Search

The author explores evidence of the existence of cancer stem cells (CSCs) in hepatocellular carcinoma (HCC). Topics discussed include the first evidence of the existence of CSC, various markers used to identify CSCs, and the findings of several studies based on immunophenotyping of HCCs which showed that 20 to 50% of tumor cells in a HCC express progenitor cell markers such as albumin, CK7 and CK19.

Background and Aims: Extrahepatic biliary atresia is one of the most challenging conditions in pediatric surgery. The definition of prognostic factors is controversial. Surgical outcomes after bilioenteric drainage procedures are variable. This study attempts to correlate the pre- and post-operative liver histology with clinical factors in order to define early predictors of success. Materials and Methods: Twenty consecutive patients, treated by Kasai's portoenterostomy (KP) over a 3 years period were included in this study. Tissue obtained from the porta hepatis was analyzed for duct size using an optical micrometer and was categorized into three types: I-No demonstrable ducts; II - <50 μ; III - >50 μ. Pre- and post-operative liver biopsy was analyzed for architectural changes and fibrosis; hepatic fibrosis was quantified using existing criteria. Pre- and post-operative liver function tests (LFTs) were also done. Surgical outcomes were defined as: (A) Disappearance of jaundice within 3 months; (B) initial disappearance of jaundice with recurrence by 6 months and (C) persistence of jaundice. Duct diameters, fibrosis score, and LFT were correlated with age and clinical outcomes. Results: The surgical outcomes were: A-6 patients (30%), B-6 patients (30%), C-8 patients (40%). The duct size at the porta was I-3 patients, II-11 patients, and III- 4 patients (tissue was not available in 2 cases). The change in total serum bilirubin (mg%) from pre- to post-operative period was 13.6 ± 3.9 (Group A), 4.6 ± 2.8 (Group B), and 3.4 ± 3.9 (group C) (P < 0.001) and direct and indirect fractions followed a similar trend; the changes in liver enzymes were not significant. The changes in hepatic histopathological changes (ballooning of hepatocytes, giant cells, cholestasis, portal tract infiltration, ductular proliferation, lobular necrosis, and fibrosis) were also not significant but there was a definite trend in the change in fibrosis -1.500 ± 1.643 (Group A), 0.667 ± 2.582 (Group B), and 1.500 ± 1.852 (Group C) - reduction of fibrosis with good results and progression of fibrosis with poor results. Conclusions: Following KP, jaundice persisted in 40% patients; it disappeared in 60% patients but reappeared in half of these patients 6 months postoperatively. The duct size at the porta hepatis did not correlate with age or surgical outcome. Serum bilirubin showed the best correlation with surgical outcome. Postoperative changes in hepatic fibrosis seem to have some bearing on surgical outcomes-progressive fibrosis is a poor prognostic factor. [ABSTRACT FROM AUTHOR]

Serous ovarian cancer (SOC) is a significant cause of morbidity and mortality in females with poor prognosis because of advanced stage at presentation. Recently, neoadjuvant chemotherapy (NACT) is being used for management of advanced SOC, but role of tissue biomarkers in prognostication following NACT is not well established. The study was conducted on advanced stage SOC patients (n = 100) that were treated either conventionally (n = 50) or with NACT (n = 50), followed by surgery. In order to evaluate the expression of tissue biomarkers (p53, MIB1, estrogen and progesterone receptors, Her-2/neu, E-cadherin, and Bcl2), immunohistochemistry and semiquantitative scoring were done following morphological examination. Following NACT, significant differences in tumor histomorphologywere observed as compared to the native neoplasms. MIB 1was significantly lower in cases treated with NACT and survival outcome was significantly better in cases with low MIB 1. ER expression was associated with poor overall survival. No other marker displayed any significant difference in expression or correlation with survival between the two groups. Immunophenotype of SOC does not differ significantly in samples from cases treated with NACT, compared to upfront surgically treated cases. The proliferating capacity of the residual tumor cells is less, depicted by low mean MIB1 LI. MIB 1 and ER inversely correlate with survival. [ABSTRACT FROM AUTHOR]

Purpose: Role of (18 [F] fluorine-18-labeled 2-fluoro-2-deoxy-D-glucose [FDG] positron emission tomography-computed tomography [PET-CT]) in the evaluation of axillary lymph node involvement in T1T2N0 breast cancer and compare results with sentinel lymph node biopsy (SLNB). Methods: A total of 37 patients of proven T1T2N0 breast cancer were included in the study. Patients with past history of breast surgery, T3T4 disease, uncontrolled diabetes mellitus and pregnant patients were excluded from the study. Pre-operative FDG PET-CT was performed followed by sentinel lymph node (SLN) biopsy with blue dye or combined technique. Results: SLN was identified in 32 of 37 patients with an identification rate of 86.48% (32/37). With combined technique SLN identification rate was 100% (6/6) while with blue dye alone; it was 83.8% (26/31). Among 37 patients, 16 had axillary metastases of which 12 had macrometastases and four had micrometastases detected by immunohistochemistry (IHC). Of 12 patients with axillary macrometastases, skip metastases were present in two patients in whom SLN was negative and in two patients SLN was not identified, but axillary dissection showed metastases. PET-CT had shown sensitivity, specificity, negative predictive value and positive predictive value of 56%, 90%, 73%, and 81.8%, respectively. IHC of SLN detected four patients with micrometastases upstaging the disease by 11% (4/37). Conclusion: Because FDG PET-CT has a high specificity in the evaluation of axillary lymph node involvement in T1T2N0 breast cancer patients according to the results of this study if FDG PET-CT is positive in axillary lymph nodes, axillary lymph node dissection may be considered instead of SLNB. [ABSTRACT FROM AUTHOR]

AIMS AND OBJECTIVES: To determine the efficacy of integrated 18F-fluorodeoxy glucose positron emission tomography-computed tomography (18F-FDG PET-CT) in the evaluation and characterization of mediastinal lymph nodes into benign and malignant pathology. METHODS: Thirty-five patients with mediastinal lymphadenopathies without primary neoplastic or infective lung pathologies were included in the study. The lymph nodes were detected on contrast-enhanced CT scan of the chest. All patients underwent 18F-FDG PET-CT scan for evaluation of mediastinal lymph nodes. Results of PET-CT were compared with histopathology of the lymph nodes and sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated. STATISTICAL ANALYSIS: The data were collected prospectively and analyzed using (SPSS Inc., Chicago, IL) 11.5 software. RESULTS: Histopathology results in 35 patients revealed tuberculosis in 12, sarcoidosis in 8, and lymphoma in 15. Maximum standardized uptake value (SUVmax) of the benign lymph nodes ranged from 2.3 to 11.8 with a mean±standard deviation (SD) of 5.02±3.26. SUVmax of the malignant lymph nodes ranged from 2.4 to 34 with a mean±SD of 10.8±8.12. There was a statistically significant difference between benign and malignant pathology (P<0.0059). 18F-FDG PET-CT has sensitivity of 93% and specificity of 40% with SUVmax 2.5 as the cutoff. We found the optimal SUVmax cutoff to be 6.2 as determined by the receiver-operator characteristic curve. With 6.2 as cutoff, the sensitivity, specificity, and accuracy were 87%, 70%, and 77%, respectively. CONCLUSION: In countries where tuberculosis and other granulomatous diseases are endemic, SUVmax cutoff value of 2.5 has low specificity. Increasing the cutoff value can improve the specificity, while maintaining an acceptable sensitivity. [ABSTRACT FROM AUTHOR]

AIMS AND OBJECTIVES: To determine the efficacy of integrated 18F-fluorodeoxy glucose positron emission tomography-computed tomography (18F-FDG PET-CT) in the evaluation and characterization of mediastinal lymph nodes into benign and malignant pathology. METHODS: Thirty-five patients with mediastinal lymphadenopathies without primary neoplastic or infective lung pathologies were included in the study. The lymph nodes were detected on contrast-enhanced CT scan of the chest. All patients underwent 18F-FDG PET-CT scan for evaluation of mediastinal lymph nodes. Results of PET-CT were compared with histopathology of the lymph nodes and sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated. STATISTICAL ANALYSIS: The data were collected prospectively and analyzed using (SPSS Inc., Chicago, IL) 11.5 software. RESULTS: Histopathology results in 35 patients revealed tuberculosis in 12, sarcoidosis in 8, and lymphoma in 15. Maximum standardized uptake value (SUVmax) of the benign lymph nodes ranged from 2.3 to 11.8 with a mean±standard deviation (SD) of 5.02±3.26. SUVmax of the malignant lymph nodes ranged from 2.4 to 34 with a mean±SD of 10.8±8.12. There was a statistically significant difference between benign and malignant pathology (P<0.0059). 18F-FDG PET-CT has sensitivity of 93% and specificity of 40% with SUVmax 2.5 as the cutoff. We found the optimal SUVmax cutoff to be 6.2 as determined by the receiver-operator characteristic curve. With 6.2 as cutoff, the sensitivity, specificity, and accuracy were 87%, 70%, and 77%, respectively. CONCLUSION: In countries where tuberculosis and other granulomatous diseases are endemic, SUVmax cutoff value of 2.5 has low specificity. Increasing the cutoff value can improve the specificity, while maintaining an acceptable sensitivity. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis is one of the major health problems in India. Genitourinary tuberculosis comprises 20% of all extrapulmonary tuberculosis, and is the most common extrapulmonary system to be affected by this disease. The recent surge in the incidence of HIV-infected patients in India has further ignited the fury. Though the members of the Mycobacterium species are well identified, the incidence could not be controlled due to its complex etiopathogenesis and genetic background. Pathological Spectrum: The spectrum of pathological changes of genitourinary tuberculosis is wide, which varies from normal morphology to markedly scarred kidney, bladder, and epididymis with autocystectomy. A thorough knowledge is required to prevent the end-stage complications. The sequel can be detrimental for the patient's physical, behavioral, psychological, and financial health. Diagnostic Dilemmas: Though culture and polymerase chain reaction are available for the detection of tuberculosis, the sensitivity and specificity varies widely and one should be aware. Conclusions: A thorough knowledge of epidemiology, immunopathogenesis, spectrum of the disease and the possible sequels, will help better and effective management of the disease. [ABSTRACT FROM AUTHOR]

Background & objectives: Standard of care for chronic hepatitis C (CHC) in India is peginterferon and ribavirin (RBV). The response to treatment in real life stetting is unclear. The objectives of this study were to evaluate the demographic profile and assess the virological response and predictors of response in CHC patients. Methods: Consecutive patients with CHC were included in this study. Detailed clinical history, risk factors, and predictive factors of response were noted. Patients were treated with peginterferon α2b (1.5 μg/kg/wk) and RBV (12 mg/kg/day) for 6 to 18 months based on response. Results: A total of 211 patients were included in the analysis, mean age 40.6±12.3 yr, 144 (68%) were males and 71 (34%) had compensated cirrhosis. Commonest risk factor for acquiring CHC was previous transfusion and surgery (51%). Genotype 3 (72%) was most common followed by genotype 1 (23%). Overall sustained virologic response (SVR) was 64 per cent [95% CI 57.1%-70.4%]. The SVR was 66.5 per cent [95% CI 58.34-73.89%] for genotype 3 and 61.2 per cent [95% CI 46.23 to 74.80%] for genotype 1. Non-cirrhotics had better SVR rates compared to cirrhotics (76 vs 41%, P<0.001). On multivariate analysis, BMI ≥23 kg/m2, HOMA-IR ≥2, compliance (≤80%), and fibrosis >2 were predictors of low SVR. Interpretation & conclusions: Genotype 3 was the commonest HCV genotype. The commonest source of infection was previous transfusion and surgery. SVR rates for genotypes 3 were better than genotype 1 patients. Predictors of non-response were high BMI, insulin resistance, significant fibrosis and inadequate compliance. [ABSTRACT FROM AUTHOR]

Background: There is limited information on the impact of cytomegalovirus (CMV) infection on clinical outcomes and operative histopathology in children with biliary atresia (BA). We hypothesized that CMV infection is associated with greater histopathological damage and unfavorable short-term clinical outcomes., Materials and Methods: A prospective single-center study was conducted with effect from January 2011-July 2012 including all infants with BA who underwent surgery. Diagnosis of CMV infection was confirmed by serum immunoglobulin M (IgM) positivity or the presence of CMV-deoxyribonucleic acid (DNA) in the liver tissue. Four short-term outcome variables were observed. The cohort was divided into subgroups on the basis of seropositivity (IgM + or IgM-); the presence of CMV-DNA in the liver (polymerase chain reaction [PCR]+ or PCR-); and composite CMV groups (Group 1 - IgM+, PCR+; Group 2 - IgM+, PCR-; Group 3 -- IgM-, PCR+; and Group 4 - IgM-, PCR-). Outcomes and histopathology were compared in these subgroups., Results: A total of 32 infants with BA were operated at a mean age of 3.5 (range: 1-6) months. Serum IgM+ and PCR+ were observed in 50% and 37.5% of the patients. Unfavorable outcomes showed a significant association with IgM+ and not PCR+. Similarly, outcomes were poor for CMV Groups 1 and 2 at 1-month follow-up. Infants with IgM+ and PCR+ showed a greater degree of histopathological damage in terms of bile duct proliferation and severe bile duct fibrosis, respectively., Conclusion: In the present study, there was a high incidence of serum IgM+ (50%) and PCR+ of biopsy specimens (37.5%) in infants with BA. This CMV-infected subgroup was associated with greater histopathological damage and unfavorable short-term outcomes after surgery., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Indian Association of Pediatric Surgeons.)

Background: The pancreatobiliary carcinomas are characterized by presence of desmoplastic stroma. Overexpression of secreted protein acid and rich in cysteine (SPARC), a matrix producing agent has been documented in pancreatic ductal adenocarcinomas, with survival benefits. This study was targeted to see if SPARC expression in pancreatobiliary carcinomas is responsible for stromal desmoplasia and its prognostic significance., Methods: In this retrospective study 48 cases of pancreatic cancer and 27 cases of cholangiocarcinoma were analyzed. The expression pattern of SPARC and vascular endothelial growth factor (VEGF) (angiogenic factors) was evaluated by immunohistochemistry on formalin fixed paraffin embedded tissues. Immunoreactivity was scored semi quantitatively based on stain intensity and stain distribution. SPARC expression was correlated with tumor histology, stromal desmoplasia, VEGF expression, various histological parameters and overall survival in patients. Real time polymerase chain reaction was performed in few cases to validate the immunohistochemistry expression pattern., Results: SPARC expression was high in peritumoral stroma in pancreatic carcinoma than in pancreatic controls; however, SPARC expression pattern was not grossly different in desmoplastic and non-desmoplastic pancreatobiliary carcinomas and in cholangiocarcinomas. No definite correlation was noted between SPARC expression and histological markers of severity and overall survival data., Conclusions: The relevance of SPARC expression in pancreato-biliary carcinomas though may still be important for therapeutic decision making, it is not responsible for peritumoral stromal desmoplasia in these tumors and it does not have any significant prognostic implication., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Background and Aim: While the prevalence of celiac disease (CD) is increasing globally, the prevalence of tropical sprue (TS) is declining. Still, there are certain regions in the world where both patients with CD and TS exist and differentiation between them is a challenging task. We conducted a systematic review of the literature to find out differentiating clinical, endoscopic, and histological characteristics between CD and TS., Methods: Medline, PubMed, and EMBASE databases were searched for keywords: celiac disease, coeliac, celiac, tropical sprue, sprue, clinical presentation, endoscopy, and histology. Studies published between August 1960 and January 2018 were reviewed. Out of 1063 articles available, 12 articles were included in the final analysis., Results: Between the patients with CD and TS, there was no difference in the prevalence and duration of chronic diarrhea, abdominal distension, weight loss, extent of abnormal fecal fat content, and density of intestinal inflammation. The following features were more common in CD: short stature, vomiting/dyspepsia, endoscopic scalloping/attenuation of duodenal folds, histological high modified Marsh changes, crescendo type of IELosis, surface epithelial denudation, surface mucosal flattening, thickening of subepithelial basement membrane and celiac seropositivity; while those in TS include anemia, abnormal urinary D-xylose test, endoscopic either normal duodenal folds or mild attenuation, histologically decrescendo type of IELosis, low modified Marsh changes, patchy mucosal changes, and mucosal eosinophilia., Conclusions: Both patients with CD and TS have overlapping clinical, endoscopic, and histological characteristics, and there is no single diagnostic feature for differentiating CD from TS except for celiac specific serological tests., (© 2018 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Histological assessment of dysplasia in Barrett's esophagus (BE) has high inter-observer variability. Hence, use of ancillary markers for early detection of dysplasia in BE is an important clinical question., Methods: In this retrospective study consecutive cases of BE (n = 59), over a period of 4 years were included. Hematoxylin and eosin stained sections were reviewed independently by 3 senior qualified pathologists, who graded the dysplasia according to the Vienna Classification system and inter-observer agreement was analysed using the Kappa statistics. Subsequently Alpha-Methyl Acyl-CoA Racemase (AMACR), p53, CyclinD1, β-catenin, H2AX and M30 immunohistochemical (IHC) stains were examined on the following disease categories: BE with no dysplasia [NFD] (45), BE with indefinite for dysplasia (IFD) (4), low grade dysplasia (LGD) (3), high grade dysplasia (HGD) (2) and in adenocarcinomas (5). H score was calculated by adding up products of different grades of stain distribution and stain intensities (range of scores 0-300)., Results: Among the 3 pathologists, overall agreement was poor (k 0.06; 95% CI -0.089 to 0.145), with highest disagreement noted for differentiating the LGD and IFDs (k = 0.21). After revising the histological criteria, the kappa improved to 0.53. Among the IHC stains performed, p53, β-catenin, H2AX and M30 stains were significantly useful to differentiate between IFD and LGD (P values: 0.04, 0.004, 0.05 & 0.04, respectively). AMACR and β-catenin stains though were up-regulated in HGD/adenocarcinomas than in other categories, their expression were not statistically different between the IFD and LGDs., Conclusions: A detail histological scoring system may bring uniformity in histological interpretation of dysplasia in BE. Using a combined panel of IHC stains seems helpful in detection of dysplasia in BE, especially to differentiate the IFD and LGD changes in BE., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Background: We aimed to determine the prevalence of coeliac disease among children with short stature at a tertiary care centre and to define the predictors for coeliac disease, if any, in them., Methods: In this retrospective study, we reviewed the case records of children and adolescents with growth retardation attending the Paediatric Endocrinology Clinic from January 2008 to June 2011. All patients underwent the multi-tier stratified diagnostic protocol for complete evaluation of short stature. Coeliac disease was screened using IgA-anti-tissue transglutaminase antibody. The diagnosis of coeliac disease was made on the basis of the modified European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) criteria., Results: Of 432 patients (238 boys) who presented with short stature, 72 (16.7%) had physiological, while 360 (83.3%) had pathological causes. Endocrine causes were growth hormone deficiency (86 patients, 19.9%), hypopituitarism (31, 7.2%), hypothyroidism (22, 5.1%) and others (7, 1.6%). The systemic causes were: coeliac disease (47, 10.9%), haematological diseases (14, 3.2%), renal diseases (11, 2.5%) and others (24, 5.6%). Chronic diarrhoea (OR 15.7, 95% CI 7.8-31.5) and anaemia (OR 4.9, 95% CI 1.9-12.7]) were significant predictors for coeliac disease in patients with short stature. There was a definite response to gluten-free diet in them and the mean (SD) growth velocity measured over at least 6 months of gluten-free diet was 8.1 (3.0) cm/year., Conclusion: Nearly 11% of patients presenting with short stature have coeliac disease. In these patients chronic diarrhoea and anaemia were significant predictors of coeliac disease., (Copyright 2015, NMJI.)

Objective: To study the histological and proliferation characteristics of the pars tensa retraction pocket. To investigate the hypothesis that such retraction pockets may demonstrate breaks in the epithelial basement membrane., Study Design: Prospective evaluation. Fifty stage II-IV surgically resected retraction pockets., Setting: Tertiary care academic hospital., Methods: Paraffin sections stained with hematoxylin and eosin. Basement membrane evaluation by Periodic acid-Schiff (PAS) and silver-methenamine (SM). Evaluation of cellular proliferation by immunohistochemistry (MIB-1 score)., Results: Following are findings noted as frequent but not invariable in pars tensa retraction pockets: (1) subepithelial chronic inflammation (86%), (2) proliferation and hyperkeratinization of the outer epithelial layer, (3) epithelial cones with proliferating cells (increased MIB-1 score) in the basal epithelial layer (39%), (4) loss of the middle double collagen layer (71%), and (5) loss of the inner mucosal layer (33%). Inflammation and cellular proliferation were noted as ubiquitous among all grades. A trend was noted along progressive grades of retraction (II-IV) for an increasing incidence of basal epithelial cones, middle collagen layer loss, and inner mucosal layer loss. Focal loss of basement membrane was noted in several cases with PAS staining, but further staining with the SM in all such cases indicated the basement membrane to be intact., Conclusion: A continuum of progressive histological features akin to cholesteatoma is noted with increasing grades of retraction (II-IV). Breach of the basement membrane was recently reported as a feature of cholesteatoma but is not a feature of retraction. The near universal presence of inflammation as noted suggests an etiological role.

This study was aimed at evaluating the association between tumor vascularity and other known prognostic factors in different histopathological subtypes of renal cell carcinoma (RCC). In 41 cases of RCC, immunohistochemistry was performed using anti-CD34 antibody and Ki-67 (MIB-1). Microvessel density was estimated in an area of 0.23 mm(2) representative of the highest microvessel density ("hot spot"). The microvessel area (MVA) was expressed as percentage of total tumor area occupied by vessels. Endothelial proliferation index (EPI) was determined from sections stained by Ki-67. The relationship between MVD, MVA, EPI and prognostic parameters of RCC like stage, grade and tumor cells proliferation index (TPI) was evaluated. The tumor MVA increased significantly with the higher stage of the tumor (P < 0.001) and increase in TPI (P < 0.05). The MVD, however, did not show significant correlation with grade and stage of the tumor. Microvessel area appears to be a better prognostic marker for RCC when compared to microvessel density. The increase in MVA, without increase in MVD, with increasing stage may be due to the development of larger diameter vascular channels in higher-stage tumors, and this is thought to facilitate metastasis.

Aim: Tropical sprue was considered to be the most important cause of malabsorption in adults in India. However, several reports indicate that celiac disease is now recognized more frequently., Methods: We analyzed the clinical presentation, endoscopic and histological features of 94 consecutive patients (age >12 years) with chronic diarrhea and malabsorption syndrome. The spectrum of disease in these patients and features differentiating celiac disease and tropical sprue are reported here., Results: Celiac disease (n = 61, 65%) was the most common cause of malabsorption followed by tropical sprue (21, 22%). Other conditions including cyclosporiasis (3), Crohn's disease (2), common variable immunodeficiency (2), lymphangiectasia (1), William's syndrome (1), and idiopathic malabsorption (3) accounted for the remainder. A greater number (21, 34%) of patients with celiac disease than those with tropical sprue (4, 19%) presented with atypical manifestations. Patients with celiac disease were younger (p = 0.001), more often had anemia, (p = 0.001), scalloping of folds (p = 0.001), moderate (p = 0.02) or severe (p = 0.001) villous atrophy, higher grade of intraepithelial lymphocytic infiltration (p = 0.001), crypt hyperplasia (p = 0.001), cuboidal (p = 0.001) and pseudostratified (p = 0.009) surface epithelial cells, and diffuse (p = 0.001) epithelial damage. In comparison, patients with tropical sprue were older and more often had normal duodenal folds, normal villi, tall columnar epithelial cells and focal epithelial damage., Conclusions: Celiac disease was the most frequent cause of malabsorption syndrome in this series of patients. There are significant clinical and histological differences between celiac disease and tropical sprue.

Aims and Objectives: To determine the efficacy of integrated (18)F-fluorodeoxy glucose positron emission tomography-computed tomography ((18)F-FDG PET-CT) in the evaluation and characterization of mediastinal lymph nodes into benign and malignant pathology., Methods: Thirty-five patients with mediastinal lymphadenopathies without primary neoplastic or infective lung pathologies were included in the study. The lymph nodes were detected on contrast-enhanced CT scan of the chest. All patients underwent (18)F-FDG PET-CT scan for evaluation of mediastinal lymph nodes. Results of PET-CT were compared with histopathology of the lymph nodes and sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated., Statistical Analysis: The data were collected prospectively and analyzed using (SPSS Inc., Chicago, IL) 11.5 software., Results: Histopathology results in 35 patients revealed tuberculosis in 12, sarcoidosis in 8, and lymphoma in 15. Maximum standardized uptake value (SUVmax) of the benign lymph nodes ranged from 2.3 to 11.8 with a mean±standard deviation (SD) of 5.02±3.26. SUVmax of the malignant lymph nodes ranged from 2.4 to 34 with a mean±SD of 10.8±8.12. There was a statistically significant difference between benign and malignant pathology (P<0.0059). (18)F-FDG PET-CT has sensitivity of 93% and specificity of 40% with SUVmax 2.5 as the cutoff. We found the optimal SUVmax cutoff to be 6.2 as determined by the receiver-operator characteristic curve. With 6.2 as cutoff, the sensitivity, specificity, and accuracy were 87%, 70%, and 77%, respectively., Conclusion: In countries where tuberculosis and other granulomatous diseases are endemic, SUVmax cutoff value of 2.5 has low specificity. Increasing the cutoff value can improve the specificity, while maintaining an acceptable sensitivity.

Background: The resectability and survival may be improved in thymoma and thymic carcinoma with multimodality therapy. Various diagnostic imaging modalities are required for accurate diagnosis and preoperative staging of thymic masses. The present prospective study was planned to evaluate if Fluorodeoxyglucose (FDG) PET-CT can help differentiate various thymic lesions noted on conventional imaging modalities., Methods: A prospective study was undertaken in 23 patients who had shown either an anterior mediastinal mass consistent with thymic origin or suspicious for a thymic mass on contrast-enhanced computed tomography scan. All patients underwent whole body FDG PET-CT after intravenous injection of 370 MBq of FDG. The interpretation of PET-CT images was based on the following criteria: FDG uptake (present or absent), SUVmax, pattern of uptake, invasion to surrounding structures, presence of metastasis and necrosis. The results of PET-CT were correlated with the final histopathology following surgery. Statistical analysis was performed with SPSS 11.5 for Windows software. The mean SUVmax of the 3 groups of pathology was compared using the Kruskal-Wallis Test., Results: Thymic hyperplasia had an enlarged thymus with mean SUVmax of 1.1. Low risk thymoma had large tumors and their mean SUVmax was 3. High risk thymoma had small tumors with mean SUVmax of 2.1. As a group, thymoma had mean SUVmax value of 2.3. All thymic carcinomas were large, and their mean SUVmax was 7. The difference between the mean SUVmax for thymic hyperplasia, thymoma and thymic carcinoma was statistically significant. The difference between the SUVmax of high risk and low risk thymoma was not significant., Conclusion: (18)F-FDG PET-CT can help characterize various thymic lesions noted on conventional imaging modalities. However, larger prospective studies are further required to substantiate these findings.

Early metastasis and a poor five-year survival make lung cancer the leading cause of cancer related deaths worldwide. The clinical profile of lung cancer patients in India differs from the West as they present earlier, with squamous cell carcinoma being the commonest histological type. We compared gene expression profiles in primary lung squamous cell carcinoma (LSCC) and matched normal lung tissues in Asian Indians. Using suppression subtractive hybridization, two subtracted cDNA libraries containing differentially expressed genes in the tumors were constructed. Differential expression was confirmed by reverse Northern blot analysis. DNA of confirmed clones was sequenced and subjected to GenBank Blast searches. RNA expression levels were then analyzed by Northern blotting and validated by semiquantitative RT-PCR (in 10 cases of NSCLC). Seventeen differentially expressed gene cDNA fragments of LSCC were analyzed. The differentially expressed genes included those associated with cellular metabolism, cell-cycle, -structure, -adhesion, transcription, proliferation, apoptosis and signal transduction. The study provided first evidence that KIAA0767, a Death Inducing Protein, a novel p53 independent target of E2F1, and Geminin, an inhibitor of DNA replication are differentially expressed in LSCC. Identification of the differentially expressed genes in lung cancer in this study may serve as better molecular markers for early diagnosis and identifying novel intervention sites for anticancer therapy.

Chronic diarrhea and steatorrhea occur frequently in patients with autoimmune polyglandular syndrome (APS) type I. Intestinal lymphangiectasia has been reported earlier as a cause of steatorrhea in a young girl with APS Type I. We describe 2 patients with APS Type I who were found to have intestinal lymphangiectasia, one of whom had symptomatic protein-losing enteropathy.

Introduction: The incidence of microscopic colitis has recently increased. Although collagenous colitis and lymphocytic colitis are the two main subtypes of microscopic colitis, many patients may not fit into either category and are thus included under the header nonspecific colitis. Of late, the spectrum of microscopic colitis has widened to include minimal change colitis, microscopic colitis not otherwise specified and microscopic colitis with giant cells. There is a lack of information concerning the spectrum of microscopic colitis in Asia., Method: In a retrospective analysis, case records of 29 patients diagnosed with microscopic colitis between 1999-2005 were analysed. Drug use parasitic infection and common bacterial infections were excluded. Colonoscopic/ sigmoidoscopic examination was done and multiple colonic mucosal biopsies were stained serially with haematoxylin and eosin for detailed histological examination and Masson trichrome for sub-epithelial collagen band. Based on histological criteria, patients were categorised into five subtypes: collagenous colitis (presence of collagenous thickening of surface epithelium basement membrane > 10 microm), lymphocytic colitis (intra-epithelial lymphocytes more than 20 per 100 colonocytes), minimal change colitis (crypt architectural abnormality in the form of cryptitis and crypt dilatation in the absence of increase in intraepithelial lymphocytes and subepithelial collagenous band), microscopic colitis not otherwise specified (increased inflammatory cell infiltrates in the lamina propria in the absence of other abnormalities) and microscopic colitis with giant cells., Results: Mean age of patients was 38.59 years (range 12-62). Of 29 patients with microscopic colitis, 7 (24.1%), 4 (13.8%), 7 (24.1%) and 11 (37.9%) were classified as collagenous colitis, lymphocytic colitis, minimal change colitis and microscopic colitis not otherwise specified, respectively. None of these patients had giant cells. There was no significant correlation between disease type and clinical manifestations., Conclusion: Microscopic colitis has a wide histological spectrum. Cases reported as non-specific colitis, may be categorised into definite subtypes of microscopic colitis.

Chronic diarrhea and malabsorption are uncommon in immunocompetent patients with visceral leishmaniasis. We report two immunocompetent patients with visceral leishmaniasis where the predominant presentation was chronic diarrhea. One of them had clinically overt malabsorption and duodenal mucosa was loaded with Leishmania donovani bodies. The other patient had diffuse colonic aphthous and discrete ulcerations and Leishmania donovani bodies were seen in the crush smears of the colonic mucosa. With amphotericin B, there was reversal of malabsorption and healing of colonic ulcers.

Aim: Disabled-2 (DAB2) is a candidate tumor-suppressor gene identified in ovarian cancer that negatively influences mitogenic signal transduction of growth factors and blocks ras activity. In a recent study, we observed down-regulation of DAB2 transcripts in ESCCs using cDNA microarrays. In the present study, we aimed to determine the clinical significance of loss of DAB2 protein in esophageal tumorigenesis, hypothesizing that DAB2 promoter hypermethylation-mediated gene silencing may account for loss of the protein., Methods: DAB2 expression was analyzed by immunohistochemistry in 50 primary esophageal squamous cell carcinomas (ESCCs), 30 distinct hyperplasia, 15 dysplasia and 10 non-malignant esophageal tissues. To determine whether promoter hypermethylation contributes to loss of DAB2 expression in ESCCs, methylation status of DAB2 promoter was analyzed in DAB2 immuno-negative tumors using methylation-specific PCR., Results: Loss of DAB2 protein was observed in 5/30 (17%) hyperplasia, 10/15 (67%) dysplasia and 34/50 (68%) ESCCs. Significant loss of DAB2 protein was observed from esophageal normal mucosa to hyperplasia, dysplasia and invasive cancer (P(trend) < 0.001). Promoter hypermethylation of DAB2 was observed in 2 of 10 (20%) DAB2 immuno-negative ESCCs., Conclusion: Loss of DAB2 protein expression occurs in early pre-neoplastic stages of development of esophageal cancer and is sustained down the tumorigenic pathway. Infrequent DAB2 promoter methylation in ESCCs suggests that epigenetic gene silencing is only one of the mechanisms causing loss of DAB2 expression in ESCCs.

Dubin-Johnson syndrome is neither complicated by liver cell necrosis nor associated with portal hypertension. We report a 22-year-old man who had recurrent episodes of jaundice (conjugated hyperbilirubinemia) because of Dubin-Johnson syndrome and portal hypertension secondary to portal vein thrombosis. The relationship between Dubin-Johnson syndrome and portal vein thrombosis in this case is most likely a chance occurrence.