Clinicopathological Significance and Prognostic Role of Her2neu Protein Expression in Patients with Carcinoma Stomach: A Prospective Study from Northern India.

Manas Kumar BeheraBackground and Aims Gastric cancer is the third most common cause of cancer-related mortality worldwide after lungs and colorectum. Although controversial, Her2neu overexpression by immunohistochemistry is usually associated with poor prognosis in patients with carcinoma stomach. We conducted a prospective study to evaluate the prognostic role of Her2neu and its correlation with clinical, pathologic type, and stage of the disease. Methods A prospective study was performed on paraffin blocks of 111 gastric cancer specimens (88 patients were biopsy specimens and 23 were gastrectomy specimens). The paraffin blocks were processed for Her2neu receptor immunohistochemical staining and fluorescence in situ hybridization, and scoring was done. Results Her2neu overexpression was detected in 30 out of 111 (27%) patients. The mean age was 57.68 ± 12.82 years, with males constituting two-thirds of total patients. Tobacco addiction was found in 44% of the patients and smoking in 33% of the patients. Her2neu expression was similar in Lauren's intestinal and diffuse histologic type; however, proximal gastric tumors overexpressed Her2neu as compared with distal tumors. Her2neu 2+ or 3 + (odds ratio: 2.52, 95% CI: 1.61-3.95, p = 0.001) was the only independent predictor of survival in gastric cancer patients. Kaplan-Meir survival analysis showed that the survival of gastric cancer patients with Her2neu overexpression (Her2neu 2+ or 3 + ) was significantly lower than that of those with Her2neu nonexpression ( p = 0.001). Conclusion Her2neu positivity was a significant predictor of mortality in patients with carcinoma stomach, and Her2neu overexpression was associated with a lower overall survival rate compared with Her2neu nonexpression.

C-reactive protein/albumin and ferritin as predictive markers for severity and mortality in patients with acute pancreatitis.

Introduction: Acute pancreatitis (AP) is a life-threatening gastrointestinal disease with high mortality and morbidity. However, scoring systems or prognostic indicators for assessing AP are cumbersome and expensive, and have not proved accurately to predict outcomes. Aim: We conducted a study with the aim of evaluating the predictive accuracy of C-reactive protein (CRP)/albumin and ferritin regarding outcomes in patients with AP. Material and methods: A prospective study was conducted in a tertiary care referral centre in Odisha from March 2020 to April 2021. A total of 116 consecutive patients of AP were enrolled in the study. CTSI, APACHE II, ferritin, and the CRP/albumin ratio were calculated. Results: The mean age of patients was 40.63 ±5.49 years with a male predominance (73%). Alcohol was most common aetiology (46.6%), and the overall mortality was 18%. Mean ferritin and the CRP/albumin ratio were also significantly higher in severe AP as compared to moderately severe AP and mild AP (p < 0.001). The CRP/albumin ratio (AOR = 1.26, 95% CI: 1.02-1.56, p = 0.02) was found to be independent predictor of mortality in Cox regression multivariate analysis and had the highest AUC for predicting the severity of acute pancreatitis. Serum ferritin had higher AUC (0.89, 0.83-0.91, p < 0.001) for the development of necrosis in acute pancreatitis, but it failed to be proven as an independent predictor of mortality. Conclusions: CRP/albumin is a simple, cheap, and easily available biomarker predicting the development of severe pancreatitis, and it was found to be an independent predictor of mortality in AP.

Prevalence and predictors of functional evacuation disorder in patients with chronic constipation

Background: Functional evacuation disorder (FED) is the second most common cause of functional constipation (FC) after constipation-predominant irritable bowel syndrome. However, the data on FED is relatively scanty in our region. Hence, the present study was performed to evaluate the demographics of FED and to find out the predictors of FED in patients with chronic constipation. Methods: A total of 134 patients with chronic constipation diagnosed according to the Rome IV criteria who were referred for high-resolution anorectal manometry (HRAM) were retrospectively enrolled in the present study. All FC patients who underwent HRAM were asked to fill a questionnaire and underwent anorectal manometry and were submitted to the balloon expulsion test (BET). Results: The mean age of patients was 43.09 ± 9.32 years old, with a total of 76 (54%) males. The most common symptom was straining during defecation (87%) followed by incomplete evacuation (86%). The prevalence of FED, diagnosed by HRAM and by the BET was 39%. Patients with FED had a significantly higher percentage of straining and sensation of anorectal blockade compared with those without FED (96 versus 82%; p < 0.01; 81 versus 44%; p < 0.001, respectively). On the multivariate regression analysis, straining > 30 minutes (odds ratio [OR] = 3.63; p = 0.03), maximum squeeze pressure (OR = 1.05; p < 0.001), and balloon volume at maximal sensation (OR = 1.06; p < 0.001) were found to be significant independent predictors of FED. Conclusion: Prolonged straining and sensation of anorectal blockade were significant indicators of FED in patients with chronic constipation. (AU)

Diastolic Dysfunction Is a Predictor of Poor Survival in Patients with Decompensated Cirrhosis.

BACKGROUND: Left ventricular diastolic dysfunction (LVDD) appears to be the earliest cardiac disturbance in cirrhosis patients. There are many previous reports reporting the significance of severity of LVDD on the outcome of liver transplantation or TIPS insertion, a few Indian studies have addressed the role of LVDD on survival in decompensated cirrhosis. The objective of this study is to assess the effect of LVDD on the survival of decompensated cirrhotic patients. METHODS: We prospectively evaluated 92 decompensated cirrhotic patients from April 2015 to March 2017 at IMS and SUM Hospital, Bhubaneswar, India. 2D echocardiography with tissue Doppler imaging was used to evaluate cardiac function, as per the American society of echocardiography guidelines. The primary endpoint was to evaluate the effect of LVDD on overall mortality. RESULTS: Ninety-two decompensated cirrhotic patients were evaluated in this prospective cohort study. Twenty-eight out of 92 patients (30%) died due to liver-related complications after a follow-up of 24 months. The decompensated cirrhotic patients with MELD score ≥ 15 had a significantly higher E/e' ratio (11.94 ± 4.24 vs. 8.74 ± 3.32, p < 0.001) suggesting severe LV dysfunction in advanced cirrhosis. Patients with E/e' ratio > 10 had significantly higher MELD score and Child-Pugh score (19.88 ± 7.72 vs. 14.31 ± 5.83; 10.25 ± 1.74 vs. 9.02 ± 1.74, p < 0.01, respectively) as compared to theE/e' ratio < 10 group. In Cox proportional hazard multivariate analysis, E/e' ≥ 10 (HR 2.72, 95% CI 1.07-6.9, p = 0.03) and serum albumin (HR 0.32, 95% CI 0.14-0.7, p < 0.01) were found to be independent predictors of mortality in decompensated cirrhotic patients. CONCLUSION: : The presence of LVDD and low serum albumin were independent predictors of mortality in decompensated cirrhotic patients. Hence, LVDD is an indicator of advanced cirrhosis and mortality.

Factors Predicting Cardiac Dysfunction in Patients with Liver Cirrhosis.

BACKGROUND Left ventricular diastolic dysfunction (LVDD) is the earliest cardiac dysfunction noted in patients with liver cirrhosis, which increases the morbidity and mortality in such patients. There are sparse studies from India evaluating the predictive factors of LVDD in patients with cirrhosis. Hence we undertook this prospective study with an aim to evaluate the factors predicting the development of LVDD in liver cirrhosis. METHODS 104 patients with cirrhosis were enrolled in this prospective study. A detailed cardiac evaluation was done by 2 D echocardiography with tissue Doppler imaging by an experienced senior cardiologist. The severity of liver disease was defined by Model For End-Stage Liver Disease (MELD) and Child-Pugh score. RESULTS The prevalence of LVDD was 46% in our study. Multivariate logistic regression analysis revealed that serum albumin, MELD score, and presence of ascites (OR = 0.1, 95%CI 0.03-0.3, p < 0.001; Or = 1.12, 95%CI 1.03-1.22, p < 0.001; OR = 4.19, 95%CI 1.38-12.65, p < 0.01, respectively) were independent predictors of LVDD in patients with cirrhosis. Diastolic dysfunction was unrelated to age, sex, and etiology of cirrhosis. The patients with cirrhosis and LVDD had significantly higher child Pugh score, MELD score, and lower serum albumin than patients without LVDD. The echocardiographic parameters like E/e' ratio, Deceleration time (DT), and Left atrial volume index (LAVI) were significantly different in cirrhotic patients with higher MELD and child Pugh score than lower. CONCLUSION The present study showed a significant correlation of diastolic dysfunction with the severity of the liver disease. Low serum albumin, high MELD score, and presence of ascites significantly predict the development of LVDD in patients with cirrhosis.

Abdominal tuberculosis in Indians: Still very pertinent.

INTRODUCTION: Tuberculosis is a disease that has been affecting mankind since time immemorial and it still continues to be a global health concern. Objective of the study was to evaluate the burden, clinical profile, diagnosis and diagnostic difficulties and outcome of abdominal tuberculosis (AbT) in non human immunodeficiency virus (HIV) infected adults in the department of gastroenterology at a tertiary care hospital over a period of two years. MATERIAL & METHODS: It was an observational study and the study period was from January 2016 till January 2018. The patients who were sero positive for HIV virus were excluded from the study. RESULTS: The number of patients hospitalized during the period of 2016-2018 with abdominal tuberculosis was 58. The burden of tuberculosis of indoor patients was 1.3 cases per every 100 patients admitted. Presenting complaint of most of these patients [61%] was abdominal pain. Constitutional symptoms like fever; weight loss and loss of appetite were present in only 40% of the patients. Ascites was the presenting sign in around 45% of the patients. Peritoneum was the most common site of involvement [27 out of 58]. Almost all of these patients [25 out of 27] presented with abdominal pain and abdominal distension. Intestine was the second most common site. Ileocaecal involvement was present in fourteen patients, while other areas of colon were involved in five patients. All the 58 patients were given anti tubercular therapy. There was complete resolution of tuberculosis in 91% of cases [53 out of 58 patients]. Six patients developed drug induced liver injury. Death occurred in two patients who had disseminated tuberculosis. CONCLUSION: Although the burden of the disease remains the same, availability of newer investigations has aided in its early diagnosis and availability of good drugs has reduced the mortality and morbidity.

Effect of vitamin D supplementation on sustained virological response in genotype 1/4 chronic hepatitis C treatment-naïve patients from India.

BACKGROUND & OBJECTIVES: The effect of vitamin D supplementation on response to antiviral therapy in hepatitis C virus (HCV) genotype 1 and 4 infection still remains unclear, with studies yielding inconsistent results. The aim of the present study was to assess the effect of vitamin D supplementation on treatment outcome in patients with genotype 1/4 chronic hepatitis C (CHC) infection. METHODS: Sixty consecutive, treatment-naïve, genotype 1 and 4 chronic HCV patients were included in the study. The patients were randomized into two groups: Vitamin D supplemented group received pegylated (PEG)-interferon α-2a 180 µg per week plus ribavirin (RBV) (1000-1200 mg/d) together with vitamin D3 (2000 IU/d) and control group received identical therapy without vitamin D (32 patients). RESULTS: There were no significant differences between the two groups in terms of age, sex, body mass index and baseline laboratory values. Lower vitamin D levels were associated with higher grades of fibrosis in liver histology (vitamin D >20 ng/ml - 70% vs vitamin D <20 ng/ml - 37%, P<0.05). Vitamin D supplemented group had similar rapid viral response (40 vs 28%, P=0.36), complete early viral response (53.2 vs 40%, P=0.34), end of treatment response (64 vs 46%, P=0.17) and sustained virological response (SVR) (60 vs 44%, P=0.19) as compared to control group. Interleukin 28B polymorphism [odds ratio (OR)-15.37, 95% confidence interval (CI)-2.32-101.76, P=0.04] and baseline serum vitamin D levels (OR-6.36, 95% CI-1.36-29.61 P=0.02) were independent predictors of SVR in genotype 1/4 CHC. Vitamin D supplementation was not found to be predictor of response in genotype 1/4 CHC on multivariate analysis (OR-2.79, 95% CI- 0.63-12.34, P=0.74). INTERPRETATION & CONCLUSIONS: The present study showed that addition of vitamin D to PEG/RBV combination therapy in treatment-naïve patients who were infected with HCV genotype 1/4 had no effect on the rates of rapid, early and sustained viral responses.

Efficacy of aspiration in amebic liver abscess.

BACKGROUND: Amebic liver abscess (ALA) is a common and serious problem in our country. There are only a few controlled trials on the efficacy and advantages of combination therapy with percutaneous needle aspiration and pharmacotherapy, over pharmacotherapy alone for amebic liver abscess. MATERIAL AND METHODS: This study was conducted to compare the efficacy of two different treatment modalities i.e. drug treatment alone vs. drug treatment and aspiration of abscess cavity in patients with small (up to 5 cm) and large (5 cm to 10 cm) size ALA. This is one of the largest single center, prospective, randomized studies comparing the efficacy of aspiration in ALA. RESULTS: (i) Mean body temperature, liver tenderness, total leukocyte count (TLC), serum alanine aminotransferase (ALT) and liver span were significantly decreased in the aspiration group on days 8 and 15 as compared to non-aspiration group especially in large abscess (5 cm to 10 cm). (ii) Abscess cavity maximum diameter decreased significantly in aspiration group on days 8 and 15, and 1 month & 3 months in large abscess (5cm to 10 cm). CONCLUSIONS: (i) Needle aspiration along with metronidazole hastens clinical improvement especially in large (5 cm up to 10 cm) cavities in patients with ALA. (ii) Aspiration is safe and no major complications occurred. (iii) Hence, combination therapy should be the first choice especially in large ALA (5 cm to 10 cm).

Beta-cell function and insulin resistance in pregnancy and their relation to fetal development.

BACKGROUND: Insulin resistance in pregnancy is consequent to the physiological adaptation necessary to provide glucose to the growing fetus. Disturbance in the maternal metabolism can induce structural and functional adaptations during fetal development. METHODS: Pregnant women with duration of conception between 24 and 28 weeks were assessed for insulin resistance (IR) and beta-cell function by using homeostatic model assessment IR (HOMA-IR) and homeostatic model assessment of beta-cell function (HOMA-B) models, respectively. One hundred pregnant women and 42 age-matched controls were taken for the study. Fourteen pregnant women were diagnosed as gestational diabetes mellitus (GDM) as per World Health Organization (WHO) criteria. RESULTS: Pregnant women with normal glucose tolerance (NGT) did not reveal significant IR as compared to controls but the HOMA-B was higher (268.91 +/- 197.16 vs 188.6 +/- 88.83, P < 0.01), suggesting excessive beta-cell function to maintain glucose homeostasis. The subset of pregnant women who presented with GDM had significantly higher HOMA-IR values (6.59 +/- 2.93 vs. 1.77 +/- 1.49, P < 0.001) and similar HOMA-B values as compared to pregnant women with NGT. Pregnant women with severe IR manifested as GDM, even without any previous history of dysglycemia. CONCLUSIONS: With regard to fetal outcome, HOMA-IR is an independent predictor in pregnant women with NGT (biparietal diameter r(2) = 0.204, P < 0.01; weight r(2) = 0.097, P < 0.01), whereas beta-cell function (HOMA-B) is a strong independent predictor of fetal outcome in pregnant GDM (biparietal diameter r(2) = 0.58, P < 0.05; FL r(2) = 0.71, P < 0.01 AC r(2) = 0.79, P < 0.001; weight r(2) = 0.57, P < 0.01).