Consensus guidelines on the role of cholangioscopy to diagnose indeterminate biliary stricture.

BACKGROUND: Indeterminate strictures pose a therapeutic dilemma. In recent years, cholangioscopy has evolved and the availability of cholangioscopy has increased. However, the position of cholangioscopy in the diagnostic algorithm to diagnose malignancy have not been well established. We aim to develop a consensus statement regarding the clinical role of cholangioscopy in the diagnosis of indeterminate biliary strictures. METHODS: The international experts reviewed the evidence and modified the statements using a three-step modified Delphi method. Each statement achieves consensus when it has at least 80% agreement. RESULTS: Nine final statements were formulated. An indeterminate biliary stricture is defined as that of uncertain etiology under imaging or tissue diagnosis. When available, cholangioscopic assessment and guided biopsy during the first round of ERCP may reduce the need to perform multiple procedures. Cholangioscopy are helpful in diagnosing malignant biliary strictures by both direct visualization and targeted biopsy. The absence of disease progression for at least 6 months is supportive of non-malignant etiology. Direct per-oral cholangioscopy provides the largest accessory channel, better image definition, with image enhancement but is technically demanding. Image enhancement during cholangioscopy may increase the diagnostic sensitivity of visual impression of malignant biliary strictures. Cholangioscopic imaging characteristics including tumor vessels, papillary projection, nodular or polypoid mass, and infiltrative lesions are highly suggestive for neoplastic/malignant biliary disease. The risk of cholangioscopy related cholangitis is higher than in standard ERCP, necessitating prophylactic antibiotics and ensuring adequate biliary drainage. Per-oral cholangioscopy may not be the modality of choice in the evaluation of distal biliary strictures due to inherent technical difficulties. CONCLUSION: Evidence supports that cholangioscopy has an adjunct role to abdominal imaging and ERCP tissue acquisition in order to evaluate and diagnose indeterminate biliary strictures.

ERCP plus endoscopic ultrasound-guided biliary drainage versus percutaneous transhepatic biliary drainage for malignant hilar biliary obstruction: a multicenter observational open-label study.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) may not provide complete biliary drainage in patients with Bismuth III/IV malignant hilar biliary obstruction (MHBO). Complete biliary drainage is accomplished by adding percutaneous transhepatic biliary drainage (PTBD). We prospectively compared recurrent biliary obstruction (RBO) rates between combined ERCP and endoscopic ultrasound-guided biliary drainage (EUS-BD) vs. bilateral PTBD. METHODS: Patients with MHBO undergoing endoscopic procedures (group A) were compared with those undergoing bilateral PTBD (group B). The primary outcome was the 3-month RBO rate. RESULTS: 36 patients were recruited into groups A (n = 19) and B (n = 17). Rates of technical and clinical success, and complications of group A vs. B were 84.2 % (16/19) vs. 100 % (17/17; P = 0.23), 78.9 % (15/19) vs. 76.5 % (13/17; P > 0.99), and 26.3 % (5/19) vs. 35.3 % (6/17; P = 0.56), respectively. Within 3 and 6 months, RBO rates of group A vs. group B were 26.7 % (4/15) vs. 88.2 % (15/17; P  = 0.001) and 22.2 % (2/9) vs. 100 % (9/9; P = 0.002), respectively. At 3 months, median number of biliary reinterventions in group A was significantly lower than in group B (0 [interquartile range] 0-1 vs. 1 [1-2.5]), respectively (P < 0.001). Median time to development of RBO was longer in group A than in group B (92 [56-217] vs. 40 [13.5-57.8] days, respectively; P  =  0.06). CONCLUSIONS: Combined ERCP and EUS procedures provided significantly lower RBO rates at 3 and 6 months vs. bilateral PTBD, with similar complication rates and no significant mortality difference.

Drainage of pancreatic fluid collections using a lumen-apposing metal stent with an electrocautery-enhanced delivery system.

BACKGROUND AND AIM: Our aim was to evaluate the efficacy and safety of a lumen-apposing metal stent with an electrocautery-enhanced delivery system (EDS-LAMS) for endoscopic ultrasound (EUS)-guided drainage of pancreatic fluid collections (PFCs) in regular clinical practice. METHODS: A retrospective and subsequent prospective analysis was undertaken of all patients who underwent EUS-guided drainage of their PFCs using the EDS-LAMS at 17 tertiary therapeutic endoscopy centers. RESULTS: Two hundred eight cases of EDS-LAMS deployment were attempted in 202 patients (mean age 52.9 years) at time of evaluation. Ninety-seven patients had pancreatic pseudocysts (PPs), 75 walled-off pancreatic necrosis (WOPN), 10 acute peripancreatic fluid collections (APFCs), 6 acute necrotic collections (ANCs), and 14 postoperative collections (POCs). Procedural technical success was achieved in 202/208 cases (97.1%). Maldeployment occurred in 7/208 cases (3.4%). Clinical success was achieved in 142/160 (88.8%) patients (PP 90%, WOPN 85.2%, APFC 100%, ANC 75%, POC 100%). Delayed adverse events included stent migration in 15/202 (7.4%), stent occlusion and infection in 16/202 (7.9%), major bleeding in 4/202 (2%), and buried EDS-LAMS in 2/202 (1%). PFC recurrence occurred in 13/142 (9.2%) patients; 9/202 (4.5%) required surgical or radiological intervention for PFC management after EDS-LAMS insertion. CONCLUSIONS: This large international multicenter study evaluating the EDS-LAMS for drainage of PFCs in routine clinical practice suggests that the EDS-LAMS are safe and effective for drainage of all types of PFCs; however, further endoscopic therapy is often required for WOPN. Major bleeding was a rare complication in our cohort.

Serum Helicobacter pylori antibody reactivity in seven Asian countries using an automated latex aggregation turbidity assay.

BACKGROUND AND AIM: To determine the application range of diagnostic kits utilizing anti-Helicobacter pylori antibody, we tested a newly developed latex aggregation turbidity assay (latex) and a conventional enzyme-linked immunosorbent assay (E-plate), both containing Japanese H. pylori protein lysates as antigens, using sera from seven Asian countries. METHODS: Serum samples (1797) were obtained, and standard H. pylori infection status and atrophy status were determined by culture and histology (immunohistochemistry) using gastric biopsy samples from the same individuals. The two tests (enzyme-linked immunosorbent assay and latex) were applied, and receiver operating characteristics analysis was performed. RESULTS: Area under the curve (AUC) from the receiver operating characteristic of E-plate and latex curves were almost the same and the highest in Vietnam. The latex AUC was slightly lower than the E-plate AUC in other countries, and the difference became statistically significant in Myanmar and then Bangladesh as the lowest. To consider past infection cases, atrophy was additionally evaluated. Most of the AUCs decreased using this atrophy-evaluated status; however, the difference between the two kits was not significant in each country, but the latex AUC was better using all samples. Practical cut-off values were 3.0 U/mL in the E-test and 3.5 U/mL in the latex test, to avoid missing gastric cancer patients to the greatest extent possible. CONCLUSIONS: The kits were applicable in all countries, but new kits using regional H. pylori strains are recommended for Myanmar and Bangladesh. Use of a cut-off value lower than the best cut-off value is essential for screening gastric cancer patients.

Characterization of a novel Helicobacter pylori East Asian-type CagA ELISA for detecting patients infected with various cagA genotypes.

Currently, Western-type CagA is used in most commercial Helicobacter pylori CagA ELISA kits for CagA detection rather than East Asian-type CagA. We evaluated the ability of the East Asian-type CagA ELISA developed by our group to detect anti-CagA antibody in patients infected with different cagA genotypes of H. pylori from four different countries in South Asia and Southeast Asia. The recombinant CagA protein was expressed and later purified using GST-tag affinity chromatography. The East Asian-type CagA-immobilized ELISA was used to measure the levels of anti-CagA antibody in 750 serum samples from Bhutan, Indonesia, Myanmar, and Bangladesh. The cutoff value of the serum antibody in each country was determined via Receiver-Operating Characteristic (ROC) analysis. The cutoff values were different among the four countries studied (Bhutan, 18.16 U/mL; Indonesia, 6.01 U/mL; Myanmar, 10.57 U/mL; and Bangladesh, 6.19 U/mL). Our ELISA had better sensitivity, specificity, and accuracy of anti-CagA antibody detection in subjects predominantly infected with East Asian-type CagA H. pylori (Bhutan and Indonesia) than in those infected with Western-type CagA H. pylori predominant (Myanmar and Bangladesh). We found positive correlations between the anti-CagA antibody and antral monocyte infiltration in subjects from all four countries. There was no significant association between bacterial density and the anti-CagA antibody in the antrum or the corpus. The East Asian-type CagA ELISA had improved detection of the anti-CagA antibody in subjects infected with East Asian-type CagA H. pylori. The East Asian-type CagA ELISA should, therefore, be used in populations predominantly infected with East Asian-type CagA.

International consensus statements for endoscopic management of distal biliary stricture.

Distal biliary strictures (DBS) are common and may be caused by both malignant and benign pathologies. While endoscopic procedures play a major role in their management, a comprehensive review of the subject is still lacking. Our consensus statements were formulated by a group of expert Asian pancreatico-biliary interventional endoscopists, following a proposal from the Digestive Endoscopy Society of Taiwan, the Thai Association for Gastrointestinal Endoscopy, and the Tokyo Conference of Asian Pancreato-biliary Interventional Endoscopy. Based on a literature review utilizing Medline, Cochrane library, and Embase databases, a total of 19 consensus statements on DBS were made on diagnosis, endoscopic drainage, benign biliary stricture, malignant biliary stricture, and management of recurrent biliary obstruction and other complications. Our consensus statements provide comprehensive guidance for the endoscopic management of DBS.

Interleukin-17C in Human Helicobacter pylori Gastritis.

The interleukin-17 (IL-17) family of cytokines (IL-17A to IL-17F) is involved in many inflammatory diseases. Although IL-17A is recognized as being involved in the pathophysiology of Helicobacter pylori-associated diseases, the role of other IL-17 cytokine family members remains unclear. Microarray analysis of IL-17 family cytokines was performed in H. pylori-infected and uninfected gastric biopsy specimens. IL-17C mRNA was upregulated approximately 4.5-fold in H. pylori-infected gastric biopsy specimens. This was confirmed by quantitative reverse transcriptase PCR in infected and uninfected gastric mucosa obtained from Bhutan and from the Dominican Republic. Immunohistochemical analysis showed that IL-17C expression in H. pylori-infected gastric biopsy specimens was predominantly localized to epithelial and chromogranin A-positive endocrine cells. IL-17C mRNA levels were also significantly greater among cagA-positive than cagA-negative H. pylori infections (P = 0.012). In vitro studies confirmed an increase in IL-17C mRNA and protein levels in cells infected with cagA-positive infections compared to cells infected with either cagA-negative or cag pathogenicity island (PAI) mutant. Chemical inhibition of IκB kinase (IKK), mitogen-activated protein extracellular signal-regulated kinase (MEK), and Jun N-terminal kinase (JNK) inhibited induction of IL-17C proteins in infected cells, whereas p38 inhibition had no effect on IL-17C protein secretion. In conclusion, H. pylori infection was associated with a significant increase in IL-17C expression in human gastric mucosa. The role of IL-17C in the pathogenesis of H. pylori-induced diseases remains to be determined.

Endoscopic ultrasonography evaluation for pancreatic cysts: Necessity or overkill?

Incidental pancreatic cysts have become gradually more recognized in clinical practice as a result of increased use of transabdominal ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI). These lesions consist of inflammatory cysts (pseudocysts) and pancreatic cystic neoplasms (PCN) which have been classified as benign, premalignant and malignant. The diagnosis and management strategy of incidentally discovered pancreatic cysts can be challenging as the majority of them are PCN and CT or MRI alone may not be sufficient to provide an accurate diagnosis. Endoscopic ultrasound (EUS)-guided fine-needle aspiration provides a method to obtain cyst fluid for analysis and the recently developed EUS-based technology including contrast-enhanced ultrasound, cystoscopy and needle-based confocal laser endomicroscopy allows endosonographers to gain additional useful information. The current data suggest that EUS evaluation of pancreatic cysts offers some benefits especially in cases of inconclusive CT or MRI.

Prospective comparison of three risk scoring systems in non-variceal and variceal upper gastrointestinal bleeding.

BACKGROUND AND AIM: Data regarding the efficacy of the Glasgow Blatchford score (GBS), full Rockall score (FRS) and pre-endoscopic Rockall scores (PRS) in comparing non-variceal and variceal upper gastrointestinal bleeding (UGIB) are limited. Our aim was to determine the performance of these three risk scores in predicting the need for treatment, mortality, and re-bleeding among patients with non-variceal and variceal UGIB. METHODS: During January, 2010 and September, 2011, patients with UGIB from 11 hospitals were prospectively enrolled. The GBS, FRS, and PRS were calculated. Discriminative ability for each score was assessed using the receiver operated characteristics curve (ROC) analysis. RESULTS: A total of 981 patients presented with acute UGIB, 225 patients (22.9%) had variceal UGIB. The areas under the ROC (AUC) of the GBS, FRS, and PRS for predicting the need for treatment were 0.77, 0.69, and 0.61 in non-variceal versus 0.66, 0.66, and 0.59 in variceal UGIB. The AUC for predicting mortality and re-bleeding during admission were 0.66, 0.80, and 0.76 in non-variceal versus 0.63, 0.57, and 0.63 in variceal UGIB. AUC score was not statistically significant for predicting need for therapy and clinical outcome in variceal UGIB. The GBS ≤ 2 and FRS ≤ 1 identified low-risk non-variceal UGIB patients for death and re-bleeding during hospitalization. CONCLUSION: In contrast to non-variceal UGIB, the GBS, FRS, and PRS were not precise scores for assessing the need for therapy, mortality, and re-bleeding during admission in variceal UGIB.

Asian consensus statements on endoscopic management of walled-off necrosis. Part 2: Endoscopic management.

Walled-off necrosis (WON) is a new term for encapsulated necrotic tissue after severe acute pancreatitis. Various terminologies such as pseudocyst, necroma, pancreatic abscess, and infected necrosis were previously used in the literature, resulting in confusion. The current and past terminologies must be reconciled to meaningfully interpret past data. Recently, endoscopic necrosectomy was introduced as a treatment option and is now preferred over surgical necrosectomy when the expertise is available. However, high-quality evidence is still lacking, and there is no standard management strategy for WON. The consensus meeting aimed to clarify the diagnostic criteria for WON and the role of endoscopic interventions in its management. In the Consensus Conference, 27 experts from eight Asian countries took an active role and examined key clinical aspects of WON diagnosis and endoscopic management. Statements were crafted based on literature review and expert opinion, employing the modified Delphi method. All statements were substantiated by the level of evidence and the strength of the recommendation. We created 27 consensus statements for WON diagnosis and management, including details of endoscopic procedures. When there was not enough solid evidence to support the statements, this was clearly acknowledged to facilitate future research. Proposed management strategies were formulated and are illustrated using flow charts. These recommendations, which are based on the best current scientific evidence and expert opinion, will be useful for guiding endoscopic management of WON. Part 2 of this statement focused on the endoscopic management of WON.

Asian consensus statements on endoscopic management of walled-off necrosis Part 1: Epidemiology, diagnosis, and treatment.

Walled-off necrosis (WON) is a relatively new term for encapsulated necrotic tissue after severe acute pancreatitis. Various terminologies such as pseudocyst, necroma, pancreatic abscess, and infected necrosis were previously used in the literature, resulting in confusion. The current and past terminologies must be reconciled to meaningfully interpret past data. Recently, endoscopic necrosectomy was introduced as a treatment option and is now preferred over surgical necrosectomy when the expertise is available. However, high-quality evidence is still lacking, and there is no standard management strategy for WON. The consensus meeting aimed to clarify the diagnostic criteria for WON and the role of endoscopic interventions in its management. In the Consensus Conference, 27 experts from eight Asian countries took an active role and examined key clinical aspects of WON diagnosis and endoscopic management. Statements were crafted based on literature review and expert opinion, employing the modified Delphi method. All statements were substantiated by the level of evidence and the strength of the recommendation. We created 27 consensus statements for WON diagnosis and management, including details of endoscopic procedures. When there was not enough solid evidence to support the statements, this was clearly acknowledged to facilitate future research. Proposed management strategies were formulated and are illustrated using flow charts. These recommendations, which are based on the best current scientific evidence and expert opinion, will be useful for guiding endoscopic management of WON. Part 1 of this statement focused on the epidemiology, diagnosis, and timing of intervention.

Structured endoscopic ultrasonography (EUS) training program improved knowledge and skills of trainees: Results from the Asian EUS Group.

BACKGROUND AND AIM: A major reason impeding the growth of endoscopic ultrasound (EUS) in Asia is the lack of training availability. We aimed to prospectively evaluate the effectiveness of a short-term structured EUS training program in improving the knowledge and skill of EUS among trainees. METHODS: The study was conducted in six workshops in six countries including Sri Lanka, Pakistan, Thailand, Vietnam, Singapore and Philippines, within a year. Trainees were evaluated using written and skill tests before and after completion of the training. RESULTS: Pre- and post-workshop written tests from a total of 62 trainees were analyzed. Compared with pre-training, the trainees improved significantly in the overall mean (± SD) scores after the training (66.0 ± 0.3% to 77.5 ± 0.2%, P < 0.0001). Thirty-one trainees were randomly selected to undergo a skill test before and after the course. Compared with pre-training, the proportions of trainees who succeeded in locating each structure post-training were: celiac axis (36-80.5%), pancreatic body (51.5-80.5%), pancreatic body and tail (42-77.5%), splenic vein and artery (48.5-84%), left kidney (60-83%), and spleen (47-83%). Overall, there was a significant improvement in the proportion of trainees' successful localization of structures post-training compared to before training (P < 0.0001). CONCLUSION: Following a structured training program, trainees' knowledge and skills in EUS improved significantly. Structured training courses appear to be an effective way of imparting EUS knowledge and skills to aspiring endosonographers in the Asian region.

Revolution of hands-on model for interventional EUS: How to make a training model.

EUS interventions have an increasing role in the treatment for hepatobiliary-pancreatic diseases. However, the procedure itself is not frequently performed, needs expertise, and carries a high risk of complications. With these limitations, the hands-on practice model is very important for the endoscopist in training for EUS intervention. There have been various hands-on models for EUS interventions, ranging from in vivo living pig model to all-synthetic model. Although a living model provides realistic sensation, the preparation is complex and increases concerns for zoonotic issues. All-synthetic models are easier to prepare and store but not realistic and still need the room for improvement. Hybrid ex vivo model is more widely available and provides various training procedures but still needs special preparation for the porcine tissue.

The updated Asia-Pacific consensus statement on the role of endoscopic management in malignant hilar biliary obstruction.

The first Asia-Pacific consensus recommendations for endoscopic and interventional management of hilar cholangiocarcinoma were published in 2013. Since then, new evidence on the role of endoscopy for management of malignant hilar biliary obstruction (MHBO) has emerged. To update the recommendation, we reviewed the literature using a PICO (population/intervention/comparison/outcomes) framework and created consensus statements. The expert panel voted anonymously using the modified Delphi method and all final statements were evaluated for the quality of evidence and strength of recommendation. The important points with inadequate supporting evidence were classified as key concepts. There were seven statements and five key concepts that reached consensus. The statements and key concepts dealt with multiple aspects of endoscopy-based management in MHBO starting from diagnosis, strategies and options for biliary drainage, management of recurrent biliary obstruction, management of cholecystitis after biliary stenting, and adjunctive treatment before stenting. Although the recommendations may assist physicians in planning the treatment for MHBO patients, they should not replace the decision of a multidisciplinary team in the management of individual patients.

Asia-Pacific consensus recommendations for endoscopic and interventional management of hilar cholangiocarcinoma.

Hilar cholangiocarcinoma (HCCA) is one of the most common types of hepatobiliary cancers reported in the world including Asia-Pacific region. Early HCCA may be completely asymptomatic. When significant hilar obstruction develops, the patient presents with jaundice, pale stools, dark urine, pruritus, abdominal pain, and sometimes fever. Because no single test can establish the definite diagnosis then, a combination of many investigations such as tumor markers, tissue acquisition, computed tomography scan, magnetic resonance imaging/magnetic resonance cholangiopancreatography, endoscopic ultrasonography/intraductal ultrasonography, and advanced cholangioscopy is required. Surgery is the only curative treatment. Unfortunately, the majority of HCCA has a poor prognosis due to their advanced stage on presentation. Although there is no survival advantage, inoperable HCCA managed by palliative drainage may benefit from symptomatic improvement. Currently, there are three techniques of biliary drainage which include endoscopic, percutaneous, and surgical approaches. For nonsurgical approaches, stent is the most preferred device and there are two types of stents i.e. plastic and metal. Type of stent and number of stent for HCCA biliary drainage are subjected to debate because the decision is made under many grounds i.e. volume of liver drainage, life expectancy, expertise of the facility, etc. Recently, radio-frequency ablation and photodynamic therapy are promising techniques that may extend drainage patency. Through a review in the literature and regional data, the Asia-Pacific Working Group for hepatobiliary cancers has developed statements to assist clinicians in diagnosing and managing of HCCA. After voting anonymously using modified Delphi method, all final statements were determined for the level of evidence quality and strength of recommendation.

Contrast-enhanced endoscopic ultrasound for swollen lymph nodes.

Endoscopic ultrasound (EUS) is an important tool for the evaluation of lymphadenopathy, especially in intra-thoracic or intra-abdominal regions. EUS also provides tissue diagnosis via EUS fine-needle aspiration or biopsy. To select the target for biopsy or aspiration, conventional B-mode images are used for the evaluation, but this approach still lacks diagnostic accuracy. Contrast-enhanced EUS has been used to evaluate the vascularity of lesions. Most malignant lymphadenopathy shows heterogenous enhancement or defect of enhancement, while quantitative studies using time-intensity curves in contrast-enhanced harmonic EUS show a rapid decline in enhancement pattern. These findings are useful as an auxiliary method for tissue diagnosis or in cases in which tissue diagnosis is contraindicated.