Impact of the Supra-papilla Method on Patency in Distal Malignant Biliary Obstruction: A Multicenter Randomized Controlled Trial.

BACKGROUND: /aims: Placement of a self-expandable metal stent (SEMS) across the duodenal major papilla carries a risk of duodenobiliary reflux (DBR). The supra-papilla method of stenting may reduce DBR and improve stent patency compared to the trans-papilla method. This study aimed to compare the clinical outcomes between the supra-papilla and trans-papilla methods for distal malignant biliary obstruction (DMBO). METHODS: Between January 2021 and January 2023, consecutive patients with DMBO from six centers in Korea were randomly assigned to either the supra-papilla or trans-papilla method arm in a 1:1 ratio. The primary outcome was the duration of stent patency, and secondary outcomes included the cause of stent dysfunction, adverse events, and overall survival rate. RESULTS: A total of 84 patients were equally assigned to each group. The most common cause of DMBO was pancreatic cancer (n=50, 59.5%), followed by bile duct (n=20, 23.8%), gallbladder (n=11, 13.1%), and other cancers (n=3, 3.6%). Stent patency was significantly longer in the supra-papilla group (median [95% confidence interval], 369 [289-497] vs. 154 [78-361] days; P < 0.01). Development of DBR was significantly lower in the supra-papilla group (9.4% vs 40.8%, P < 0.01). Adverse events and overall survival rate were not significantly different between the two groups. CONCLUSIONS: The placement of SEMS using the supra-papilla method resulted in a significantly longer duration of stent patency. It is advisable to place the SEMS using the supra-papilla method in DMBO. Further studies with a larger number of patients are required to validate the benefits of the supra-papilla method.

Development of artificial intelligence system for quality control of photo documentation in esophagogastroduodenoscopy.

BACKGROUND: Esophagogastroduodenoscopy (EGD) is generally a safe procedure, but adverse events often occur. This highlights the necessity of the quality control of EGD. Complete visualization and photo documentation of upper gastrointestinal (UGI) tracts are important measures in quality control of EGD. To evaluate these measures in large scale, we developed an AI-driven quality control system for EGD through convolutional neural networks (CNNs) using archived endoscopic images. METHODS: We retrospectively collected and labeled images from 250 EGD procedures, a total of 2599 images from eight locations of the UGI tract, using the European Society of Gastrointestinal Endoscopy (ESGE) photo documentation methods. The label confirmed by five experts was considered the gold standard. We developed a CNN model for multi-class classification of EGD images to one of the eight locations and binary classification of each EGD procedure based on its completeness. RESULTS: Our CNN model successfully classified the EGD images into one of the eight regions of UGI tracts with 97.58% accuracy, 97.42% sensitivity, 99.66% specificity, 97.50% positive predictive value (PPV), and 99.66% negative predictive value (NPV). Our model classified the completeness of EGD with 89.20% accuracy, 89.20% sensitivity, 100.00% specificity, 100.00% PPV, and 64.94% NPV. We analyzed the credibility of our model using a probability heatmap. CONCLUSIONS: We constructed a CNN model that could be used in the quality control of photo documentation in EGD. Our model needs further validation with a large dataset, and we expect our model to help both endoscopists and patients by improving the quality of EGD procedures.

Low insertion of cystic duct increases risk for common bile duct stone recurrence.

BACKGROUND: Common bile duct (CBD) stone is one of the most frequent biliary diseases. Recurrence after the complete removal of CBD stones is high, and we aim to evaluate the rate and risk factors for symptomatic recurrence of CBD stones after endoscopic retrograde cholangiopancreatography (ERCP). METHODS: We, retrospectively, reviewed the database of patients who underwent ERCP for CBD stones and subsequent cholecystectomy between January 2015 and December 2017 at a tertiary hospital. The recurrence of symptomatic CBD stones was defined as the presence of a CBD stone with related symptoms at least 6 months after the ERCP procedure. The primary outcomes were recurrence of symptomatic CBD stones and its risk factors. RESULTS: Among the 362 enrolled patients, 60 experienced a symptomatic recurrence of CBD stones between 6 months and 5 years after the procedure. The mean duration of follow-up was 32.3 ± 8.1 months. The patients with recurrences were older and had a longer follow-up duration. Low insertion of the cystic duct (HR = 2.893, p = 0.016), distal CBD angulation (HR = 1.015, p = 0.034), maximum CBD diameter (HR = 1.070, p = 0.012), number of ERCP sessions at first admission (HR = 1.558, p = 0.032), and cannulation time (HR = 1.030, p = 0.008) were the independent risk factors for symptomatic recurrent CBD stones. CONCLUSIONS: Patients with risk factors, especially those with low cystic duct insertion, are more prone to symptomatic recurrent CBD stones and should be followed more carefully.

Association of Microbial Dysbiosis with Gallbladder Diseases Identified by Bile Microbiome Profiling.

BACKGROUND: Cholecystitis is an important risk factor for gallbladder cancer, but the bile microbiome and its association with gallbladder disease has not been investigated fully. We aimed to analyze the bile microbiome in normal conditions, chronic cholecystitis, and gallbladder cancer, and to identify candidate bacteria that play an important role in gallbladder carcinogenesis. METHODS: We performed metagenome sequencing on bile samples of 10 healthy individuals, 10 patients with chronic cholecystitis, and 5 patients with gallbladder cancer, and compared the clinical, radiological, and pathological characteristics of the participants. RESULTS: No significant bacterial signal was identified in the normal bile. The predominant dysbiotic bacteria in both chronic cholecystitis and gallbladder cancer were those belonging to the Enterobacteriaceae family. Klebsiella increased significantly in the order of normal, chronic cholecystitis, and gallbladder cancer. Patients with chronic cholecystitis and dysbiotic microbiome patterns had larger gallstones and showed marked epithelial atypia, which are considered as precancerous conditions. CONCLUSION: We investigated the bile microbiome in normal, chronic cholecystitis, and gallbladder cancer. We suggest possible roles of Enterobacteriaceae, including Klebsiella, in gallbladder carcinogenesis. Our findings reveal a possible link between a dysbiotic bile microbiome and the development of chronic calculous cholecystitis and gallbladder cancer.

Differential Impact of Serum 25-Hydroxyvitamin D3 Levels on the Prognosis of Patients with Liver Cirrhosis According to MELD and Child-Pugh Scores.

BACKGROUND: Prognosis of patients with diverse chronic diseases is reportedly associated with 25-hydroxyvitamin D levels. In this study, we investigated the potential role of 25-hydroxyvitamin D3 (25[OH]D3) levels in improving the predictive power of conventional prognostic models for patients with liver cirrhosis. METHODS: We investigated clinical findings, including serum 25(OH)D3 levels at admission, of 155 patients with cirrhosis who were followed up for a median of 16.9 months. RESULTS: Median 25(OH)D3 levels were significantly different among patients exhibiting Child-Pugh grades A, B, and C. Mortality, including urgent transplantation, was significantly associated with 25(OH)D3 levels in univariate analysis. Severe vitamin-D deficiency (serum 25[OH]D3 level < 5.0 ng/mL) was significantly related to increased mortality, even after adjusting for Child-Pugh and Model for End-stage Liver Disease (MELD) scores. In particular, the presence of severe vitamin D deficiency clearly defined a subgroup with significantly poorer survival among patients with Child-Pugh scores of 5-10 or MELD scores ≤ 20. A new combination model of MELD score and severe vitamin D deficiency showed significantly more accurate predictive power for short- and long-term mortality than MELD scores alone. Additionally, serum 25(OH)D3 levels and new model scores were significantly associated with the development of spontaneous bacterial peritonitis, overt encephalopathy, and acute kidney injury. CONCLUSION: Serum 25(OH)D3 level is an independent prognostic factor for patients with liver cirrhosis and has a differential impact on disease outcomes according to MELD and Child-Pugh scores.

Two-Photon Probe for TNF-α. Assessment of the Transmembrane TNF-α Level in Human Colon Tissue by Two-Photon Microscopy.

We developed Pyr1-infliximab: a two-photon probe for TNF-α. Pyr1-infliximab showed absorption maxima at 280 and 438 nm and an emission maximum at 610 nm in an aqueous buffer and effective two-photon action cross-section values of (520-2830) × 10-50 cm4s/photon in RAW 264.7 cells. After this probe was labeled, it was possible to detect Pyr1-infliximab-transmembrane TNF-α complexes in a live cell and to determine the relative proportion of these complexes in human colon tissues. This proportion among healthy, possibly inflamed, and inflamed tissues of patients with ulcerative colitis was found to be 1.0/4.5/10. This probe may find useful applications for selective detection of transmembrane TNF-α in a live cell or tissue, for quantification of inflammation in human colon tissue or of antidrug antibodies in patients who stop responding to anti-TNF therapy, and for monitoring of the response to this therapy.

A novel technique for repositioning a nasobiliary catheter from the mouth to nostril in endoscopic retrograde cholangiopancreatography.

BACKGROUND: Endoscopic nasobiliary drainage (ENBD) is widely used for biliary decompression in patients with biliary disease. However, it is difficult to reposition a nasobiliary catheter from the mouth to nostril. We developed a new device, which has a curved flexible loop and bar-handle, for repositioning of ENBD catheter. The aim of this study was to evaluate the usefulness of the new loop-device for facilitating the repositioning of an ENBD catheter from the mouth to nostril. METHODS: Between January 2015 and December 2017, a comparative observational study was performed to evaluate the time taken for repositioning a nasobiliary catheter during endoscopic retrograde cholangiopancreatography (ERCP) and compare the results of ENBD procedure between the new loop-device and conventional techniques. In the subgroup analysis, we evaluated the occurrence of oral cavity injury and the time taken to transfer ENBD catheter from the mouth to nostril. RESULTS: In all, 145 ENBD procedures were performed using these two techniques. The procedure time was significantly shorter in the new technique group than in the conventional group. (44 s vs. 194 s, p < 0.001). The total success rate of new device technique was 97.3%. No complication, including oral cavity injury, was observed. CONCLUSIONS: The technique using our new loop-device was useful for repositioning a nasobiliary catheter from the mouth to nostril in ERCP. The new device does not require the removal of the mouthpiece before ENBD positioning, which can help perform the ENBD procedure rapidly and avoid the finger injury of endoscopists.

A randomized controlled trial comparing the efficacy of 1-L polyethylene glycol solution with ascorbic acid plus prucalopride versus 2-L polyethylene glycol solution with ascorbic acid for bowel preparation.

OBJECTIVES: Bowel cleansing is a major patient complaint during colonoscopy. Adding laxatives to the bowel preparation is effective in replacing a portion of bowel preparation solution and reducing its volume. Prucalopride is a serotonin receptor agonist that stimulates gastrointestinal motility and provides propulsive force for defecation. This study aimed to compare 1 L polyethylene glycol (PEG) with ascorbic acid (Asc) plus 2 mg prucalopride (1LP/AP) and 2 L PEG with Asc (2LP/A) for colonoscopy preparation with respect to bowel-cleansing quality and side effects. METHODS: A single-center, randomized, prospective study was conducted with 260 outpatients administered either 1LP/AP or 2LP/A. The primary endpoint was bowel preparation quality, which was evaluated using the Boston Bowel Preparation Scale and Aronchick Bowel Preparation Scale, and the secondary endpoints were patient tolerability and acceptability, assessed by a questionnaire-based survey. RESULTS: The adequate bowel preparation rates were 88.5% and 83.1% in the 2LP/A and 1LP/AP groups, respectively, and the efficacy of 1LP/AP was equivalent to the control regimen (p=.216). Other colonoscopic variables including adenoma detection rate were similar in both groups. Patient tolerability and acceptability were not significantly different, but patients in the 1LP/AP group were more willing to repeat the same regimen (p=.039). CONCLUSIONS: Bowel preparation quality with 1LP/AP was equivalent to that with 2LP/A, which did not increase the occurrence of side effects, but it reduced the volume of the solution ingested, and increased patient satisfaction.

Radiation recall gastritis secondary to combination of gemcitabine and erlotinib in pancreatic cancer and response to PPI - a case report.

BACKGROUND: Radiation recall gastritis is rare but can be induced after concurrent chemoradiation for pancreatic cancer. We report a patient with pancreatic cancer who developed radiation-recall gastritis related to a combination of gemcitabine and erlotinib. CASE PRESENTATION: A 54-year-old female with unresectable pancreatic cancer received gemcitabine in combination with radiation therapy followed by chemotherapy with gemcitabine and erlotinib. After completing 2 cycles of chemotherapy, the patient had epigastric pain, nausea, and vomiting. Abdominal computed tomography (CT) scan revealed diffuse wall thickening of the stomach, and esophagogastroduodenoscopy (EGD) showed multiple gastric ulcers. The patient was treated with proton pump inhibitors (PPI) and was continued on maintenance chemotherapy. Two months later, the patient presented with the similar symptoms and persistent gastric ulcers were observed during subsequent EGD. Nevertheless, the patient's symptom had resolved with PPI therapy. Thus, the patient underwent maintenance chemotherapy with gemcitabine and erlotinib for additional 4 cycles. Eventually, follow-up abdominal CT Scan and EGD at 6 months demonstrated resolution of the gastric ulcers. CONCLUSIONS: Physicians should be aware of the possibility of radiation recall gastritis associated with a combination of gemcitabine and erlotinib. Administration of PPIs may mitigate the adverse effects of gemcitabine and erlotinib in the presence of radiation recall gastritis; however further studies are warranted.

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.

Practice guidelines for managing extrahepatic biliary tract cancers.

Backgrounds/Aims: Reported incidence of extrahepatic bile duct cancer is higher in Asians than in Western populations. Korea, in particular, is one of the countries with the highest incidence rates of extrahepatic bile duct cancer in the world. Although research and innovative therapeutic modalities for extrahepatic bile duct cancer are emerging, clinical guidelines are currently unavailable in Korea. The Korean Society of Hepato-Biliary-Pancreatic Surgery in collaboration with related societies (Korean Pancreatic and Biliary Surgery Society, Korean Society of Abdominal Radiology, Korean Society of Medical Oncology, Korean Society of Radiation Oncology, Korean Society of Pathologists, and Korean Society of Nuclear Medicine) decided to establish clinical guideline for extrahepatic bile duct cancer in June 2021. Methods: Contents of the guidelines were developed through subgroup meetings for each key question and a preliminary draft was finalized through a Clinical Guidelines Committee workshop. Results: In November 2021, the finalized draft was presented for public scrutiny during a formal hearing. Conclusions: The extrahepatic guideline committee believed that this guideline could be helpful in the treatment of patients.

[A Systematic Approach to Patients with Elevated Levels of Serum Amylase or Lipase].

Serum amylase and lipase tests are routinely performed in patients presenting with abdominal pain or even during regular health screening. Elevated serum levels of these two enzymes are often encountered in clinical practice. The differential diagnosis is broad and includes acute pancreatitis, chronic pancreatitis, gastrointestinal tract obstruction, malignancies, and other disease conditions. In this article, we review the pathophysiology of elevated amylase and lipase, possible conditions that cause the increase, and diagnostic strategies for such patients. We conclude that a systematic approach to patients with elevated amylase and/or lipase is critical to making an accurate diagnosis and initiating appropriate treatment.

Clinical outcomes of endoscopic papillectomy of ampullary adenoma: A multi-center study.

BACKGROUND: Ampullary adenoma is a rare premalignant lesion, but its incidence is increasing. Endoscopic papillectomy has become the first treatment of choice for ampullary adenomas due to its safety and effectiveness, thereby replacing surgical resection. However, recurrence rates and adverse events after endoscopic papillectomy were reported in up to 30% of cases. AIM: To review the long-term outcomes of endoscopic papillectomy and investigate the factors that affect these outcomes. METHODS: We retrospectively analyzed the data of patients who underwent endoscopic papillectomy for ampullary adenoma at five tertiary hospitals between 2013 and 2020. We evaluated clinical outcomes and their risk factors. The definitions of outcomes were as follow: (1) curative resection: complete endoscopic resection without recurrence; (2) endoscopic success: treatment of ampullary adenoma with endoscopy without surgical intervention; (3) early recurrence: reconfirmed adenoma at the first endoscopic surveillance; and (4) late recurrence: reconfirmed adenoma after the first endoscopic surveillance. RESULTS: A total of 106 patients were included for analysis. Of the included patients, 81 (76.4%) underwent curative resection, 99 (93.4%) had endoscopic success, showing that most patients with non-curative resection were successfully managed with endoscopy. Sixteen patients (15.1%) had piecemeal resection, 22 patients (20.8%) had shown positive/uncertain resection margin, 11 patients (16.1%) had an early recurrence, 13 patients (10.4%) had a late recurrence, and 6 patients (5.7%) had a re-recurrence. In multivariate analysis, a positive/uncertain margin [Odds ratio (OR) = 4.023, P = 0.048] and piecemeal resection (OR = 6.610, P = 0.005) were significant risk factors for early and late recurrence, respectively. Piecemeal resection was also a significant risk factor for non-curative resection (OR = 5.424, P = 0.007). Twenty-six patients experienced adverse events (24.5%). CONCLUSION: Endoscopic papillectomy is a safe and effective treatment for ampullary adenomas. Careful selection and follow-up of patients is mandatory, particularly in cases with positive/uncertain margin and piecemeal resection.

Prediction of the histology of colorectal neoplasm in white light colonoscopic images using deep learning algorithms.

The treatment plan of colorectal neoplasm differs based on histology. Although new endoscopic imaging systems have been developed, there are clear diagnostic thresholds and requirements in using them. To overcome these limitations, we trained convolutional neural networks (CNNs) with endoscopic images and developed a computer-aided diagnostic (CAD) system which predicts the pathologic histology of colorectal adenoma. We retrospectively collected colonoscopic images from two tertiary hospitals and labeled 3400 images into one of 4 classes according to the final histology: normal, low-grade dysplasia, high-grade dysplasia, and adenocarcinoma. We implemented a CAD system based on ensemble learning with three CNN models which transfer the knowledge learned from common digital photography images to the colonoscopic image domain. The deep learning models were trained to classify the colorectal adenoma into these 4 classes. We compared the outcomes of the CNN models to those of two endoscopist groups having different years of experience, and visualized the model predictions using Class Activation Mapping. In our multi-center study, our CNN-CAD system identified the histology of colorectal adenoma with as sensitivity 77.25%, specificity of 92.42%, positive predictive value of 77.16%, negative predictive value of 92.58% averaged over the 4 classes, and mean diagnostic time of 0.12 s per image. Our experiments demonstrate that the CNN-CAD showed a similar performance to that of endoscopic experts and outperformed that of trainees. The model visualization results also showed reasonable regions of interest to explain the classification decisions of CAD systems. We suggest that CNN-CAD system can predict the histology of colorectal adenoma.

Is There Pathological Uniformity between the Periphery and Center of a Gastrointestinal Stromal Tumor?

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors and have some malignant potential. Mitotic count is important for predicting the malignant potential of GISTs. Proper treatment of GISTs requires accurate pathological diagnosis. In general, endoscopic ultrasound-guided fine-needle aspiration and deep biopsy are used for pathological diagnosis of GIST before making decisions about surgery. This study sought to evaluate the pathological uniformity of gastric GISTs for mitotic index of the center and periphery of the GIST. METHODS: We retrospectively reviewed the data of 37 gastric GIST patients who underwent wedge resection at Hanyang University Hospital. We used Armed Forces Institute of Pathology criteria to classify gastric GISTs. To determine the pathological uniformity of gastric GISTs, we compared GIST risk stratification between the center and periphery of GISTs. RESULTS: The mean size of GISTs was 3.56 ± 2.10 cm. Three lesions were located in the antrum, 11 in the fundus, 9 in the cardia, and 14 in the body. The mean age of patients was 58.65 ± 9.44 years; 18 patients were male and 19 were female. Thirty-five patients (94.6%) showed the same level of risk stratification between the center and periphery of gastric GISTs, while two patients (5.4%) presented different levels of risk between the two sites. No significant difference in mitotic count was observed between the two sites (kappa value = 0.863; p = 0.001). CONCLUSIONS: Mitotic index category (either more than five mitoses per high-power field or five or fewer mitoses per high-power field) of GISTs showed good concurrence between the center and periphery.

Effect of histological examination on the diagnosis of pancreatic mass using endoscopic ultrasound fine-needle aspiration.

BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a well-established method for the diagnosis of solid pancreatic lesions. However, the diagnostic yield of EUS-FNA for pancreatic lesions varies at around 70-90%. Samples from EUS-FNA consist of cells and tissues that can be analyzed separately, and the results can be combined for a final diagnosis. OBJECTIVES: To investigate the effect of cytological and histological analysis of EUS-FNA samples on the final diagnosis, and identify factors that may affect the accuracy of the cytological, histological, and overall analysis. MATERIAL AND METHODS: A single-center prospective observational study was conducted at a tertiary university hospital from July 2018 to June 2019. Patients who underwent EUS-FNA for pancreatic solid lesions with a 22-gauge EUS-FNA needle were included in our study. Liquid-based cytological analysis of the specimen and histological analysis of the whitish core were performed, and factors that affected the diagnostic accuracy of each analysis were evaluated. RESULTS: In 63 EUS-FNA samples, the overall diagnostic accuracy was 87.3%, which was significantly higher than the cytological accuracy of 73.8% (p = 0.031) and the histological accuracy of 69.8% (p = 0.001). Factors that affected the results differed in each group: 1) cytological analysis: size, location, and approach method; 2) histological analysis: specimen weight; and 3) overall analysis: size, location, and approach method. CONCLUSIONS: Histologic evaluation of core material obtained from EUS-FNA improved diagnostic accuracy, and factors that affected each result were analyzed. Further studies with prospective randomized trials are recommended to support our data.

Computer-Aided Diagonosis for Colorectal Cancer using Deep Learning with Visual Explanations.

Detection, diagnosis, and removal of colorectal neoplasms are well-accepted colorectal cancer prevention methods. Although promising endoscopic imaging techniques including narrow-band imaging have been developed, these techniques are operator-dependent and interpretations of the results may vary. To overcome these limitations, we applied deep learning to develop a computer-aided diagnostic (CAD) system of colorectal adenoma. We collected and divided 3000 colonoscopic images into 4 categories according to the final pathology, normal, low-grade dysplasia, high-grade dysplasia, and adenocarcinoma. We implemented three convolutional neural networks (CNNs) using Inception-v3, ResNet-50, and DenseNet-161 as baseline models. We further altered the models using several strategies: replacement of the top layer, transfer learning from pre-trained models, fine-tuning of the model weights, rebalancing and augmentation of the training data, and 10-fold cross-validation. We compared the outcomes of the three CNN models to those of two endoscopist groups having different years of experience, and visualized the model predictions using Class Activation Mapping (CAM). The CNN-CAD achieved the best performance in our experiments with a 92.48% classification accuracy rate. The CNN-CAD results showed a better performance in all criteria than those of endoscopic experts. The model visualization results showed reasonable regions of interest to explain pathology classification decisions. We demonstrated that CNN-CAD can distinguish the pathology of colorectal adenoma, yielding better outcomes than the endoscopic experts group.

Higher risk of tuberculosis in combination therapy for inflammatory bowel disease: A nationwide population-based cohort study in South Korea.

Inflammatory bowel disease (IBD) in Asia has become increasingly prevalent. As a treatment of IBD, many immunomodulators and biological agents were introduced and shown to be effective in inducing and maintaining remission. However, many cases with treatment failure were reported. To overcome the failure, combination therapy of immunomodulatory and biologics have emerged, showing better outcomes by optimizing biologic pharmacokinetics and minimizing immunogenicity. Adversely, rates of tuberculosis (TB) have been increased as a result. The aim of this study is to compare the risk of TB according to the therapy using large population data.We used data from the South Korean Health Insurance and Review Agency over the period 2008-2016 and calculated the hazard ratio (HR) for TB in IBD. We compared the risk of TB according to the medication: infliximab only, azathioprine only (AZA), combination of azathioprine and infliximab (CAI), azathioprine monotherapy and infliximab monotherapy (AIM), and azathioprine and infliximab whether simultaneously or separately (AISS).In IBD patients, a total of 249 patients were identified as active TB. After one-to-one matching with age, sex and disease duration, the risks of TB were significantly higher in AZA group (HR, 2.06; 95% CI, 1.35-3.12, P < .001), AIM group (HR, 3.26; 95% CI, 1.18-9.05, P = .02), AISS group (HR, 3.50; 95% CI, 1.92-6.37, P < .001), and CAI group (HR, 5.67; 95% CI, 2.42-10.21, P < .001), and the HR increased gradually in this order. In UC patients, the results were in similar pattern, but this pattern was not observed in CD patients in our study.Our study shows that Korean IBD patients are at risk of TB, and the risk increases with usage of IBD medication; moreover, the risk is the highest if combination therapy is used. These results highlight the importance of screening for TB in IBD patients, especially in combination therapy.