Postoperative Prognostic Predictors of Bile Duct Cancers: Clinical Analysis and Immunoassays of Tissue Microarrays

Background/Aims@#Cholangiocarcinoma frequently recurs even after curative resection. Expression levels of proteins such as epidermal growth factor receptor (EGFR), Snail, epithelial cadherin (E-cadherin), and interleukin-6 (IL-6) examined by immunohistochemistry have been studied as potential prognostic factors for cholangiocarcinoma. The aim of this study was to investigate significant factors affecting the prognosis of resectable cholangiocarcinoma. @*Methods@#Ninety-one patients who underwent surgical resection at Samsung Medical Center for cholangiocarcinoma from 1995 to 2013 were included in this study. Expression levels of Ecadherin, Snail, IL-6, membranous EGFR, and cytoplasmic EGFR were analyzed by immunohistochemistry using tissue microarray blocks made from surgical specimens. @*Results@#Patients with high levels of membranous EGFR in tissue microarrays had significantly shorter overall survival (OS) and disease-free survival (DFS): high membranous EGFR (score 0–2) 38.0 months versus low membranous EGFR (score 3) 14.4 months (p=0.008) and high membranous EGFR (score 0–2) 23.2 months versus low membranous EGFR (score 3) 6.1 months (p=0.004), respectively. On the other hand, E-cadherin, Snail, cytoplasmic EGFR, and IL-6 did not show significant association with OS or DFS. Patients with distant metastasis had significantly higher IL-6 levels than those with locoregional recurrence (p=0.01). @*Conclusions@#This study showed that overexpression of membranous EGFR was significantly associated with shorter OS and DFS in surgically resected bile duct cancer patients. In addition, higher IL-6 expression was a predictive marker for recurrence in cholangiocarcinoma patients with distant organ metastasis after surgical resection.

Intrahepatic Cholangiocarcinoma Arising from Biliary Hamartomas in Patients with Recurrent Acute Cholangitis: A Case Report and Literature Review / 대한소화기학회지

Biliary hamartomas are tumor-like malformations of the liver. Biliary hamartomas are a type of fibrocystic disorder originating from ductal plate malformation and are typically considered benign, but with the risk of malignant transformation. In this case report, we present a rare occurrence of intrahepatic cholangiocarcinoma (ICC) that developed from biliary hamartomas, along with a literature review. A 76-year-old man with a diagnosis of biliary hamartomas had a history of recurrent cholangitis for 12 years, necessitating cholecystectomy, ERCP, and repeated antibiotic treatments. During his last episode, imaging studies revealed a hypervascular infiltrative mass in the right posterior liver segment. A liver biopsy confirmed adenocarcinoma and subsequent surgical pathology revealed ICC originating from biliary hamartomas. Chronic inflammation in the bile duct associated with biliary hamartomas may serve as a potential trigger for malignant transformation, as observed in this case. Therefore, close surveillance is essential for patients with biliary hamartomas presenting with infectious complications.

Primary Pancreatic Candidiasis Mimicking Pancreatic Cancer in an Immunocompetent Patient / 대한소화기학회지

Pancreatic candidiasis can develop in patients with acute pancreatitis, compromised immune responses, or iatrogenic intervention. This paper reports a case of pancreatic candidiasis presenting as a solid pancreatic mass in a patient without the risk factors. A previously healthy 37-year-old man visited the emergency department with left flank pain. Abdominal CT revealed a 5 cm, irregular heterogeneous enhancing mass accompanied by a left adrenal mass. Positron emission tomography-computed tomography and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) could not discriminate pancreatic cancer from infectious disease. A laparoscopic exploration was performed for an accurate diagnosis. After distal pancreatectomy with splenectomy and left adrenalectomy, pancreatic candidiasis and adrenal cortical adenoma were diagnosed based on the pathology findings. His condition improved after the treatment with fluconazole. This paper reports a case of primary pancreatic candidiasis mimicking pancreatic cancer in an immunocompetent patient with a review of the relevant literature.

Esophageal Stricture Caused by the Ingestion of Undissolved Picosulfate Powder

Picosulfate solution is widely used as a small volume bowel cleansing agent and is considered to be effective and relatively safe. A case of a 75-year-old woman ingested picosulfate powder and drank a small volume of water, subsequently experienced severe burning pain in the chest. Endoscopy was performed and showed a submucosal hemorrhage and exudative ulcers at the mid to lower esophagus. At 2 weeks, her symptoms improved with conservative treatment. However, liquid food dysphagia developed 11 weeks after ingestion. A follow-up endoscopy revealed multiple esophageal strictures, which were treated with a fully covered metal stent and esophageal balloon dilation. Consequently, the esophageal strictures improved after one year. As this case demonstrates, detailed information about picosulfate powder ingestion after dissolving it in more than 200 mL of water should be presented to patients to avoid esophageal injury.

Papillary Cannulation Facilitated by Submucosal Saline Injection into an Intradiverticular Papilla

Endoscopic retrograde cholangiopancreatography (ERCP) of the intradiverticular papilla with its invisible orifice remains challenging. Several techniques have been introduced to evert the papillary opening to facilitate cannulation. A 79-year-old woman with bile duct stones underwent ERCP, which revealed that the papilla was located inside a large diverticulum and tended to rotate inward with a trial of papillary cannulation. Submucosal papillary injection of 3 cc of normal saline was performed at 3 and 9 o’clock. Eversion and fixation of a papilla in the diverticulum with this technique allowed selective cannulation of the biliary tree. Stones were retrieved after endoscopic papillary balloon dilation without complications. She had an uneventful post-procedural course. Our findings suggest that submucosal saline injection technique is safe and effective for selective cannulation and can be recommended when cannulation is very difficult because of an intradiverticular papilla.

Importance of a Diversity Committee in Advancing the Korean Society of Gastroenterology: A Survey Analysis / 대한소화기학회지

BACKGROUND/AIMS: The numbers of women, young doctors, and foreigners in the medical field have increased continuously. On the other hand, the environment for these minority groups has not improved, particularly in Eastern countries. The authors aimed to increase the awareness of the importance of a Diversity Committee in the Korean Society of Gastroenterology (KSG) by an analysis of a survey.METHODS: From January to February in 2019, a survey was conducted on physicians and a few medical students by googling. The questionnaire consisted of the target doctors of the Diversity Committee, purpose, specific activities, and expected effects of Diversity Committee to the KSG. The participants requested to respond with yes/no or a 5-point scale.RESULTS: A total of 202 participants completed the questionnaire, and 93.5% (189/202) were medical specialists. The proportion of males was 61.9% (125/202), and 39.6% (80/202) and 36.1% (73/202) participants were in their 30s and 40s, respectively. A total of 174 participants (86.1%) agreed with the necessity of a Diversity Committee, and 180 participants (89.1%) answered this committee would help advance the KSG with significant differences between males and females (80.8% vs. 94.8%, p=0.006; 84.8% vs. 96.1%, p=0.011). Similarly, there were significant differences in the responses according to sex in most questions.CONCLUSIONS: Most participants of the survey expected a contribution of the Diversity Committee to the advancement of the KSG. On the other hand, in most of the priorities of the target, purpose, specific activities, and expected effects of the Diversity Committee, there was a difference in the perceptions between males and females. Therefore, continuous efforts are needed to reduce the differences within the KSG.

Pneumoperitoneum after Endoscopic Duodenal Stent Insertion in a Patient with Percutaneous Transhepatic Biliary Drainage and Biliary Stent: A Case Report

Early removal of a percutaneous transhepatic biliary drainage (PTBD) tube commonly causes pneumoperitoneum. However, we encountered a patient who developed pneumoperitoneum even with an indwelling PTBD tube. An 84-year-old man was admitted with type III combined duodenal and biliary obstruction secondary to metastatic bladder cancer. A biliary stent was placed using a percutaneous approach, and a duodenal stent was placed endoscopically. A large amount of subphrenic free air was detected after the procedures. Laboratory tests indicated intestinal perforation; however, peritoneal signs were absent. The patient was treated conservatively using an indwelling Levin tube. Seven days later, the massive amount of subphrenic free air disappeared. Follow-up tubography revealed unrestricted bile flow into the small intestine, and the PTBD tube was removed. Prolonged endoscopic procedures in patients with a PTBD tract communicating with the gastrointestinal tract can precipitate pneumoperitoneum. Clinicians should be careful to avoid misdiagnosing this condition as intestinal perforation.

Practice of Endoscopic Retrograde Cholangiopancreatography in Korea: Results from a National Survey / 대한췌담도학회지

BACKGROUND/AIMS: The aim of this study is to describe the outcome of the national survey and to determine the endoscopic retrograde cholangiopancreatography (ERCP) quality in Korea by comparing with the quality indicators. METHODS: We used the database of Health Insurance Review & Assessment Service and then performed anonymous national survey. RESULTS: Completed questionnaires were returned by 129 of 157 ERCP endoscopists. In Korea, annual ERCP rates have been consistently increased over years. Individual ERCP volume was high (>200 per year) in about half of ERCP endoscopists. Most ERCP endoscopists performed all of level I procedures. However, manometry, cholangiopancreatoscopy, and pancreatic procedures were performed mostly in institutions with high hospital volume. The rate of overall success was more than 90% in most ERCP endoscopists. However, the rate of precut sphincterotomy was high in more than a fourth of ERCP endoscopists. Twelve ERCP endoscopists experienced post-ERCP mortality within recent 1 year. ERCP training and radiation protection during ERCP did not meet the standard of quality indicators especially in institutions with low or moderate hospital volume. CONCLUSIONS: Technical issues during ERCP procedures in Korea fulfill the standard of quality indicators. However, a great effort is needed to improve issues about ERCP training and radiation protection.

Sex and Gender Medicine in Pancreatobiliary Diseases / 대한췌담도학회지

Sex and gender medicine investigates the impact of sex and gender differences on normal conditions, pathogenesis, and clinical features of diseases. By considering sex and gender differences during diagnosis, treatment and prevention, a person can receive the best individualized treatment based on scientific evidence. In this review, sex and gender differences in the field of pancreatobiliary diseases are described regarding gallstones, acute cholecystitis, acute and chronic pancreatitis, and cancers of the pancreas and biliary tract. In addition, recent policy on clinical and preclinical research which states that sex and gender analysis should be included during planning, conducting, and interpretation of the researches and websites containing resources about sex and gender medicine are introduced. This review highlights the importance of considering sex and gender aspect in research, clinics, and medical education.

Clonorchis sinensis Infection Presenting as Acute Cholangitis and Acute Cholecystitis / 대한췌담도학회지

A 59-year-old woman presented with abdominal pain. Abdominal computerized tomography was suggestive of biliary stones. During endoscopic retrograde cholangiopancreatography, adult worms resembling Clonorchis sinensis (C. sinensis) were drained. Eggs were detected in stool using the formalin-ether concentration method and C. sinensis-specific antibody was detected in the serum. A diagnosis of C. sinensis infection was made. The symptoms of the patient gradually resolved after treatment with anti-parasite medication. The patient lived in a non-endemic region for C. sinensis infection and had no history of intake of raw or undercooked freshwater fishes. South Korea is one of the endemic countries for C. sinensis infection and people can be infected via indirect routes of transmission such as cooking utensils. Therefore, the possibility of C. sinensis infection should be considered in patients presenting with biliary diseases in South Korea. We describe the clinical findings of this case with a review of literature.

Importance of a Diversity Committee in Advancing the Korean Society of Gastroenterology: A Survey Analysis / 대한소화기병학회잡지

BACKGROUND/AIMS: The numbers of women, young doctors, and foreigners in the medical field have increased continuously. On the other hand, the environment for these minority groups has not improved, particularly in Eastern countries. The authors aimed to increase the awareness of the importance of a Diversity Committee in the Korean Society of Gastroenterology (KSG) by an analysis of a survey. METHODS: From January to February in 2019, a survey was conducted on physicians and a few medical students by googling. The questionnaire consisted of the target doctors of the Diversity Committee, purpose, specific activities, and expected effects of Diversity Committee to the KSG. The participants requested to respond with yes/no or a 5-point scale. RESULTS: A total of 202 participants completed the questionnaire, and 93.5% (189/202) were medical specialists. The proportion of males was 61.9% (125/202), and 39.6% (80/202) and 36.1% (73/202) participants were in their 30s and 40s, respectively. A total of 174 participants (86.1%) agreed with the necessity of a Diversity Committee, and 180 participants (89.1%) answered this committee would help advance the KSG with significant differences between males and females (80.8% vs. 94.8%, p=0.006; 84.8% vs. 96.1%, p=0.011). Similarly, there were significant differences in the responses according to sex in most questions. CONCLUSIONS: Most participants of the survey expected a contribution of the Diversity Committee to the advancement of the KSG. On the other hand, in most of the priorities of the target, purpose, specific activities, and expected effects of the Diversity Committee, there was a difference in the perceptions between males and females. Therefore, continuous efforts are needed to reduce the differences within the KSG.

Comparison of liquid-based cytology (CellPrepPlus) and conventional smears in pancreaticobiliary disease

BACKGROUND/AIMS: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and brushing cytology are used worldwide to diagnose pancreatic and biliary malignant tumors. Liquid-based cytology (LBC) has been developed and it is currently used to overcome the limitations of conventional smears (CS). In this study, the authors aimed to compare the diagnostic value of the CellPrepPlus (CP; Biodyne) LBC method with CS in samples obtained using EUS-FNA and brushing cytology. METHODS: This study prospectively enrolled 75 patients with pancreatic or biliary lesions from June 2012 to October 2013. For cytological analyses, including inadequate specimens, benign and atypical were further classified into benign, and suspicious and malignant were subcategorized as malignant. Sensitivity, specificity, accuracy, and positive predictive values (PPV) and negative predictive values (NPV) were evaluated. RESULTS: In the EUS-FNA based cytological analysis of pancreatic specimens, CP had a sensitivity of 60.7%; specificity, 100%; accuracy, 77.1%; PPV, 100%; and NPV, 64.5%. CS had a sensitivity of 85.7%; specificity, 100%; accuracy, 91.7%; PPV, 100%; and NPV, 83.3%. In the brushing cytology based analysis of biliary specimens, CP had sensitivity of 53.1%; specificity, 100%; accuracy, 54.5%; PPV, 100%; and NPV, 6.3%. CS had a sensitivity of 78.1%; specificity, 100%; accuracy, 78.8%; PPV, 100%; and NPV, 12.5%. CONCLUSIONS: Our study found that CP had a lower sensitivity because of low cellularity compared with CS. Therefore, CP (LBC) has a lower diagnostic accuracy for pancreatic EUS-FNA based and biliary brush cytology based analyses compared with CS.

Validation of Administrative Big Database for Colorectal Cancer Searched by International Classification of Disease 10th Codes in Korean: A Retrospective Big-cohort Study

BACKGROUND: As the number of big-cohort studies increases, validation becomes increasingly more important. We aimed to validate administrative database categorized as colorectal cancer (CRC) by the International Classification of Disease (ICD) 10th code. METHODS: Big-cohort was collected from Clinical Data Warehouse using ICD 10th codes from May 1, 2003 to November 30, 2016 at Seoul National University Bundang Hospital. The patients in the study group had been diagnosed with cancer and were recorded in the ICD 10th code of CRC by the National Health Insurance Service. Subjects with codes of inflammatory bowel disease or tuberculosis colitis were selected for the control group. For the accuracy of registered CRC codes (C18–21), the chart, imaging results, and pathologic findings were examined by two reviewers. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for CRC were calculated. RESULTS: A total of 6,780 subjects with CRC and 1,899 control subjects were enrolled. Of these patients, 22 subjects did not have evidence of CRC by colonoscopy, computed tomography, magnetic resonance imaging, or positron emission tomography. The sensitivity and specificity of hospitalization data for identifying CRC were 100.00% and 98.86%, respectively. PPV and NPV were 99.68% and 100.00%, respectively. CONCLUSIONS: The big-cohort database using the ICD 10th code for CRC appears to be accurate.

Predictors of Malignancies in Patients with Inconclusive or Negative Results of Endoscopic Ultrasound-guided Fine-needle Aspiration for Solid Pancreatic Masses / 대한소화기학회지

BACKGROUND/AIMS: This study analyzed the diagnostic accuracy of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for pancreatic solid masses in patients with or without chronic pancreatitis as well as the clinical parameters relevant to a malignancy when EUS-FNA was negative or inconclusive. METHODS: A total of 97 patients, who underwent EUS-FNA for solid pancreatic masses over 2 years at a single institution, were evaluated. All patients underwent EUS-FNA for 3-5 passes with 22 or 25 G needles without an on-site cytopathologist. The final diagnosis was obtained by surgery or compatible clinical outcomes for a more than 12 month follow-up. The diagnostic yields in the patients with or without chronic pancreatitis were compared and the histories and laboratory data relevant to pancreatic ductal adenocarcinoma (PDAC) or pseudo-tumor were analyzed. RESULTS: The final diagnoses were adenocarcinoma in 88 patients (90.7%) and inflammatory pseudo-tumor in 9 (9.3%). The results of EUS-FNA were adenocarcinoma (74), suspicious (7), atypical (5), negative (10), and inadequate specimen (1). The diagnostic accuracies were 76.9% and 91.6% in patients with or without chronic pancreatitis, respectively. Among the 23 cases with non-diagnostic results of EUS-FNA, PDAC was finally diagnosed in 5 out of 7 suspicious, 3 out of 5 atypical, and 5 out of 10 negative cytology cases. The clinical parameters related to a pseudo-tumor were a history of alcohol consumption and pancreatitis, and normal alkaline phosphatase levels. CONCLUSIONS: The diagnostic accuracy of pancreatic masses in the background of chronic pancreatitis was low. When EUS-FNA produced inconclusive results, the histories of alcohol consumption, pancreatitis, and serum levels of alkaline phosphatase are useful for making a final diagnosis.

Experiences with a graduate course on sex and gender medicine in Korea / 보건의료교육평가

No abstract available.

Female Gender is a Poor Predictive Factor of Functional Dyspepsia Resolution after Helicobacter pylori Eradication: A Prospective, Multi-center Korean Trial / 대한소화기학회지

BACKGROUND/AIMS: The predictive factors of functional dyspepsia (FD) remain controversial. Therefore, we sought to investigate symptom responses in FD patients after Helicobacter pylori (H. pylori) eradication and used predictive factor analysis to identify significant factors of FD resolution at one-year after commencing eradication therapy. METHODS: This prospective, multi-center clinical trial was performed on 65 FD patients that met Rome III criteria and had H. pylori infection. Symptom responses and factors that predicted poor response were determined by analysis one year after commencing H. pylori eradication therapy. RESULTS: A total of 63 patients completed the one-year follow-up. When an eradication success group (n=60) and an eradication failure group (n=3) were compared with respect to FD response rate at one year, results were as follows; complete response 73.3% and 0.0%, satisfactory response 1.7% and 0.0%, partial response 10.0% and 33.3%, and refractory response 15.0% and 66.7%, respectively (p=0.013). Univariate analysis showed persistent H. pylori infection (p=0.021), female gender (p=0.025), and medication for FD during the study period (p=0.013) were associated with poor FD response at one year. However, age, smoking, alcohol consumption, and underlying disease were not found to affect response. Finally, multivariate analysis showed that female gender (OR, 4.70; 95% CI, 1.17-18.88) was the sole independent risk factor of poor FD response at one year after commencing H. pylori eradication therapy. CONCLUSIONS: Female gender was found to predict poor response in FD patients despite H. pylori eradication. Furthermore, successful H. pylori eradication appears to be associated with FD improvement, but the number of non-eradicated patients was too small to conclude.

Two Cases of Plug or Stone in Remnant Intrapancreatic Choledochal Cysts Treated with Endoscopic Retrograde Cholangiopancreatography

Incomplete resection of choledochal cysts (CCs) that extend deep into the pancreas can lead to protein plug or stone formation, pancreatitis, and cholangiocarcinoma. We encountered two cases of choledocholithiasis in remnant intrapancreatic CCs, in which the patients exhibited symptoms after 3 and 21 years of cyst excision. A 21-year-old woman who had undergone excision of a CC, as a neonate, presented with epigastric pain. Abdominal computed tomography (CT) revealed stones inside the remnant pancreatic cyst, which were removed by endoscopic retrograde cholangiopancreatography (ERCP), and her symptoms improved. A 33-year-old woman, who underwent cyst excision 3 years ago, presented with pancreatitis. Abdominal CT showed a radiolucent plug inside the remnant pancreatic cyst. The soft, whitish plug was removed by ERCP, and the pancreatitis improved. These cases indicate that plugs and stones in CCs have the same pathogenetic mechanism, and their form depends on the time since the incomplete excision surgery.

Post-Endoscopic Sphincterotomy Bleeding: Strategic Approach with Multiple Endoscopic Arms / 대한췌담도학회지

Endoscopic retrograde cholangiopancreatography (ERCP) is an essential method for diagnosis and treatment of various pancreatobiliary diseases and endoscopic sphincterotomy (EST) is the gateway to complete ERCP. Although techniques and instruments for EST have improved, bleeding is still the most common complication. Treatment of immediate post-EST bleeding is important because blood can interfere with subsequent procedures. Additionally, endoscopists should be cautious about delayed bleeding may cause hemobilia, cholangitis, and hemodynamic shock. Most cases of post-EST bleedings will stop spontaneously, however, endoscopic management is necessary in case of clinically significant and persistent bleeding. Various endoscopic methods including epinephrine or fibrin glue injection, electrocoagulation, hemoclipping and band ligation et al can be used through a sideviewing or forward-viewing endoscope similar to those used in hemostasis of peptic ulcer bleeding. Endoscopists who perform ERCP should use various methods of endoscopic hemostasis strategically.

Post-Endoscopic Sphincterotomy Bleeding: Strategic Approach with Multiple Endoscopic Arms / 대한췌담도학회지

Endoscopic retrograde cholangiopancreatography (ERCP) is an essential method for diagnosis and treatment of various pancreatobiliary diseases and endoscopic sphincterotomy (EST) is the gateway to complete ERCP. Although techniques and instruments for EST have improved, bleeding is still the most common complication. Treatment of immediate post-EST bleeding is important because blood can interfere with subsequent procedures. Additionally, endoscopists should be cautious about delayed bleeding may cause hemobilia, cholangitis, and hemodynamic shock. Most cases of post-EST bleedings will stop spontaneously, however, endoscopic management is necessary in case of clinically significant and persistent bleeding. Various endoscopic methods including epinephrine or fibrin glue injection, electrocoagulation, hemoclipping and band ligation et al can be used through a sideviewing or forward-viewing endoscope similar to those used in hemostasis of peptic ulcer bleeding. Endoscopists who perform ERCP should use various methods of endoscopic hemostasis strategically.

Diagnostic and prognostic value of preoperative ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography for colorectal cancer: comparison with conventional computed tomography

BACKGROUND/AIMS: ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) has been used for preoperative staging of colorectal cancer (CRC). However, the diagnostic accuracy of FDG-PET/CT for detection of lymph node or distant metastasis and its prognostic role have not been well established. We therefore evaluated the diagnostic and prognostic value of FDG-PET/CT in comparison with conventional CT for CRC. METHODS: We investigated 220 patients who underwent preoperative FDG-PET/CT and CT, followed by curative surgery for CRC. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of FDG-PET/CT and CT for detection of lymph node metastasis and distant metastasis were evaluated. In addition, we assessed the findings of FDG-PET/CT and CT according to outcomes, including cancer recurrence and cancer-related death, for evaluation of prognostic value. RESULTS: For detection of lymph node metastasis, FDG-PET/CT had a sensitivity of 44%, a specificity of 84%, and an accuracy of 67%, compared with 59%, 65%, and 62%, respectively, for CT (P=0.029, P=0.000, and P=0.022). For distant metastasis, FDG-PET/CT had a sensitivity of 79%, a specificity of 94%, and an accuracy of 93%, compared with 79%, 87%, and 86%, respectively, for CT (P=1.000, P=0.004, and P=0.037). In addition, positive findings of lymph node metastasis and distant metastasis on FDG-PET/CT were associated significantly with cancer recurrence or cancer-related death (P=0.009, P=0.001, respectively). CONCLUSIONS: Preoperative FDG-PET/CT had a higher specificity and accuracy compared to CT for detection of lymph node metastasis and distant metastasis of CRC. In addition, FDG-PET/CT could be a valuable prognostic tool for CRC.