Evaluation of p53 protein expression in Barrett esophagus.

BACKGROUND: Loss of heterozygosity of p53 along with aneuploidy is deemed to be the early molecular steps in Barrett metaplasia-dysplasia-adenocarcinoma sequence. Objective biomarkers need to be used along with microscopy for risk stratification to predict the progression of Barrett esophagus (BE) to carcinoma. AIM: This study aims to study p53 protein expression in dysplasia and correlate the same with morphology in BE. MATERIALS AND METHODS: A time-bound study was conducted from January 2011 to June 2015. All esophageal biopsies showing histological evidence of columnar epithelium with the presence of goblet cells were included. The cases which showed dysplasia were graded on hematoxylin and eosin stain. Evaluation of p53 immunohistochemistry staining was done on all the cases of BE. Dysplasia was correlated with the expression of p53 using Chi-square value (χ2) and Fischer's exact test wherever appropriate. P < 0.05 was considered to be statistically significant. RESULTS: Of 829 esophageal biopsies received, 119 were endoscopically suspected to be BE, of which 85 cases were confirmed on microscopy. In our study, there were 75 cases negative for dysplasia (88.2%), 8 with low-grade dysplasia (LGD) (9.4%), and two with high-grade dysplasia (HGD) (2.4%). Three cases of BE had associated adenocarcinoma. Immunostaining with p53 done on all the 85 cases showed positive staining in all cases with LGD, one with HGD and two with adenocarcinoma. In the present study, immunostaining with p53 showed 90% sensitivity, 89.3% specificity, positive predictive value of 52.9%, and negative predictive value of 98.5%. CONCLUSION: The technical simplicity, easy availability, and comparatively lower cost enhance the role of p53 as a biomarker in risk stratification for patients with BE.

Comparative analysis of copy number variations in ulcerative colitis associated and sporadic colorectal neoplasia.

BACKGROUND: The incidence of and mortality from colorectal cancers (CRC) can be reduced by early detection. Currently there is a lack of established markers to detect early neoplastic changes. We aimed to identify the copy number variations (CNVs) and the associated genes which could be potential markers for the detection of neoplasia in both ulcerative colitis-associated neoplasia (UC-CRN) and sporadic colorectal neoplasia (S-CRN). METHODS: We employed array comparative genome hybridization (aCGH) to identify CNVs in tissue samples of UC nonprogressor, progressor and sporadic CRC. Select genes within these CNV regions as a panel of markers were validated using quantitative real time PCR (qRT-PCR) method along with the microsatellite instability (MSI) in an independent cohort of samples. Immunohistochemistry (IHC) analysis was also performed. RESULTS: Integrated analysis showed 10 overlapping CNV regions between UC-Progressor and S-CRN, with the 8q and 12p regions showing greater overlap. The qRT-PCR based panel of MYC, MYCN, CCND1, CCND2, EGFR and FNDC3A was successful in detecting neoplasia with an overall accuracy of 54% in S-CRN compared to that of 29% in UC neoplastic samples. IHC study showed that p53 and CCND1 were significantly overexpressed with an increasing frequency from pre-neoplastic to neoplastic stages. EGFR and AMACR were expressed only in the neoplastic conditions. CONCLUSION: CNVs that are common and unique to both UC-associated and sporadic colorectal neoplasm could be the key players driving carcinogenesis. Comparative analysis of CNVs provides testable driver aberrations but needs further evaluation in larger cohorts of samples. These markers may help in developing more effective neoplasia-detection strategies during screening and surveillance programs.

Clinicomicrobiological analysis of patients with cholangitis.

Acute cholangitis is inflammation of biliary ductal system from infection with an associated biliary obstruction. This retrospective study was done to determine the factors responsible for cholangitis and the microbiological profile of the bile in patients with cholangitis. In the study involving 348 patients, 36.4% had associated malignancy. A total of 54% of the bile samples were positive for aerobic culture. Nearly 66-73% of the Escherichia coli and Klebsiella isolates were Extended spectrum beta lactamases (ESBL) producers. Two isolates of Candida spps were also obtained. Polymicrobial infection was seen in 31.5% of the culture positive cases. Ideal antibiotics in case of cholangitis would be those which are excreted in the bile such as third-generation cephalosporins, ureidopenicillins, carbapenems and fluoroquinolones to combat resistance and polymicrobial aetiology. Anti-fungal drugs may also be necessary if the patient is not responding to biliary decompression and antibacterial agents to prevent fungaemia.

Pseudomembranous colitis in a pregnant woman.

Pseudomembranous colitis in association with pregnancy has not been well described in English literature. Recent studies show a drastic increase in the incidence and severity of Pseudomembranous colitis in pregnant women, who were once thought to be at low risk. We report here a case of Pseudomembranous colitis in a young healthy immunocompetent pregnant lady. An early suspicion of this entity with the characteristic appearance of pseudomembranes on colonoscopy and histology confirmed the diagnosis enabling prompt treatment and complete recovery without any serious consequences.

Solitary rectal ulcer syndrome in childhood.

Solitary rectal ulcer syndrome is a rare disorder of childhood and usually goes unrecognised or misdiagnosed because it can mimic various other rectal entities. Here a 9-year old boy presented with bleeding per rectum and altered bowel habits. Colonoscopy revealed multiple ulcers which on histopathological examination showed features of SRUS with severe reactive changes of regeneration mimicking malignancy.

Role of anxiety and personality in non-ulcer dyspepsia: a comparative study with duodenal ulcer.

BACKGROUND: Though emotional factors are known to influence gut functions, studies evaluating the role of anxiety and personality in non-ulcer dyspepsia (NUD) are few and have not yielded consistent results. AIMS: To find out whether anxiety and abnormal personality pattern are specifically associated with NUD. METHODS: 33 patients with NUD and 30 patients with duodenal ulcer, who were randomly selected from among those attending a gastroenterology out-patient clinic, were administered a) the Eyesenck Personality Inventory, to measure neuroticism and extroversion; and b) a short self-rating scale for anxiety, to measure state and trait anxiety. RESULTS: There were no significant differences between the two groups in state anxiety, neuroticism and extroversion. Trait anxiety, however, was significantly higher in the NUD group (p = 0.05). CONCLUSIONS: Though the difference in trait anxiety score between the two groups attained significance, this finding needs further support to indicate a causal role for anxiety in NUD. There is need for further studies about the role of anxiety in various subgroups of NUD.

Psychiatric disorders in non - ulcer dyspepsia.

Systematic studies of psychiatric disorders in non -ulcer dyspepsia are rare. The aim of the present study was to find out the nature and prevalence of psychiatric morbidity in non-ulcer dyspepsia. Thirty three patients with non-ulcer dyspepsia and thirty with duodenal ulcer were assessed for psychiatric morbidity with the help of the regular version of the SADS, and diagnosed according to DSM-IIIR criteria. Non-ulcer dyspepsia was defined precisely and investigators who made the psychiatric diagnosis were blind to the gastroenterological diagnosis. In the non-ulcer dyspepsia group, 69.7% of patients had psychiatric morbidity, compared to 26.7% in the ulcer group. The difference between the two groups in the frequency of psychiatric morbidity was statistically significant. Dysthymic disorder (39.4%) was the most frequent psychiatric disorder in the non-ulcer dyspepsia group.

Medical myotomy for achalasia cardia. Long term results.

Pneumatic dilatation was effective in relieving dysphagia in 16/17 subjects with achalasia cardia. It was also effective and safe in those with sigmoid oesophagus, although dilatation persisted in them. Recurrences were noted in one quarter of cases which were managed satisfactorily with subsequent dilatations. There were no complications. Pneumatic dilatation appears very useful in the management of achalasia cardia.

Poor response to long-term albendazole therapy of hydatid liver cysts.

Seven patients with uncomplicated hepatic hydatid cysts (Echinococcus granulosus) were treated with albendazole 10 mg/kg/day for 2-6 months (mean 4 months). Serial sonographic evaluation showed reduction in cyst size in only 1 patient (the anteroposterior diameter decreased from 16.5 cm to 4.9 cm). Therapy in this patient was discontinued after 4 months due to development of jaundice. Albendazole appears to have a limited role in the treatment of hydatid disease of the liver.

Post sclerotherapy esophageal ulcers: a prospective analysis of their behaviour.

The reported incidence of post sclerotherapy esophageal ulcers has shown marked variation, possibly due to lack of uniform criteria for their diagnosis. Using fixed criteria (size greater than or equal to 5 mm, duration greater than or equal to 2 weeks), we prospectively studied 82 patients with portal hypertension, who underwent four or more sessions of endoscopic sclerotherapy (EST), for the occurrence and behaviour of these ulcers. Post sclerotherapy ulcers occurred after 43 (9.2%) of 465 EST sessions in 30 (36.6%) of 82 patients. Ulcers were significantly associated with two complications: rebleed during the course of sclerotherapy (33% of ulcers bled compared to 3% from variceal rupture; p less than 0.001) and esophageal stricture formation (66.7% of strictures occurred in patients who had ulcers; p less than 0.05). Ulcers occurred more frequently in patients with poor liver function (61.5% in Child's C grade compared with 31.9% in Child's A or B grades; p less than 0.05) and after injection into larger varices (83.7% in varices grades 3 and 4, 16.3% in lower grades; p less than 0.005). Severe persistent chest pain (p less than 0.001) and pyrexia (p less than 0.01) after sclerotherapy were clinical pointers of ulcerogenesis.

Evaluation of leukocyte adherence inhibition (LAI) test in primary and secondary hepatic malignancies.

Leukocyte adherence inhibition (LAI) has been demonstrated to be a simple, rapid, and reliable technique in the diagnosis of various malignancies including hepatocellular carcinoma. The LAI test was carried out employing modified tube LAI technique in patients with primary hepatocellular carcinoma (HCC) and secondary carcinomas of liver. Positive LAI response to HCC antigen was obtained in all six (100%) cases of hepatocellular carcinoma tested. None of the control cases, which included 8 healthy subjects and 16 cases of benign liver diseases, gave positive LAI response. Two out of 19 cases of secondary carcinoma gave a positive LAI reaction to HCC antigen. In secondary carcinomas, 19 out of 21 cases (90.48%) gave positive LAI reaction to secondary adenocarcinoma antigen. There were two false positives in controls (1 each of cirrhosis and amebic liver abscess), and 1 out of 8 cases of HCC also gave positive response to secondary carcinoma antigen. Thus, LAI test was found to be useful in the diagnosis of hepatic malignancies.