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.

Pulmonary Cryptococcosis Mimicking Metastasis in a Distal Common Bile Duct Cancer Patient after Recent COVID-19 Infection / 대한췌담도학회지

The only curative treatment option for cholangiocarcinoma is surgery, making the assessment of operability a crucial step in the diagnosis. We report a case of distal common bile duct cancer in a 64-year-old male, who exhibited multiple pulmonary nodules in pre-operative chest imaging following a COVID-19 infection. As the local progression of disease was not prominent, the possibility of pulmonary metastasis was considered unlikely. A surgical biopsy was performed, which confirmed the diagnosis of pulmonary cryptococcosis.

A Case of Five-Year Survival in Metastatic Pancreatic Cancer / 대한췌담도학회지

Pancreatic cancer is often diagnosed at advanced stage, where chemotherapy is the mainstay of treatment. Despite new chemotherapy regimens improving overall survival over the past decade, the median survival for advanced pancreatic cancer remains around one year. However, we occasionally encounter long-term survivors among patients with advanced pancreatic cancer. Analyzing these cases may provide valuable insights for understanding pancreatic cancer and improving treatment strategies. We report a case of 61-year-old patient with metastatic pancreatic cancer who survived for approximately five years. Single-cell transcriptome analysis of tissues obtained at the time of pancreatic cancer diagnosis and at 57 months post-diagnosis revealed changes in the tumor immune microenvironment.

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.

Diagnostic Concordance and Preoperative Risk Factors for Malignancy in Pancreatic Mucinous Cystic Neoplasms

Background/Aims@#As pancreatic mucinous cystic neoplasms (MCNs) are considered premalignant lesions, the current guidelines recommend their surgical resection. We aimed to investigate the concordance between preoperative and postoperative diagnoses and evaluate preoperative clinical parameters that could predict the malignant potential of MCNs. @*Methods@#Patients who underwent surgical resection at Samsung Medical Center for pancreatic cystic lesions and whose pathology was confirmed to be MCN, between July 2000 and December 2017, were retrospectively analyzed. @*Results@#Among a total of 132 patients 99 (75%) were diagnosed with MCN preoperatively. The most discordant preoperative diagnosis was an indeterminate pancreatic cyst. The proportion of male patients was higher (24.2% vs 7.1%, p=0.05) in the diagnosis-discordance group and the presence of worrisome features in radiologic imaging studies, such as wall thickening/enhancement (12.1% vs 37.4%, p=0.02) or solid component/mural nodule (3.0% vs 27.3%, p=0.02), was lower in the diagnosis-discordance group. The presence of symptoms (57.7% vs 34.9%, p=0.02), tumor size greater than 4 cm (80.8% vs 55.7%, p=0.04), and radiologic presence of a solid component/mural nodule (42.3% vs 16.0%, p=0.01) or duct dilatation (19.2% vs 6.6%, p=0.01) were significantly associated with malignant MCNs. @*Conclusions@#In our study, the overall diagnostic concordance rate was confirmed to be 75%, and our findings suggest that MCNs have a low malignancy potential when they are less than 4cm in size, are asymptomatic and lack worrisome features on preoperative images.

The Comparison of Endoscopic Biliary Drainage in Malignant Hilar Obstruction by Cholangiocarcinoma: Bilateral Metal Stents versus Multiple Plastic Stents

Background/Aims@#For the management of hilar malignant biliary obstruction (HMBO), endoscopic biliary drainage (EBD) is preferred over percutaneous transhepatic biliary drainage (PTBD) because of its convenience. However, there is no established guideline for malignant hilar obstruction that requires multiple stenting. In this study, we compared the efficacy of bilateral metal stents (BMS) versus multiple plastic stents (MPS). @*Methods@#In this retrospective study, we analyzed 102 patients who underwent EBD with either BMS or MPS due to HMBO caused by hilar cholangiocarcinoma between 1996 and 2018 at Samsung Medical Center. We compared the successful drainage rates, cholangitis events, overall complications, mortality, and conversion rates to PTBD between the two groups. @*Results@#The successful drainage rates in the BMS group and the MPS group were 71.4% (25/35) and 65.6% (44/67), respectively, with no significant difference. The MPS group had a higher cholangitis risk (hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.21 to 3.58) and higher 6-month mortality (HR, 2.91; 95% CI, 1.26 to 6.71) than the BMS group. There were no significant differences in overall complications or the conversion rate to PTBD between the groups. @*Conclusions@#In patients with malignant HMBO, the BMS group showed better outcomes in terms of the cholangitis rate and 6-month mortality than the MPS group. Therefore, if possible, bilateral metal stenting is recommended for HMBO caused by hilar cholangiocarcinoma.

Diagnostic model for pancreatic cancer using a multi-biomarker panel

Purpose@#Diagnostic biomarkers of pancreatic ductal adenocarcinoma (PDAC) have been used for early detection to reduce its dismal survival rate. However, clinically feasible biomarkers are still rare. Therefore, in this study, we developed an automated multi-marker enzyme-linked immunosorbent assay (ELISA) kit using 3 biomarkers (leucine-rich alpha-2-glycoprotein [LRG1], transthyretin [TTR], and CA 19-9) that were previously discovered and proposed a diagnostic model for PDAC based on this kit for clinical usage. @*Methods@#Individual LRG1, TTR, and CA 19-9 panels were combined into a single automated ELISA panel and tested on 728 plasma samples, including PDAC (n = 381) and normal samples (n = 347). The consistency between individual panels of 3 biomarkers and the automated multi-panel ELISA kit were accessed by correlation. The diagnostic model was developed using logistic regression according to the automated ELISA kit to predict the risk of pancreatic cancer (high-, intermediate-, and low-risk groups). @*Results@#The Pearson correlation coefficient of predicted values between the triple-marker automated ELISA panel and the former individual ELISA was 0.865. The proposed model provided reliable prediction results with a positive predictive value of 92.05%, negative predictive value of 90.69%, specificity of 90.69%, and sensitivity of 92.05%, which all simultaneously exceed 90% cutoff value. @*Conclusion@#This diagnostic model based on the triple ELISA kit showed better diagnostic performance than previous markers for PDAC. In the future, it needs external validation to be used in the clinic.

Long-term Outcome of Endoscopic Retrograde Biliary Drainage of Biliary Stricture Following Living Donor Liver Transplantation

Background/Aims@#Biliary strictures remain one of the most challenging aspects after living donor liver transplantation (LDLT). The aim of this study was to assess long-term outcome of endoscopic treatment of biliary strictures occurring after LDLT and to identify risk factors of recurrent biliary strictures following endoscopic retrograde biliary drainage (ERBD) in LDLT. @*Methods@#A total of 1,106 patients underwent LDLT from May 1995 to May 2014. We compared the risk factors between patients with and without recurrent biliary strictures. @*Results@#Biliary strictures developed in 24.0% of patients. Technical success rate of ERBD for biliary stricture after LDLT was 66.2% (145/219). Among 145 patients managed by endoscopic drainage, stricture resolution occurred in 69 with median duration of stent indwelling of 13.6 months (range, 0.5 to 67.3 months), and stricture recurrence was seen in 20 (21.3%) out of 94. The median recurrence-free duration after final endoscopic success was 13.1 months (range, 0.5 to 67.3 months). Older donor age (hazard ratio [HR], 1.10; 95% confidence interval [CI], 1.03 to 1.17; p=0.004) and non-B, non-C liver cirrhosis (HR, 5.10; 95% CI, 1.10 to 25.00; p=0.043) were associated with higher recurrence of biliary stricture. @*Conclusions@#Long-term stricture resolution rate after ERBD insertion for biliary stricture occurring after LDLT was 73.4%. Clinicians should pay careful attention during following-up to decide when to remove ERBD in patients who have factors associated with recurrent biliary strictures.

Factors of Endoscopic Ultrasound-Guided Tissue Acquisition for Successful Next-Generation Sequencing in Pancreatic Ductal Adenocarcinoma

Background/Aims@#Recent advances in understanding the genetics of pancreatic ductal adenocarcinoma (PDAC) have led to the potential for a personalized approach. Several studies have described the feasibility of generating genetic profiles of PDAC with next-generation sequencing (NGS) of samples obtained through endoscopic ultrasound-guided tissue acquisition (EUS-TA). The aim of this study was to find the best EUS-TA approach for successful NGS of PDAC. @*Methods@#We attempted to perform NGS with tissues from 190 patients with histologically proven PDAC by endoscopic ultrasound-guided fine-needle aspiration and endoscopic ultrasound-guided fine-needle biopsy at Samsung Medical Center between November 2011 and February 2015. The medical records of these patients were retrospectively reviewed for parameters including tumor factors (size, location, and T stage), EUS-TA factors (needle gauge [G], needle type, and number of needle passes) and histologic factors (cellularity and blood contamination). The sample used for NGS was part of the EUS-TA specimen that underwent cytological and histological analysis. @*Results@#NGS could be successfully performed in 109 patients (57.4%). In the univariate analysis, a large needle G (p=0.003) and tumor located in the body/tail (p=0.005) were associated with successful NGS. The multivariate logistic regression analysis revealed that the needle G was an independent factor of successful NGS (odds ratio, 2.19; 95% confidence interval, 1.08 to 4.47; p=0.031). @*Conclusions@#The needle G is an independent factor associated with successful NGS. This finding may suggest that the quantity of cells obtained from EUS-TA specimens is important for successful NGS.

Risk Factors for Pancreatitis and Cholecystitis after Endoscopic Biliary Stenting in Patients with Malignant Extrahepatic Bile Duct Obstruction

BACKGROUND/AIMS: For the treatment of malignant biliary obstruction, endoscopic retrograde biliary drainage (ERBD) has been widely accepted as a standard procedure. However, post-ERBD complications can affect the lives of patients. The purpose of this study was to identify the predictive factors for these complications, including the patient’s status, cancer status, and stent type.METHODS: This was a retrospective analysis conducted in a single tertiary hospital from January 2007 to July 2017. The following variables were evaluated: sex, age, body mass index, cancer type, history of pancreatitis, gallbladder stone, previous biliary stenting, precut papillotomy, stent type, contrast injection into the pancreatic duct or gallbladder, cystic duct invasion by the tumor, and occlusion of the cystic duct orifice by a metal stent.RESULTS: Multivariate analysis showed that contrast injection into the pancreatic duct was a risk factor for pancreatitis. Patients with a history of bile drainage showed a lower risk of pancreatitis. For cholecystitis, the analysis revealed contrast injection into the gallbladder and cystic duct invasion by the tumor as important predictive factors. Metal stents showed a greater risk of post-procedure pancreatitis than plastic stents, but did not affect the incidence of cholecystitis.CONCLUSIONS: Considering that contrast injection is the most important factor for both complications, a careful approach by the physician is essential in preventing the occurrence of any complications. Further, choosing the type of stent is an important factor for patients at a risk of post-procedure pancreatitis.

Which Is the Better Treatment for the Removal of Large Biliary Stones? Endoscopic Papillary Large Balloon Dilation versus Endoscopic Sphincterotomy

BACKGROUND/AIMS: We evaluated the efficacy and cost-effectiveness of endoscopic papillary large balloon dilation (EPLBD) for large common bile duct (CBD) stone removal compared with endoscopic sphincterotomy (EST). METHODS: A total of 1,580 patients who underwent endoscopic CBD stone extraction between January 2001 and July 2010 were reviewed. The following inclusion criteria were applied: choledocholithiasis treated by EPLBD with minor EST or EST with mechanical lithotripsy; and follow-up >9 months after treatment. RESULTS: Forty-nine patients with EPLBD and 41 with EST were compared. There was no significant difference in the complication rates and stone recurrence rates between the two groups. However, significantly more endoscopic retrograde cholangiopancreatography (ERCP) sessions were required in the EST group to achieve the complete removal of stones (1.7 times vs 1.3 times; p=0.03). The mean cost required for complete stone removal per patient was significantly higher in the EST group compared to the EPLBD group (USD $1,644 vs $1,225, respectively; p=0.04). Dilated CBD was the only significant factor associated with recurrent biliary stones (relative risk, 1.09; 95% confidence interval, 1.02 to 1.17; p=0.02). CONCLUSIONS: EPLBD is the better treatment (compared to EST) for removing large CBD stones because EPLBD requires fewer ERCP sessions and is less expensive.

Risk Factors of Post Endoscopic Retrograde Cholangiopancreatography Bacteremia

BACKGROUND/AIMS: Bacteremia following endoscopic retrograde cholangiopancreatography (ERCP) is a severe complication, but the risk factors for this condition have not yet been clearly determined. Thus, the aim of this study was to investigate the risk factors of post-ERCP bacteremia. METHODS: Among patients who underwent ERCP from June 2006 to May 2009, we selected patients without any signs of infection prior to the ERCP procedures. Of these patients, we further selected those who experienced bacteremia after ERCP as well as two-fold age and sex-matched controls who did not experience bacteremia after ERCP procedures. We compared clinical, laboratory and technical aspects between these two groups. RESULTS: There were 70 patients (3.1%) who developed bacteremia after ERCP. In the multivariate analysis, a history of previous liver transplantation, an elevated serum alkaline phosphatase level and an endoscopic retrograde biliary drainage procedure were independent risk factors of post-ERCP bacteremia (p=0.006, p=0.001, and p=0.004, respectively). The microbiologic analysis revealed the presence of gram-negative organisms in 80% of the cases, and 11 patients had infections with bacteria expressing extended spectrum beta-lactamases. Pseudomonas infection was significantly more common in patients who received liver transplantation as compared to patients without transplantation (p=0.014). CONCLUSIONS: A history of liver transplantation, elevated serum alkaline phosphatase levels and endoscopic retrograde biliary drainage procedure were independent risk factors of post-ERCP bacteremia and require additional attention in future studies.

A Multicenter Phase II Trial of Gemcitabine Plus Oxaliplatin in Unresectable Gallbladder Cancer

BACKGROUND/AIMS: No standard chemotherapy has been established for advanced gallbladder cancer. The authors studied the activity and tolerability of a gemcitabine and oxaliplatin (GEMOX) combination in unresectable gallbladder cancer (GBC). METHODS: Adult patients with pathologically confirmed unresectable GBC were prospectively recruited at three centers. No patient had received prior chemotherapy or radiotherapy. Patients received cycles of gemcitabine at 1,000 mg/m2 on day 1, followed by oxaliplatin at 100 mg/m2 on day 2, every 2 weeks. The primary study endpoint was time to progression. RESULTS: Forty patients with unresectable GBC were enrolled. The median age was 60 years (range, 38 to 79 years). All patients showed good performance status. Of the 33 analyzable patients, 12 achieved partial response (36%), 17 stable disease (52%), and four progressive disease (12%). No patient achieved a complete response. The tumor control rate was 88%. At a median follow-up of 6.8 months, the median time to progression was 5.3 months (95% confidence interval [CI], 3.7 to 6.9), and median overall survival was 6.8 months (95% CI, 6.1 to 7.5). Nine of the 40 patients (23%) experienced at least a grade-3 adverse event, but no patient experienced a grade-4 adverse event. CONCLUSIONS: GEMOX combination therapy is a feasible option and is well tolerated in unresectable GBC.

Clinical Usefulness of Plasma Chromogranin A in Pancreatic Neuroendocrine Neoplasm

Chromogranin A (CgA) is widely used as an immunohistochemical marker of neuroendocrine neoplasms and has been measurable in plasma of patients. We assessed the clinical role of plasma CgA in diagnosing pancreatic neuroendocrine neoplasm (PNEN). CgA was checked in 44 patients with pancreatic mass who underwent surgical resection from 2009 through 2011. The cutoff value for diagnosing PNEN and the relationships between CgA and clinicopathologic variables were analyzed. Twenty-six patients were PNENs and 18 patients were other pancreatic disorders. ROC analysis showed a cutoff of 60.7 ng/mL with 77% sensitivity and 56% specificity, and the area under the curve (AUC) was 0.679. Among PNEN group, the sensitivity and specificity of diagnosing metastasis were 100% and 90% respectively when CgA cutoff was 156.5 ng/mL. The AUC was 0.958. High Ki-67 index (160.8 vs 62.1 ng/mL, P = 0.001) and mitotic count (173.5 vs 74.6 ng/mL, P = 0.044) were significantly correlated with plasma CgA, but the tumor size was not. In conclusion, CgA has a little value in diagnosing PNEN. However, the high level of CgA (more than 156.5 ng/mL) can predict the metastasis. Also, plasma CgA level correlates with Ki-67 index and mitotic count which represents prognosis of PNENs.

The Roles of Endoscopic Sphincterotomy and Cholecystectomy in Acute Biliary Pancreatitis / 대한소화기내시경학회지

No abstract available.

Forecasting and Retreatment of Unsuccessful Endoscopic Mechanical Lithotripsy in Patients with Difficult Bile Duct Stones / 대한소화기내시경학회지

No abstract available.

Management Strategies for Gallbladder Polyps: Is It Possible to Predict Malignant Gallbladder Polyps?

BACKGROUND/AIMS: Gallbladder (GB) polyps are commonly encountered in clinical practice, and are found more frequently as the number of medical screening examinations increases. The aim of this study was to determine optimal practice guideline for surgical treatment and follow-up of GB polyps. METHODS: Data from healthy subjects of Seoul National University Hospital (SNUH) Health Care System of Gangnam Center were used to investigate the true prevalence of GB polyps. We also enrolled 689 patients with GB polyps diagnosed at SNUH from May 1st, 1988 to April 30th, 2006. RESULTS: The GB polyp prevalence was 6.1% (7.1% in males and 4.8% in females). The median follow-up duration in the 689 study patients was 60 months, and 139 (20%) of them had polyps > or =10 mm in size. Twenty-five of the 180 patients who underwent cholecystectomy had adenocarcinomas. The chi-square test was used to identify which of the following were risk factors of malignancy: age, sex, symptoms, size, rate of growth, multiplicity, accompanying stones, and shape. Age (> or =57 years), presence of symptoms, size (> or =10 mm), and shape (sessile) were found to be statistically significant risk factors by univariate analysis. However, multivariate analysis identified only age (> or =57 years) and size (> or =10 mm) as independent predictors of malignancy. CONCLUSIONS: The present study shows that GB polyps > or =10 mm in size in patients aged > or =57 years are the independent factors predicting malignancy of the GB.

Pancreatic Endocrine Tumors: Clinical Manifestations and Predictive Factors Associated with Survival / 대한소화기학회지

BACKGROUND/AIMS: Since pancreatic endocrine tumors (PET) are rare and heterogeneous diseases, their survival and prognosis are not well known. Due to recent advances in CT/MRI technology, incidentalomas of the pancreas are detected with increasing frequency. This study presents results of clinical manifestations of PET and predictive factors associated with survival. METHODS: From year 1990 through 2006, medical records of 98 patients (56 men, 42 women) who were diagnosed as PET pathologically at Seoul National University Hospital were reviewed retrospectively. RESULTS: Ages ranged from 17 to 76 years (mean 51.6+/-1.3 years) with a mean follow-up of 3.6+/-0.4 years (range 0-10.1 years). Overall 5-year survival rate was 68.1%, and 5-year survival rate of the patients who had distant metastases at initial diagnosis was 43.9%. Functioning tumors [hazard ratio (HR) 0.229, 95% confidence interval (CI) 0.056-0.943, p=0.041] and lymph node or liver metastases (HR 5.537, 95% CI 2.106-14.555, p<0.001) were the significant prognostic factors associated with survival rate. However, tumor size and pathology showed no significant association with survival. CONCLUSIONS: Because small and pathologically benign nature do not predict good prognosis in PET, aggressive treatment such as curative resection would be considered initially even in the case of incidental PET.

Natural History of Branch-Duct Type Intraductal Papillary Mucinous Neoplasms of the Pancreas / 대한소화기학회지

BACKGROUND/AIMS: Intraductal papillary mucinous neoplasms of the pancreas (IPMNs) are consisted of two types; branch-duct type and main-duct type. Branch-duct type is more common and follows a better course than main-duct type. However, the natural history of branch-duct type IPMN has not been exactly verified yet. The aim of this study was to investigate the natural course of branch-duct type IPMN. METHODS: The medical records of 45 patients with branch-duct type IPMN diagnosed by pancreatogram were reviewed retrospectively. The mean age was 62.9+/-8.3 years old and the mean follow-up duration was 27.4+/-18.9 months. Demographic, clinical and radiologic characteristics were evaluated. The histological findings of specimens resected during the follow-up period were also analyzed. RESULTS: Ten (22.2%) out of 45 patients showed enlargement of the cysts during follow-up. Initial size of the cyst in patients with cyst enlargement were smaller than in patients without it in univariate analysis (p<0.01). Cysts less than 1.0 cm were significantly associated with cyst enlargement with odds ratio of 4.48 in multivariate analysis. Ten patients underwent surgical resection and pathologic examination revealed one carcinoma in situ and one invasive adenocarcinoma. The presence of mural nodule was associated with malignant change of IPMNs (p=0.02). None of unresected cases showed metastasis or disease-related death. CONCLUSIONS: Natural history of branch-duct type IPMNs is generally good. The occurrence of mural nodule is associated with the malignant change of the cyst but not the speed of size increment.