Role of ultra-high definition endoscopy (endomicroscopy and endocytoscopy) and real-time histologic examination in inflammatory bowel disease: Scoping review.

OBJECTIVES: Confocal laser endomicroscopy (CLE) and endocytoscopy (EC) are ultra-high definition (HD) imaging modalities that enable real-time histological assessment. Although existent for nearly two decades, their role in current clinical decision making in inflammatory bowel disease management is not well defined. METHODS: We searched PubMed using keywords ("confocal" OR "CLE" OR "endocytoscopy") AND ("IBD" OR "inflammatory bowel" OR "Crohn*" OR "Crohn's" OR "colitis ulcerosa" OR "ulcerative colitis") between 2005 and March 2023. We identified 52 studies for detailed review. RESULTS: Confocal laser endomicroscopy was useful in real-time assessment of histologic inflammation and dysplasia characterization in both ulcerative colitis (UC) and Crohn's disease. Although CLE was associated with higher per-biopsy yield for UC-associated neoplasia (UCAN), the benefit was offset by higher procedure time, frequent equipment failure, and conflicting results on incremental yield over chromoendoscopy. Assessment of barrier dysfunction by CLE did not correlate with disease/endoscopic activity but could predict major adverse outcomes. The implications of residual CLE abnormalities in endoscopic remission remain uncertain. Ex vivo binding of labeled biologics can help in predicting biologic response in UC. EC can discriminate mucosal inflammatory cells by morphology and allows assessment of histologic activity. EC combined with pit pattern was better than pit pattern alone for UCAN. Artificial intelligence-assisted EC in UCAN needs further study. CONCLUSION: Ultra-HD imaging in inflammatory bowel disease can be useful in assessment of UCAN, barrier dysfunction, predicting histologic remission, and biologic response. Future controlled studies are warranted to define the role of these novel technologies in clinical decision making.

Inflammatory bowel disease (IBD) in rural and urban India: results from community colonoscopic evaluation of more than 30,000 symptomatic patients.

Background: Traditionally, infectious diarrhoea has been the major cause of lower GI symptoms across the developing world. Increasing urbanization has been implicated for the rising IBD cases despite very limited data in the rural setting. We aimed to assess the relative proportion of IBD and other intestinal diseases among symptomatic patients from rural and urban India. Methods: Patients with lower GI symptoms attending urban out-patient clinics and/or specially conducted mobile rural health camps were evaluated using basic laboratory parameters, abdominal ultrasound and colonoscopy. Data including patient demographics, symptom profile, rural/urban residence and final diagnosis were analyzed. Current data was compared with previous rural survey in 2006. Findings: Of 32,021 patients investigated, 30,835 with complete dataset [67% male; 21% (6362) rural median 44 years:6-78 years] were included. Predominant symptoms were chronic abdominal pain (55%), change in bowel habit (45%), rectal bleeding (16%), chronic diarrhoea (13%), un-intended weight loss (9%) and anaemia (3%). Final diagnoses included IBD: (1687; 5.4%; 2.2% ulcerative colitis (UC), 3.2% Crohn's disease, CD), intestinal tuberculosis (364; 1.2%), infective colitis (1427; 4.6%), colorectal cancer (488; 1.6%) and polyps (2372; 7.7%). Proportions of UC (2.1% rural, 2.3% urban, p = 0.66) and CD (3.5% rural, 3.1%,urban, p = 0.12) were similar in both groups. There was no rural-urban divide in the relative proportion of other intestinal diseases. Interpretation: IBD accounts for more than 5% of patients presenting with lower GI symptoms, a rate that is higher than that of infectious colitis. The proportion of IBD cases was not different between the rural and urban populations. These data appear to indicate the changing disease prevalence patterns in India that require further research. Funding: The study was funded by Leona M. and Harry B. Helmsley Charitable Trust.

Management of Pancreatic Duct Stones: Extracorporeal Approach.

Stone clearance with extracorporeal shock wave lithotripsy is a safe and effective procedure for large pancreatic calculi not extractable by the standard endoscopic retrograde cholangiopancreatography techniques. In properly selected patients, this minimally invasive approach should be offered as the first line of therapy instead of surgery. Complete stone clearance can be achieved in three-fourths with long-term pain relief in two-thirds of patients. Re-intervention is required in less than half of the patients. Future studies should compare the extracorporeal approach with intraductal lithotripsy using the pancreatoscope.

Safety and efficacy of terlipressin in acute-on-chronic liver failure with hepatorenal syndrome-acute kidney injury (HRS-AKI): a prospective cohort study.

Terlipressin with albumin, the recommended treatment for hepatorenal syndrome-acute kidney injury (HRS-AKI), is associated with adverse events. Furthermore, the course of AKI in patients with acute-on-chronic liver failure (ACLF) is unknown. We aimed to analyze the safety and efficacy of terlipressin infusion and AKI course in patients with ACLF. We prospectively enrolled consecutive adult patients with ACLF with HRS-AKI (satisfying EASL criteria) treated with terlipressin infusion between 14 October 2019 and 24 July 2020. The objectives were to assess the incidence of adverse events, response to terlipressin, course of HRS-AKI and predictors of mortality. A total of 116 patients were included. Twenty-one percent of patients developed adverse effects. Only 1/3rd of patients who developed adverse events were alive at day 90. Sixty-five percent of the patients responded to terlipressin. Nearly 22% developed recurrence of HRS, and 5.2% progressed to HRS-chronic kidney disease. TFS was 70.4% at day 30 and 57.8% at day 90. On multivariate stepwise Cox regression analysis terlipressin non-response (hazard ratio [HR], 3.49 [1.85-6.57]; P < 0.001) and MELD NA score (HR,1.12 [1.06-1.18]; P < 0.001) predicted mortality at day-90. Patients with ACLF who develop terlipressin related adverse events have dismal prognoses. Terlipressin non-response predicts mortality in patients with ACLF and HRS-AKI.

A Pro-Endocrine Pancreatic Islet Transcriptional Program Established During Development Is Retained in Human Gallbladder Epithelial Cells.

BACKGROUND & AIMS: Pancreatic islet ß-cells are factories for insulin production; however, ectopic expression of insulin also is well recognized. The gallbladder is a next-door neighbor to the developing pancreas. Here, we wanted to understand if gallbladders contain functional insulin-producing cells. METHODS: We compared developing and adult mouse as well as human gallbladder epithelial cells and islets using immunohistochemistry, flow cytometry, enzyme-linked immunosorbent assays, RNA sequencing, real-time polymerase chain reaction, chromatin immunoprecipitation, and functional studies. RESULTS: We show that the epithelial lining of developing, as well as adult, mouse and human gallbladders naturally contain interspersed cells that retain the capacity to actively transcribe, translate, package, and release insulin. We show that human gallbladders also contain functional insulin-secreting cells with the potential to naturally respond to glucose in vitro and in situ. Notably, in a non-obese diabetic (NOD) mouse model of type 1 diabetes, we observed that insulin-producing cells in the gallbladder are not targeted by autoimmune cells. Interestingly, in human gallbladders, insulin splice variants are absent, although insulin splice forms are observed in human islets. CONCLUSIONS: In summary, our biochemical, transcriptomic, and functional data in mouse and human gallbladder epithelial cells collectively show the evolutionary and developmental similarities between gallbladder and the pancreas that allow gallbladder epithelial cells to continue insulin production in adult life. Understanding the mechanisms regulating insulin transcription and translation in gallbladder epithelial cells would help guide future studies in type 1 diabetes therapy.

Impact of COVID-19 on liver transplant recipients-A systematic review and meta-analysis.

BACKGROUND: Immunosuppression and comorbidities increase the risk of severe coronavirus disease-2019 (COVID-19) in solid organ transplant (SOT) recipients. The outcomes of COVID-19 in liver transplant (LT) recipients remain unclear. We aimed to analyse the outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in LT recipients. METHODS: The electronic databases were searched for articles published from 1 December 2019 to 20 May 2021 with MeSH terms COVID-19, SARS-CoV-2, and liver transplantation. Studies reporting outcomes in more than 10 LT recipients were included for analysis. LT vs non-LT patients with COVID-19 infection were compared for all-cause mortality, which was the primary outcome studied. We also evaluated the relation between the timing of COVID-19 infection post-LT (< one year vs > one year) and mortality. FINDINGS: Eighteen articles reporting 1,522 COVID-19 infected LT recipients were included for the systematic review. The mean age (standard deviation [SD]) was 60·38 (5·24) years, and 68·5% were men. The mean time (SD) to COVID-19 infection was 5·72 (1·75) years. Based on 17 studies (I2 = 7·34) among 1,481 LT recipients, the cumulative incidence of mortality was 17·4% (95% confidence interval [CI], 15·4-19·6). Mortality was comparable between LT (n = 610) and non-LT (n = 239,704) patients, based on four studies (odds ratio [OR], 0·8 [0·6-1·08]; P = 0·14). Additionally, there was no significant difference in mortality between those infected within one year vs after one year of LT (OR, 1·5 [0·63-3·56]; P = 0·35). The cumulative incidence of graft dysfunction was 2·3% (1·3-4·1). Nearly 23% (20·71-25) of the LT patients developed severe COVID-19 infection. Before infection, 71% and 49% of patients were on tacrolimus and mycophenolate mofetil, respectively. Immunosuppression was modified in 55·9% (38·1-72·2) patients after COVID-19 infection. INTERPRETATION: LT and non-LT patients with COVID-19 have a similar risk of adverse outcomes.

Impact of Demographic, Clinical and Psychosocial Variables on Drug Adherence and Outcomes in Indian Patients With Inflammatory Bowel Disease: Cost is not the Only Factor!

BACKGROUND AND AIMS: Barriers to drug adherence in the developing world are multifactorial and under evaluated. We aimed to evaluate predictive factors of medication adherence in Indian patients with inflammatory bowel disease (IBD) and association of adherence with quality of life (QOL) and relapse free remission. MATERIALS AND METHODS: Adherence was assessed in consecutive IBD patients using a self-administered survey questionnaire including Morisky Medication Adherence Scale together with interview and Short Inflammatory Bowel Disease Questionnaire (SIBDQ) to assess QOL. Logistic regression analysis was used to identify variables correlating with adherence, Cox proportional hazards method used for variables associated with relapse and Kaplan-Meier survival curve used for comparing relapse free remission in adherent and nonadherent. RESULTS: A total of 467 consecutive outpatients (279 ulcerative colitis, 188 Crohn's disease, mean age 38.6 y) were mostly on mesalazine 439 (94%) or thiopurines 213 (46%). Self-reported nonadherence was noted in 236/467 (51%). Disease remission was associated with medication adherence [P=0.003, odds ratio (OR): 1.75, 95% confidence interval (CI): 1.21-2.52]. Medication-related factors like high dosing frequency (>3/d) (OR: 0.39, P=0.005) and concomitant non-IBD medications (OR: 0.44, P=0.007) were associated with nonadherence. Psychosocial factors associated with nonadherence were lack of drug information (OR: 0.30, P<0.001), feeling depressed (OR: 0.43, P<0.001), comorbidities (OR: 0.47, P=0.005), doubts about efficacy (OR: 0.49, P=0.001) and perceived poor QOL (OR: 0.61, P=0.01). High-cost perception was associated with nonadherence in univariate analysis (OR: 0.47, P<0.001) but lost significance on multivariate analysis (OR: 0.68, P=0.07). Physician imparting disease information (OR: 2.5, P=0.14) and physician reinforcement (OR: 1.8, P=0.049) were associated with adherence.Adherence was associated with improved QOL (SIBDQ, R=0.724). Nonadherence was associated with >3-fold risk of recurrence within 2 years (hazard ratio: 3.89, 95% CI: 2.74-5.52, P<0.001). CONCLUSIONS: Nonadherence is common in Indian IBD patients but adherence is associated with improved QoL and lower probability of relapse. Psychosocial and medication-related factors are important determinants of adherence compared with demographic or clinical variables and should be addressed.

Acute Intermittent Porphyria Presenting with Posterior Reversible Encephalopathy Syndrome: A Rare Cause of Abdominal Pain and Seizures.

Acute intermittent porphyria (AIP) is an acute neurovisceral porphyria caused due to inherited deficiency of porphobilinogen deaminase (also called hydroxymethylbilane synthase) (HMBS) in the heme biosynthesis pathway. AIP is rarely associated with posterior reversible encephalopathy syndrome (PRES), which is a clinicoradiological condition caused by the failure of the posterior circulation to autoregulate, resulting in cerebral edema, headaches, nausea, and seizures. AIP should be considered when a patient presents with unexplained abdominal pain and seizures. This association is important because drugs used in the management of seizures may worsen an attack of AIP. This case report describes a young woman who presented with AIP and PRES with seizures. HOW TO CITE THIS ARTICLE: Sarala Kumari D, Murthy NLN Arumilli, Siva Kumar Reddy L, Nageshwar Reddy D, Motor R. Acute Intermittent Porphyria Presenting with Posterior Reversible Encephalopathy Syndrome: A Rare Cause of Abdominal Pain and Seizures. Indian J Crit Care Med 2020;24(8):724-726.

Terlipressin has stood the test of time: Clinical overview in 2020 and future perspectives.

Vasoactive drugs form the mainstay of therapy for two of the most important complications of liver disease: hepatorenal syndrome (HRS) and acute variceal bleed (AVB). With cumulative evidence supporting the use in cirrhosis, terlipressin has been recommended for the management of HRS and AVB. However, owing to the safety concerns, terlipressin was not approved by food and drug administration (FDA) until now. In this review, we discuss the pharmacology and the major practice-changing studies on the safety and efficacy of terlipressin in patients with cirrhosis particularly focusing on existing indications like AVB and HRS and reviewing new data on the expanding indications in liver disease. The references for this review were identified from PUBMED with MeSH terms such as "terlipressin," "hepatorenal syndrome," "varices, esophagal and gastric," "ascites" and "cirrhosis." Terlipressin, a synthetic analogue of vasopressin, was introduced in 1975 to overcome the adverse effects of vasopressin. Terlipressin is an effective drug for HRS reversal in patients with liver cirrhosis and acute-on-chronic liver failure. There is documented mortality benefit with terlipressin therapy in HRS and AVB. Adverse effects are common with terlipressin and need to be monitored strictly. There is some evidence to support the use of this drug in refractory ascites, hepatic hydrothorax, paracentesis-induced circulatory dysfunction and perioperatively during liver transplantation. However, terlipressin is not yet recommended for such indications. In conclusion, terlipressin has stood the test of time with expanding indications and clear prerequisites for clinical use. Our review warrants a fresh perspective on the efficacy and safety of terlipressin.

Systematic review with meta-analysis: liver manifestations and outcomes in COVID-19.

BACKGROUND: The incidence of elevated liver chemistries and the presence of pre-existing chronic liver disease (CLD) have been variably reported in COVID-19. AIMS: To assess the prevalence of CLD, the incidence of elevated liver chemistries and the outcomes of patients with and without underlying CLD/elevated liver chemistries in COVID-19. METHODS: A comprehensive search of electronic databases from 1 December 2019 to 24 April 2020 was done. We included studies reporting underlying CLD or elevated liver chemistries and patient outcomes in COVID-19. RESULTS: 107 articles (n = 20 874 patients) were included for the systematic review. The pooled prevalence of underlying CLD was 3.6% (95% CI, 2.5-5.1) among the 15 407 COVID-19 patients. The pooled incidence of elevated liver chemistries in COVID-19 was 23.1% (19.3-27.3) at initial presentation. Additionally, 24.4% (13.5-40) developed elevated liver chemistries during the illness. The pooled incidence of drug-induced liver injury was 25.4% (14.2-41.4). The pooled prevalence of CLD among 1587 severely infected patients was 3.9% (3%-5.2%). The odds of developing severe COVID-19 in CLD patients was 0.81 (0.31-2.09; P = 0.67) compared to non-CLD patients. COVID-19 patients with elevated liver chemistries had increased risk of mortality (OR-3.46 [2.42-4.95, P < 0.001]) and severe disease (OR-2.87 [95% CI, 2.29-3.6, P < 0.001]) compared to patients without elevated liver chemistries. CONCLUSIONS: Elevated liver chemistries are common at presentation and during COVID-19. The severity of elevated liver chemistries correlates with the outcome of COVID-19. The presence of CLD does not alter the outcome of COVID-19. Further studies are needed to analyse the outcomes of compensated and decompensated liver disease.

Hemophagocytic Lymphohistiocytosis Masquerading as Acute Liver Failure: A Single Center Experience.

BACKGROUND/AIM: Hemophagocytic lymphohistiocytosis (HLH) is a potentially life-threatening disorder of extreme inflammation and unregulated immune response which require prompt recognition and early introduction of definitive therapy. HLH can present with wide range of hepatic dysfunction ranging from mild elevation of transaminases to liver failure. This study is carried out to describe the clinical and laboratory presentation of HLH. METHODS: Patients who were diagnosed with HLH between January 2013 and December 2015 were retrospectively included in this study. RESULTS: Six patients were diagnosed as secondary HLH with median age of 28.5 years at diagnosis. All patients were presented with history of deep jaundice and high grade fever with pancytopenia and splenomegaly. Underlying diagnosis was viral infections in 4 and probable viral infection in remaining two. Bone marrow hemophagocytosis was present in 3 cases. Three patients were treated with corticosteroids only and one each with corticosteroids with cyclosporine or intravenous immunoglobulin (IVIG) and HLH treatment protocol. One patient died due to acute respiratory distress syndrome (ARDS); another patient died in follow-up due to respiratory failure due to pneumonia. CONCLUSIONS: HLH is rare and potentially life-threatening cause of prolonged fever, jaundice and pancytopenia. Early diagnosis and initiation of specific therapy can improve clinical outcome.

Genetics of non-alcoholic fatty liver disease: From susceptibility and nutrient interactions to management.

Genetics plays an important role in determining the susceptibility of an individual to develop a disease. Complex, multi factorial diseases of modern day (diabetes, cardiovascular disease, hypertension and obesity) are a result of disparity between the type of food consumed and genes, suggesting that food which does not match the host genes is probably one of the major reasons for developing life style diseases. Non-alcoholic fatty liver is becoming a global epidemic leading to substantial morbidity. While various genotyping approaches such as whole exome sequencing using next generation sequencers and genome wide association studies have identified susceptibility loci for non-alcoholic fatty liver disease (NAFLD) including variants in patatin-like phospholipase domain containing 3 and transmembrane 6 superfamily member 2 genes apart from others; nutrient based studies emphasized on a combination of vitamin D, E and omega-3 fatty acids to manage fatty liver disease. However majority of the studies were conducted independent of each other and very few studies explored the interactions between the genetic susceptibility and nutrient interactions. Identifying such interactions will aid in optimizing the nutrition tailor made to an individual's genetic makeup, thereby aiding in delaying the onset of the disease and its progression. The present topic focuses on studies that identified the genetic susceptibility for NAFLD, nutritional recommendations, and their interactions for better management of NAFLD.

T-Helper Cell-Mediated Islet Inflammation Contributes to ß-Cell Dysfunction in Chronic Pancreatitis.

OBJECTIVES: Beta-cell dysfunction and endocrine insufficiency in chronic pancreatitis (CP) is considered as a late manifestation emanating from fibrosis. To ascertain the role of T-helper cells in ß-cell dysfunction, we enumerated circulating T-cell subsets, examined their infiltration into pancreatic islets, and assessed islet functions. METHODS: Pancreatic tissues and peripheral blood were obtained from CP patients with/without diabetes. T cells were enumerated on flow cytometry and by immunostaining. Islets were assessed for glucose-stimulated insulin release (GSIR) and apoptosis (Annexin V/caspase-3). Islet proteins were probed for insulin gene transcription factor. RESULTS: Circulating T-helper type 1 (Th1) cells were higher (P < 0.003) in CP patients with diabetes in comparison with control and CP patients without diabetes. Intra-islet colocalization of Th1 and Th17 cells was evident. In comparison with the controls, 2% ± 0.87% ß cells from CP patients without diabetes were apoptotic whereas GSIR was decreased by 60% ± 12%, and 40% ± 9% from CP patients with diabetes were apoptotic, with minimal GSIR (1.42% ± 0.9%) in the remaining 60% viable cells. Western blots of islet proteins revealed an increase in STAT1 (signal transducer and activator of transcription 1) and a decrease in phosphorylated pancreatic duodenal homeobox (Pdx-1). CONCLUSIONS: T cell-mediated inflammation is associated with ß-cell dysfunction during progression of CP.

Complications of ERCP.

Endoscopic retrograde cholangiopancreatography (ERCP) is performed commonly for therapy. Its role in pancreaticobiliary diagnostic imaging has significantly decreased over time. Despite advances in our knowledge of the risk factors, complications, (especially post-ERCP pancreatitis), remain a significant problem. This review highlights the risk factors as related to the patient, procedure and the endoscopist, and the possible means to prevent complications. The best way to avoid any complication is "to avoid any procedure where the indication is not strong" and especially to refrain from doing diagnostic ERCP when alternate noninvasive imaging such as magnetic resonance cholangiopancreatography is available.

Feasibility and efficiency of a new 22G core needle: a prospective comparison study.

BACKGROUND AND STUDY AIMS: Histological examination of core tissue samples may have advantages over cytology in endoscopic ultrasound (EUS)-guided sampling. We aimed to evaluate the feasibility and efficiency of a new 22G core biopsy needle. PATIENTS AND METHODS: Consecutive patients with a pancreatic mass lesion or peri-intestinal lymphadenopathy sequentially underwent fine needle biopsy with both a newly developed 22G core needle (the FNB needle) and a standard 22G fine needle aspiration (FNA) needle, in randomized order. RESULTS: In 144 patients, mean age 48 years (± standard deviation [SD] 14; range 18 - 82), with 145 lesions (mean lesion size 39 ± 15 mm, range 15 - 99), EUS-guided sampling was technically feasible with both needles in all patients. Mean number of passes to obtain sufficient tissue was 1.2 ± 0.5 with the core needle vs. 2.5 ± 0.9 with the standard needle (P < 0.001). FNB specimens were adequate for evaluation in 125 (86.2 %) vs. 127 (87.6 %) with FNA (P = 0.72). Among 139 patients available for follow-up, FNB provided a correct diagnosis in 110 (79.1 %) and FNA in 112 (80.6 %) (P = 0.73). Sensitivity, specificity, positive and negative predictive values, and accuracy for diagnosis of malignancy were 90 %, 100 %, 100 %, 93 %, 96 % for FNB and 77 %, 100 %, 100 %, 85 %, 92 % for FNA, respectively (P > 0.05). CONCLUSION: FNB with the new 22G core needle was technically feasible, efficient and comparable to FNA with a standard needle. The core needle required fewer passes to provide an adequate sample, offering potentially shorter procedure time.

Association of vascular endothelial growth factor (VEGF) gene polymorphism and increased serum VEGF concentration with pancreatic adenocarcinoma.

UNLABELLED: BACKGROUND &AIM: Pancreatic cancer is related to high mortality rate. The vascular endothelial growth factor (VEGF) has a strong influence in tumor-related angiogenesis having association with the grade of angiogenesis and the prognosis of different solid tumors including pancreatic cancer. The present study was aimed to analyze the genotype and haplotype distribution of VEGF gene single nucleotide polymorphisms (SNPs), -460T/C, +405G/C, +936C/T, in patients with pancreatic adenocarcinoma from South India, and the effect of these SNPs on serum VEGF level. METHODS: Total 80 patients with pancreatic adenocarcinoma and 87 controls were recruited. The genotype of VEGF gene polymorphisms was determined in both patients and controls using polymerase chain reaction-restriction fragment length polymorphism method. The serum VEGF protein was estimated by standard enzyme-linked immunosorbent assay. RESULTS: The genotype, +405G/G of VEGF gene showed a significant association with the patients with pancreatic adenocarcinoma (P = 0.012, Odds ratio: 2.133), whereas no significant difference was found in the genotype distribution of SNPs, -460C/T and +936C/T between patient and control groups (P > 0.05). Serum VEGF level was found to be significantly high in patients (1315.10 pg/Ml, SD ± 230.79) when compared to controls (591.35 pg/mL, SD ± 92.48) (P < 0.0001), which showed a strong genotype-phenotype correlation between genotype +405G/G and serum VEGF level. Further, the haplotype C-G-T showed a strong association with the disease, and no specific haplotype was associated with increased serum VEGF level. CONCLUSION: The polymorphism, +405G/C but not -460T/C and +936C/T, of VEGF gene is strongly associated with pancreatic adenocarcinoma, and this SNP has significant influence on serum VEGF level.

The diagnostic accuracy and strength of agreement between endoscopic ultrasound and histopathology in the staging of ampullary tumors.

AIM: Ampullary tumors are rare. Reports on ampullary tumor staging are heterogeneous and combine both periampullary and ampullary tumors. This study assessed the performance of endoscopic ultrasound (EUS) in the local staging of ampullary tumors only. METHODS: Data were collected retrospectively. We included patients with an ampullary tumor who underwent EUS and surgical resection. Tumor (T) and nodal (N) TNM staging for EUS and histopathological (HP) staging were compared. RESULTS: From 2009 to 2010, a total of 79 patients with ampullary tumors were identified. Of these, 26 had both EUS and Whipple's surgery and were included (28 did not undergo resection, 13 had palliative surgery only and 12 had resection without EUS). For T staging by HP, there were 2 (7.7 %) T1, 11 (42.3 %) T2, 12 (46.2 %) T3 and 1 (3.8 %) T4 tumors. The accuracy of EUS T staging was 73.1 % with a Kappa value of 0.564 (p < 0.0001). The sensitivity, specificity, positive predictive value (PPV), negative predictive values (NPV) of EUS, respectively were 50.0 %, 91.7 %, 33.3 % and 95.7 % for T1 tumors; 81.8 %, 80.0 %, 75.0 % and 85.7 % for T2; 75.0 %, 92.9 %, 90.0 % and 81.3 % for T3 tumors. For N staging by HP, 17 (65.4 %) were N0 and 9 (34.6 %) N1. The N staging diagnostic accuracy was 80.8 % with a Kappa value of 0.586 (p = 0.003). The sensitivity, specificity, PPV, NPV for N0 disease were 82.4 %, 77.8 %, 87.5 % and 70.0 %, respectively while for N1 they were 77.8 %, 82.4 %, 70.0 % and 87.5 %, respectively. CONCLUSIONS: EUS had a moderate strength of agreement with histopathology for both T and N staging, and a high diagnostic accuracy for nodal staging.

HER2 expression in gastric cancer in Indian population--an immunohistochemistry and fluorescence in situ hybridization study.

AIM: Human epidermal growth factor receptor (HER2, also known neu, ERBB2) protein expression in gastric cancer is associated with poor prognosis, aggressive disease and poor response to chemotherapy. Trastuzumab, a monoclonal antibody against HER2, in combination with chemotherapy is currently advocated as a new standard option for patients with HER2-positive advanced gastric and gastroesophageal junction carcinoma. Frequency of HER2 expression in gastric cancer has been reported from different geographic zones with a wide range of 13 % to 91 %. There are no reported data of HER2 protein expression in gastric cancer tissue from India. The purpose of this study was to evaluate the frequency of HER2 expression in gastric cancer. METHODS: The frequency of HER2 expression in 52 patients with gastric adenocarcinoma was prospectively evaluated over a six month period at Asian Institute of Gastroenterology from January 2010 to July 2010, using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). RESULTS: HER2 overexpression was confirmed in 23 of 52 (44.2 %) patients. Two patients had equivocal result by IHC (2+), one of whom was positive on analysis by FISH. There was no difference in HER2 overexpression (positivity) or negativity in relation to age, gender, tumor site, histological subtype, tumor differentiation, serosal involvement or lymph nodal status. HER2 overexpression rates were similar for intestinal type as compared to diffuse histological type (OR 1.84), as also for proximal as compared to distal gastric cancers (OR 0.81). CONCLUSION: HER2 overexpression was observed in significant number of advanced gastric adenocarcinoma patients. There was no difference in HER2 overexpression in relation to clinicopathological parameters.