was observed: encephalopathy-encephalitis (464), seizures or epileptic status (369), stroke (12), ADEM (8), transverse myelitis (4), and others (469). Some important clinical features registered in both groups were pregnancy, obesity, asthma, and other chronic diseases in 170 patients. Adults were more frequently affected in the post-vaccine group, 250 (72·9%), while children predominated in the infection group, 1256 (97·1%), chi-square value = 914, P = 0·0001. Clinical outcome was less severe in the post-vaccine group than in the infectious group, where more cases of permanent sequels and deadly events were recorded. GBS was prevalent in the post-vaccine group (64·1% versus 35·9%) chi-square value = 328, P = 0·0001), whereas the encephalopathy-encephalitis spectrum predominated in the infection group (92% versus 8%) chi-square value = 45·8, P = 0·0001). It is important to note that deaths were recorded in the viral infection group only, most of them in pediatric age band, 50 of 60 (83·3%). Neuroimaging analysis revealed two main patterns: demyelinating and vascular. The main differences between both groups are summarized in Table 1 . A 27-year-old woman with a history of atopic dermatitis received monovalent inactivated influenza A (H1N1) vaccination on December 2009; 4 weeks later, she presented cephalgia, generalized weakness, progressive left-sided hemiparesis, and hypersomnia. She was evaluated at another institution. CT scan revealed brain edema. CSF-cytochemical analysis showed 81 mg/dl of glucose and 31 mg/dl of proteins without cells. Bacterial and tuberculosis cultures were negative. Serological test against Coxsackie virus, CMV, and cysticerci, as well as CSF-PCR for herpesvirus, were negative. Acute phase reactants were normal. She was treated with acyclovir and corticosteroids for 21 days, with some clinical improvement. Four weeks later, she showed abrupt changes in social behavior and dromomania (an uncontrollable psychological urge to wander). Clinical deterioration progressed with disarthria, paresthesias, and consciousness impairment. Upon admission to our Institution, neurological examination revealed stupor, left-central facial paralysis, hypertonic reflexes, grasp reflexes, persistent postures, generalized rigidity, and a left Babinski sign, making up a catatonic syndrome. MRI scan showed demyelinating lesions involving bilateral basal ganglia and brainstem . A new evaluation with cultures and serological tests was not contributory. The patient received corticosteroids, olanzapine, and lorazepam, with slow improvement. She was discharged 3 weeks later. As an outpatient, complex neuropsychiatric symptoms appeared with hyperorality, hypermetamorphosis (an irresistible impulse to notice and react to everything within sight), and hypersexuality, also known as Klüver-Bucy syndrome. A control MRI scan performed 15 months later showed radiological improvement . During a 27-month follow-up, the patient required multiple hospitalizations at a psychiatric ward for depression and impulsivity with suicidal ideation. She is still under antipsychotic treatment and requires continuous supervision by relatives. A 64-year-old woman was referred with a 2-month history of treated arterial hypertension and vitiligo, diagnosed 6 months before. She received trivalent inactivated A (H1N1) influenza vaccination on November 2011. One month later, she developed irritability, semantic paraphasias, and memory impairment. Upon neurological examination she was alert, oriented with euthymic mood, low fluent spontaneous speech, and increased latency of verbal responses. She was unable to keep or focus attention; constructional praxis and calculation-abstraction were seriously affected. Clinical findings were consistent with a frontal lobe syndrome. Electroencephalogram showed mild generalized dysfunction. CSF-cytochemical analysis rendered 82 mg/dl of glucose and 26 mg/dl of proteins without cells. PCR-viral panel for herpesvirus family was negative, as well as VDRL, cryptococcal antigen, bacterial, fungal, and mycobacterial cultures. Other evaluations, including HIV serology, IgM serology for EBV, CMV, antinuclear antibodies, and antineuronal antibodies, were all negative. A first MRI scan taken 1 month after the initial symptoms showed diffuse cortico-subcortical white matter involvement and edema . Patient was treated with intravenous methylprednisolone for 3 days, followed by oral tapering corticosteroids. On a control MRI scan, 4 months after the symptoms onset , a significant reduction in white matter abnormalities was seen. Neurological improvement has been progressive, and at 6 months of follow-up, the patient still receives rehabilitation and psychotherapy). Although influenza virus A (H1N1) pdm09 has become a public health threat of global concern, 109 , 110 there are no accurate data regarding the worldwide frequency of neurological complications related to this disease. Here, we reviewed the reported neurological complications from this disease from pandemic onset until December 2012; we found more reports of neurological complications due to the infection itself than to vaccination. The Vaccine Adverse Event Reporting System estimated that from October 2009 through January 2010, 82·4 million doses of 2009 H1N1 vaccine were administered; death, GBS, and anaphylaxis reports after 2009-H1N1 vaccination were rare (<2 per million doses administered, each). 111 On the other hand, WHO aimed to provide access to A (H1N1) pdm09 vaccine for all countries as soon as the vaccine was available and approved. Each recipient country established its vaccination programs, with some degree of variation depending on national priorities. Some chose to vaccinate only specific priority groups, including at least some children and younger adults (including pregnant women), and healthcare workers. 112 – 118 According to our review, fatal cases and permanent neurological sequelae were reported in about 11% of patients with influenza-related neurological complications. With respect to vaccination, aging appears to be related to a higher risk of having neurological sequelae, as in our two reported cases. The clinical outcome was generally more favorable in post-vaccine neurological complications. In fact, no fatalities occurred in this group, but permanent sequelae were observed in 2/287 patients, our two ADEM post-vaccine cases, patients were female and developed severe and complex neuropsychiatric sequelae. Most patients with neurological complications related to influenza A H1N1 infection developed necrotizing or non-necrotizing encephalopathy; an antecedent of chronic diseases was found in some of these patients. 8 , 9 , 14 , 23 , 31 , 37 , 47 , 48 , 50 , 62 , 64 A number of individual factors such as the patient's age may be involved; children and elderly are the groups with the highest risk of having neurological complications, but also are those suffering underlying immune disorders, chronic diseases, or obesity. 119 , 120 In our review, most neurological complications occurred in the population younger than 16 years Graph. 1 . This result, along with the pivotal role of the young in spreading the infection, highlights the relevance of enforcing vaccination in this population group, where severe post-vaccination complications are infrequent. There are insufficient details in the published reports about neurological complications related to influenza A (H1N1) infection or vaccination to reveal other individual and circumstantial factors that may participate in the susceptibility or development of such complications, and their optimal management is unknown. With respect to pathogenesis, while influenza viruses do not seem to show a direct tropism to the nervous system, virus detection within both retina and the olfactory bulb has been described in animal models. 121 , 122 Influenza virus has been also detected by isolation or nested RT-PCR in human cerebrospinal fluid 59 , 74 , 123 , 124 on brain tissue in neuropil, ependyma, Purkinje cells, and other neurons. 125 Although in most influenza cases, no virus has been detected in CSF, the reported information stresses the relevance of searching for the virus in the central nervous system in different infection stages, particularly when neurological symptoms are present. On the other hand, other pathogenesis factors may be linked with neurological disorders related to influenza vaccination. As it is reported, the vaccine itself may promote an exacerbated peripheral inflammatory response, 126 the extension of which may be modulated by individual biological factors, that is, age, sex, and genetic background. Furthermore, an increased systemic or peripheral inflammatory response may promote neuroinflammation, which may underlie the neurological symptoms observed in the two cases reported herein, and in those published elsewhere. 127 In this regard, the severity of brain dysfunction even in cases with non-clinical neurological findings may be correlated with high levels of pro-inflammatory cytokines in blood and CSF (cytokine storm). 128 However, in some cases of CNS involvement, no cytokine storm or tissue inflammatory infiltrate has been found. 63 , 129 It is also possible that both the viral infection and the vaccination promote blood–brain barrier (BBB) dysfunction, 130 producing neuroinflammation and neurological disorders. With respect to neurological diseases related to the infection, it is important to consider the higher prevalence of encephalopathy or encephalitis in the pediatric population. The size of the influenza viral particle may prevent it from crossing the barrier in adults, but an immature BBB may be prone to virus invasion. 103 Even though our analyses show clear limitations due to the incomplete information in most of the case reports retrieved from medical literature, and also to their descriptive nature, the information reviewed in this article highlights the relevance of an accurate neurological evaluation in all suspicious cases and of an appropriate long-term clinical and imaging follow-up of infection and post-vaccination events related to influenza A (H1N1)pdm09, to clearly estimate the magnitude of neurological complications that could lead to permanent disability. | Study | biomedical | en | 0.999998 |
24938492 | Whilst self-management support is widely advocated it is clear that existing strategies are of limited benefit because they fail to take account of everyday circumstances of patients and the range of work required to manage their health within the context of their daily lives . Self-management support is frequently disconnected from the realities of social deprivation and the mundane everyday demands of living life with a long-term condition (LTC) are overlooked as are the capacity and personal support needed to balance everyday life practicalities with the additional work required to manage a LTC . Furthermore, the focus of self-management support for LTC management tends to be on moments of crisis or the temporary and transient, and lack engagement with a wider set of resources and networks . As part of a Randomised Controlled Trial aimed at managing chronic kidney disease in primary care, a needs-led intervention to improve networks of support for people with long-term health problems, Patient-Led Assessment for Network Support (PLANS) was developed . PLANS was designed to address the problem of engagement with and the mobilisation of community resources to support people with generic long-term health problems and can be used to prioritise people’s own health and social needs in a way which tailors access to local community services . Delivery of PLANS for the BRIGHT trial and Summary of the PLANS support calls conducted for the BRIGHT trial sections elucidate how PLANS was delivered in the trial. While PLANS was developed with the underlying assumption that chronic illness management and broader well-being are closely intertwined in people’s everyday lives, it was also assumed that sustainable behaviour change and engagement with available resources could only be feasible by putting the emphasis on what is acceptable to people. The BRIGHT trial led to significant improvement in health outcomes. These results will be reported in more detail elsewhere. Therefore this qualitative study was designed to understand the active ingredients of the intervention to aid generalizability and facilitate translation into everyday practice by a) understanding the ‘work’ required of participants and telephone support workers and the skills required to effectively deliver and engage with PLANS; b) understanding who it works for and why and what contexts make successful implementation more likely; c) exploring the experience of PLANS and the processes of delivery and engagement from the perspectives of participants and the telephone support workers who delivered it; and d) to gain insight into the perceived relevance of PLANS to patients who received it and determine how patient-directed resources are implemented in people’s everyday lives. Chronic kidney disease (CKD) is a developing area of research . CKD is growing in prevalence and can lead to cardiovascular morbidity and mortality which has led to clinical guidance highlighting the importance of early identification and active management of CKD to maintain vascular health in primary care . CKD is categorised into five stages with stage 5 indicating renal failure. Stages 1 to 3 are managed in primary care and are common with around 5% of the population having early stage kidney disease. There is little or no specific support or information for CKD stage 3 but there is great potential for avoiding future health problems if managed more effectively. Chronic kidney disease often exists with other conditions such as hypertension, diabetes and ischaemic heart disease and is associated with low socioeconomic status . The methods of recruitment to the BRIGHT trial are described in Blickem et al . 20 patients in the intervention arm of the BRIGHT trial were interviewed and their telephone support calls were recorded. These included 15 women and 5 men. At the baseline assessment, participants in the intervention arm of the trial were invited to take part in the current study which involved the audio recording of the telephone support calls (baseline and follow up) and a qualitative interview. Following the delivery of the telephone support call, a convenience sample of participants who consented to be contacted for this qualitative study were contacted by a researcher to arrange an interview within two weeks of delivery of the telephone support call. At the interview informed consent was obtained to conduct and audio record the interview. The length of interviews varied from approximately 40 to 90 minutes. Normalisation Process Theory (NPT) was used as a sensitising tool to explore the processes of delivery and engagement . We considered that Normalization Process Theory would be a useful analytical tool because NPT is a robust theory of implementation that helps provide awareness of the work involved in embedding and sustaining practices associated with an intervention, and thus aids understanding of what becomes normalized into everyday settings. NPT was developed to understand the embedding of new technologies into health systems PLANS is such a technology and our focus was on the work that patients and support workers needed to do to ensure the effectiveness of PLANS in accessing better support. NPT is divided into four constructs which were used to evaluate: the relevance of PLANS to patients who received it (coherence); the processes of engagement and buy-in (cognitive participation); the work done to enable PLANS to happen and who this implicates (collective action); the perceived benefits and costs of PLANS (reflexive monitoring) . All authors contributed to the analysis. A coding framework was developed by CB and AK which was informed by NPT (Additional file 3 ) and a first round of analysis was conducted using this framework. It was agreed that the analysis should also be inductive and to examine data that did not appear to ‘fit’ with the chosen theoretical framework so that important concepts or themes were not missed. All transcripts were each analysed and coded by both the first author and one of the other authors. After this round of analysis all authors attended two meetings to discuss and reach consensus about the consistency of the coding and share emergent themes from the analysis. After consensus was agreed on themes and codes a second round of analysis was conducted. CB with AK wrote the first draft of the paper and co-authors provided feedback on iterations. The invisibility or lack of awareness of CKD could be a hindrance to engagement with PLANS because some participants could not see the relevance of doing so and in some cases participants were upset because of the introduction of a new diagnosis. Therefore PLANS or any self-management resource is likely to struggle for relevance where there is an unclear health rationale for action. These findings suggest the need for greater consistency in the management of CKD within primary care for self-management support to be effective. It is reasonable to imagine that PLANS might have been more relevant or useful if delivered to a population with more ‘visible’ long-term health problems such as arthritis, heart disease or diabetes. However the ‘invisibility’ of CKD exposed some of the problems of delivering self-management support to people who do not prioritise their health in the context of other everyday life priorities and so demonstrates the value of an intervention like PLANS which operates at different levels, e.g. offering the opportunity to reflect on practical, personal or health-related problems which make life difficult but which have become normative. NPT was an appropriate heuristic device with which to analyse this data as each of the four constructs relate well to the processes of engagement and the implementation of PLANS as experienced by participants in the study. Although we looked for data that fell outside of our coding framework, we were in fact able to code all relevant data with reference to one of the NPT constructs. However, whilst NPT is presented as a temporal process, this analysis showed that many participants experience the constructs of NPT simultaneously. For example, the work of sense-making necessarily involves an appraisal of the cost-benefits of PLANS for participants. Correspondingly, the work of engagement or ‘buy-in’ was influenced by these processes. This suggests that NPT is a useful way of understanding the experience of the PLANS intervention but best understood as a non-linear progression towards successful (or not) implementation. Improving awareness of and access to local resources offers a complementary approach to traditional individually-focused models of self-management which aim to increase the capacity and resources available to people with LTCs. Appreciation of the complex challenges faced by people in socially and economically deprived circumstances draws attention towards potentially valuable ways of supporting these groups. Whilst this study provides evidence for self-care strategies which consider the everyday life contexts in which health management takes place in order to tailor support, how it works in practice raises the relevance of how novel interventions based on this more social model lead to tensions both with the norms of practice operating in primary care (e.g. the non-disclosure of a diagnosis) and of people who have accommodated to a way of life in which isolation or the burden of competing activities has become normalised, as well as the dominance of a healthcare model where there is an underlying assumption (among both patients and professionals) that there is a sharp divide between illness management support and one’s broader well-being. Hence, the design and delivery of social interventions like PLANS need to take account of personal circumstances and commitments as a key priority, but it may need to also address issues of legitimacy, which may in turn require a closer and sustainable over time involvement by health professionals in the process of its delivery. This study aimed to create understanding about pushing the boundaries of support that can be offered to people with LTCs to facilitate the adoption of this innovative and effective approach. Shifting the emphasis of self-management towards personal and community resources allows for building strategies which brings into the frame the utilisation of existing community, voluntary and third sector resources to support people with long-term health problems within socially disadvantaged communities. However, focussing on the everyday life contexts of health management raises debate about the need to address social and structural factors such as access to resources, available support, and home and work environment – but also suggests that the notion of engagement needs to be seen in the broader context of other agencies norms of practice and existing patient expectation. | Review | biomedical | en | 0.999997 |
25161799 | Acute peritonitis may be classified as primary (spontaneous), where an infection has been raised de novo within the peritoneum, or secondary, where the inflammation involving the peritoneum is the result of an identifiable primary process. Secondary peritonitis is one of the most common indications for urgent abdominal surgery. Despite great advancements in diagnostic tools, surgical equipment, and technique, management of patients with severe secondary peritonitis remains a surgical challenge, with major morbidity and a mortality rate over 50% in most series . In comparison with its levels one hour before anesthesia, plasma levels of TNF- α decreased insignificantly during surgery until immediately after the abdominal wall closure. Median values were 10.4 and 9.1 pg/mL ( P = 0.273), respectively. At 48 hours after abdominal wall closure, a mild increase in TNF- α levels was noticed, with a median value of 14.2 pg/mL ( P = 0.225) . In contrast, IL-6 increased during surgery from 362 pg/mL to 540 pg/mL ( P = 0.5), ending with 400 pg/mL 48 hours after abdominal wall closure ( P = 0.686) . The patterns of values distribution concerning TNF- α and IL-6 were not statistically different ( P = 0.449 and P = 0.375, resp.). The suggested mechanism of morbidity and mortality due to secondary peritonitis is a vicious circle, started by intraperitoneal inflammatory and toxic mediators. These induce vasodilatation and enhance the permeability of the visceral and parietal capillary vessels, thus facilitating the translocation of microorganisms, their toxic products, or cytokines from the peritoneal cavity to the circulation of the blood. This leads to a cascade of events: the onset is the systemic inflammatory response syndrome (SIRS), leading to the multiple organ failure syndrome (MOFS) and often ending with death. Analysis of our data showed no significant changes in the levels of plasma inflammatory mediators during surgical laparotomy, except for platelet count. Despite the decreasing trend of WBC, CRP, and TNF- α levels, they were statistically insignificant ( P = 0.438, P = 0.262, and P = 0.449, resp.). On the other hand, the IL-6 levels showed an increasing trend during surgery but still without statistical significance ( P = 0.375). The only significant change in the systemic inflammatory response identified in our study was attributed to the PLT count, which decreased during surgery ( P = 0.001). | Review | biomedical | en | 0.999995 |
25386373 | Uterine leiomyosarcomas (LMSs) constitute 1% of all uterine malignancies and approximately 25% of uterine sarcomas, that are rare tumors that account for only 3% to 7% of all uterine cancers . They demonstrate an aggressive growth pattern with a high rate of recurrence with hematologic dissemination; the most common sites are lung, liver, and peritoneal cavity . Head and neck district is rarely interested, and only other four cases of metastasis in the oral cavity have been previously described . In particular, we illustrate the second case of metastasis in the upper buccal gingiva in a 63-year-old woman in which lung metastasis was also present. A 63-year-old woman with a history of advanced uterine LMS presented to our center with a painful, ulcerated swelling on the right upper buccal gingiva . She underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy for a diagnosis of LMS staged as pT2bN0 fourteen months previously. Eight months after primary treatment she developed two bilateral lung masses (SUV max: 7.8 at (18)F-fluoride PET/CT); histological examination of the 11 mm lung mass in the right chest revealed a metastasis of LMS. An adjunctive lung mass was present in the left chest. Chemotherapy was administered, initially with isofosfamide-epidoxorubicin, with scarce tolerance (grade 3-4 neuthropenia) so that it was decided to administer taxotere. During this treatment she developed a rapidly growing mass in the right upper buccal gingiva. She was referred to her dentistry that performed an excisional biopsy under local anesthesia suspecting a “haemorragic epulis.” Histological examination was compatible with metastasis of leiomyosarcoma, incompletely excised. A CT scan performed about 1 month after resection revealed an osteolytic lesion of 30 × 35 mm of the upper maxilla ; MRI was not performed because the patient was claustrophobic. Because of the rapid growth observed just in 40 days, it was decided according to oncologist to perform a partial maxillectomy and contemporary reconstruction with temporalis muscle pedicled flap even if a lung metastasis was present. Histological examination confirmed the presence of a 6 cm spindle cells LMS, entirely excised. Immunohistochemical analysis against monoclonal antibodies for a-smooth muscle actin (a-SMA), desmin, HHF-35, caldesmon, and vimentin was positive; mitotic index (Ki67) was of 90% . Considering the radical excision, no “adjuvant” radiotherapy on the oral cavity was administered. In order to control lung metastasis and considering the aggressiveness of the disease, it was decided to perform two other cycles of chemotherapy with ifofosfamide-epidoxorubicin. A partial regression of the lung metastasis was obtained, but again it was impossible to continue treatment because of high toxicity. A PET-CT performed 3 months after surgery revealed a right femur metastasis, so that radiotherapy was performed. Two months later, after an episode of epistaxis, head and neck CT scan with contrast revealed a relapse in the masticatory space and rinopharynx: the patient was referred to palliative radiotherapy. LMSs usually arise in anatomical sites with abundant smooth muscle, such as gastrointestinal tract, retroperitoneum, and uterus; nevertheless, uterine LMSs constitute only 1% of all uterine malignancies . Despite variable results, patients with uterine LMS have an overall poor prognosis with a long-term 5-year survival and risk of recurrence ranging from 25% to 75%, even if these tumors are usually confined to the uterus at the time of diagnosis . The majority of patients who recur do so within 2 years of initial diagnosis, and up to 90% of patients who fail show distant metastases either alone or concurrent with pelvic recurrence. In our case, the tumor was confined to the uterus at the time of diagnosis, and distant metastases to the lung were detected eight months after primary treatment. The most common sites of recurrence are peritoneal cavity (30–50% of cases), lung (30–40%), and liver (about 10%); only rarely do they involve the brain and skull (<1%) owing to pulmonary arterial circulation . Metastatic uterine LMS to the oral cavity are extremely rare, and only four other cases have been previously described . Also considering LMSs originated from other primary sites, only other three cases with metastasis to oral cavity can be found . The rarity of buccal mucosa involvement can be due to the fact that in the oral cavity smooth muscle is very scarce, being present in the blood vessel walls and the circumvallate papillae of the tongue. Kim et al. hypothesize that “the metastatic mass must be related to the blood vessels in the buccal cheek, and the maxillary gingivae with haematogenous spread from the uterus via lung to the oral cavity” . In our case oral metastasis to the upper gingival developed after lung metastases. They also found that metastatic tissue was different from tissue from primary site, being more vascularized and composed by cells more spindle-shaped moderately positive to the a-SMA antibody . In our case it was impossible to compare the two specimens, because the patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy at another center. The treatment of choice of uterine LMS is surgery and the use of adjuvant treatment has limited impact on clinical outcome, and radiotherapy seems only to improve local control, because most recurrences develop at distant sites . The most common chemotherapic agent used for LMSs is doxorubicin, usually associated with ifofosfamide . In this case no adjuvant radiotherapy was administered after total abdominal hysterectomy with bilateral salpingo-oophorectomy, and chemotherapy was started after the detection of lung metastases. In case of metastatic disease, factors that would contribute to the decision of operability would include extent of tumor (TNM), number and type of metastases, disease free interval from the initial diagnosis to the time of metastases, and expected life span . In our case, the decision to proceed with surgical removal of the upper gingiva mass, even in presence of advanced disease, was taken in order to improve quality of life, being chemotherapy and radiotherapy inadequate to control the oral recurrence. Obviously, reconstruction has been achieved using the “simplest” methods, using temporalis muscle flaps, even if a free flap reconstruction is the treatment of choice in order to reconstruct both bone and soft tissue . Bone grafts were not use in order to avoid complication in case of irradiation . Adjuvant radiotherapy was not considered because of resection in free margins with no suspect of residual disease. Nevertheless, local recurrence was observed 5 months after surgical removal so that patient was referred to palliative radiotherapy. In conclusion, even if head and neck metastases from uterine leiomyosarcoma are rare, they have to be suspected in case of rapidly growing haemorrhagic mass. Due to the aggressive growth pattern of the tumor, wide surgical excision in free margins of metastatic lesions could not be sufficient, so that in selected cases, in order to improve local control, the use of adjuvant radiotherapy can be considered. Obviously, this can lead to improving quality of life not influencing clinical outcome. | Clinical case | biomedical | en | 0.999998 |
25431599 | Mastocytosis is a clonal myeloproliferative disorder characterized by dysregulation of various organs infiltrated with abnormal mast cells and by symptoms attributed to histamine release. According to the location of mast cell proliferation it is classified into cutaneous mastocytosis (CM), affecting solely the skin, and to systemic mastocytosis (SM), involving at least one extracutaneous organ with more severe clinical manifestations. SM is further divided to six subtypes, according to the recent World Health Organization (WHO) classification, reflecting progressive mast cell clonal expansion and severity of symptoms . In up to 40% of cases, SM is accompanied by a nonmast cell hematologic disorder (SM-AHNMD) , resulting in a combination of symptoms, related to each separate component . A form of reactive mast cell hyperplasia, which is observed in other hematologic neoplasms, such as lymphoplasmacytic lymphoma and hairy cell leukemia (HCL) must be excluded . A predominance of associated myeloid disorders, especially chronic myelomonocytic leukemia (CMML) is reported in SM-AHNMD . Lymphoproliferative neoplasms are much less commonly implicated , referring to 10 reported cases of non-Hodgkin lymphomas (NHL), 3 cases of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), 1 case of HCL, 6 cases of multiple myeloma (MM), and 1 case of Hodgkin lymphoma (HL). SM associated with adult acute lymphoblastic leukemia (ALL) has been documented in the case of a patient with SM associated with B-ALL carrying the (13;13) (q12;q22) translocation . Two other cases concerning adults with concurrent CM and ALL have also been reported . Among children with ALL, six cases of concomitant CM have been described [ 8 – 11 ]. A 40-year-old Caucasian female was admitted displaying symptoms of weakness and fatigue, being febrile (37.9°C) with moderate pallor. Her liver was palpable, as well as a slightly enlarged left inguinal lymph node. She also manifested diffuse cutaneous brown macular lesions on her trunk. Her complete blood count (CBC) revealed normocytic normochromic anemia with a normal leukocyte count and moderate thrombocytopenia. Bone marrow (BM) trephine biopsy and immunophenotype showed extensive infiltration from B-ALL expressing the surface markers CD10, CD19, CD22, CD79a, CD34, CD123, CD38, and Tdt, with an aberrant coexpression of the myeloid markers CD13, CD33. Eosinophilia was noted and spindle-shaped mast cells were present, scattered or in small aggregates, being positive in c-kit and negative in CD2 staining . Polymerase chain reaction (PCR) for KITD816V mutation, fibroblast growth factor receptor 1 and platelet derived growth factor receptor (FGFR1, PDGFR) rearrangements, and breakpoint cluster region/Abelson tyrosine kinase (BCR/ABL) fusion gene was negative. Conventional cytogenetics was normal in all studied metaphases. The patient received induction therapy for B-ALL, consisting of dexamethasone, vincristine, idarubicin, cyclophosphamide, cytarabine, and thioguanine, along with intrathecal methotrexate. During induction, she developed severe low respiratory tract infections. BM immunophenotyping and trephine biopsy following induction revealed residual leukemic disease consisting of 10% lymphoblasts and an extensive mast cell infiltration exceeding 50% of nucleated BM cells . The majority of mast cells (>25%) were spindle-shaped, distributed either in a diffuse pattern or forming dense aggregates of more than 15 cells, synchronously expressing the surface markers c-kit (CD117) and CD2. Serum tryptase levels were normal. Thus, the major criterion and two out of the four minor recent diagnostic WHO criteria for SM were fulfilled, unequivocally establishing the diagnosis of SM-AHNMD, in terms of the preexisting B-lymphoid neoplasm . A subsequent skin biopsy revealed only sparse mast cells in the dermis. SM-AHNMD is a distinct form of SM characterized by synchronous evolution of two separate clonal populations, one consisting of mast cells and one as a second hematologic malignancy. CMML is the most prevalent concomitant hematologic disorder, followed by other myelodysplastic/myeloproliferative syndromes (MPN/MPDs), MPNs, MDS, and acute myeloid leukemia (AML) . Lymphoproliferative neoplasms are much less frequently found in this setting with reported cases of CLL/SLL, HCL, plasma cell dyscrasias, and lymphomas [ 3 – 5 ]. Among the latter, HL, splenic marginal zone lymphoma, diffuse large B-cell lymphoma, hepatosplenic T-cell γ / δ lymphoma, and cutaneous B-cell lymphoma have rarely been described. We are currently aware of a sole published case of an adult with KITD816V mutated SM associated with B-ALL carrying a (13;13) (q12;q22) translocation . The authors reported that B-ALL was cured by alloHSCT, while SM persisted for more than a decade. The other two reported adult patients suffered from concomitant ALL with cutaneous forms of mastocytosis . The combined nature of SM-AHNMD underlies the need to confront each malignant entity separately but simultaneously. Both its clinical course and prognosis strongly correlate with those of the associated nonmast cell neoplasm and standard regimens are required for the latter. Management of histamine related symptoms, such as anaphylaxis, pruritus, flashing, or malabsorption, lies on relevant pharmaceutical agents. Interferon- α , corticosteroids, and cytoreductive therapies, mostly cladribine, have been used to treat the SM component, with minor responses . Data on the beneficial role of allo-HSCT are scarce and conflicting, due to the rarity of relevant cases . In addition, leukemias arising in the context of SM are considered of poor risk . This was also the case for our patient, who was primarily refractory to all treatment modalities. The duration of response is a prerequisite for its estimation according to the recent International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) & European Competence Network on Mastocytosis (ECNM) consensus criteria, taking into account ascites and pleural effusions, spleen size, liver function, serum tryptase, albumin and CBC values, and mast cell infiltrates in tissue biopsy sections . Prior to duration of response, assessing organ damage is the most crucial parameter in order to apply the previously mentioned criteria in SM-AHNMD cases and may prove difficult due to shared clinicopathological features between the two components of the disease . In our case, response to IM administration could not be assessed because of chemotherapy-related toxicity. Eligible organ damage mostly consisted of transfusion dependent anemia and thrombocytopenia, due to BM infiltration from both diseases. Infiltration from the ALL clone in the performed BM biopsy was around 10% and, thus, not compatible with the severity and duration of cytopenias. Liver biopsy was not carried out due to the patient's poor performance status. As anticipated, the clinical course and prognosis of our patient were principally determined by her poor response to all applied antileukemic treatment modalities, failing to achieve CR. We should acknowledge that the concurrent SM complicated the chemotherapy related marrow and liver toxicities. IM administration enhanced transient hematologic improvement and permitted the administration of subsequent chemotherapeutic agents for ALL. In conclusion, the diagnosis of SM-AHNMD requires careful consideration of both clinical and laboratory findings. The choice of treatment depends on the nature and clinical behaviour of both disorders . | Review | biomedical | en | 0.999998 |
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