Narendra Krishnani

Tropical sprue is associated with contamination of small bowel with aerobic bacteria and reversible prolongation of orocecal transit time.

Background:  In tropical sprue (TS), response to antibiotics may suggest a role for bacterial contamination of the small bowel, which is known in diseases with prolonged orocecal transit time (OCTT).

Gastric carcinogenesis: Possible role of polymorphisms of GSTM1, GSTT1, and GSTP1 genes

Objective. Although Helicobacter pylori infection is associated with gastric cancer (GC), only 1% of patients develop a malignancy, which suggests a role of host genetic factors. The aim of this study was to investigate the role of polymorphisms of GSTM1, GSTT1, and GSTP1 genes, which encode for carcinogen-detoxifying enzymes, in gastric mutagenesis. Material andmethods. Genotyping of GSTT1 and GSTM1 was done using PCR, while PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) was used for genotyping of GSTP1 in 76 patients with gastric neoplasm (GN), 67 with non-ulcer dyspepsia (NUD), 44 with peptic ulcer (PU), and 100 healthy controls (HC). Results. The study population included: GN (intestinal 40 (53%), diffuse 26 (34%), primary gastric lymphoma 8 (11%) and unclassified 2 (2%)), PU (duodenal ulcer (DU) 33 (75%), gastric ulcer (GU) 10 (23%), both PU and DU 1 (2%)). GSTT1 null genotype (GSTT1*0) was more common in patients with GN (30/76 (40%)) than in those with PU (5/44 (11%); p=0.001, odds ratio (OR) 5; 95% CI=1–4) and HC (23/100 (23%); p=0.02, OR 2; 95% CI=1–4). GSTT1*0 conferred a higher cancer risk for patients with DU (2/33 (6%), OR 10; 95% CI=2–45; p=0.00). GSTM1*0 and GSTP1 variant genotypes (ile/val and val/val) not alone but in combination with GSTT1*0 conferred a higher risk in PU patients (21 (28%) versus 5 (11%); OR 3; 95% CI=1–9; p=0.04). Both GSTM1*0 (16/26 (61%) versus 10/40 (25%); p=0.003, OR 5; 95% CI=2–14) and GSTT1*0 (12/26 (46%) versus 13/40 (33%); p=0.2, OR 2; 95% CI=0.6–5) were associated with a higher risk of diffuse tumor than of intestinal tumor. Conclusions. GSTT1*0 alone and in combination with GSTM1*0 and GSTP1 variant genotypes is a risk factor for GN in the Indian population. Low GSTT1*0 in DU patients may play a protective role against GN. GSTM1*0 and GSTT1*0 are risk factors for diffuse GC.

Predictors of long-term survival in patients with gallbladder cancer

The aim of this study was to examine the predictors of long-term survival (>24 months) in patients with gall bladder cancer. A retrospective review of 117 cases of gall bladder cancer resected between 1989 and 2000. The resections included 80 simple cholecystectomies and 37 extended procedures. Patients with survival >24 months (n=44) were compared with those having survival <24 months (n=73) for 17 prognostic factors. Overall median survival was 16 months with a 5-year survival of 27%. T status (P=.000) and adjuvant chemoradiotherapy (P=.001) were independent predictors of long-term survival. Survival advantage was seen in T3N+ve disease (P=.007) with extended procedures. Complete (R0) resection was attained in 30 patients with a 5-year survival advantage of 30% as compared with incomplete (R1) resection (P=.0002). Adjuvant chemoradiotherapy improved survival in simple cholecystectomy group (P=.0008) but no advantage was seen after extended procedures. Stage III (P=.001) and node-positive disease (P=.0005) had significant benefit with adjuvant therapy. Poor differentiation and vascular invasion were associated with poor long-term survival. R0 resection was associated with prolonged survival. Extended procedures improved survival in patients with T3N+ve disease. Addition of chemoradiotherapy made significant improvement in long-term survival in stage III and node-positive lesions and in patients undergoing simple cholecystectomy. R0 resection predicted long-term survival in gall bladder cancer. T3 N+ve disease had better survival after extended procedures. Adjuvant chemoradiotherapy improved survival in stage III and node-positive disease. Poor differentiation and vascular invasion were adverse predictors of survival.

Early gallbladder cancer1 1No competing interests declared.

Abstract Background: The majority of patients with gallbladder cancer (GBC) have advanced disease at the time of diagnosis and are unresectable. Longterm survival is usually seen in a subset of patients with early GBC (EGBC)—cancer confined to the mucosa (pT1a) and muscularis (pT1b). Management guidelines of EGBC are not yet defined and are controversial. The purpose of this article is to evaluate the diagnostic aspects and effects of resectional procedures on survival outcome in patients with EGBC. Study Design: EGBC was defined as cancer confined to the mucosa (pT1a) or muscularis (pT1b) according to the TNM classification. Clinicopathological details and survival data of 14 patients who had EGBC were analyzed. There were 9 women and 5 men, with a mean age of 60 years. Results: A definite preoperative diagnosis was possible in only three patients and three patients were diagnosed at surgery; the majority of patients were diagnosed incidentally after cholecystectomy for associated gallstones. Two patients underwent extended cholecystectomy and 12 patients underwent simple cholecystectomy. Two patients had pT1a and 12 had pT1b lesions. Mean (SD) survival was 71.5 (12.2) months and median survival was 42 months. There were five treatment failures with locoregional recurrence and death. All patients with pT1b tumors were treated by simple cholecystectomy. Cumulative 1-, 3-, and 5-year survival was 92%, 68%, and 68% respectively. Conclusions: Simple cholecystectomy is an adequate treatment only for mucosal GBC. Patients with pT1b tumors require extended cholecystectomy. Incidental GBC extending up to the muscularis merits early reoperation for completion of extended cholecystectomy, which offers the only chance of cure.

Long-term survival and recurrence patterns in ampullary cancer.

Objective: Ampullary cancers are associated with high resectability rates and good long-term survival. However, the small number of patients in various series has hampered survival analysis. Methods: One hundred thirteen patients with ampullary cancer underwent pancreaticoduodenectomy between 1989 and 2000, with 48% morbidity and 8% mortality. One hundred four patients who survived the operation were analyzed to identify predictors of long-term survival. Results: The overall median survival was 30.1 (1.6-140.0) months with actuarial 1-, 3-, and 5-year survival rates of 79%, 43%, and 33%, respectively. Lymph node metastasis (P = 0.002) and vascular invasion (P = 0.008) were 2 independent factors adversely influencing survival. Perioperative blood transfusion (P = 0.001) and vascular invasion (P = 0.026) were important factors predicting recurrent disease. Conclusions: Lymph node metastasis and vascular invasion were 2 important factors, which adversely influenced survival in patients with ampullary cancer. Perioperative blood transfusion and vascular invasion were associated with recurrent disease.

Fine needle aspiration cytology in xanthogranulomatous cholecystitis, gallbladder adenocarcinoma and coexistent lesions.

OBJECTIVE To evaluate the diagnostic efficacy of fine needle aspiration cytology (FNAC) in gallbladder mass lesions and to explore the possibility of overlooking malignancy in coexistent adenocarcinoma with xanthogranulomatous cholecystitis (XGC) on fine needle aspiration smears. STUDY DESIGN In a retrospective, seven-year study, ultrasound-guided needle aspirates from 25 histologically proven cases of gallbladder adenocarcinoma, 11 cases of gallbladder adenocarcinoma associated with XGC and 20 cases of XGC were evaluated for the presence of mesotheliumlike, foam, inflammatory and multinucleate giant cells; pink, granular background; bile; and degenerated cells, along with atypical or frankly malignant cells. Detailed clinical findings were retrieved from the records. RESULTS The overall sensitivity of detecting carcinoma was 90.63% and specificity 94.74%. The sensitivity of detecting malignancy was 80% when adenocarcinoma was associated with XGC. CONCLUSION FNAC plays an important role in making the preoperative diagnosis of adenocarcinoma, XGC and coexistent lesions. The probability of detecting malignancy is greater than with XGC in coexistent lesions. Thus, a preoperative FNAC diagnosis would help in determining the urgency of treatment and in planning for the surgical procedure in gallbladder lesions.

Indian Primary Hyperparathyroidism Patients with Parathyroid Carcinoma do not Differ in Clinicoinvestigative Characteristics from Those with Benign Parathyroid Pathology

IntroductionNo foolproof preoperative diagnostic indicators of parathyroid carcinoma (PC) exist in absence of nonskeletal metastases. Palpable parathyroid tumor, advanced skeletal and renal manifestations, and very high serum calcium and parathyroid hormone levels are considered strong predictors. Most of these features are common in Indian primary hyperparathyroidism (PHPT) patients although only few have PC. The aim of this study was to identify dependable clinicoinvestigative predictors of PC in Indian PHPT patients.Materials and MethodsClinical, biochemical, radiological, and densitometric attributes of 100 PHPT patients who underwent successful parathyroidectomy (1990–2004) were studied. Various parameters of patient groups with parathyroid adenoma (n = 84), primary hyperplasia (n = 12), and carcinoma (n = 4) were compared using ANOVA, with P value < 0.05 considered significant.ResultsMean age of patients was 37.4 years, with no difference in the 3 groups (P = 0.92). Patients in 3 groups had comparably severe bone disease; 36 had coexistent renal disease. Two patients with PC and 27 (32%) with adenoma had palpable parathyroid tumor. None of the biochemical parameters predicted malignant pathology. Mean tumor weight (milligram) in carcinoma patients (15,080 ± 5,638.02) was significantly higher than those with adenoma (5,724 ± 1,257.9) (P = 0.002). Postoperative course and recovery in carcinoma patients were similar to those with adenoma. In follow-up (mean: 33 months), none of the adenoma patients were found to have persistent/recurrent PHPT attributable to missed PC.ConclusionIndian patients with parathyroid adenoma, hyperplasia, and carcinoma were not found to differ in their clinical, biochemical, and pathological characteristics except for significantly higher tumor weight in the carcinoma group.

Genotypes of Helicobacter pylori in children with upper abdominal pain

Background:  Studies related to genotypes of Helicobacter pylori infection and upper abdominal pain (UAP) in children are scarce all over the world. We prospectively analyzed the association between H. pylori infection and UAP in our study group of children and evaluated the vacA genotypes associated with this disorder.

Association of Helicobacter pylori and Epstein-Barr virus with gastric cancer and peptic ulcer disease.

Objective. Helicobacter pylori and Epstein-Barr virus (EBV) infections are common world-wide. Though H. pylori infection is a major factor in gastroduodenal diseases, its role in association with EBV infection is unknown. We prospectively studied the association of H. pylori and EBV in patients with gastric cancer (GC) and peptic ulcer disease (PUD). Material and methods. A total of 348 adult patients (non-ulcer dyspepsia (NUD) 241, PUD 45, GC 62) undergoing upper gastrointestinal endoscopy between September 2003 and May 2007 were enrolled in the study. H. pylori infection was diagnosed by rapid urease test, culture, histopathology and polymerase chain reaction (PCR). EBV DNA was detected by non-polymorphic Epstein-Barr nuclear antigen-1 (EBNA-1) gene-based PCR and sequence analysis. Results. The rate of H. pylori infection was higher in patients with PUD than in those with GC (80% versus 56.5%, p=0.01) and NUD (80% versus 55.2%, p=0.002). In patients with GC and PUD, EBV DNA was detected more often than in those with NUD (GC versus NUD – 82.3% versus 37.3%, p<0.001; PUD versus NUD – 75.5% versus 37.3%, p<0.001). H. pylori infection and EBV DNA detected in different groups of patients was as follows: 62.2% in PUD, 46.8% in GC and 29.5% in NUD. PUD and GC were significantly associated (p<0.001 and <0.05, respectively) with the presence of H. pylori infection and EBV DNA as compared with NUD. Conclusions. EBV DNA either alone or in combination with H. pylori infection was significantly associated with GC and PUD, suggesting that EBV might play an important role in gastroduodenal pathology.

Kinetics of cytokine profile during intraperitoneal inoculation of Japanese encephalitis virus in BALB/c mice model.

Infection with Japanese encephalitis virus (JEV) is mostly asymptomatic/subclinical in 90% of the individuals. Host immune response during subclinical JEV infection is poorly understood. We assessed iNOS, IFN-gamma, TNF-alpha, IL-10 and IL-4 production in spleen, brain and sera of intraperitoneally challenged BALB/c mice by RT-PCR and ELISA along with brain histopathology at different days post inoculation (d.p.i.). In spleen of virus infected mice, expression of all cytokines including iNOS mRNA were upregulated till 5d.p.i. followed by decline. At 5d.p.i., IL-10 expression outcompeted TNF-alpha, IFN-gamma and IL-4. However, in the virus infected mice sera, IL-4 production predominated over TNF-alpha and IL-10 at 5d.p.i. Conversely, cytokines expression and iNOS mRNA remained unchanged in the brain of virus infected mice from 1 to 7d.p.i. A significant increase in the cytokine expression was observed at 11d.p.i. (P<0.05) in virus infected mice brain, with the predominance of IL-10 along with the presence of meningeal inflammation and viral RNA by histology and RT-PCR, respectively. We report a biased pattern of cytokine production in sera, brain and spleen of mice intraperitoneally challenged with JEV. IL-10 exerts neuroprotective function during JEV and regulates deleterious effects of proinflammatory cytokines; however, its mechanism needs further investigation.