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Background: Aberrant crypt foci (ACF) are the earliest preneoplastic lesions in human colon, identifiable on chromoendoscopic screening. Our objective was to evaluate the %methylation of APC, CDKN2A, MLH1, RASSF1, MGMT, and WIF1 tumor suppressor genes (TSG) in ACF, corresponding colorectal carcinomas (CRC), and normal colonic mucosal controls. Methods: In this study, macroscopically normal-appearing mucosal flaps were sampled 5-10 cm away from the tumor mass from 302 fresh colectomy specimens to identify ACF-like lesions. Thirty-five cases with multiple ACFs were selected (n 35) as the main study group, with corresponding sections from CRC (n 35) as disease controls, and mucosal tissue blocks from 20 colectomy specimens (normal controls), operated for non-neoplastic pathologies. Genomic DNA was extracted, and methylation-specific polymerase chain reaction (PCR) was performed on a customized methylation array model. %Methylation data were compared among the groups and with clinicopathological parameters. Selected target mRNA and protein expression studies were performed. Results: %Methylation of TSGs in ACF was intermediate between normal colon and CRC, although a statistically significant difference was observed only for the WIF1 gene (P < 0.01). Also, there was increased nuclear α-catenin expression and upregulation of CD44-positive cancer-stem cells in ACF and CRCs than in controls. Right-sided ACFs and dysplastic ACFs had a higher %methylation of CDKN2A (P < 0.01), whereas hyperplastic ACFs had a higher %methylation of RASSF1 (P 0.04). The topographic characteristics of ACFs did not correlate with TSG %methylation. Conclusions: Early epigenetic methylation of WIF1 gene is one of the mechanisms for ACF development in human colon. [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. [ABSTRACT FROM AUTHOR]

Aim: This study investigates the fall in total serum bilirubin levels within 1 week after surgery, as a marker to predict early outcome in biliary atresia (BA) patients post-Kasai portoenterostomy (KP). Methods: The ratio of total serum bilirubin levels at the 7th postoperative day to the preoperative level (TB7/TB0) in patients undergoing KP was calculated (January 2011-July 2015). Patients were stratified after 3-months follow-up into outcome groups depending on the clinical clearance of jaundice and TB7/TB0 ratio was correlated to outcome and liver histopathological changes in these groups. Results: Sixty-one patients (M:F = 44:17), median age 75 days were included. At the end of 3 months, 27 (44.39%) were anicteric while 26 (42.6%) were still clinically jaundiced. Patients with a higher median value of TB7/TB0, that is, 0.856 were more likely to have jaundice at the end of 3 months as compared to patients with a lower median value of 0.615 (P < 0.0001). A cutoff TB7/TB0 ratio >0.723 predicted the KP outcome with 84.6% sensitivity and 81.5% specificity. The difference in TB7/TB0 ratio between patients with varying severity of liver histopathological changes was also significant, namely, cholestasis (P = 0.01), hepatocellular damage (P = 0.03), portal inflammation (P = 0.04), and portal fibrosis (P = 0.02). Conclusions: The rapidity of fall in the total serum bilirubin levels within 1 week post-KP was able to predict the likely outcome in BA patients. [ABSTRACT FROM AUTHOR]

Objective: This study focused on whether primary cultures of ovarian cancer (OC) cells established from ascites can be used to evaluate response to chemotherapeutic agents and if curcumin could enhance the efficacy of these agents.Materials and Methods: We established five primary cultures of ascitic cells from OC patients and treated them with curcumin, carboplatin, and paclitaxel singly and in combinations. The percentage of apoptotic cells was determined by flow cytometry.Results: There was a wide variation in the response of individual primary cultures to treatment with the chemotherapeutic agents. Curcumin by itself was as good as carboplatin or paclitaxel in inducing apoptosis in the primary OC cells. Curcumin was not able to affect the carboplatin mediated cell killing. However, a combination of curcumin and paclitaxel was additive and was equally effective as a combination of carboplatin and paclitaxel. A combination of curcumin carboplatin, and paclitaxel was also found to be additive and, in fact, turned out to be the best combination that gave the highest percentage of apoptosis in vitro.Conclusion: This study highlights the fact that primary cultures of OC cells can be used to detect response to chemotherapeutic agents and help to individualize the treatment offered to OC patients. [ABSTRACT FROM AUTHOR]

Context: The recent advent of bipolar energy in bladder tumor resection has raised many questions regarding density of current and its effect on histopathology of the resected transurethral resection of bladder tumor (TURBT) chips. Aims: The aim of this study is to evaluate the histomorphological features in resected bladder tumors comparing bipolar versus conventional (monopolar) energy. Settings and Design: Inclusion criteria were patients with primary presentation of carcinoma urinary bladder undergoing TURBT. The patients with prior resections were excluded as these could jeopardize the results of cautery artifacts. Materials and Methods: From February 2010 to December 2011, 61 patients with primary carcinoma bladder and meeting our inclusion criteria were compared. Group 1 (n = 31) underwent bipolar-TURBT (B-TURBT) and Group 2 (n = 30) monopolar-TURBT (M-TURBT). Two pathologists, who were blinded to the form of electrocautery used, examined the resected tissue. The degree of cautery artifact in each specimen was recorded. The severity of the cautery artifact was graded as absent, mild, moderate, or severe. The mean age, tumor size, and resection time were recorded in both groups. Statistical Analysis Used: Data were analyzed using SPSS 16. Data were compared in between groups using paired t-test and Pearson's Chi-square test. The significance level was set at 0.05. Results: The mean age, tumor size, and resection time were similar in between the two groups. The pathologists had no obscurity in reaching a correct diagnosis in all cases. The cautery artifacts were graded as absent in 10 (32.2%) and 8 (26.67%), mild in 12 (38.7%) and 11 (36.67%), moderate in 5 (16.1%) and 7 (23.33%) and severe in 4 (12.9%) and 5 (16.66%) cases, respectively in Group 1 and 2. There was no statistically significant histomorphogical dissimilarity between specimens according to the type of cautery used. Conclusions: Bladder tissue obtained from B-TURBT is of equivalent histomorphological feature as that of standard M-TURBT. [ABSTRACT FROM AUTHOR]

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]

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: To correlate the age at surgery, liver function tests, and hepatic and portal tract histo-pathological changes with surgical outcome in the form of disappearance of jaundice in extrahepatic biliary atresia (EHBA). Materials and Methods: This is a retrospective study of 39 cases of EHBA. There were 19 males and 10 females. Kasai's portoenterostomy (KPE) along with liver biopsy was performed in these patients; for purpose of correlation this biopsy was considered to be the preoperative biopsy. These patients were divided into three groups based upon surgical outcome: (A) disappearance of jaundice; (B) initial disappearance of jaundice with recurrence after 3 months; and (C) persistence of jaundice. Postoperatively, liver function tests and liver biopsies were repeated at 3 months after the KPE. Results: There were 11 patients in group A (28%), 21 patients in group B (54%), and seven patients in group C (18%). The age at surgery was comparable in all the three groups. The postoperative levels of serum bilirubin, alkaline phosphatase (ALP), and gamma glutamyl transpeptidase (GGTP) showed statistically significant improvement as compared with the preoperative levels in group A and B patients. Patients belonging to group C showed no improvement in the liver functions following surgery. The preoperative hepatic histopathological changes (hepatocellular alteration, cholestasis, bile ductular proliferation, and bile duct inflammation) showed a significant difference among the three groups; patients with lesser degrees of pre-existing histopathological changes had better outcome following surgery. Fibrosis was seen in all the three groups preoperatively but the difference was not statistically significant. Group C had significant fibrosis in more than 50% patients. Additional findings, viz. ductal plate malformation (9 patients, 23%) and giant cell transformation (19 patients, 49%) did not show any correlation with surgical outcomes. Conclusions: The liver function tests and the histopathological features appeared to affect the final surgical outcome of these patients. Higher degree of cholestasis, hepatocellular alteration, bile ductule proliferation, bile duct inflammation showed definite correlation with poor surgical outcome. High grade hepatic fibrosis and portal edema showed a trend towards poor outcome but did not achieve statistical significance. [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]