Expression Profile of KRAS and p16 in Periampullary Cancer.

Activating point mutations in codons 12, 13, and 61 of the KRAS gene and loss of p16 expression, a tumor suppressor gene, are common genetic alterations in periampullary cancer (PAC). The present study explores expression profile of KRAS and p16 genes in PAC and its prognostic relevance. A total of 50 patients with PAC who underwent potentially curative pancreaticoduodenectomy were included in the study. Formalin-fixed, paraffin-embedded tissue samples were analyzed for point mutations in codons 12 and 13 of KRAS and codon 9 of p16 using polymerase chain reaction. KRAS mutation in codon 12/13 was found in 32 (64%) and loss of p16 expression in 36 (72%) cases. KRAS mutation was significantly associated with higher grade, higher pathological tumor (pT) stage, lymphovascular invasion (LVI), perineural invasion (PNI), and pathological lymph nodes (pN) involvement on univariate analysis. On multivariate analysis, significant association of KRAS remained with higher grade (p = 0.031), pT stage (p = 0.09), and LVI (p = 0.028). On univariate analysis, loss of p16 expression was significantly associated with higher grade, pN involvement, LVI, PNI, and pT stage whereas on multivariate analysis, statistical significant association of p16 was found with higher grade of tumor only (p = 0.04). Patients with KRAS mutation had significantly (p = 0.018) worse disease-free survival (DFS) whereas no significant association was found in overall survival (OS). Loss of p16 expression had no association with either DFS or OS. The presence of p16 and KRAS alterations in patients with PAC suggests aggressive tumor biology. KRAS mutations confer a significantly poor DFS in PAC.

Clinical profile of patients presenting with dysphagia - an experience from a tertiary care center in North India.

BACKGROUND AND AIM: Dysphagia can lead to substantial morbidity and mortality, especially in the elderly. It has both benign and malignant causes. Despite having a varied etiology, there have been few studies in India. Therefore, a study was undertaken to evaluate the clinical profile and various etiologies of dysphagia. METHODS: A prospective study was conducted on 220 patients with a complaint of dysphagia. Detailed history and examination, endoscopy and biopsies, and barium swallow were performed. Computed tomography and magnetic resonance imaging were performed wherever required. Patients who had an oropharyngeal or neurological cause of dysphagia were excluded. RESULTS: The mean age of patients was 57.2 years, with the male: female ratio being 1.7:1. Of the patients, 35% (78 patients) had malignant etiology, with a mean age of 65.2 years, and 65% (142 patients) had a benign etiology, with a mean age of 51 years. Among the patients with malignancy, 56 had squamous cell carcinoma of esophagus (71.7%), 20 had adenocarcinoma of esophagus (25.7%), and 2 had gastric cardia adenocarcinoma (2.6%). Malignancy was most commonly located in distal esophagus (48 patients), and among the cases, 18 had involvement of the gastroesophageal junction. The most common benign cause was esophagitis secondary to reflux in 25.5% (56 patients), followed by esophageal ulcer in 5.9%, achalasia in 5%, corrosive stricture in 4.5%, and peptic stricture in 3.6%. CONCLUSION: Dysphagia has diverse etiology, and a majority can be diagnosed by endoscopy and barium swallow. Malignancy is an important cause of dysphagia in elderly. Esophageal squamous cell carcinoma remains the most common malignancy, but the incidence of gastroesophageal junctional adenocarcinoma is increasing.

2019 Update of Indian National Association for Study of the Liver Consensus on Prevention, Diagnosis, and Management of Hepatocellular Carcinoma in India: The Puri II Recommendations.

Hepatocellular carcinoma (HCC) is one of the major causes of morbidity, mortality, and healthcare expenditure in patients with chronic liver disease in India. The Indian National Association for Study of the Liver (INASL) had published its first guidelines on diagnosis and management of HCC (The Puri Recommendations) in 2014, and these guidelines were very well received by the healthcare community involved in diagnosis and management of HCC in India and neighboring countries. However, since 2014, many new developments have taken place in the field of HCC diagnosis and management, hence INASL endeavored to update its 2014 consensus guidelines. A new Task Force on HCC was constituted that reviewed the previous guidelines as well as the recent developments in various aspects of HCC that needed to be incorporated in the new guidelines. A 2-day round table discussion was held on 5th and 6th May 2018 at Puri, Odisha, to discuss, debate, and finalize the revised consensus statements. Each statement of the guideline was graded according to the Grading of Recommendations Assessment Development and Evaluation system with minor modifications. We present here the 2019 Update of INASL Consensus on Prevention, Diagnosis, and Management of Hepatocellular Carcinoma in India: The Puri-2 Recommendations.

INASL Guidelines on Management of Hepatitis B Virus Infection in Patients receiving Chemotherapy, Biologicals, Immunosupressants, or Corticosteroids.

Hepatitis B Virus (HBV) reactivation in patients receiving chemotherapy, biologicals, immunosupressants, or corticosteroids is emerging to be an important cause of morbidity and mortality in patients with current or prior exposure to HBV infection. These patients suffer a dual onslaught of illness: one from the primary disease for which they are receiving the culprit drug that led to HBV reactivation, and the other from HBV reactivation itself. The HBV reactivation not only leads to a compromised liver function, which may culminate into hepatic failure; it also adversely impacts the treatment outcome of the primary illness. Hence, identification of patients at risk of reactivation before starting these drugs, and starting treatment aimed at prevention of HBV reactivation is the best strategy of managing these patients. There are no Indian guidelines on management of HBV infection in patients receiving chemotherapy, biologicals, immunosupressants, or corticosteroids for the treatment of rheumatologic conditions, malignancies, inflammatory bowel disease, dermatologic conditions, or solid-organ or bone marrow transplantation. The Indian National Association for Study of the Liver (INASL) had set up a taskforce on HBV in 2016, with a mandate to develop consensus guidelines for management of various aspects of HBV infection, relevant to India. In 2017 the taskforce had published the first INASL guidelines on management of HBV infection in India. In the present guidelines, which are in continuation with the previous guidelines, the issues on management of HBV infection in patients receiving chemotherapy, biologicals, immunosupressants, or corticosteroids are addressed.

INASL Position Statements on Prevention, Diagnosis and Management of Hepatitis B Virus Infection in India: The Andaman Statements.

Hepatitis B Virus (HBV) infection is one of the major causes of morbidity, mortality and healthcare expenditure in India. There are no Indian consensus guidelines on prevention, diagnosis and management of HBV infection. The Indian National Association for Study of the Liver (INASL) set up a taskforce on HBV in 2016, with a mandate to develop consensus guidelines for diagnosis and management of HBV infection, relevant to disease patterns and clinical practices in India. The taskforce first identified contentious issues on various aspects of HBV management, which were allotted to individual members of the taskforce who reviewed them in detail. A 2-day round table discussion was held on 11th and 12th February 2017 at Port Blair, Andaman & Nicobar Islands, to discuss, debate, and finalize the consensus statements. The members of the taskforce reviewed and discussed the existing literature threadbare at this meeting and formulated the 'INASL position statements' on each of the issues. The evidence and recommendations in these guidelines have been graded according to the Grading of Recommendations Assessment Development and Evaluation (GRADE) system with minor modifications. The strength of recommendations (strong: 1, weak: 2) thus reflects the quality (grade) of underlying evidence (A, B, C, D). We present here the INASL position statements on prevention, diagnosis and management of HBV in India.

Ulcerative Colitis and Its Association with Salmonella Species.

Ulcerative colitis (UC) is characterized by presence of ulcer in colon and bloody diarrhea. The present study explores the possibility of association between Salmonella and ulcerative colitis. The present study comprised 59 cases of UC, 28 of colon cancer (CC), 127 of irritable bowel syndrome (IBS), and 190 of healthy control. The serological study was done by Widal and Indirect Haemagglutination Assay (IHA) for ViAb. Nested PCR was performed targeting fliC, staA, and stkG gene for Typhi and Paratyphi A, respectively. A total of 15.3% patients were positive for Salmonella "O" antigen among them 18.6% UC, 35.5% CC, 12.6% IBS, and 15.3% healthy control. A total of 36.9% patients were positive for "H" antigen including 39.0%, 57.1%, and 67.7% UC, CC, and IBS, respectively. About 1.73% show positive agglutination for AH antigen including 3.4%, 3.6%, and 1.6%, UC, CC, and IBS. A total of 10.89% were positive for ViAb. While 6.8% of UC, 10.7% of CC, 11.0% of IBS, and 12.1% of healthy subjects were positive for the antibody, the PCR positivity rates for Salmonella specific sequences were 79.7% in UC, 53.6% in CC, 66.1% in IBS, and 16.3% in healthy controls. The present study suggested that higher prevalence of Salmonella might play important role in etiopathogenesis of UC, IBS, and CC.

HBsAg Level as Predictor of Liver Fibrosis in HBeAg Positive Patients With Chronic Hepatitis B Virus Infection.

BACKGROUND AND AIMS: Preliminary data suggests lower serum hepatitis B surface antigen level is associated with more severe liver fibrosis in HBeAg positive patients. We evaluated the association of HBsAg level with biochemical, virological, and histological features in asymptomatic patients with chronic HBV infection. METHODS: HBsAg levels were measured at baseline in 481 asymptomatic, treatment naive patients with chronic HBV infection. Subjects were followed-up prospectively (median, 12; range, 8-36 months). Phases of HBV infection were defined after regular monitoring of HBV-DNA and transaminases. Liver histology was scored using the METAVIR system. RESULTS: HBeAg positive (n, 126) patients were significantly younger than HBeAg negative (n, 355), median age 26 vs 30 years; P < 0.01. HBV genotype could be determined in 350 patients, 240 (68.57%) had genotype D and 100 (28.57%) had genotype A. HBsAg level had modest correlation with serum HBV DNA(r = 0.6 vs 0.4 in eAg positive & negative respectively). HBeAg + ve patients with fibrosis score ≥ F2 showed significantly lower median serum HBsAg levels and serum HBV DNA levels compared with patients with F0-F1 score (median, range; 4.51, 2.99-6.10 vs 5.06, 4.13-5.89, P < 0.01) and (8.39, 3.85-10.60, P < 0.01) respectively. Significant inverse correlation of HBsAg level was found with liver fibrosis in eAg positive group (r = -0.76; P < 0.001). HBsAg level cut off value 4.7 log10 IU/ml predicted moderate to advance fibrosis (F ≥ 2) with 92% sensitivity, 85% specificity & 91% negative predictive value. CONCLUSION: Lower HBsAg level might reflect the status of advanced liver fibrosis in HBeAg positive chronic hepatitis B subjects.

Assessment of the Model for End-stage Liver Disease (MELD) Score in Predicting Prognosis of Patients with Alcoholic Hepatitis.

BACKGROUND: Traditionally, Maddrey discriminant function (DF) score has been used for stratifying the prognosis of alcoholic hepatitis. Recently, the Model for end-stage liver disease (MELD) score has been applied to alcoholic hepatitis and some investigators consider MELD score as a better prognostic indicator. Another new prognostic approach, Lille model has been also suggested to accurately identify patients at high risk of death. Therefore, this prospective study was aimed to compare MELD, DF, Child-Turcotte-Pugh (CTP) scores and Lille model for predicting the short-term mortality in Indian patients with alcoholic hepatitis. METHODS: We calculated the DF, CTP, MELD and Lille scores in patients hospitalized with alcoholic hepatitis & evaluated if the scores predicted in-hospital mortality. RESULTS: A total of 104 patients were enrolled and thirty-two (30.7%) patients died during the hospitalization (2-30 days). Admission DF score (OR 1.1, P < 0.04), CTP (OR 2, P < 0.05) MELD score (OR 2.2, P < 0.005) and first week MELD score (OR 1.1, P < 0.05) were independently associated with in-hospital mortality. The area under the receiver-operating curve (AUROC) for the admission and day 7 MELD score was significantly higher than CTP score and was comparable to DF score and Lille model (AUC & 95% CI: 0.97 [0.95-1.0], 0.99 [0.99-1.0], 0.91 [0.83-0.91] and 0.92 [0.86-0.98] for MELD at admission & day 7, admission DF and Lille model, respectively). The MELD score >14 at admission and >12 at day 7 had high sensitivity and specificity in predicting short-term mortality (96%, 89% and 95%, 98% respectively). The cutoff of 0.45 for the Lille model was able to identify 79% of the observed deaths, whereas DF score ≥32 for DF were able to identify 85%. CONCLUSION: MELD score, as a predictive model for assessment of short-term mortality in alcoholic hepatitis is better than CTP and comparable to DF and Lille model.

Hydatid Cyst of Liver Presented as Obstructive Jaundice in Pregnancy; Managed by PAIR.

Incidence of Hydatid disease in pregnancy ranges from 1in 20,000 to 1 in 30,000. The most common site of hydatid cysts is the liver. The diagnosis of liver hydatid cysts is not difficult but the management during pregnancy is problematic. Both medical and surgical treatments are available but there is no consensus and each case has to be individualized. We present a case of liver hydatid cyst presented with obstructive jaundice during pregnancy which was managed by Puncture of the cyst under USG guidance; Aspiration of the cystic fluid, Injection of hypertonic saline, and Re-aspiration of solution without drainage (PAIR) and albendazole therapy. Very few cases of liver hydatosis were reported previously which had been managed by PAIR.

Effect of petroleum ether and ethanol fractions of seeds of Abrus precatorius on androgenic alopecia

Seeds of Abrus precatorius L., Fabaceae, are commonly used as purgative, emetic, aphrodisiac and in nervous disorder in traditional and folk medicines. In present study petroleum ether and ethanolic extracts of A. precatorius seeds are evaluated for reversal of androgen (testosterone by i.m route) induced alopecia in male albino wistar rats and compared to topical administration of standard antiandrogenic drug finasteride for 21 days. The results were reflected from visual observation and histological study of several skin sections via various parameters as anagen to telogen ratio and follicle density/mm area of skin surface. The animal of group 1 who were treated with only testosterone became alopecic on visual observation. Animals of Group 2, 3 and 4 who were treated with finasteride, petroleum ether and ethanolic extract of seed respectively topically along with testosterone (i.m) did not developed alopecia. To investigate the mechanism of observed activity, in vitro experiments were performed. Inhibition of 5α-reductase activity by extracts and finasteride suggest that they reversed androgen induced alopecia by inhibiting conversion of testosterone to dihydrotestosterone (potent androgen responsible for androgenic alopecia). So it may be concluded that petroleum ether and ethanolic extract of A. precatorius seed posses anti androgenic alopecia activity due to inhibition of 5α-reductase enzyme.

An update on Murraya koenigii spreng: a multifunctional Ayurvedic herb.

Murraya koenigii Spreng (Rutaceae), a medicinally important herb of Indian origin, has been used for centuries in the Ayurvedic system of medicine. Leaves, fruits, roots and bark of this plant are a rich source of carbazole alkaloids. These alkaloids have been reported for their various pharmacological activities such as antitumor, antiviral, anti-inflammatory, antidiarrhoeal, diuretic and antioxidant activities. Apart from these activities, the plant is reported to possess a wide spectrum of biological activities. Phytochemistry and pharmacology of this plant make a demand of an exhaustive review of its potential as a valuable therapeutic agent for the treatment and management of various ailments frequently affecting humans. The present review gives a detailed description of the phytochemical, pharmacological, clinical and pre-clinical works carried out on this medicinal herb and also throws light on its therapeutic potential.

AgNOR count and subjective AgNOR pattern assessment (SAPA) score in carcinoma of the pancreatic head including periampullary tumors.

CONTEXT: Only a few studies are available in the literature regarding the AgNOR (argyrophilic nucleolar organizer region) count in pancreatic adenocarcinoma but studies on the SAPA (subjective AgNOR pattern assessment) score are completely lacking. OBJECTIVE: We attempted to estimate the AgNOR count and the SAPA score in carcinoma of the pancreatic head including periampullary tumors and to correlate them with other various clinico-histological parameters. SETTING: Patients undergoing pancreatic resection at the University Hospital, Banaras Hindu University, Varanasi, India. PATIENTS: Twenty-four cases of carcinoma of the pancreatic head including periampullary tumors. In addition, on the resected specimen of the pancreas, the area which was normal was chosen and, in that normal tissue, the AgNOR was also studied. MAIN OUTCOME MEASURES: Patients were studied for the AgNOR count and the SAPA score, and the values were correlated with the size of the tumor, the type of tumor and histological type and grade of tumor. RESULTS: The values of the AgNOR count and the SAPA score were significantly higher in cases of pancreatic cancer than in the healthy pancreas. The AgNOR count was 1.6+/-0.1 in the healthy pancreas while it was 2.8+/-0.5 in cases of pancreatic carcinoma (P<0.001). The SAPA score was 5.6+/-0.2 in the healthy pancreas while it was 8.0+/-1.4 in pancreatic carcinoma (P<0.001). Tumors less than or equal to 2 cm in size had an AgNOR count of 2.6+/-0.08 while the AgNOR count was 3.4+/-0.02 in tumors larger than 2 cm (P<0.001). The SAPA score was also higher in tumors greater than 2 cm in size (7.3+/-0.2 vs. 9.4+/-0.8; P<0.001). Periampullary tumors had a significantly lower (P<0.001) AgNOR count (2.7+/-0.06) and SAPA score (7.8+/-0.2) as compared to carcinoma of the head of the pancreas (AgNOR count 3.3+/-0.03 and SAPA score 9.2+/-0.7). Well-differentiated carcinomas had significantly lower AgNOR counts as compared to other tumors except acinar cell carcinomas since acinar cell carcinomas are also well-differentiated tumors. The SAPA score was also higher in moderately-differentiated tumors and the difference between moderately-differentiated tumor and other types of tumors was significant although there was no significant difference between cystadenocarcinomas and unclassified tumors, and between acinar cell carcinomas and well-differentiated tumors on SAPA scoring. CONCLUSIONS: The values of the AgNOR count and the SAPA score are well-correlated with the size of the tumor, the type of tumor and the histological grade.