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Endoscopic biliary drainage is the treatment of choice for patients with malignant distal common bile duct obstruction. Self-expandable metal stents have clinical advantages including an increased duration of patency that may be prolonged by acetylsalicylic acid (ASA) use. The aim of this study was to investigate whether ASA had a positive effect on the patency of self-expandable metal stents compared with placebo.This prospective, multicenter, double-blinded, and randomized placebo-controlled trial was conducted from October 2017 to May 2020 in Korea. Patients who underwent palliative endoscopic biliary drainage with self-expandable metal stents for malignant distal bile duct obstruction were enrolled, and allocated to ASA treatment or placebo. The study outcomes were the rate of stent dysfunction at 6 months, duration of stent patency, risk factors for stent dysfunction, and any adverse events.Interim analysis included 24 and 28 patients in the ASA and placebo groups, respectively. There was no significant difference between the ASA and placebo groups in stent dysfunction (25.0% vs. 20.7%, P = 0.761) or the duration of stent patency (150.97 ± 10.55 vs. 158.07 ± 8.70 days, P = 0.497). Six patients experienced suspected ASA-related adverse events, and there was one lethal case.ASA did not prolong stent patency. This study was terminated early because of the possibility of serious adverse events related to ASA treatment of these patients receiving palliative care.

In the Asian population, existing studies regarding the association between smoking and acute pancreatitis are few in number. The aim of this study was to investigate the incidence of acute pancreatitis according to smoking habits and smoking habit changes of the Korean population.We used clinical data from individuals (aged 20 years or older) who received health examinations arranged by the Korean National Health Insurance Service in 2009 (n = 4 238 822) or in 2009 and 2011 (n = 2 617 306). The incidence of acute pancreatitis was analyzed according to smoking status or smoking habit change reported by individuals during their health examination. Newly diagnosed acute pancreatitis was identified using claims data from baseline to the date of diagnosis or until December 31, 2018.The risk of acute pancreatitis was significantly higher in current smokers compared with never-smokers regardless of age or sex. The adjusted hazard ratio (HR) of acute pancreatitis in current smokers increased according to the amount of smoking (HR 1.28; 95% confidence interval [CI], 1.12-1.45 in10 cigarettes/day, HR 1.4; CI, 1.3-1.52 in 10-19 cigarettes/day, HR 1.66; CI, 1.55-1.78 in ≥20 cigarettes/day). The adjusted HR of acute pancreatitis in continuous smokers was 1.66 (CI, 1.53-1.8) compared with never-smokers and was higher than smokers who quit smoking (HR 1.34; CI, 1.17-1.54).In this Korean population-based cohort study, smoking increased the incidence of acute pancreatitis in a dose-dependent manner, and smoking cessation helped decrease the incidence of acute pancreatitis.

The combinatorial effects of prophylactic methods for postendoscopic retrograde cholangiopancreatography pancreatitis (PEP) in patients with risk factors remain unclear. In this network meta-analysis, we compared the efficacy of various prophylactic strategies to decrease the risk of PEP among patients with risk factors.A systematic review was performed to identify randomized controlled trials from PubMed, Embase, and the Cochrane Library through July 2021. We used frequentist network meta-analysis to compare the rates of PEP among patients who received prophylactic treatments as follows: class A, rectal nonsteroidal anti-inflammatory drugs; class B, prophylactic pancreatic stent; class C, aggressive hydration; or control, no prophylaxis or active control. We selected those studies that included patients with risk factors for PEP.We identified 19 trials, comprising 4,328 participants. Class ABC (odds ratio [OR], 0.08; 95% confidence interval [CI], 0.03 to 0.24), class AC (OR, 0.10; 95% CI, 0.02 to 0.47), class AB (OR, 0.12; 95% CI, 0.05 to 0.26), class BC (OR, 0.13; 95% CI, 0.04 to 0.41), class A (OR, 0.16; 95% CI, 0.05 to 0.50), and class B (OR, 0.26; 95% CI, 0.14 to 0.46), were associated with a reduced risk of PEP as compared to that of the control. The most effective prophylaxis was ABC (0.87), followed by AC (0.68), AB (0.65), BC (0.56), A (0.49), and B (0.24) according to P-score.The results of this network meta-analysis suggest that the more prophylactic methods are employed, the better the outcomes. It appears that for patients with risk factors, we need to prevent PEP through the use of these well proven combination strategies.

Background/purpose Patients who undergo gastric surgery are prone to form postsurgical gallstones. Debates still exist about the need for prevention and the selection of preventive methods. No studies had been reported comparing the efficacy of prophylactic ursodeoxycholic acid (UDCA) and prophylactic cholecystectomy (PC) for lowering postsurgical gallstone formation and subsequent cholecystectomy (SC) in patients who have undergone gastric surgery. Methods We did a systematic review to identify studies from PUBMED, EMBASE, and the Cochrane database through June 30, 2020. We conducted direct and indirect comparisons of each prophylaxis using conventional and network meta-analysis. Studies with patients who have no history of cholecystectomy and who have not had preoperative gallstone were included. Results The excellent preventive effects of PC and UDCA were demonstrated for gallstone formation (odds ratio [OR] 0.05, [95% CI 0.01, 0.22] and 0.20, [95% CI 0.16, 0.24], respectively) and the need for SC (OR 0.10, [95% CI 0.02, 0.57] and OR 0.22, [95% CI 0.14, 0.35], respectively) than control group. The UDCA group showed a tendency to generate more gallstones (OR 3.74, [95% CI 0.88, 15.82]) and a greater need for SC (OR 2.19, [95% CI 0.47-10.14]) than did the PC group without statistical significance. Conclusions Prophylaxis for gallstone formation may be needed for patients who undergo gastric surgery to reduce troublesome morbidities. Prophylactic UDCA seem to be a reasonable preventive method for postsurgical gallstone formation to ensure clinical benefit while reducing the burden of subsequent cholecystectomy for the patient as compared to a PC.

Background There is a lack of studies regarding the optimal timing for endoscopic retrograde cholangiopancreatography (ERCP) in patients with cholangitis caused by distal malignant biliary obstruction (MBO). This study aims to investigate the optimal timing of ERCP in patients with acute cholangitis associated with distal MBO with a naïve papilla. Methods A total of 421 patients with acute cholangitis, associated with distal MBO, were enrolled for this study. An urgent ERCP was defined as being an ERCP performed within 24 h following emergency room (ER) arrival, and early ERCP was defined as an ERCP performed between 24 and 48 h following ER arrival. We evaluated both 30-day and 180-day mortality as primary outcomes, according to the timing of the ERCP. Results The urgent ERCP group showed the lowest 30-day mortality rate (2.2%), as compared to the early and delayed ERCP groups (4.3% and 13.5%) (P P = 0.006). A subgroup analysis showed that in both the primary distal MBO group, as well as in the moderate-to-severe cholangitis group, the urgent ERCP had significantly improved in both 30-day and 180-day mortality rates. However, in the secondary MBO and mild cholangitis groups, the difference in mortality rate between urgent, early, and delayed ERCP groups was not significant. Conclusions In patients with acute cholangitis associated with distal MBO, urgent ERCP might be helpful in improving the prognosis, especially in patients with primary distal MBO or moderate-to-severe cholangitis.

Background and Objectives: The prevalence of choledocholithiasis in the high-risk group of choledocholithiasis has been reported to be slightly more than 50% when there is no definite cholangitis. Replacement of diagnostic endoscopic retrograde cholangiography (ERC) with an EUS-first approach may be beneficial in these patients. Materials and Methods: In this prospective, multicenter study, patients with dilated common bile duct and serum total bilirubin levels of 1.8–4 mg/dL were randomly allocated to undergo either EUS first, followed by subsequent ERC if necessary (EUS group) or ERC only (ERC group). The primary endpoint was the incidence of negative outcomes associated with a false-negative diagnosis of the choledocholithiasis or the endoscopic procedure. The secondary endpoints were the rate of diagnostic ERC and hospital stay length related to the endoscopic procedure. Results: Of 90 patients who were randomly assigned, the final analysis involved 42 in the EUS group and 44 in the ERC group. The negative outcomes were not significantly different between the EUS and ERC groups (2.4% vs. 6.8%; P = 0.62). The rate of diagnostic ERC was significantly lower in the EUS group (2.4% vs. 47.7%; P < 0.001). The hospital stay length related to the endoscopic procedure was significantly shorter in the EUS group (1.8 ± 1.0 vs. 2.5 ± 1.2 days; P = 0.001). Conclusion: In selected high-risk choledocholithiasis patients, an EUS-first strategy significantly decreased the rate of diagnostic ERC and hospital stay but did not achieve a significant reduction in negative endoscopic procedure outcomes.

BACKGROUND: Locally advanced (unresectable) pancreatic cancer (LAPC) is surgically unresectable and often treated with chemotherapy. Most of previous studies, that have evaluated conversion surgery after chemotherapy, included heterogeneous patients and chemotherapy regimens, making it challenging to determine the impact of FOLFIRINOX. The present study evaluated the survival benefit of conversion surgery in patients with LAPC who received FOLFIRINOX chemotherapy, and analyzed the prognostic factors. METHODS: Patients with LAPC who received FOLFIRINOX as first-line therapy for at least four cycles were included. During chemotherapy, surgical eligibility was determined based on radiologic and metabolic response to the treatment. Clinicopathologic characteristics were compared between the curative-intent surgery and non-resection groups, and the prognostic factors were analyzed. RESULTS: A total of 279 patients were included. The rates of partial response (PR) and stable disease (SD) were 34.1% and 51.4%, respectively, and 16.8% patients underwent curative-intent surgery. The median survival was significantly longer in the resection group than in the non-resection group (56 vs. 21 months, P

Background/Aims Recurrent pyogenic cholangitis (RPC) is a chronic progressive disease frequently accompanied by cholangiocarcinoma (CCA). This study aimed to investigate the natural course of RPC and identify factors associated with CCA. Methods From January 2005 to December 2016, 310 patients diagnosed with RPC at Seoul National University Hospital were included. Complications and management during follow-up were recorded. CCA-free probability was estimated by Kaplan-Meier method, and risk factors associated with CCA were analyzed using log-rank test and Cox’s proportional hazard regression model. Results Mean age at diagnosis was 59.1±10.9 years and mean follow-up duration was 84.0±64.1 months. An intrahepatic duct stone was found in 253 patients (81.6%). Liver atrophy was identified in 185 patients (59.7%) and most commonly located at the left lobe (65.4%). Acute cholangitis, liver abscesses, cirrhotic complications, and CCA developed in 41.3%, 19.4%, 9.7%, and 7.4%, respectively. During follow-up, complete resolution rate after hepatectomy, biliary bypass surgery, and choledocholithotomy with T-tube insertion reached 82.3%, 55.2%, and 42.1%, respectively. None of the patients who maintained complete resolution by the last follow-up day developed CCA. In univariate analysis, female, both-sided intrahepatic duct stones, and liver atrophy at any location were associated with increased risk of CCA. Multivariate analysis revealed that both-sided atrophy significantly increased risk of CCA (hazard ratio, 4.56; 95% confidence interval, 1.48 to 14.09; p=0.008). In 21 patients who developed intrahepatic CCA, tumor was located mostly in the atrophied lobe (p=0.023). Conclusions In RPC patients, acute cholangitis, liver abscess, cirrhotic complications, and CCA frequently developed. Both-sided liver atrophy was a significant risk factor for developing CCA.

Three-dimensional cultures of human pancreatic cancer tissue also known as "organoids" have largely been developed from surgical specimens. Given that most patients present with locally advanced and/or metastatic disease, such organoids are not representative of the majority of patients. Therefore, we used endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) to collect pancreatic cancer tissues from patients with advanced pancreatic cancer to create organoids, and evaluated their utility in pancreatic cancer research.Single-pass EUS-FNA samplings were employed to obtain the tissue for organoid generation. After establishment of the organoid, we compared the core biopsy tissues with organoids using hematoxylin and eosin staining, and performed whole exome sequencing (WES) to detect mutational variants. Furthermore, we compared patient outcome with the organoid drug response to determine the potential utility of the clinical application of such organoid-based assays.Organoids were successfully generated in 14 of 20 tumors (70%) and were able to be passaged greater than 5 times in 12 of 20 tumors (60%). Among them, we selected eight pairs of organoid and core biopsy tissues for detailed analyses. They showed similar patterns in hematoxylin and eosin staining. WES revealed mutations inThe established organoids from EUS-FNA core biopsies can be used for a suitable model system for pancreatic cancer research.

Background/Aims: Although many studies have reported the promising effect of neoadjuvant treatment for borderline resectable pancreatic cancer (BRPC) to increase resectability, only a few studies have recommended the use of first-line chemotherapeutic agents as neoadjuvant treatment for BRPC. The current study compared clinical outcomes between gemcitabine and FOLFIRINOX (5-fluorouracil, leucovorin, oxaliplatin, and irinotecan) in patients with BRPC. Methods: In this single-center retrospective study, 100 BRPC patients treated with neoadjuvant chemotherapy and resection from 2008 to 2018 were reviewed. Clinical outcomes included overall survival, resectability, and recurrence patterns after gemcitabine or FOLFIRINOX treatment. Results: For neoadjuvant chemotherapy, gemcitabine was administered to 34 patients and FOLFIRINOX to 66. Neoadjuvant radiotherapy was administered to 27 patients (79.4%) treated with gemcitabine and 19 (28.8%) treated with FOLFIRINOX (p

Background/Aims: The combination of nab-paclitaxel and gemcitabine (nab-P/Gem) is widely used for treating metastatic pancreatic cancer (MPC). We aimed to evaluate the therapeutic outcomes and prognostic role of treatment-related peripheral neuropathy in patients with MPC treated with nab-P/Gem in clinical practice. Methods: MPC patients treated with nab-P/Gem as the first-line chemotherapy were included. All 88 Korean patients underwent at least two cycles of nab-P/Gem combination chemotherapy (125 and 1,000 mg/m2, respectively). Treatment-related adverse events were monitored through periodic follow-ups. Overall survival and progression-free survival were estimated by the Kaplan- Meier method, and the Cox proportional hazards regression linear model was applied to assess prognostic factors. To evaluate the prognostic value of treatment-related peripheral neuropathy, the landmark point analysis was used. Results: Patients underwent a mean of 6.7±4.2 cycles during 6.3±4.4 months. The median overall survival and progression-free survival rates were 14.2 months (95% confidence interval [CI], 11.8 to 20.3 months) and 8.4 months (95% CI, 7.1 to 13.2 months), respectively. The disease control rate was 84.1%; a partial response and stable disease were achieved in 30 (34.1%) and 44 (50.0%) patients, respectively. Treatment-related peripheral neuropathy developed in 52 patients (59.1%), and 13 (14.8%) and 16 (18.2%) patients experienced grades 2 and 3 neuropathy, respectively. In the landmark model, at 6 months, treatment-related peripheral neuropathy did not have a significant correlation with survival (p=0.089). Conclusions: Nab-P/Gem is a reasonable choice for treating MPC, as it shows a considerable disease control rate while the treatment-related peripheral neuropathy was tolerable. The prognostic role of treatment-related neuropathy was limited. (Gut Liver 2018;12:728-735)

Background/Aims Although endoscopic bilateral stent-in-stent placement is challenging, many recent studies have reported promising outcomes regarding technical success and endoscopic re-intervention. This study aimed to evaluate the technical accessibility of stent-in-stent placement using large cell-type stents in patients with inoperable malignant hilar biliary obstruction. Methods Forty-three patients with inoperable malignant hilar biliary obstruction from four academic centers were prospectively enrolled from March 2013 to June 2015. Results Bilateral stent-in-stent placement using two large cell-type stents was successfully performed in 88.4% of the patients (38/43). In four of the five cases with technical failure, the delivery sheath of the second stent became caught in the hook-cross-type vertex of the large cell of the first stent, and subsequent attempts to pass a guidewire and stent assembly through the mesh failed. Functional success was achieved in all cases of technical success. Stent occlusion occurred in 63.2% of the patients (24/38), with a median patient survival of 300 days. The median stent patency was 198 days. The stent patency rate was 82.9%, 63.1%, and 32.1% at 3, 6, and 12 months postoperatively, respectively. Endoscopic re-intervention was performed in 14 patients, whereas 10 underwent percutaneous drainage. Conclusions Large cell-type stents for endoscopic bilateral stent-in-stent placement had acceptable functional success and stent patency when technically successful. However, the technical difficulty associated with the entanglement of the second stent delivery sheath in the hook-cross-type vertex of the first stent may preclude large cell-type stents from being considered as a dedicated standard tool for stent-in-stent placement.

Background and aim Pancreatic neuroendocrine neoplasms (PanNENs) are rare diseases but gradually increasing in prevalence with different prognosis. Multiphase contrast-enhanced computed tomography (CT) is known as widely used imaging modality for the diagnosis of pancreatic tumors. We aimed to investigate whether CT enhancement pattern is associated with the pathologic tumor grade and can predict that of PanNEN. Methods Ninety PanNEN patients who underwent multiphase enhanced CT before pathologic diagnosis were retrospectively reviewed. CT enhancement values at each phase were measured, and its relation with pathologic grade was assessed. Results Ninety PanNENs included 62 G1 (68.9%), 21 G2 (23.3%), and 7 G3 (7.8%). The enhancement values of the early arterial phase were significantly different among three groups (G1 119.4 HU, G2 94.7 HU, and G3 64.8 HU; G1 vs G2, P = 0.043; G1 vs G3, P = 0.001; and G2 vs G3, P = 0.027). In the late arterial phase, there was a difference between grade 1/2 and 3 but no significant difference between grade 1 and grade 2 (G1 164.3 HU, G2 142.9 HU, and G3 94.1 HU; G1 vs G2, P = 0.804; G1 vs G3, P = 0.016; and G2 vs G3, P = 0.022). The enhancement value of the portal phase did not differ significantly among the three groups. Diagnostic ability of the early arterial enhancement value for the differentiation of the G1 (cutoff 109.5 HU, sensitivity 73.3%, and specificity 62.5%) was comparable with that of the tumor size (cutoff 20.5 mm, sensitivity 68.9%, and specificity 66.7%). Conclusions Computed tomography enhancement value at early arterial phase and its changing pattern can be a useful predictor for the differentiation of pathologic grade of PanNENs.

Background Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has become a crucial diagnostic technique for pancreatic malignancies. The specimen obtained by EUS-FNA can be prepared for either cytological or histological examinations. This study was to compare diagnostic performance of cytological and histological preparations using EUS-FNA in the same lesions when pancreatic malignancies were suspected. Methods One hundred and eighteen patients who underwent EUS-FNA for suspected pancreatic malignancies were consecutively enrolled. All procedures were conducted by a single echoendoscopist under the same conditions. Four adequate preparations were obtained by 22-gauge needles with 20 to-and-fro movements for each pass. The 4 preparations included 2 cytological and 2 histological specimens. The pathologic reviews of all specimens were conducted independently by a single experienced cytopathologist. Sensitivity, specificity, and accuracy of the 2 preparations were compared. Results The enrolled patients consisted of 62 males (52.5%), with the mean age of 64.6±10.5 years. Surgery was performed in 23 (19.5%) patients. One hundred and sixteen (98.3%) lesions were classified as malignant, while 2 (1.7%) were benign. Sensitivity of cytology and histology were 87.9% and 81.9%, respectively, with no significant difference (P=0.190). Accuracy was also not significantly different. Cytological preparation was more sensitive when the size of lesion was Conclusions Our results suggested that the diagnostic performances of cytological and histological preparations are not significantly different for the diagnosis of pancreatic malignancies. However, cytological preparation might be more sensitive for pancreatic lesions

Objectives This study was conducted to assess the preventive/therapeutic effects of combined administration of resveratrol and guggulsterone on cerulein-induced acute pancreatitis in mice. Methods Acute pancreatitis was induced by intraperitoneal injection of cerulein in mice. Serum amylase assay and histology were performed to measure the severity of pancreatitis. Western blotting and multiplex cytokine/chemokine analysis were conducted to understand the action mechanisms of the reagents. Results Serum amylase assay and histology revealed that the severity of acute pancreatitis was reduced by the combinatory treatment with resveratrol and guggulsterone, but the ratio of the band intensity implied that reduced nuclear factor-κB activation is primarily responsible for the effect. The reduced amounts of keratinocyte chemoattractant (chemokine [C-X-C motif] ligand 1), interferon gamma-induced protein 10 (C-X-C motif chemokine 10) and interleukin 6 expression in the sera could be involved in attenuated immune cell migration and reduced inflammation by these reagents. Conclusions Combinatory treatment with resveratrol and guggulsterone marginally reduced cerulein-induced mild acute pancreatitis in mice.

Background Bilateral stent-in-stent (SIS) self-expandable metal stent placement is technically challenging for palliation of unresectable malignant hilar obstruction. In the SIS technique, the uniform large cell type biliary stent facilitates contralateral stent deployment through the mesh of the first metallic stent. This study aimed to assess the technical success and clinical effectiveness of this technique with a uniform large cell type biliary stent. Methods Thirty-one patients who underwent bilateral SIS placement using a large cell type stent were reviewed retrospectively. All patients showed malignant hilar obstruction (Bismuth types II, III, IV) with different etiologies. Results Sixteen (51.6%) patients were male. The mean age of the patients was 67.0±14.0 years. Most patients were diagnosed as having hilar cholangiocarcinoma (58.1%) and gallbladder cancer (29.0%). Technical success rate was 83.9%. Success was achieved more frequently in patients without masses obstructing the biliary confluence (MOC) than those with MOC (95.2% vs 60.0%, P=0.03). Functional success rate was 77.4%. Complications occurred in 29.0% of the patients. These tended to occur more frequently in patients with MOC (50.0% vs 19.0%, P=0.11). Median time to recurrent biliary obstruction was 188 days and median survival was 175 days. Conclusions The large cell type stent can be used efficiently for bilateral SIS placement in malignant hilar obstruction. However, the risk of technical failure increases in patients with MOC, and caution is needed to prevent complications for these patients.

Stent insertion for biliary decompression to relieve jaundice and subsequent biliary infection is necessary for patients with biliary obstruction caused by pancreatic cancer, and it is important to keep the stent patent as long as possible. However, few studies have compared stent patency in terms of chemotherapy in patients with pancreatic cancer. This study aimed to evaluate the differences in stent patency in terms of recently evolving chemotherapy.Between January 2015 and May 2017, 161 patients with pancreatic cancer who had undergone biliary stent insertion with a metal stent were retrospectively analyzed. The relationship between chemotherapy and stent patency was assessed. Additionally, overall survival according to the treatment, risk factors for stent patency, and long-term adverse events were evaluated.Median stent patency was 42 days for patients with the best supportive care and 217 days for patients with chemotherapy (conventional gemcitabine-based chemotherapy and folfirinox) (P 0.001). Furthermore, the folfirinox group showed the longest median stent patency and overall survival, with 283 days and 466 days, respectively (P 0.001) despite higher adverse events rate. Patients who underwent folfirinox chemotherapy after stent insertion had better stent patency in multivariate analysis (HR = 0.26; 95% CI: 0.12-0.60; P = 0.001).Compared with patients who received best supportive care only, patients who underwent chemotherapy after stent insertion had better stent patency. More prolonged stent patency can be expected for patients with folfirinox than conventional gemcitabine-based chemotherapy.

Background The introduction of FOLFIRINOX regimen greatly changed the treatment for advanced pancreatic cancers. However, detailed studies on the clinical effects and factors affecting the prognosis are insufficient. We performed this study to evaluate the effects of FOLFIRINOX and the surgical resection in advanced pancreatic cancer. Methods Three hundred and thirty-seven patients with advanced pancreatic cancer who initially received FOLFIRINOX, from January 2011 to December 2017, were retrospectively reviewed. Patients were evaluated according to the National Comprehensive Cancer Network guideline, responses after four to six cycles of FOLFIRINOX were re-evaluated according to the response evaluation criteria in solid tumors, and further treatment was decided in the multidisciplinary meeting. Results Sixty-seven (19.9%) patients had borderline resectable pancreatic cancer, 135 (40.1%) locally advanced pancreatic cancer, and 135 (40.1%) metastatic pancreatic cancer. The median survival period was significantly longer in the surgical group than in the nonsurgical group in each clinical stage, even in metastatic pancreatic cancer (32 vs. 14, P = 0.012). In multivariate analysis, metastatic status at diagnosis, progressive disease after FOLFIRINOX, surgical resection, and declined CA19-9 after FOLFIRINOX were significant prognostic factors. Conclusions Surgical treatment greatly affects survival outcomes in advanced pancreatic cancer treated with FOLFIRINOX. Further studies on the optimal indication of operation and the protocol are needed.

Background/Aims There has been growing evidence on the utility of neoadjuvant FOLFIRINOX in borderline resectable (BR) or locally advanced (LA) pancreatic cancer. However, factors predicting survival in these patients remain to be identified, and we aimed to identify these prognostic factors. Methods Between January 2013 and April 2017, patients with BR or LA pancreatic cancer who received FOLFIRINOX as their initial treatment were identified. Demographic data and clinical outcomes, including the chemotherapy response, conversion to resection, and survival, were reviewed. Results A total of 117 patients with BR (n=39) or LA (n=78) pancreatic cancer were included. Of these patients, 29 (24.8%) underwent curative surgery, and R0 resection was achieved in 21 patients (72.4%). The median progression-free survival and overall survival time of all patients were 11.6 and 19.0 months, respectively. In resected patients, the median relapse-free survival and overall survival times were 14.8 and 28.6 months, respectively. In the multivariate Cox model, the lowest level of serum carbohydrate antigen 19-9 (CA 19-9) and resection after FOLFIRINOX were independent factors for improved overall survival. In the subgroup analysis of patients with initial 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) images, the maximum standardized uptake value (SUVmax) of the pancreatic mass was also shown as an independent factor for improved overall survival. Conclusions In patients with BR or LA pancreatic cancer, FOLFIRINOX is a valuable neoadjuvant treatment that enables curative surgery in approximately one-quarter of patients and significantly improves overall survival. In these patients, the prognosis can be estimated using the lowest level of serum CA 19-9, operative status, and initial FDG-PET SUVmax.

Endoscopic ultrasound-guided ethanol ablation (EUS-EA) for pancreatic cystic lesions (PCLs) has been used in recent years as a feasible treatment modality for low malignant probability PCLs or patients considered high-risk for surgery. The present study aimed to confirm the safety of EUS-EA and to find predictive factors for adverse event (AE).A retrospective review was performed from the prospectively maintained database of patients who underwent EUS-EA for PCLs from June 2006 to April 2018 at Seoul National University Hospital. The primary outcomes of the study were the rates of AEs and severe AEs by EUS-EA. The secondary outcome was the predictive factors of AEs including acute pancreatitis and abdominal pain.A total of 214 patients were evaluated and the diagnoses of PCLs according to cystic fluid analysis and clinical features were as follows: serous cystic neoplasm (32.2%), mucinous cystic neoplasm (26.6%), branch duct type intraductal papillary mucinous neoplasm (BD-IPMN) (29.4%), and pseudocyst (11.7%). Three patients (1.4%) experienced severe AEs. Overall, AEs occurred in 71 (33.2%) patients. BD-IPMN (OR: 2.87; 95% CI: 1.05-7.84; P = 0.040), multilocular cysts (OR: 3.59; 95% CI: 1.09-11.85; P = 0.036), suspected ethanol leakage during procedure (OR: 10.68; 95% CI: 1.98-57.53; P = 0.006), and sticky cystic fluid (OR: 3.83; 95% CI: 1.20-12.24; P = 0.024) were predictive factors for post-procedural acute pancreatitis. PCLs of uncinate process (OR: 2.99; 95% CI: 1.22-7.35; P = 0.017) and PCLs with exophytic portion (OR: 3.70; 95% CI: 1.96-7.01; P 0.001) were predictive factors for post-procedural abdominal pain.EUS-EA is a safe procedure with a very low rate of severe AEs. It seems possible to predict the AEs according to the features of the procedure and PCLs.

Right lobe (RL) living donor liver transplantation (LDLT) usually includes 2 bile duct anastomosis sites, namely, the right anterior and the right posterior segmental ducts. This study aimed to evaluate the optimal treatment for biliary strictures following RL LDLT with respect to unilateral or bilateral drainage techniques. From January 2005 to December 2017, 883 patients at Seoul National University Hospital underwent RL LDLT. Of these, 110 patients were enrolled who had 2 duct-to-duct anastomosis sites and who were considered at risk of developing biliary anastomotic strictures. Unilateral or bilateral biliary drainage during the follow-up period was identified by endoscopic retrograde cholangiopancreatography (ERCP) and/or percutaneous transhepatic biliary drainage (PTBD). The clinical success, complication, and 180-day mortality rates were compared between the unilateral and bilateral biliary drainage groups according to the initial ERCP findings. The mean age at the time of LDLT was 54.2 ± 8.2 years. The median time from LDLT to initial biliary anastomotic strictures was 177 (interquartile range, 18-1085) days. At the initial ERCP, unilateral drainage was performed in 55 (50.0%) patients, and bilateral drainage was performed in 11 (10.0%) patients. Of the patients who underwent unilateral drainage, 35 (63.6%) patients required conversion to bilateral drainage during follow-up. Overall, 71 (64.5%) patients required bilateral drainage more than once, whereas only 27 (24.5%) patients reached a resolution with unilateral biliary drainage. In this study, most patients required bilateral biliary drainage more than once during follow-up. An active attempt should be made to drain bilaterally in patients with biliary anastomotic strictures following RL LDLT.

Background and aim No prospective data are available on comparing covered and uncovered self-expandable metal stent (SEMS) for reintervention of occluded uncovered metal stents during endoscopic retrograde cholangiopancreatography in patients with malignant distal biliary obstruction. Methods From June 2010 to November 2014, 43 patients with inoperable distal biliary obstruction of a previously placed uncovered SEMS were enrolled from three centers in Korea and randomly assigned to covered (n = 22) or uncovered SEMS group (n = 21). The primary outcome was overall stent patency. Secondary outcome was time-to-stent occlusion, patient survival, cause of stent occlusion, and adverse events. Results Overall median patency of secondary stent was 112.0 days. Median stent patency of covered and uncovered SEMS was 112.0 and 181.0 days, respectively, (P = 0.373). There was a tendency towards a longer time-to-stent occlusion in uncovered SEMS group (median: 112.0 vs 181.0 days). However, it did not reach statistical significance (P = 0.214). Most common causes of occlusion were stent clogging (36.4%) and tumor ingrowth (33.3%) in covered and uncovered SEMS groups, respectively. There was no significant difference in median survival between the groups (median: 308 vs 300 days; P = 0.325). Acute cholangitis occurred in four patients (three in covered vs one in uncovered SEMS group, P = 0.607). Conclusions In this exploratory trial, there were no statistically significant differences in stent patency, time-to-stent occlusion, patient survival, and complication rates between covered and uncovered SEMS groups. Larger confirmatory multicenter trial is needed for the clear conclusion (ClinicalTrials.gov: NCT01315522).

BACKGROUND/AIMS In recent years, a large number of microribonucleic acids (miRNAs) have been identified as putative prognostic biomarkers for solid cancers because of their role in controlling the expression of oncogenes and tumor suppressor genes. The aim of this study was to verify the utility of miRNA 141 as a prognostic biomarker of biliary tract cancers. METHODS From June 2010 to June 2012, common bile duct cancer tissue samples and matched noncancerous tissues from the ampulla of Vater were obtained from patients with biliary tract cancer undergoing endoscopic retrograde cholangiopancreatography. Using quantitative real-time polymerase chain reaction assays, we measured the mean relative expression levels of miRNA 141 in both groups of tissues. Overexpression of miRNA 141 was defined as a greater than 2-fold increase in expression levels as determined by the 2(-ΔΔCt) method. RESULTS In a cohort of 38 patients with biliary tract cancers (seven gallbladder, 13 hilar, and 18 distal bile duct cancers), 26 patients (68.4%) were male, and the median age was 69.5 (52 to 85) years. Nineteen patients (50%) had undergone R0 resection procedures, including three Whipple operations, seven pylorus-preserving pancreaticoduodenectomies, six bile duct resections, and three extended lobectomies. Among the patients who had undergone R0 resection, the overexpression of miRNA 141 was significantly associated with shorter disease-free survival and a greater risk of angiolymphatic invasion. Among the patients who did not undergo R0 resection, miRNA 141 overexpression was significantly associated with reduced overall survival. CONCLUSIONS Overexpression of miRNA 141 is an indicator of a poor prognosis in patients with biliary tract cancer, suggesting that miRNA 141 may be a valuable prognostic biomarker of this disease.

Objectives The 2012 international guidelines state that surgery should be considered for all surgically fit patients with pancreatic main-duct (MD)/mixed intraductal papillary mucinous neoplasms (IPMNs). This study evaluated the follow-up results of MD/mixed IPMNs and risk factors for progression or malignancy. Methods Patients with MD/mixed IPMNs were retrospectively enrolled and divided into surgical and nonsurgical groups. These 2 groups were compared and further categorized as progression/malignancy or not. In the nonsurgical group, disease progression was defined as radiologic tumor growth or adjacent organ invasion. Results Data from 101 patients (73 males; mean [SD] age, 66.3 [9.1] years), including 27 and 74 in the nonsurgical and surgical groups, respectively, were analyzed. Mural nodules were more frequently detected in the surgical group (7.4% vs 31.1%, P = 0.018), whereas more multifocal cysts were observed in the nonsurgical group (40.7% vs 20.3%, P = 0.037). Forty-one patients (40.6%) showed progression or malignancy. Multivariate analysis showed that main pancreatic duct of 10 mm or greater (odds ratio, 4.368; P = 0.024) and pre-existing diabetes (odds ratio, 3.077; P = 0.046) were independent risk factors for progression or malignancy. Conclusions A watchful waiting strategy could be feasible for some patients with MD/mixed IPMNs, particularly those with a main pancreatic duct of less than 10 mm and without diabetes.

OBJECTIVES Pancreatic neuroendocrine tumors (pNETs) are diverse diseases with different prognosis. The American Joint Committee on Cancer (AJCC) and the European Neuroendocrine Tumor Society (ENETS) introduced 2 different tumor node metastasis (TNM) stages, and the World Health Organization (WHO) proposed WHO 2010 grading system for pNETs. Therefore, we aimed to validate the prognostic relevance of these 3 systems for pNETs in South Korea. METHODS The Korean Society of Gastrointestinal Cancer created a retrospective registry of pNETs in 153 patients from 15 hospitals between 2002 and 2012. RESULTS On the basis of the WHO 2010 grade, 2-year progression-free-survival (PFS) rates for G1, G2, and G3 were 92%, 62%, and 25% (P < 0.01). According to ENETS and AJCC staging, 2-year PFS rates for stages I through IV were 94%, 87%, 49%, 20%, and 92%, 61%, 60%, 20%, respectively (P < 0.01). A Cox multivariate regression analysis revealed that the only statistically significant prognostic factor was the TNM classification of either the AJCC or the ENETS stage (P < 0.01). In addition, the κ value between the AJCC and the ENETS stages was 0.46 indicating a "moderate" agreement (P < 0.01). CONCLUSIONS The AJCC and ENETS TNM classifications for pNETs are prognostic for PFS and can be adopted in clinical practice in South Korea.

OBJECTIVES Endoscopic ultrasonography-guided ethanol ablation therapy for pancreatic cystic lesions is a minimally invasive treatment but still is an experimental therapy. The aims were to investigate the safety and efficacy of endoscopic ultrasonography-guided ethanol ablation therapy. METHODS The inclusion criteria were the following: clinically indeterminate pancreatic cystic lesions in radiologic imaging studies, 2 to 5 cm unilocular or oligolocular cysts without communication to main pancreatic duct, and patients with high-risk operation. RESULTS There were 91 study patients with median follow-up of 40 months. The response rate was as follows: complete resolution, 41 (45%); partial resolution, 37; and persistent cysts, 13. Pancreatic cystic lesions were categorized based on cystic fluid analysis: 9 intraductal papillary mucinous neoplasms (IPMNs), 12 mucinous cystic neoplasms, 33 serous cystic neoplasms, and 28 uncategorized cysts. The success rate was significantly different according to cystic fluid analysis (serous cystic neoplasm, 58%; mucinous cystic neoplasm, 50%; IPMN, 11%; uncategorized cysts, 39%; P < 0.0001). There were 3 patients with mild pancreatitis after the treatment. CONCLUSIONS Endoscopic ultrasonography-guided ethanol ablation therapy seems to be a safe treatment modality. However, it was only effective in 11% of IPMNs. Therefore, the clinical application should be very limited for certain patients who could not tolerate the surgical treatment.

Background Little is known of the prognostic value of CEA/CA 19-9 kinetics during chemotherapy in patients with advanced cholangiocarcinoma (CCA). Methods A total of 236 patients with pathologically confirmed advanced CCA received gemcitabine-based chemotherapy were reviewed, and 179 were eligible for analysis. Baseline, pre-, and post-treatment (after two cycles of chemotherapy) CEA and CA 19-9 values were checked, and survival was compared according to various cutting points of baseline measurement or extent of change of tumor marker level. Results Patients with a ≥ 50% decline in CA 19-9 level had better survival than the others (16.0 vs 9.0 months). However, CEA decline did not predict survival gain. Significant favorable prognostic factors of survival in multivariable analysis included initial treatment response (HR 0.61), distal location of tumor (HR 0.46), baseline CA 19-9 level ≤ 1000 U/mL (HR 0.58), and ≥ 50% decline in CA 19-9 level (HR 0.50). Subgroup analysis was conducted in 114 patients with pre-treatment CA 19-9 > 37 U/mL and bilirubin ≤ 2 mg/dL. Decline ≥ 50% in CA 19-9 level still showed an independent prognostic significance (HR 0.45). Conclusion CA 19-9 but not CEA kinetics serves as a predictor of better survival in patients with advanced CCA on gemcitabine-based chemotherapy. A ≥ 50% decline in CA 19-9 level after two cycles of chemotherapy may have clinical utility as an early indicator of better response to gemcitabine-based chemotherapy.

BACKGROUND AND AIM The role of carbohydrate antigen 19-9 (CA 19-9) for predicting treatment outcome in pancreatic ductal adenocarcinoma (PDAC) remains to be elucidated. This study was aimed to determine the correlation between early decrement in CA 19-9 concentration and prognosis of advanced PDAC after chemotherapy. METHODS All patients confirmed with locally advanced or metastatic PDAC who received initial systemic chemotherapy for at least two cycles in our institution between January 2012 and December 2013 were included. Serum CA 19-9 concentrations at baseline and 8 weeks after the initiation of chemotherapy were obtained. Correlation between CA 19-9 decrement and survival outcomes (time to progression [TTP] and overall survival [OS]) were evaluated. RESULTS A total of 183 patients with initially elevated CA 19-9 were included. OS and TTP was significantly longer for patients whose serum CA 19-9 concentration decreased more than 10% from baseline (n = 103), than that for patients whose serum CA 19-9 was not decreased (n = 80) (423 vs 155 days, P

OBJECTIVES Nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs) are a rare disease but have been diagnosed more frequently than before. The aim of this study was to evaluate the natural course of small NF-PNETs. METHODS We performed a retrospective analysis of patients with incidentally found small NF-PNETs (

Background/aims Cholecystectomy is necessary for the treatment of symptomatic or complicated gallbladder (GB) stones, but oral litholysis with bile acids is an attractive alternative therapeutic option for asymptomatic or mildly symptomatic patients. This study was conducted to evaluate the efficacy of magnesium trihydrate of ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) on gallstone dissolution and to investigate improvements in gallstone-related symptoms. Methods A prospective, multicenter, phase 4 clinical study to determine the efficacy of orally administered magnesium trihydrate of UDCA and CDCA was performed from January 2011 to June 2013. The inclusion criteria were GB stone diameter ≤15 mm, GB ejection fraction ≥50%, radiolucency on plain X-ray, and asymptomatic/mildly symptomatic patients. The patients were prescribed one capsule of magnesium trihydrate of UDCA and CDCA at breakfast and two capsules at bedtime for 6 months. The dissolution rate, response rate, and change in symptom score were evaluated. Results A total of 237 subjects were enrolled, and 195 subjects completed the treatment. The dissolution rate was 45.1% and the response rate was 47.2% (92/195) after 6 months of administration of magnesium trihydrate of UDCA and CDCA. Only the stone diameter was significantly associated with the response rate. Both the symptom score and the number of patients with symptoms significantly decreased regardless of stone dissolution. Adverse events necessitating discontinuation of the drug, surgery, or endoscopic management occurred in 2.5% (6/237) of patients. Conclusions Magnesium trihydrate of UDCA and CDCA is a well-tolerated bile acid that showed similar efficacy for gallstone dissolution and improvement of gallstone-related symptoms as that shown in previous studies.

Background Endoscopic biliary decompression using bilateral self-expandable metallic stent (SEMS) placed using the stent-in-stent (SIS) technique is considered favorable for unresectable malignant hilar biliary obstruction (MHBO). However, occlusion of the bilateral SIS placement is frequent and revision can be challenging. This study was performed to investigate the efficacy, the long-term patency and the appropriate approach for revision of occluded bilateral SIS placement in unresectable MHBO. Methods From January 2011 to July 2016, thirty-eight patients with unresectable MHBO underwent revision of occluded bilateral SIS placement. Clinical data including success rates and patency of revision, were retrospectively analyzed. Results The technical success rate of revision was 76.3%. The clinical success rate of revision was 51.7% and mean patency of revision was 49.1 days. No significant predictive factor for clinical failure of revision was observed. The cell size of SEMS was not found to have significant effects on clinical success rates or revision patency. Conclusions Revision of occluded bilateral SIS placement for MHBO showed fair patency and clinical success rate. Revision method and cell size of SEMS were not found to influence clinical outcomes.

In clinical practice, recurrent cholangitis due to residual common bile duct (CBD) stone occurs frequently even after endoscopic stone removal. This study aimed to determine whether preventive saline irrigation of the bile duct (PSIB) after endoscopic removal of CBD stones would decrease the residual CBD stones.In this multicenter, prospective, randomized study, patients who received endoscopic retrograde cholangiopancreatography for removal of CBD stone were randomized to either receiving PSIB after stone removal (PSIB group) or not receiving PSIB (non-PSIB group). Patients were prospectively followed up and the presence of residual CBD stones was evaluated within 6 months after endoscopic stone removal.A total of 148 patients were enrolled and completed follow-up (73 in PSIB group and 75 in non-PSIB group). The two groups were similar with regard to baseline characteristics. Residual CBD stones were detected in 22 patients (14.9%). The incidences of residual CBD stones were 6.8% in PSIB group and 22.7% in non-PSIB group (P=0.010). Multivariate analysis revealed that the performance of PSIB and the presence of only a single-CBD stone were the significant factors for the decrease of the occurrence of the residual CBD stones. Although, procedure time was slightly longer in PSIB group (22.0 vs 19.2 min, P=0.037), no significant difference was observed in the procedure-related complications between the two groups.PSIB could reduce the residual CBD stones without increasing complications. Considering the efficacy and safety, routine PSIB after endoscopic CBD stone removal seems to be preferred (ClinicalTrials.gov identifier: NCT01425177).

One major adverse event of endoscopic sphincterotomy (EST) is bleeding, which could be more common and severe in patients receiving anticoagulant therapy. However, the cessation of anticoagulants for long periods could lead to thromboembolic events. We aimed to evaluate the optimal timing of resumption of anticoagulants after EST in patients at risk for thromboembolism.From January 2010 through October 2017, a retrospective cohort at risk for thromboembolism who had taken warfarin and bridging therapy with heparin around EST from three tertiary hospitals in South Korea was investigated. The primary outcome was to compare the incidence of post-EST delayed bleeding according to the resumption time of anticoagulant. The secondary outcome was to investigate any thromboembolic adverse events related to interruption of the anticoagulant.A total of 96 patients (46 males and 50 females; median age 75 years [range, 24-91 years]) were enrolled. Overall, the patient numbers of very early ( 24 h), early (24-48 h), and late resumption ( 48 h) of anticoagulant after EST were 56, 23, and 17, respectively. The baseline characteristics were similar between groups except resumption time of anticoagulant. There was no significant difference in the rate of post-EST delayed bleeding (5% in very early group vs. 9% in early group vs. 0 in late group, p = 0.47). The rate of thromboembolic adverse events was significantly higher in the late resumption of anticoagulant group (0 vs. 0 vs. 24%, p 0.001).There was no significant difference in the incidence of post-EST delayed bleeding according to the resuming time of anticoagulant. Since long cessation of anticoagulant could increase the risk of thrombotic adverse events, the early resumption of anticoagulant seems to be preferred.

Self-expandable metal stents (SEMSs) have been a good treatment option for malignant intestinal obstruction. However, stent placement with a gastroscope can be technically difficult for the distal duodenum obstruction. A side-viewing duodenoscope may be helpful for these patients. We report our experiences in the insertion of SEMSs to distal duodenum with a side-viewing endoscope. We retrospectively analyzed our database of SEMS placement for malignant distal duodenum obstruction between April 2006 and April 2013. All patients underwent SEMS placement using the side-viewing endoscope (duodenoscope). Main outcomes are technical success, clinical success, complication rates, stent patency, and overall survival. In addition, database from other tertiary center was analyzed, where SEMS insertion was performed with forward-viewing endoscopes (gastroscope or colonoscope). Success and complication rates were compared with ours. A total of 31 patients were reviewed. Pancreatic cancer was the most common cause (87.1 %). Technical and clinical success was achieved in all cases. Procedure-related complication occurred in one patient, who experienced micro-perforation of the duodenum. The patient improved with conservative treatment. Median duration of stent patency was 125 days (95 % CI 75–175), and median overall survival was 134 days (95 % CI 77–191). Biliary obstruction was present in 12.9 % of patients, who underwent biliary stent placement at the same time without changing endoscopes. In forward-viewing endoscopes group, 15 cases were included. Technical and clinical success was achieved in all cases, and no procedure-related complication occurred. The insertion of SEMSs to distal duodenum with a duodenoscope could be performed effectively and safely in patients with malignant obstruction.

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).

Background and Aims Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is a safe and effective technique for tissue diagnosis in patients with pancreatic or peripancreatic solid masses. However, the procedure is difficult to accomplish without an on-site cytopathologist. The aims of this study were to examine the outcomes of EUS-FNA for pancreatic or peripancreatic solid masses without an on-site cytopathologist and to determine the factors associated with diagnostic accuracy. Methods From December 2005 to November 2011, 230 patients with pancreatic or peripancreatic solid masses had 240 EUS-FNAs performed without an on-site cytopathologist. The medical records of the 230 patients from a single tertiary center were retrospectively reviewed. Results Among the 230 patients who underwent EUS-FNA, 201 patients (88%) had malignancy, which included 171 adenocarcinomas (74%). Assuming that the cytopathological malignancy was positive or suspicious for malignant cells with cytology, the accuracy without an on-site cytopathologist was 67.9%. However, the accuracy increased from 40.0% for the first 30 cases (from 2006 to 2008) to 83.3% for the last 30 cases (in 2011) and was constantly over 80.0% starting from the sixth octile onwards for every 30 cases (in 2011). From the analysis of factors associated with the accuracy of the diagnosis using logistic regression analysis, the number of needle passes and the experience of endosonographer were statistically associated with the diagnostic accuracy. Conclusions In the case of performing EUS-FNA for pancreatic or peripancreatic solid masses without an on-site cytopathologist, the experience of the endosonographer, and the number of needle passes were associated with the diagnostic accuracy.

Background/Aims To determine the prognostic value of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 in gallbladder cancer (GBC) during palliative chemotherapy. Methods One hundred and twenty-three patients with pathologically confirmed unresectable GBC were included. Differences in serum CEA and CA 19-9 levels before and after chemotherapy were measured. Receiver operating characteristic curve analysis, Kaplan-Meier analyses of CEA, CA 19-9, and combined changes were performed to assess the optimal cutoff values and survival rates. Results Patients with decreased tumor markers had significantly better progression-free survival (PFS) and overall survival (OS) than patients with increased tumor markers. The pre- and postchemotherapy CA 19-9 ratio had the highest area-under-the-curve values for predicting 3-month PFS and 1-year OS. In the multivariate analysis, increases in serum CA 19-9 during palliative chemotherapy in patients with unresectable GBC was an independent prognosticator of poor PFS and OS, with hazard ratios of 2.20 (p=0.001) and 1.67 (p=0.020), respectively. Patients with increases ＞10-fold were considered to have progressive disease, whereas individuals with increases ＞3-fold were likely to benefit from early imaging follow-up. Conclusions CA 19-9 kinetics was a reliable prognosticator of PFS and OS in patients with unresectable GBC who underwent palliative chemotherapy.

Background/Aims The aim of this study was to investigate changes in the clinical and demographical characteristics of gallstone disease in Korea, based on 30 years of surgically treated patients at a single institute. Methods In total, 7,949 gallstone patients who underwent surgery between 1981 and 2010 were analyzed. Patients were divided into six time periods: period I (1981 to 1985, n=831), period II (1986 to 1990, n=888), period III (1991 to 1995, n=1,040), period IV (1996 to 2000, n=1,261), period V (2001 to 2005, n=1,651) and period VI (2006 to 2010, n=2,278). Results The total number and mean age of the patients gradually increased, and the male/female ratio decreased. The proportion of gallbladder (GB)-stone cases increased, whereas the proportions of common bile duct (CBD)- and intrahepatic duct (IHD)-stone cases decreased. Differences in patient geographical origins also decreased. Based on the relationship between changes in the prevalence of gallstone disease and socioeconomic status, the prevalence of CBD stones showed a strong correlation with Engel's coefficient (p