Diagnosis and Treatment of Perihilar Cholangiocarcinoma:A National Survey from the Korean Pancreatobiliary Association

Background/Aims@#Based on their anatomy, cholangiocarcinomas (CCAs) are classified into intrahepatic, hilar, and distal CCAs. Although the diagnosis and treatment of each type of CCA are thought to be different, real-world data studies on the current practice are limited. Therefore, this study was designed to capture the current practice of diagnosing and treating perihilar CCA in Korea. @*Methods@#We conducted a survey using an online platform. The questionnaire consisted of 18 questions designed to evaluate the current practice of diagnosing and treating perihilar CCA in Korea. The targets of this survey were biliary endoscopists who are members of the Korean Pancreatobiliary Association. @*Results@#In total, 119 biliary endoscopists completed the survey. Of the respondents, 89.9% thought that the use of the International Classification of Diseases, 11th Revision (ICD-11) system is necessary to classify CCA. Approximately half of the respondents would recommend surgery or chemotherapy until patients were 80 years of age. For the pathological diagnosis of CCA, endoscopic retrograde cholangiopancreatography with biopsy was the most preferred modality. Routine preoperative biliary drainage was performed by 44.5% of the respondents. For operable CCAs, 64.7% of the respondents preferred endoscopic biliary drainage using plastic stents. For palliative biliary drainage, 69.7% of the respondents used plastic stents. For palliative endoscopic biliary drainage using metal stents, 63% of the respondents preferred the stent-in-stent method. @*Conclusions@#A new coding system using the ICD-11 is needed for classifying CCAs. Guidelines for diagnosing and treating CCA based on the clinical situation in Korea are needed.

Outcomes of Palliative Chemotherapy for Ampulla of Vater Adenocarcinoma: A Multicenter Cohort Study

Background/Aims@#Palliative chemotherapy (PC) is not standardized for patients with advanced ampulla of Vater adenocarcinoma (AA). This multicenter, retrospective study evaluated first-line PC outcomes in patients with AA. @*Methods@#Patients diagnosed with AA between January 2010 and December 2020 who underwent PC were enrolled from 10 institutions. Overall survival (OS) and progression-free survival (PFS) according to the chemotherapy regimen were analyzed. @*Results@#Of 255 patients (mean age, 64.0±10.0 years; male, 57.6%), 14 (5.5%) had locally advanced AA and 241 (94.5%) had metastatic AA. Gemcitabine plus cisplatin (GP) was administered as first-line chemotherapy to 192 patients (75.3%), whereas capecitabine plus oxaliplatin (CAPOX) was administered to 39 patients (15.3%). The median OS of all patients was 19.8 months (95% confidence interval [CI], 17.3 to 22.3), and that of patients who received GP and CAPOX was 20.4 months (95% CI, 17.2 to 23.6) and 16.0 months (95% CI, 11.2 to 20.7), respectively. The median PFS of GP and CAPOX patients were 8.4 months (95% CI, 7.1 to 9.7) and 5.1 months (95% CI, 2.5 to 7.8), respectively. PC for AA demonstrated improved median outcomes in both OS and PFS compared to conventional bile duct cancers that included AA. @*Conclusions@#While previous studies have shown mixed prognostic outcomes when AA was analyzed together with other biliary tract cancers, our study unveils a distinct clinical prognosis specific to AA on a large scale with systemic anticancer therapy. These findings suggest that AA is a distinct type of tumor, different from other biliary tract cancers, and AA itself could be expected to have a favorable response to PC.

The Use of Pancreatic Exocrine Insufficiency-Questionnaire (PEI-Q) / 대한췌담도학회지

Chronic pancreatitis is a non-reversible, progressive inflammatory disease of the pancreas that is caused by repeated inflammation. It is characterized by morphological changes in the parenchyma and main pancreatic duct as pancreatic tissue is damaged and fibrosis progresses. These changes can lead to exocrine and endocrine dysfunction in patients with chronic pancreatitis, with major complications including pain, endocrine or exocrine insufficiency, and increased risk of pancreatic cancer. Of these, pancreatic exocrine insufficiency (PEI) is a state of malabsorption in which more than 15 g of fat is excreted per day. It can be diagnosed and assessed using several methods, but these methods are currently difficult to use in Korea and have low compliance, making them low utility. Recently, the PEI-questionnaire (PEI-Q) was developed to diagnose and assess patients’ exocrine insufficiency. It has been validated in foreign countries and has the potential to be used as a tool for diagnosing exocrine insufficiency with simple questions. This paper will review the diagnostic methods for existing exocrine insufficiency and the usefulness and utilization of the PEI-Q.

The Successful Treatment of Percutaneous Transhepatic Gallbladder Drainage Related Pleurobiliary Fistula via Endoscopic Transpapillary Gallbladder Drainage / 대한췌담도학회지

The pleurobiliary fistula was not common but sometimes it could occur after percutaneous transhepatic gallbladder drainage. This report describes the case of an 83-year-old Korean male diagnosed with a pleurobiliary fistula after percutaneous transhepatic gallbladder drainage. The patient was treated with endoscopic transpapillary gallbladder drainage under the guidance of the peroral cholangioscopy with SpyGlass DS system. It can decompress pressure within the gallbladder. Leakage from the gallbladder into the pleura was reduced. Finally, his condition got better and he recovered.

Nonalcoholic Fatty Pancreas Disease / 대한췌담도학회지

Nonalcoholic fatty pancreas disease (NAFPD) is a condition characterized by theaccumulation of excess fat in the pancreas, commonly occurring in individuals withobesity. The diagnostic evaluation of NAFPD is mostly composed of image tests,but it is still less standardized. NAFPD is closely linked to metabolic syndrome, type2 diabetes, pancreatic exocrine insufficiency, acute pancreatitis, pancreatic fistula,pancreatic cancer, and nonalcoholic fatty liver disease (NAFLD). However, furtherresearch is needed to investigate the mechanisms underlying these relevant clinicalconsequences. In terms of treatment, strategies aimed at minimizing pancreaticfat accumulation through dietary modifications and regular exercise, similar to themanagement of NAFLD, may be beneficial.

Revised Clinical Practice Guidelines of the Korean Pancreatobiliary Association for Acute Pancreatitis

Acute pancreatitis can range from a mild, self-limiting disease requiring no more than supportive care, to severe disease with life-threatening complications. With the goal of providing a recommendation framework for clinicians to manage acute pancreatitis, and to contribute to improvements in national health care, the Korean Pancreatobiliary Association (KPBA) established the Korean guidelines for acute pancreatitis management in 2013. However, many challenging issues exist which often lead to differences in clinical practices. In addition, with newly obtained evidence regarding acute pancreatitis, there have been great changes in recent knowledge and information regarding this disorder. Therefore, the KPBA committee underwent an extensive revision of the guidelines. The revised guidelines were developed using the Delphi method, and the main topics of the guidelines include the following: diagnosis, severity assessment, initial treatment, nutritional support, convalescent treatment, and the treatment of local complications and necrotizing pancreatitis. Specific recommendations are presented, along with the evidence levels and recommendation grades.

Biliary Self-Expandable Metal Stent Could Be Recommended as a First Treatment Modality for Immediate Refractory Post-Endoscopic Retrograde Cholangiopancreatography Bleeding

Background/Aims@#Recent reports suggest that the biliary self-expandable metallic stent (SEMS) is highly effective for maintaining hemostasis when endoscopic hemostasis fails in endoscopic retrograde cholangiopancreatography (ERCP)-related bleeding. We compared whether temporary SEMS offers better efficacy than angioembolization for refractory immediate ERCP-related bleeding. @*Methods@#Patients who underwent SEMS placement or underwent angioembolization for bleeding control in refractory immediate ERCP-related bleeding were included in the retrospective analysis. We evaluated the hemostasis success rate, severity of bleeding, change in hemoglobin levels, amount of transfusion, and delay to the start of hemostasis. @*Results@#A total of 27 patients with SEMS and 13 patients who underwent angioembolization were enrolled. More transfusions were needed in the angioembolization group (1.0±1.4 units vs. 2.5±2.0 units; p=0.034). SEMS failure was successfully rescued by angioembolization. The partially covered SEMS (n=23, 85.1%) was generally used, and the median stent-indwelling time was 4 days. The mean delay to the start of angioembolization was 95.2±142.9 (range, 9–491) min. @*Conclusions@#Temporary SEMS had similar results to those of angioembolization (96.3% vs. 92.3%; p=0.588). Immediate SEMS insertion is considered a bridge treatment modality for immediate refractory ERCP-related bleeding. Angioembolization still has a role as rescue therapy when SEMS does not work effectively.

Revised Clinical Practice Guideline of Korean Pancreatobiliary Association for Acute Pancreatitis: Severity Assessment / 대한췌담도학회지

The severity of acute pancreatitis (AP) is classified into mild, moderately severe, and severe, considering the presence and duration of organ failure and local complications. Since patients with AP show a large difference in mortality and morbidity according to AP severity, evaluation of the severity of patients with AP in the early stage is important for predicting the prognosis and determining treatment plans including transfer to the intensive care unit or advanced facilities. In order to evaluate the initial severity of AP, it is necessary to confirm the presence of organ failure and objective evaluation using imaging or clinical examinations. In this guideline, it is recommended that evaluation using various severity indices such as bedside index for severity in acute pancreatitis (BISAP), systemic inflammatory response syndrome (SIRS), and acute physiology and chronic health evaluation (APACHE)-II scores be considered.

Revised Clinical Practice Guideline of Korean Pancreatobiliary Association for Acute Pancreatitis: Diagnosis / 대한췌담도학회지

There is general acceptance that a diagnosis of acute pancreatitis requires two of the following three features: 1) epigastric or upper abdominal pain characteristic of acute pancreatitis, 2) serum amylase and/or lipase ≥3 times the upper limit of normal, and 3) characteristic findings of acute pancreatitis on abdominal images such as ultrasonography, computed tomography (CT) or magnetic resonance imaging. Other pancreatic diseases and acute abdomen have been ruled out before making a diagnosis of acute pancreatitis. Serum lipase may be more useful than serum amylase because serum lipase is thought to be more sensitive and specific than serum amylase in the diagnosis of acute pancreatitis. Contrast-enhanced CT scan is the best imaging technique to rule out the conditions that masquerade as acute pancreatitis, to diagnose the severity of acute pancreatitis, and to identify complications of pancreatitis. The etiology of acute pancreatitis should be made clear as soon as possible to decide treatment policy of acute pancreatitis or to prevent the recurrence of pancreatitis. The etiology of acute pancreatitis in an emergency situation should be assessed by clinical history, laboratory tests such as serum liver function tests, measurement of serum calcium and serum triglycerides and ultrasonography. A differentiation of gallstone-induced acute pancreatitis should be given top priority in its etiologic diagnosis because early endoscopic retrograde cholangiopancreatography should be considered if a complication of cholangitis and a prolonged passage disorder of the biliary tract are suspected.

Multi-Center Study on Gender Difference in Resectability and Pathologic Prognosis of Gallbladder Cancer / 대한췌담도학회지

Background@#/Aim: In gallbladder cancer (GBC), gender differences in incidence and mortality rates have been reported with geographic variation. However, there is little known about sex-related difference in GBC prognosis. This study compares prognostic factors according to gender for GBC. @*Methods@#We searched clinicopathological factors in all stages of 952 GBC patients from seven medical centers in Korea. A total of 927 patients were enrolled and surgery with curative resection was performed in 499 patients. @*Results@#Carbohydrate antigen (≥37 U/mL) was a significant prognostic factor in both females and males (odd ratio [OR], 4.30; 95% confidence interval [CI], 3.13-5.89; p2; an independent predictor of poor prognosis via multivariate analysis (OR, 1.03; 95% CI, 1.01-1.05; p=0.005, OR, 1.05; 95% CI, 1.02-1.08; p=0.002). Body mass index (BMI) also showed gender difference, and lower BMI (≤25 kg/m2) was the significant good indicator of multivariate analysis for lymph node metastasis in female patients (OR, 0.42; 95% CI, 0.23-0.77; p=0.005) but, the significant poor indicator of univariate analysis for advanced T-stage in male (OR, 2.79; 95% CI, 1.40-5.54; p=0.003). @*Conclusions@#These results suggest that there is a possibility of gender difference in GBC prognosis. Age and high BMI were poor prognostic factors for curative resection for female GBC patients.

Endoscopic hemostasis using an over-the-scope clip for massive bleeding after percutaneous endoscopic gastrostomy removal: a case report

Percutaneous endoscopic gastrostomy (PEG) is a common method for providing long-term enteral nutrition to patients. PEG tube placement and removal are relatively safe; generally, a PEG tube can be removed using gentle traction, and excessive bleeding is rare. The over-the-scope clip system is a new device that can be used for gastrointestinal hemostasis and for closing gastrointestinal fistulae. In the present case, a 68-year-old male patient had to remove the PEG tube because of persistent leakage around the PEG tube. Although it was gently removed using traction, incessant bleeding continued, with a Rockall score of 5 points, even after hemocoagulation was attempted. An over-the-scope clip device was used to achieve hemostasis and fistula closure.

Difficult Biliary Cannulation from the Perspective of PostEndoscopic Retrograde Cholangiopancreatography Pancreatitis:Identifying the Optimal Timing for the Rescue Cannulation Technique

Background/Aims@#Recently, the European Society of Gastrointestinal Endoscopy (ESGE) proposed criteria for “difficult biliary cannulation” during endoscopic retrograde cholangiopancreatography (ERCP). This study aimed to investigate the clinical relevance of the ESGE criteria from the perspective of post-ERCP pancreatitis (PEP). @*Methods@#An ERCP database was prospectively maintained between November 2014 and December 2015 across six teaching hospitals in South Korea. The ESGE criteria (biliary cannulation time, the number of cannulation attempts, and inadvertent pancreatic duct [PD] manipulation) were recorded in this database as well as other technical factors. Logistic regression analysis was used to identify risk factors for PEP. Then, the PEP prediction model was investigated using decision tree analysis. @*Results@#We analyzed 1,067 consecutive patients with naïve papilla. The overall rate of PEP was 6.6%. Multivariate analysis revealed that female sex (odds ratio [OR], 1.860; 95% confidence interval [CI], 1.124 to 3.078), a selective biliary cannulation duration >5 minutes (OR, 3.282; 95% CI, 1.641 to 6.566), and inadvertent PD manipulation (OR, 2.614; 95% CI, 1.480 to 4.617) were significant factors affecting PEP. Decision tree analysis revealed that biliary cannulation time (χ2 =49.857, p5 minutes, and >5 minutes with inadvertent PD manipulation, respectively. @*Conclusions@#Biliary cannulation time and inadvertent PD manipulation could be relevant indicators of PEP, and 5 minutes might be used as a cutoff value for the implementation of the rescue cannulation technique.

Difficult Biliary Cannulation from the Perspective of PostEndoscopic Retrograde Cholangiopancreatography Pancreatitis:Identifying the Optimal Timing for the Rescue Cannulation Technique

Background/Aims@#Recently, the European Society of Gastrointestinal Endoscopy (ESGE) proposed criteria for “difficult biliary cannulation” during endoscopic retrograde cholangiopancreatography (ERCP). This study aimed to investigate the clinical relevance of the ESGE criteria from the perspective of post-ERCP pancreatitis (PEP). @*Methods@#An ERCP database was prospectively maintained between November 2014 and December 2015 across six teaching hospitals in South Korea. The ESGE criteria (biliary cannulation time, the number of cannulation attempts, and inadvertent pancreatic duct [PD] manipulation) were recorded in this database as well as other technical factors. Logistic regression analysis was used to identify risk factors for PEP. Then, the PEP prediction model was investigated using decision tree analysis. @*Results@#We analyzed 1,067 consecutive patients with naïve papilla. The overall rate of PEP was 6.6%. Multivariate analysis revealed that female sex (odds ratio [OR], 1.860; 95% confidence interval [CI], 1.124 to 3.078), a selective biliary cannulation duration >5 minutes (OR, 3.282; 95% CI, 1.641 to 6.566), and inadvertent PD manipulation (OR, 2.614; 95% CI, 1.480 to 4.617) were significant factors affecting PEP. Decision tree analysis revealed that biliary cannulation time (χ2 =49.857, p5 minutes, and >5 minutes with inadvertent PD manipulation, respectively. @*Conclusions@#Biliary cannulation time and inadvertent PD manipulation could be relevant indicators of PEP, and 5 minutes might be used as a cutoff value for the implementation of the rescue cannulation technique.

Role of Branched-chain Amino Acid Metabolism in Tumor Development and Progression

Branched-chain amino acids (BCAAs), isoleucine, leucine and valine, are essential amino acids with vital roles in protein synthesis and energy production. We reviewed the fundamentals of BCAA metabolism in advanced cancer patients. BCAAs and various catabolic products act as signalling molecules, which activate mechanisms ranging from protein synthesis to insulin secretion. Recently, BCAA metabolism has been suggested to contribute to cancer progression. Of particular interest is the modulation of the mTOR activity by BCAAs. There are likely multiple pathways involved in BCAA metabolism implicated in carcinogenesis. Understanding the mechanism(s) underlying altered BCAAs metabolism will significantly advance the current understanding of nutrient involvement in carcinogenesis and direct future studies to unravel the significance of BCCA metabolites in tumor development and progression.

Removal of a Large, Intractable Common Bile Duct Stone by Direct Peroral Cholangioscopy Using Upper Gastrointestinal Endoscopy and Polypectomy Snare / 대한소화기학회지

ERCP is the standard treatment for common bile duct stones. On the other hand, 10-15% of cases involve intractable common bile duct stones, which cannot be treated by conventional biliary sphincterotomy with a stone retrieval method. Large bile duct stones are typically managed by mechanical lithotripsy and endoscopic papillary large balloon dilatation. Peroral cholangioscopy techniques can be applied if this technique fails. In the present case, a 67-year-old woman had a large common bile duct stone that could not be retracted using the conventional ERCP stone extraction method. The common bile duct stone was eventually removed by direct peroral upper gastrointestinal endoscopy and a polypectomy snare.

Optimal Management of Chemotherapy-related Adverse Events / 대한췌담도학회지

This review article deals with the optimal management of chemotherapy-related adverse events which are the nausea, vomiting, diarrhea, neutropenia, peripheral polyneuropathy. Recent literatures are reviewed and pathogenetic mechanism and management of each of adverse events are summarized. It is not simple but complexed and wide. Most patients could be expected how much they feel the nausea before the chemotherapy. We could prescribe several types of antiemetic agent efficiently. When the patients suffered from the neutropenia after previous chemotherapy, we should closely monitor their blood cell count. And we could help them after giving the granulocyte colony stimulating factor. Diarrhea is one of big troublesome issue related with chemotherapy. We could control the diarrhea by reducing the dose of the chemotherapy and prescribing optimally loperamide. Cisplatin and oxaliplatin could make the patients feel paresthesia and numbness but it’s hard to reverse or prevent even though we use anticonvulsants (carbamazepine, oxcarbazepine), antidepressants (amitriptyline, venlafaxine), amifostine, nimodipine, vitamins and minerals.

Impact of Hospital Volume and the Experience of Endoscopist on Adverse Events Related to Endoscopic Retrograde Cholangiopancreatography:A Prospective Observational Study

Background/Aims@#Few studies have addressed the relationship between the occurrence of adverse events (AEs) in endoscopic retrograde cholangiopancreatography (ERCP) and hospital case volume or endoscopist’s experience with inconsistent results. The aim of our study was to investigate the impact of hospital case volume and endoscopist’s experience on the AEs associated with ERCP and to analyze patient- and procedure-related risk factors for post-ERCP AEs. @*Methods@#From January 2015 to December 2015, we prospectively enrolled patients with naïve papilla who underwent ERCP at six centers. Patient- and procedure-related variables were recorded on data collection sheets at the time of and after ERCP. @*Results@#A total of 1,191 patients (median age, 71 years) were consecutively enrolled. The overall success rate of biliary cannulation was 96.6%. Overall, 244 patients (20.5%) experienced post-ERCP AEs, including pancreatitis (9.0%), bleeding (11.8%), perforation (0.4%), cholangitis (1.2%), and others (0.9%). While post-ERCP pancreatitis (PEP) was more common when the procedure was performed by less experienced endoscopists, bleeding was more common in high-volume centers and by less experienced endoscopists. Multivariate analysis showed that a less experience in ERCP was significantly associated with PEP (odds ratio [OR], 1.630; 95% confidence interval [CI], 1.050 to 2.531; p=0.030) and post-ERCP bleeding (OR, 1.439; 95% CI, 1.003 to 2.062; p=0.048). @*Conclusions@#Our study demonstrated that overall AEs following ERCP were associated with the experience of the endoscopist. To minimize post-ERCP AEs, rigorous training with a sufficient case volume is required, and treatment strategies should be modified according to the endoscopist’s expertise.

Palliative Measures with Ethanol Gallbladder Ablation and Endobiliary Radiofrequency Ablation Followed by Endoscopic Biliary Stent Placement in an Advanced Case of Common Bile Duct Cancer: A Case Report / 대한소화기학회지

Endobiliary radiofrequency ablation (RFA) is a procedure performed widely to induce locoregional tumor control by the transfer of thermal energy to the lesion and subsequent tumor necrosis. A 72-year-old male with a prior history of acute calculous cholangitis and perforated cholecystitis was admitted to the Kyungpook National University Hospital complaining of fever and nausea. He had an indwelling percutaneous transhepatic gallbladder drainage (PTGBD) catheter from the previous episode of perforated cholecystitis. An abdominal CT scan showed marked dilation of both the intrahepatic and extrahepatic bile ducts. Common bile duct cancer was confirmed histologically after an endobiliary biopsy. A surgical resection was considered to be the initial treatment option. During open surgery, multiple metastatic nodules were present in the small bowel mesentery and anterior abdominal wall. Resection of the tumor was not feasible, so endobiliary RFA was performed prior to biliary stenting. Cholecystectomy was required for the removal of the PTGBD catheter, but the surgical procedure could not be performed due to a cystic ductal invasion of the tumor. Instead, chemical ablation of the gallbladder (GB) with pure ethanol was performed to breakdown the GB mucosa. Palliative treatment for a biliary obstruction was achieved successfully using these procedures. In addition, a PTGBD catheter was removed successfully without significant side effects. As a result, an improvement in the patient's quality of life was accomplished.

Quality of information on the Internet for Korean patients with inflammatory bowel disease

BACKGROUND/AIMS@#The Internet is the main resource for health-related information. The incidence of inflammatory bowel disease (IBD) is rapidly increasing in Asian countries. However, the quality of websites for IBD available in this region has not been evaluated. We aimed to evaluate the quality of the information on IBD obtained from Korean websites.@*METHODS@#Using the terms “Crohn’s disease” or “ulcerative colitis,” websites were selected from those obtained with the three most renowned search engines in Korea; 60 websites from the results of each engine were chosen. The websites were classified into institutional, commercial, charitable, supportive, or alternative medicine types according to the characteristics of each site. The websites were evaluated regarding content quality using the validated DISCERN instrument and the Journal of the American Medical Association benchmarks.@*RESULTS@#The median score of all the websites according to the DISCERN instrument was 32 (interquartile range, 25 to 47) out of 80, indicating an insufficient overall quality of information. The alternative medicine sites scored the lowest, whereas the institutional sites scored the highest (p < 0.05). The quality of information was significantly different among the search engines (p = 0.028). The rank of appearance in the Google search result did not correlate with the quality level of the information.@*CONCLUSIONS@#The quality of information on the Internet regarding IBD varied according to the website type and search engine. Accreditation and quality assurance systems should be implemented for websites to ensure that the public and patients obtain accurate information on IBD.

Nutritional Support for Patients with Pancreatic Cancer / 대한소화기학회지

Pancreatic cancer is the ninth common malignancy in South Korea. It has a dismal prognosis with a 5-year overall survival rate of less than 10%, and pancreatic cancer is associated with cancer cachexia, which is defined as the loss of muscle mass that is not reversible by conventional nutritional support. Cachexia is noted in over 85% of all pancreatic cancer patients and it is strongly related with the disease’s mortality. Nearly 30% of pancreatic cancer deaths are due to cachexia rather than being due to the tumor burden. Therefore, it is crucial to discover the mechanisms behind the development of muscle wasting in pancreatic cancer patients and find novel therapeutics for targeting cachexia. This review deals with the current understanding about the development of cachexia and nutritional support in those patients suffering with pancreatic cancer.