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Introduction: In Singapore, non-anaesthesiologists generally administer sedation during gastrointestinal endoscopy. The drugs used for sedation in hospital endoscopy centres now include propofol in addition to benzodiazepines and opiates. The requirements for peri-procedural monitoring and discharge protocols have also evolved. There is a need to develop an evidence-based clinical guideline on the safe and effective use of sedation by non-anaesthesiologists during gastrointestinal endoscopy in the hospital setting. Methods: The Academy of Medicine, Singapore appointed an expert workgroup comprising 18 gastroenterologists, general surgeons and anaesthesiologists to develop guidelines on the use of sedation during gastrointestinal endoscopy. The workgroup formulated clinical questions related to different aspects of endoscopic sedation, conducted a relevant literature search, adopted Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology and developed recommendations by consensus using a modified Delphi process. Results: The workgroup made 16 recommendations encompassing 7 areas: (1) purpose of sedation, benefits and disadvantages of sedation during gastrointestinal endoscopy; (2) pre-procedural assessment, preparation and consent taking for sedation; (3) Efficacy and safety of drugs used in sedation; (4) the role of anaesthesiologist-administered sedation during gastrointestinal endoscopy; (5) performance of sedation; (6) post-sedation care and discharge after sedation; and (7) training in sedation for gastrointestinal endoscopy for non-anaesthesiologists. Conclusion: These recommendations serve to guide clinical practice during sedation for gastrointestinal endoscopy by non-anaesthesiologists in the hospital setting. Keywords: Benzodiazepines, gastrointestinal endoscopy opiates, propofol, sedation

The prevalence of pancreatic cystic lesions (PCLs) has increased recently due to the increased use of cross-sectional abdominal imaging and the ageing global population. Current diagnostic techniques are inadequate to distinguish between PCLs that require surgery, close surveillance, or expectant management. This has resulted in increased morbidity from both inappropriately aggressive and conservative management strategies. Needle-based confocal laser endomicroscopy (nCLE) has allowed microscopic examination and visual delineation of the surface epithelium of PCLs. Landmark studies in this decade have correlated nCLE and histological findings and identified characteristics differentiating various types of PCLs. Subsequent studies have confirmed the high diagnostic yield of nCLE and its diagnostic utility in PCLs with an equivocal diagnosis. Moreover, nCLE has been shown to improve the diagnostic yield of PCLs. This will help avoid unnecessary pancreatic surgery, which carries significant morbidity and mortality risks. The early detection of high-grade dysplasia in PCLs will provide early surgical treatment and improve outcomes for pancreatic cancer. Despite the high upfront cost of nCLE, the improved diagnostic accuracy and resultant appropriate management have resulted in improved cost effectiveness. Refining the procedure technique and limiting the procedure length have significantly improved the safety of nCLE. A structured training program and device improvements to allow more complete mapping of the pancreatic cyst epithelium will be crucial for the widespread adoption of this promising technology.

Background Pancreatic adenocarcinoma (PDAC) is highly lethal. Surgery offers the only chance of cure, but 5‐year overall survival (OS) after surgical resection and adjuvant therapy remains dismal. Adjuvant trials were mostly conducted in the West enrolling fit patients. Applicability to a general population, especially Asia has not been described adequately. Aim We aimed to evaluate the clinical outcomes, prognostic factors of survival, pattern, and timing of recurrence after curative resection in an Asian institution. Methods and Results The clinicopathologic and survival outcomes of 165 PDAC patients who underwent curative resection between 1998 and 2013 were reviewed retrospectively. Median age at surgery was 62.0 years. 55.2% were male, and 73.3% had tumors involving the head of pancreas. The median OS of the entire cohort was 19.7 months. Median OS of patients who received adjuvant chemotherapy was 23.8 months. Negative predictors of survival include lymph node ratio (LNR) of >0.3 (HR = 3.36, P = .001), tumor site involving the body or tail of pancreas (HR = 1.59, P = .046), presence of perineural invasion (PNI) (HR = 2.36, P = .018) and poorly differentiated/undifferentiated tumor grade (HR = 1.86, P = .058). The median time to recurrence was 8.87 months, with 66.1% and 81.2% of patients developing recurrence at 12 months and 24 months respectively. The most common site of recurrence was the liver. Conclusion The survival of Asian patients with resected PDAC who received adjuvant chemotherapy is comparable to reported randomized trials. Clinical characteristics seem similar to Western patients. Hence, geographical locations may not be a necessary stratification factor in RCTs. Conversely, lymph node ratio and status of PNI ought to be incorporated.

Background: Epidemiological evidence suggests there are differences in gastroenteropancreatic neuroendocrine neoplasm (GEPNEN) among population groups. We aimed to contribute to the current evidence by evaluating the clinicopathological characteristics of GEPNEN in a multi-ethnic Asian group. Materials and Methods: This was a retrospective chart review of patients diagnosed with GEPNEN at a tertiary medical institution at Singhealth Outram Campus, Singapore, between 1995 and 2015. Results: Two hundred ninety-five patients were included in the evaluation, comprising Chinese (74.6%), Malay (4.4%), Indian (9.5%) and other (11.5%) ethnic backgrounds. The median age at diagnosis was 59 years; 52.5% were males. Distribution of disease stage at diagnosis was: localised (42.4%), regional (15.3%) and distant (38.0%). The three most common primary tumour sites were located in the pancreas (38.6%), rectum (19.7%) and stomach (9.5%), which varied significantly with ethnic background and age at diagnosis. Malay patients were younger (median 42 years) at diagnosis than Chinese (60 years). Patients with an appendiceal neuroendocrine neoplasm (NEN) (48 years) were younger compared to oesophageal NEN (66 years). Disease stage correlated with primary tumour site and grade (p < 0.001). Median overall survival (OS) for all GEPNEN was 10.2 years. Age at diagnosis, disease stage and grading were prognostic factors of OS in multivariable analyses. Conclusion: Our findings correspond with other studies that focus on GEPNEN incidences in Asian countries, with the pancreas, rectum and stomach being the most common primary tumour sites. Our findings suggest racial differences in primary tumour site and age at diagnosis. Further prospective population-based registries are required to understand these epidemiological differences.

Background & study aims Corona virus disease-19 (COVID-19) pandemic has markedly impacted routine medical services including gastrointestinal (GI) endoscopy. We aim to report the real-life performance in high volume GI endoscopy units during the pandemic. Patients and methods A web-based survey covering all aspects of daily performance in GI endoscopy units was sent to endoscopy units worldwide. Responses were collected and data were analyzed to reveal the effect of COVID-19 pandemic on endoscopy practice. Results Participants from 48 countries (n = 163) responded to the survey with response rate of 67.35%. The majority (85%) decreased procedure volume by over 50%, and four endoscopy units (2.45%) completely stopped. The top three indications for procedures included upper GI bleeding (89.6%), lower GI bleeding (65.6%) and cholangitis (62.6%). The majority (93.9%) triaged patients for COVID-19 prior to procedure. N95 masks were used in (57.1%), isolation gowns in (74.2%) and head covers in (78.5%). Most centers (65%) did not extend use of N95 masks, however 50.9% of centers reused N95 masks. Almost all (91.4%) centers used standard endoscopic decontamination and most (69%) had no negative pressure rooms. Forty-two centers (25.8%) reported positive cases of SARS-CoV-2 infection among patients and 50 (30.7%) centers reported positive cases of SARS-CoV-2 infection among their healthcare workers. Conclusions Most GI endoscopy centers had a significant reduction in their volume and most procedures performed were urgent. Most centers used the recommended personal protective equipment (PPE) by GI societies however there is still a possibility of transmission of SARS-CoV-2 infection in GI endoscopy units.

Background Brush cytology, the conventional method to diagnose cholangiocarcinoma, has been plagued by low diagnostic sensitivity and false-negative results. We aim to study the clinical utility of fluorescence in situ hybridization (FISH) in enhancing identification of malignant biliary strictures. Methods Brush cytologic specimens collected from endoscopic retrograde cholangiopancreatography (ERCP) for biliary strictures in a tertiary hospital in Singapore from March 2013 to July 2015 were examined by FISH technique using UroVysion probe set in this study. Results 30 patients were chosen with 5 patients having multiple FISH done due to indeterminate results. The diagnoses for biliary strictures were 13 (43.3%) cholangiocarcinomas, 7 (23.3%) pancreatic cancers, 7 (23.3%) benign biliary strictures and 3 (10%) primary sclerosing cholangitis. Conventional brush cytology had sensitivity of 53.8% with specificity of 82.4%. FISH had sensitivity of 30.8% with specificity of 100%. When FISH results were interpreted in cases with negative or atypical brush cytology, 2 patients had positive FISH results and cholangiocarcinomas. Based on this pilot study, FISH increased sensitivity of brush cytology in detection of cholangiocarcinoma from 53.8% to 69.2% while preserving specificity of 82.4%. Conclusion Compared with conventional cytology with low sensitivity, FISH may help to increase sensitivity on top of brush cytology while maintaining high specificity.

Background/aim: Pancreatic cystic lesions are increasingly diagnosed from cross-sectional imaging done for other indications. The challenge lies in the ability to correctly identify the high-risk individuals for resection surgery, which carries high morbidity and mortality. Unfortunately, present diagnostic techniques are suboptimal. Needle-based confocal laser endomicroscopy (nCLE) has been designed to bridge this diagnostic gap. We aim to assess the feasibility and safety of nCLE in the assessment of pancreatic cystic lesions. Methods: We prospectively recruited patients referred for assessment of pancreatic cystic lesions from August 2014 until July 2015. All pancreatic cystic lesions were examined with nCLE miniprobe via endoscopic ultrasound followed by fine-needle aspiration. Information regarding the cysts (morphology, location, fluid analysis etc.) was documented. Adverse event was recorded. Results: Fourteen patients were recruited, six were male with a mean age of 66.5 (range 48–80) years. Only 12 completed nCLE examination of the pancreatic cystic lesions. nCLE imaging was successful in 83.3% (10/12). Average nCLE imaging duration was 5 min 18 s. There was one (10%) adverse event. nCLE impressions were correct in eight cases (five malignant and three benign) compared with final diagnosis. Three patients underwent surgery, histology showed ductal adenocarcinoma, pancreatic neuroendocrine tumor and gastric-subtype of intraductal papillary mucinous neoplasm. The sensitivity and specificity of the nCLE impression when compared with final diagnosis were 83.3% and 75% respectively. The accuracy of nCLE was 80%. Conclusion: Our results have demonstrated that nCLE assessment of pancreatic cystic lesions is safe and feasible. It may complement the existing diagnostic modalities to improve diagnostic yield.

Background and Aims Previous studies have validated EUS-guided needle-based confocal laser endomicroscopy (nCLE) diagnosis of intraductal papillary mucinous neoplasms (IPMNs). We sought to derive EUS-guided nCLE criteria for differentiating IPMNs with high-grade dysplasia/adenocarcinoma (HGD-Ca) from those with low/intermediate-grade dysplasia (LGD). Methods We performed a post hoc analysis of consecutive IPMNs with a definitive diagnosis from a prospective study evaluating EUS-guided nCLE in the diagnosis of pancreatic cysts. Three internal endosonographers reviewed all nCLE videos for the patients and identified potential discriminatory EUS-guided nCLE variables to differentiate HGD-Ca from LGD IPMNs (phase 1). Next, an interobserver agreement (IOA) analysis of variables from phase 1 was performed among 6 blinded external nCLE experts (phase 2). Last, 7 blinded nCLE-naive observers underwent training and quantified variables with the highest IOA from phase 2 using dedicated software (phase 3). Results Among 26 IPMNs (HGD-Ca in 16), the reference standard was surgical histopathology in 24 and cytology confirmation of metastatic liver lesions in 2 patients. EUS-guided nCLE characteristics of increased papillary epithelial “width” and “darkness” were the most sensitive variables (90%; 95% confidence interval [CI], 84%-94% and 91%; 95% CI, 85%-95%, respectively) and accurate (85%; 95% CI, 78%-90% and 84%; 95% CI, 77%-89%, respectively) with substantial (κ = 0.61; 95% CI, 0.51-0.71) and moderate (κ = 0.55; 95% CI, 0.45-0.65) IOAs for detecting HGD-Ca, respectively (phase 2). Logistic regression models were fit for the outcome of HGD-Ca as predictor variables (phase 3). For papillary width (cut-off ≥50 μm), the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) for detection of HGD-Ca were 87.5% (95% CI, 62%-99%), 100% (95% CI, 69%-100%), and 0.95, respectively. For papillary darkness (cut-off ≤90 pixel intensity), the sensitivity, specificity, and AUC for detection of HGD-Ca were 87.5% (95% CI, 62%-99%), 100% (95% CI, 69%-100%), and 0.90, respectively. Conclusions In this derivation study, quantification of papillary epithelial width and darkness identified HGD-Ca in IPMNs with high accuracy. These quantifiable variables can be used in multicenter studies for risk stratification of IPMNs. (Clinical trial registration number: NCT02516488.)

Cholangiocarcinoma (CCA) is the primary cancer of the bile duct system. The role of bile duct tissue microbiomes in CCA tumorigenesis is unestablished. To address this, sixty primary CCA tumors and matched normals, from both liver fluke (Opisthorchis viverrini) associated (OVa, n = 28) and non-O. viverrini associated (non-OVa, n = 32) cancers, were profiled using high-throughput 16S rRNA sequencing. A distinct, tissue-specific microbiome dominated by the bacterial families Dietziaceae, Pseudomonadaceae and Oxalobacteraceae was observed in bile duct tissues. Systemic perturbation of the microbiome was noted in tumor and paired normal samples (vs non-cancer normals) for several bacterial families with a significant increase in Stenotrophomonas species distinguishing tumors vs paired normals. Comparison of parasite associated (OVa) vs non-associated (non-OVa) groups identified enrichment for specific enteric bacteria (Bifidobacteriaceae, Enterobacteriaceae and Enterococcaceae). One of the enriched families, Bifidobacteriaceae, was found to be dominant in the O. viverrini microbiome, providing a mechanistic link to the parasite. Functional analysis and comparison of CCA microbiomes revealed higher potential for producing bile acids and ammonia in OVa tissues, linking the altered microbiota to carcinogenesis. These results define how the unique microbial communities resident in the bile duct, parasitic infections and the tissue microenvironment can influence each other, and contribute to cancer., Highlights • Stenotrophomonas, implicated in bile duct infections, is enriched in tumor tissues of non-fluke related cholangiocarcinoma. • O. viverrini infection may alter composition of bile duct tissue microbiomes. • Enteric bacteria with metabolic outputs linked to carcinogenesis are enriched in O. viverrini associated tissue microbiomes. The link between microbiota and cancer of the gastrointestinal (GI) tract has been extensively studied. However, the role of tissue microbiome in cholangiocarcinoma (CCA), cancer of the bile duct (an organ connected to the GI tract), is largely unknown. In this study, we detected intriguing compositional differences in the tissue microbiomes of liver fluke related and non-related CCA. Taken together, our data suggests a connection between parasitic infections, tissue microbiome alterations, tissue micro-environment changes and CCA development.

An 81-year-old male presented with loss of appetite, early satiety and iron deficiency anaemia. A computed tomography (CT) scan of the abdomen and pelvis during initial work-up revealed diffuse gastric mural thickening associated with a large ulcer and adjacent gastro-hepatic lymphadenopathy. The CT appearances, together with the clinical features, were highly suspicious for an infiltrative type of gastric malignancy. Endoscopic biopsy however showed erosive inflammation, IgG4 plasmacytosis and fibrosis, raising the possibility of IgG4-related disease. A serologic assay for IgG showed normal IgG4 and elevated IgG2 serum levels. After appropriate steroid treatment, endoscopy and CT scan showed resolution of the ulcer and gastric wall thickening. This case shows yet another possible appearance of gastric involvement in IgG4-related disease on the current evolving spectrum of this disease presentation. Greater awareness and education of this disease would help in patient care, ensuring earlier diagnosis, prevention of severe organ damage and morbidity, as well as unnecessary surgery.

Brush cytology, the conventional method to diagnose cholangiocarcinoma, has been plagued by low diagnostic sensitivity and false-negative results. This paper aims to study the clinical utility of fluorescence in situ hybridization (FISH) in enhancing identification of malignant biliary strictures.Brush cytologic specimens collected from endoscopic retrograde cholangiopancreatography for biliary strictures in a tertiary hospital in Singapore from March 2013 to July 2015 were examined by FISH technique using UroVysion probe set in this study.Thirty patients were chosen with five patients having multiple FISH performed due to indeterminate results. The diagnoses for biliary strictures were 13 (43.3%) cholangiocarcinomas, seven (23.3%) pancreatic cancers, seven (23.3%) benign biliary strictures, and three (10%) primary sclerosing cholangitis. Conventional brush cytology had sensitivity of 53.8% with specificity of 82.4%. FISH had sensitivity of 30.8% with specificity of 100%. When FISH results were interpreted in cases with negative or atypical brush cytology, two patients had positive FISH results and cholangiocarcinomas. Based on this pilot study, FISH increased sensitivity of brush cytology in detection of cholangiocarcinoma from 53.8% to 69.2% while preserving specificity of 82.4%.Compared with conventional cytology with low sensitivity, FISH may help to increase sensitivity on top of brush cytology while maintaining high specificity.

Biliary stricture is a rare sequela of biliary tuberculosis (TB) infection. Early recognition with prompt treatment can result in complete resolution. A 56-year-old man was diagnosed with biliary TB after analysis of bile from ERCP showed positive results for TB. Bile duct brushings were inconclusive. Despite completing 7 months of anti-TB treatment, the patient’s liver function test results were still abnormal. MRCP showed dilated intrahepatic ducts with a stricture at the hilar bifurcation

Chronic pancreatitis (CP) is a debilitating disease that can result in chronic abdominal pain, malnutrition, and other related complications. The main aims of treatment are to control symptoms, prevent disease progression, and correct any complications. A multidisciplinary approach involving medical, endoscopic, and surgical therapy is important. Endoscopic therapy plays a specific role in carefully selected patients as primary interventional therapy when medical measures fail or in patients who are not suitable for surgery. Endoscopic therapy is also used as a bridge to surgery or as a means to assess the potential response to pancreatic surgery. This review addresses the role of endoscopic therapy in relief of obstruction of the pancreatic duct (PD) and bile du ct, closure of PD leaks, and drainage of pseudocysts in CP. The role of endoscopic ultrasound-guided celiac plexus block for pain in chronic pancreatitis is also discussed.