Publications by authors named "Jeong Youp Park"

112 Publications

Optimal drainage of anastomosis stricture after living donor liver transplantation.

Surg Endosc 2021 Apr 1. Epub 2021 Apr 1.

Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.

Background: Endoscopic biliary stenting (EBS) with a fully covered, self-expandable metallic stent (FC-SEMS) and plastic stent (PS) is safe and efficient for biliary anastomotic strictures (ASs) after a deceased donor liver transplantation. Limited studies have investigated the use of FC-SEMSs for biliary strictures post-living donor liver transplantation (LDLT). We compared the resolution rate of biliary ASs post-LDLT and the 12-month recurrence rates post-stent removal between EBS with an FC-SEMS, PS, and percutaneous transhepatic biliary drainage (PTBD).

Methods: Patients with biliary ASs after an LDLT (mean age: 57.3 years, 76.1% men) hospitalized between 2014 and 2017 were enrolled. Endoscopic retrograde cholangiopancreatography (ERCP) was repeated every 3-4 months. Patients were followed-up for at least 1-year post-stent removal.

Results: Of the 75 patients enrolled, 16, 20, and 39 underwent EBS with an FC-SEMS, PS, and PTBD, respectively. Median follow-up period was 39.2 months. Fewer ERCP procedures were needed in the FC-SEMS group than in the PS group (median, 2 vs. 3; P = 0.20). Median stent indwelling periods were 4.7, 9.3, and 5.4 months in the FC-SEMS, PS, and PTBD groups, respectively (P = 0.006). The functional resolution rate was lower in the PS group (16/20) than in the FC-SEMS (16/16) or PTBD (39/39) group (P = 0.005). The radiologic resolution rate was higher in the FC-SEMS group (16/16) than in the PS group (14/20) (P = 0.07). The 12-month recurrence rates showed no significant differences (FC-SEMS, 4/16; PS, 3/16; PTBD, 6/39; P = 0.66). The rates of complications during treatment differed significantly between the groups (P = 0.04). Stent migration occurred in 1 (6.3%) and 5 (25.0%) patients in the FC-SEMS and PS groups, respectively (P = 0.59).

Conclusions: EBS with an FC-SEMS is comparable with EBS with a PS or PTBD in terms of biliary stricture resolution and 12-month recurrence rates. The use of FC-SEMSs is potentially effective and safe for biliary AS resolution after LDLT.
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http://dx.doi.org/10.1007/s00464-021-08456-4DOI Listing
April 2021

Profiling of conditionally reprogrammed cell lines for in vitro chemotherapy response prediction of pancreatic cancer.

EBioMedicine 2021 Mar 25;65:103218. Epub 2021 Feb 25.

Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, South Korea. Electronic address:

Background: The establishment of patient-derived models for pancreatic ductal adenocarcinoma (PDAC) using conventional methods has been fraught with low success rate, mainly because of the small number of tumour cells and dense fibrotic stroma. Here, we sought to establish patient-derived model of PDAC and perform genetic analysis with responses to anticancer drug by using the conditionally reprogrammed cell (CRC) methodology.

Methods: We performed in vitro and in vivo tumourigenicity assays and analysed histological characteristics by immunostaining. We investigated genetic profiles including mutation patterns and copy number variations using targeted deep sequencing and copy-number analyses. We assessed the responses of cultured CRCs to the available clinical anticancer drugs based on patient responsiveness.

Findings: We established a total of 28 CRCs from patients. Of the 28 samples, 27 showed KRAS mutations in codon 12/13 or codon 61. We found that somatic mutations were shared in the primary-CRC pairs and shared mutations included key oncogenic mutations such as KRAS (9 pairs), TP53 (8 pairs), and SMAD4 (3 pairs). Overall, CRCs preserved the genetic characteristics of primary tumours with high concordance, with additional confirmation of low-AF NPM1 mutation in CRC (35 shared mutations out of 36 total, concordance rate=97.2%). CRCs of the responder group were more sensitive to anticancer agents than those of the non-responder group (P < 0.001).

Interpretation: These results show that a pancreatic cancer cell line model can be efficiently established using the CRC methodology, to better support a personalized therapeutic approach for pancreatic cancer patients.

Funding: 2014R1A1A1006272, HI19C0642-060019, 2019R1A2C2008050, 2020R1A2C209958611, and 2020M3E5E204028211.
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http://dx.doi.org/10.1016/j.ebiom.2021.103218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921470PMC
March 2021

Comparison of high flow nasal oxygen and conventional nasal cannula during gastrointestinal endoscopic sedation in the prone position: a randomized trial.

Can J Anaesth 2021 Apr 6;68(4):460-466. Epub 2021 Jan 6.

Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.

Purpose: Deep sedation for endoscopic retrograde cholangiopancreatography (ERCP) can be challenging in elderly patients in the prone position. This study investigated the effect of a high flow nasal oxygen (HFNO) delivery system on oxygenation in this procedure compared with that of conventional nasal cannula oxygen administration.

Methods: A prospective randomized trial was conducted using HFNO and conventional nasal cannula in patients undergoing ERCP in the prone position. For each patient, the lowest oxygen saturation (SpO), the incidence of hypoxemia defined as an SpO below 90%, and interruptions due to airway interventions were recorded during the procedure.

Results: The lowest mean (standard deviation) SpO recorded during the procedure was higher in the HFNO group than in the conventional control group [99.8 (0.6)% vs 95.1 (7.3)%; mean difference, 4.7%; 95% confidence interval, 2.3% to 7.1%; P < 0.001]. While the lowest SpO during the procedure was lower than the baseline SpO in the control group, the lowest SpO during the procedure was higher than the baseline SpO in the HFNO group. Hypoxemia occurred only in the control group (n = 7; 19%; P = 0.01). Procedural interruptions, including discontinuation of sedation, patient stimulation, and jaw thrusting, occurred only in the control group (n = 9 [25%], n = 10 [28%], and n = 10 [28%] cases, respectively; P = 0.001 for each).

Conclusion: In contrast to conventional nasal cannula, high flow nasal oxygen provided adequate oxygenation without causing procedural interruptions during ERCP, suggesting that HFNO may be used as a standard oxygen delivery method during these procedures.

Trial Registration: www.ClinicalTrials.gov (NCT03872674); registered 11 March 2019.
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http://dx.doi.org/10.1007/s12630-020-01883-2DOI Listing
April 2021

Lewis Antigen Phenotype and Survival of Patients With Pancreatic Cancer.

Pancreas 2020 Nov/Dec;49(10):1348-1354

Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.

Objectives: The association of Lewis antigen phenotype with survival of patients with pancreatic ductal adenocarcinoma was investigated.

Methods: A total of 1187 patients diagnosed with pancreatic ductal adenocarcinoma were evaluated in a prospective cohort. Patients were classified into 3 different groups according to Lewis antigen phenotype: Lewis antigen (1) A positive [Le(a+b-)], (2) B positive [Le(a-b+)], and (3) negative [Le(a-b-)]. Risk of mortality was analyzed with Cox regression after adjusting for other predictors.

Results: The risk of mortality increased in the order of Le(a+b-), Le(a-b+), and Le(a-b-) [reference; hazard ratio (HR), 1.27; 95% confidence interval (CI)], 1.03-1.57; P = 0.02; and HR, 1.65; 95% CI, 1.31-2.09; P < 0.001] after adjusting for other predictors. Among patients with serum carbohydrate antigen (CA) 19-9 lower than 37 U/mL, the association seemed more apparent (reference; HR, 1.50; 95% CI, 0.77-2.29; P = 0.22; and HR, 2.10; 95% CI, 1.10-4.02; P < 0.02).

Conclusions: The risk of mortality increased in the order of Le(a+b-), Le(a-b+), and Le(a-b-). The difference in prognosis according to the Lewis antigen phenotype was more pronounced in the low CA 19-9 group, which suggests that the Lewis antigen phenotype works as a biomarker predicting the prognosis of patients with pancreatic cancer with undetectable CA 19-9 level.
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http://dx.doi.org/10.1097/MPA.0000000000001687DOI Listing
October 2020

Peripheral natural killer cell activity is associated with poor clinical outcomes in pancreatic ductal adenocarcinoma.

J Gastroenterol Hepatol 2021 Feb 13;36(2):516-522. Epub 2020 Oct 13.

Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea.

Background And Aim: We aimed to measure the natural killer (NK) cell activity and pro-inflammatory cytokine levels in the peripheral blood of pancreatic cancer patients and investigate the correlation of NK cell activity and cytokines with cancer status and clinical outcomes.

Methods: We prospectively enrolled patients who were pathologically diagnosed with pancreatic ductal adenocarcinoma (PDAC) between 2016 and 2017 at a tertiary hospital in Seoul, South Korea. As a control group, healthy participants were enrolled by mobile application recruitment.

Results: A total of 203 patients were enrolled for this study (PDAC, n = 102; healthy participants, n = 101). The peripheral blood NK cell activity of PDAC patients was significantly lower than that of healthy participants (median level, 95 pg/mL vs 2000 pg/mL, P < 0.001), and decreased NK cell activity was correlated to poor clinical outcome in terms of response to chemotherapy, tumor progression, and survival. The pro-inflammatory cytokine interleukin-6 had a strong negative correlation with NK cell activity.

Conclusions: In pancreatic cancer patients, NK cell activity decreased as cancer progressed, and decreased NK cell activity was associated with poor clinical outcomes.
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http://dx.doi.org/10.1111/jgh.15265DOI Listing
February 2021

Radiographic portal or superior mesenteric vein invasion is an independent prognostic factor in non-metastatic pancreatic ductal adenocarcinoma: A missing block of clinical T staging?

Pancreatology 2020 Jul 27;20(5):952-959. Epub 2020 May 27.

Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address:

Background: Venous invasion is not included in the pancreatic ductal adenocarcinoma (PDAC) staging, and its correlation with prognosis remains unclear. We evaluated the prognostic impact of radiographic portal/superior mesenteric vein (PV/SMV) invasion, and its possibility of complementing T staging.

Methods: We identified patients with non-metastatic PDAC using our institutional cohort, and divided them according to PV/SMV invasion at imaging, defined as >180-degree tumor-vessel interface or contour deformity. We conducted Cox proportional hazard regression, and compared survival in the original and 1:1 propensity score matched datasets.

Results: We identified 454 patients [PV/SMV(+): 172; PV/SMV(-): 282]. In the multivariate analysis, PV/SMV invasion, age (≥70 years), performance status, tumor size (2-4, >4 cm), lymph nodes >4, and arterial invasion was correlated with prognosis. The PV/SMV(+) group had a shorter overall survival (OS) than the PV/SMV(-) group in the original (14.4 vs. 20.9 months; P < 0.001) and matched datasets (14.3 vs. 17.2 months; P = 0.009). Among patients without arterial invasion (cT1-cT3), the PV/SMV(+) group had a shorter OS (15.9 vs. 21.2 months; P = 0.002). Moreover, their OS did not differ from that of patients with arterial invasion (cT4) (15.9 vs. 14.4 months; P = 0.907). Patients with vessel (artery/vein) invasion had a shorter OS than those without vessel invasion (14.5 vs. 21.2 months; P < 0.001).

Conclusions: Radiographic PV/SMV invasion in non-metastatic PDAC was correlated with a poor prognosis. It could identify a group with shorter OS among patients without arterial invasion (cT1-cT3). It is suggested that inclusion of PV/SMV invasion in clinical T4 criteria should be considered.
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http://dx.doi.org/10.1016/j.pan.2020.05.017DOI Listing
July 2020

Efficacy and safety of palliative endobiliary radiofrequency ablation using a novel temperature-controlled catheter for malignant biliary stricture: a single-center prospective randomized phase II TRIAL.

Surg Endosc 2021 Jan 2;35(1):63-73. Epub 2020 Jun 2.

Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.

Background: Endobiliary radiofrequency ablation (EB-RFA) has emerged as a palliative treatment for malignant biliary strictures (MBSs); however, concerns about complications related to thermal injury remain. In this study, we evaluated the efficacy and safety of EB-RFA with a novel catheter for MBS.

Methods: Patients with inoperable cancer causing MBS were randomly assigned to either the radiofrequency ablation (RFA) group or the non-RFA group. The RFA group underwent EB-RFA at the stricture site with a temperature-controlled catheter (ELRA™; STARmed Co., Goyang, Korea) followed by deployment of a self-expanding metal stent (SEMS). For the non-RFA group, only SEMS placement was performed. The duration of stent patency, overall survival (OS), and 30-day complication rate were evaluated. This trial was registered at ClinicalTrials.gov (number NCT02646514).

Results: A total of 48 patients were enrolled (24 in each group). During a median follow-up period of 135.0 days (RFA group) and 119.5 days (non-RFA group), the 90-day stent patency rate, median duration of stent patency, and median OS were not different between the groups (58.3% vs. 45.8% [P = 0.386], 132.0 days vs. 116.0 days [P = 0.440], and 244.0 days vs. 180.0 days [P = 0.281], respectively). In the RFA group, procedure-related complications including thermal injury-related complications, such as bile duct perforation or hemobilia, were not reported. The early complication (< 7 days) rates were not different between the groups (4.2% vs. 12.5%, P = 0.609), and there were no late complications (7-30 days) in both groups.

Conclusion: EB-RFA with a temperature-controlled catheter followed by SEMS placement for patients with inoperable MBS can be safe and feasible with acceptable biliary patency.
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http://dx.doi.org/10.1007/s00464-020-07689-zDOI Listing
January 2021

Initial experience of irreversible electroporation for locally advanced pancreatic cancer in a Korean population.

Acta Radiol 2021 Feb 15;62(2):164-171. Epub 2020 Apr 15.

Department of Radiology, Severance Hospital, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, Republic of Korea.

Background: Locally advanced pancreatic cancer (LAPC) is one of the most aggressive malignancies. Irreversible electroporation (IRE) is a novel technique that uses a non-thermal ablation to avoid vessel or duct injury.

Purpose: To investigate the safety and efficacy of IRE for the management of LAPC in a Korean population.

Material And Methods: Twelve patients (median age 64 years; age range 46-73 years) treated between December 2015 and March 2017 underwent intraoperative IRE for LAPC. Technical success and clinical outcomes, including complications, serum pancreatic enzyme levels, overall survival (OS), and progression-free survival (PFS), were evaluated.

Results: Tumors were located in the pancreas head in 7 (58.3%) patients and in the body/tail in 5 (41.7%) patients. The median tumor diameter in the longest axis was 3.1 cm. Vascular invasion was observed in all patients and bowel abutment in 3 (25%) patients. Technical success was achieved in all patients. The median serum levels of amylase and lipase were 55 U/L and 31 U/L, respectively, at baseline, increased to 141.5 U/L ( = 0.008) and 53 U/L ( = 0.505), respectively, one day after IRE, and normalized after one week. The rate of 30-day mortality of unknown relation was 8.3% (one individual experienced massive hematemesis 12 days after IRE). The median OS from diagnosis and IRE was 24.5 months and 13.5 months, respectively. The median PFS from diagnosis and IRE was 19.2 months and 8.6 months, respectively.

Conclusion: For patients with LAPC, IRE appears to be a promising treatment modality with an acceptable safety profile.
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http://dx.doi.org/10.1177/0284185120917118DOI Listing
February 2021

Single-center risk factor analysis for FOLFIRINOX associated febrile neutropenia in patients with pancreatic cancer.

Cancer Chemother Pharmacol 2020 04 17;85(4):651-659. Epub 2020 Mar 17.

Division of Gastroenterology, Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea.

Purpose: FOLFIRINOX is the standard therapy in patients with unresectable pancreatic cancer (PC). However, FOLFIRINOX frequently induces febrile neutropenia (FN) and neutropenia. The purpose of this study was to explore risk factors for FN and grade 4 neutropenia (NP G4) in patients receiving FOLFIRINOX for PC.

Methods: We collected data on 106 patients with PC treated with first-line FOLFIRINOX between 2015 and 2017 using the Pancreatic Cancer Cohort Registry of Severance Hospital in Seoul, Korea.

Results: Multivariate logistic regression analysis showed that female (OR, 3.24; P = 0.023), Eastern Cooperative Oncology Group performance status (OR, 3.70; P = 0.024), overweight (OR, 4.25; P = 0.022), and initial biliary stent insertion (OR, 4.22; P = 0.008) were significantly related to a high risk of FN. Time-dependent bias was reduced using Cox regression analysis, which revealed that female (OR, 2.29; P = 0.041), overweight (OR, 2.67; P = 0.022), and initial biliary stent insertion (OR, 2.59; P = 0.016) were statistically significant predictors. Regarding NP G4, female sex (OR, 2.90; P = 0.016) and overweight (OR, 4.07; P = 0.033) were identified as risk factors in multivariate analysis; however, in Cox regression analysis, tumor in the head of the pancreas (OR, 1.96; P = 0.027) and hemoglobin (g/dL < 12) (OR, 1.87; P = 0.049) were also identified as risk factors.

Conclusion: Female sex, overweight, and initial biliary stent insertion were independent risk factors for the occurrence of FN in patients with unresectable PC treated with FOLFIRINOX.
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http://dx.doi.org/10.1007/s00280-020-04051-xDOI Listing
April 2020

FOLFIRINOX gemcitabine/nab-paclitaxel for treatment of metastatic pancreatic cancer: Single-center cohort study.

World J Gastrointest Oncol 2020 Feb;12(2):182-194

Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seoul 03722, South Korea.

Background: FOLFIRINOX and gemcitabine plus nab-paclitaxel (Gem + nabPTX) were recently introduced for metastatic pancreatic cancer treatment. However, studies that compared these two regimens and studies in Asian populations are lacking.

Aim: To compare the treatment outcomes of FOLFIRINOX and Gem + nabPTX regimen for metastatic pancreatic cancer treatment in Korean population.

Methods: Patients with metastatic or recurrent pancreatic cancer treated with FOLFIRINOX ( = 86) or Gem + nabPTX ( = 81) as the first-line since January 2015 were identified using the Severance Hospital Pancreatic Cancer Cohort Registry. Treatment efficacy, treatment-related adverse events and economic aspects were compared.

Results: Patients in the FOLFIRINOX group were significantly younger (54 65 years; < 0.001) and had better performance statuses at diagnosis. The median overall survival (10.7 12.1 mo; = 0.157), progression-free survival (8.0 8.4 mo; = 0.134), and objective response rates (33.7% 46.9%; = 0.067) were not significantly different when compared with Gem + nabPTX group. Grade ≥ 3 neutropenia and gastrointestinal adverse events were more common in the FOLFIRINOX group. The drug costs of both regimens were similar.

Conclusion: Treatment efficacy and economic burdens were comparable between the two regimens. But, the details of adverse event were different. Gem + nabPTX regimen might be considered preferentially in certain conditions.
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http://dx.doi.org/10.4251/wjgo.v12.i2.182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031147PMC
February 2020

[Second Primary Cancer after Treating Gastrointestinal Cancer].

Authors:
Jeong Youp Park

Korean J Gastroenterol 2019 Oct;74(4):193-196

Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

Advances in diagnosis and therapeutic technologies have brought increased life expectancy for most cancers, but paradoxically it also has increased the risk of second primary malignancies. Cancer survivors have a higher risk of developing cancer than the general population. This suggests that more studies are needed to develop screen and management programs for cancer survivors, especially patients with gastrointestinal cancers, which are the most common cancers in Korea.
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http://dx.doi.org/10.4166/kjg.2019.74.4.193DOI Listing
October 2019

A novel lumen-apposing metal stent with an anti-reflux valve for endoscopic ultrasound-guided drainage of pseudocysts and walled-off necrosis: A pilot study.

PLoS One 2019 4;14(9):e0221812. Epub 2019 Sep 4.

Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

Background: Pancreatic pseudocysts (PC) and walled-off necrosis (WON) are common complications of severe pancreatitis. Endoscopic ultrasound (EUS)-guided drainage has replaced surgery as the standard treatment for PC/WON. We developed a novel lumen-apposing metal stent (LAMS) with an anti-reflux valve to prevent infectious complications caused by food reflux into the cyst cavity. This retrospective study investigated the efficacy and safety of EUS-guided drainage using this LAMS.

Methods: We investigated and compared the treatment outcomes and complications rates between EUS-guided drainage using a novel LAMS (n = 10) versus plastic stents (n = 18) from December 2013 to October 2016. Technical success was defined as successful stent placement without immediate complications. Clinical success was defined as resolution of the PC/WON and disappearance of symptoms.

Results: Among 10 patients in LAMS group, 4 patients had complicated PC and 6 patients had WON. In the plastic stent group, 15 and 3 patients had PC and WON, respectively. The median fluid collection size before treatment was 82.5 (interquartile range [IQR], 60.75-118.25) mm and 92.0 (IQR, 75.75-130.25) mm in the LAMS and plastic stent groups, respectively. There were no statistically significant differences in technical success rates (90% vs. 94.4%; p = 0.999), clinical success rates (80% vs. 77.8%; p = 0.999), and complication rates (20% vs. 27.8%; p = 0.999) between the two groups.

Conclusions: Treatment outcomes of EUS-guided drainage using a novel LAMS were feasible despite the significantly high proportion of WON. The LAMS allowed acceptable treatment outcomes for EUS-guided drainage.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0221812PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6726198PMC
March 2020

Preoperative prediction of futile surgery in patients with radiologically resectable or borderline resectable pancreatic adenocarcinoma.

J Gastroenterol Hepatol 2020 Mar 3;35(3):499-507. Epub 2019 Sep 3.

Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.

Background And Aim: The aim of this study is to identify the predictive factors for futile surgery in patients with radiologically resectable or borderline resectable pancreatic cancer and to develop a prediction model.

Methods: This retrospective study included patients who underwent pancreatic surgery for pancreatic cancer between 2006 and 2017. To identify independent risk factors for futile surgery, logistic regression and random forest analyses were performed in the training cohort, based on which a nomogram was established. The predictive accuracy and discriminative ability of the nomogram were validated in the validation cohort.

Results: Of 389 patients who underwent pancreatic surgery, the laparotomy was futile in 40 patients (10.3%). In the training cohort, the univariate and multivariate logistic regression analyses revealed that serum carbohydrate antigen 19-9 level of ≥ 150 U/mL (P = 0.003), the presence of suspicious lymph node (P = 0.013), and more extensive peripancreatic tumor infiltration (P < 0.001) were independent predictive factors for futile surgery. The bootstrap-corrected concordance index of the nomogram was high in the training cohort, 0.826 with a 95% confidence interval of 0.745-0.907. This model also showed a good discriminative performance in the validation cohort, with a concordance index of 0.831.

Conclusions: We established and validated a novel nomogram that predicts the risk of futile surgery due to occult distant metastasis in patients with radiologically resectable or borderline resectable pancreatic cancer.
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http://dx.doi.org/10.1111/jgh.14837DOI Listing
March 2020

Plasma Chromogranin A as a Prognostic Marker in Pancreatic Ductal Adenocarcinoma.

Pancreas 2019 May/Jun;48(5):662-669

Objectives: Neuroendocrine differentiation in pancreatic ductal adenocarcinoma (PDAC) is known, but its clinical significance still remains uncertain. The clinical role of chromogranin A (CgA), a marker of neuroendocrine tumor, was evaluated in patients with PDAC.

Methods: We retrospectively analyzed 350 patients with PDAC. All patients had plasma CgA levels at diagnosis. Patients were classified as normal and high CgA groups according to the upper limit of plasma CgA.

Results: There were 202 patients (57.7%) in the normal CgA group and 148 patients (42.3%) in the high CgA group. High CgA group presented higher rate of metastatic disease (61.5% vs 45.0%; P = 0.002) and shorter median overall survival (OS) (8.2 vs 11.6 months; P = 0.015). Upon grouping patients based on clinical stages, OS was significantly different between the CgA groups only in metastatic disease (6.6 vs 7.2 months; P = 0.022). Multivariate analysis showed no association between high CgA and OS (hazard ratio, 1.22; 95% confidence interval, 0.97-1.54; P = 0.090). However, high CgA was associated with poor OS in patients with metastatic disease (hazard ratio, 1.37; 95% confidence interval, 1.01-1.87; P = 0.047).

Conclusions: High CgA levels may predict poor prognosis in patients with pancreatic cancer, especially during metastatic stages.
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http://dx.doi.org/10.1097/MPA.0000000000001319DOI Listing
February 2020

Establishment of pancreatic cancer cell lines with endoscopic ultrasound-guided biopsy via conditionally reprogrammed cell culture.

Cancer Med 2019 07 1;8(7):3339-3348. Epub 2019 May 1.

Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

Recent studies have identified the mutational landscape of pancreatic cancer and suggested tumor-specific subtypes. However, the major hurdle against personalized treatment is the difficulty to obtain sufficient cancer tissues from most inoperable cases. We investigated whether patient-derived conditionally reprogrammed cells (CRCs) can be constructed using a small piece of tumor tissue using endoscopic ultrasound (EUS)-guided fine needle biopsy (FNB). Thirty patients with pancreatic solid mass (mean size, 34.6 mm) were enrolled prospectively. Among 22 patients who were diagnosed with pancreatic ductal adenocarcinoma, we established patient-derived pancreatic cancer cell lines from eight patients (36.4%). Immunofluorescence colony staining for CRCs showed that the cytoplasm of cancer cells was clearly stained with anti-cytokeratin 19 monoclonal antibody. In the soft agar colony formation assay, CRCs formed colonies compared with the negative control by day 15. In vivo, implanted CRCs showed tumor engraftment and hematoxylin and eosin staining showed pancreatic cancer ductal structure. All established CRCs showed a KRAS mutation. In conclusion, we established patient-derived pancreatic cancer cell lines with a small tumor tissue obtained by EUS-FNB. With in vitro drug sensitivity and genomic studies, established patient-derived cell lines can be used in identification of new targets for diagnosis and treatment of pancreatic cancer.
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http://dx.doi.org/10.1002/cam4.2210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6601705PMC
July 2019

Bleeding Complications and Clinical Safety of Endoscopic Retrograde Cholangiopancreatography in Patients with Liver Cirrhosis.

Yonsei Med J 2019 May;60(5):440-445

Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.

Purpose: Patients with liver cirrhosis are considered to be at risk for additional adverse events during endoscopic retrograde cholangiopancreatography (ERCP). The present study was designed as a propensity-score matched analysis to investigate whether cirrhotic liver increases the risk of bleeding complications in patients undergoing ERCP.

Materials And Methods: In total, 8554 patients who underwent ERCP from January 2005 to December 2015 were retrospectively analyzed. To adjust for the imbalance between patients with and those without liver cirrhosis, 1:3 propensity score matching was performed according to age and sex.

Results: Liver cirrhosis was identified in 264 (3.1%) patients. After propensity score matching, a total of 768 patients were included in each of the cirrhotic (n=192) and non-cirrhotic groups (n=576). Post-procedure bleeding (10.9% vs. 4.7%, =0.003) was more frequently observed in patients with liver cirrhosis than in those without. In multivariate analyses, liver cirrhosis was identified as an independent risk factor associated with post-ERCP bleeding (=0.003) after further adjustment for prothrombin time, antiplatelet/coagulant, duration of ERCP, and stent insertion. Child-Pugh (CP) class C was found to be associated with an increased incidence of post-ERCP bleeding in patients with cirrhosis (odds ratio 6.144, 95% confidence interval 1.320-28.606; =0.021).

Conclusion: The incidence of post-ERCP bleeding in patients with liver cirrhosis was higher than that in patients without liver cirrhosis. In particular, CP class C cirrhosis was significantly associated with post-ERCP bleeding.
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http://dx.doi.org/10.3349/ymj.2019.60.5.440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6479133PMC
May 2019

Analysis of Clinical Predictive Factors Affecting the Outcome of Second-Line Chemotherapy for Gemcitabine-Refractory Advanced Pancreatic Cancer.

Gut Liver 2020 01;14(1):135-143

Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

Background/Aims: The benefit of second-line chemotherapy (SL) after failed first-line chemotherapy (FL) in patients with advanced pancreatic cancer has not yet been established. We evaluated the clinical characteristics affecting the benefits of SL compared to best supportive care (BSC), identified the prognostic factors, and ultimately devised a model of clinical parameters to assist in making decision between SL and BSC after the failure of gemcitabine-based FL. Methods: The records of patients who received gemcitabinebased FL for advanced pancreatic cancer at Yonsei University Hospital between January 2010 and December 2015 were retrospectively reviewed. Significant clinical parameters were assessed for their potential as predictive factors. Results: SL patients received a longer duration of FL compared with BSC patients with median duration being 16.0 weeks (range, 8.0 to 26.0 weeks) and 8.0 weeks (range, 4.0 to 16.0 weeks), respectively (p<0.001). When the SL group was stratified by their modified overall survival (mOS) (longer and shorter than 6 months), we found significant differences for several clinical factors, namely, metastasis to the peritoneum (p<0.001), number of metastases (p<0.001), thrombotic events (p=0.003), and level of carbohydrate antigen 19-9 (CA19- 9; p=0.011). In multivariate analysis, more than one site of metastasis, occurrence of thrombotic event during FL, and a CA19-9 level above 90 U/mL were significant independent prognostic factors for mOS in the SL group (p<0.05). When an attempt was made to devise a prognostic nomogram, Harrell's C-index of the final prognosis prediction model was 0.62. Conclusions: SL may be beneficial for patients without peritoneal metastasis or thrombotic events who have a single metastasis and a level of CA19-9 less than 90 U/mL. This prognostic nomogram can be used to predict mOS before the administration of SL after the failure of gemcitabinebased FL.
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http://dx.doi.org/10.5009/gnl18419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6974334PMC
January 2020

Skeletal Muscle Mass Predicts Poor Prognosis in Patients with Advanced Pancreatic Cancer Undergoing Second-Line FOLFIRINOX Chemotherapy.

Nutr Cancer 2019 7;71(7):1100-1107. Epub 2019 Apr 7.

Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine , Seoul , Korea.

Although the significance of skeletal muscle mass has been investigated in pancreatic cancer, there are no reports regarding the impact of skeletal muscle mass on prognosis in patients who have undergone second-line chemotherapy. We aimed to identify prognostic factors in patients with advanced pancreatic cancer treated with second-line FOLFIRINOX (folinic acid, fluorouracil, irinotecan, and oxaliplatin). We retrospectively reviewed the data of 57 pancreatic cancer patients treated with second-line FOLFIRINOX. Age, sex, body mass index, Eastern Cooperative Oncology Group (ECOG) performance status, carbohydrate antigen 19-9 levels, skeletal muscle area, skeletal muscle index (SMI), progression free survival (PFS), and overall survival (OS) were analyzed. The median age of the 57 patients (male, 56.1%) was 60.4 years (38-78). Median PFS and OS were 2.6 and 6.6 months. On Kaplan-Meier curves, high SMI was associated with prolonged OS and PFS ( value = 0.003 and 0.015). In multivariate analysis, baseline SMI was significant independent prognostic factor in patients treated with second-line FOLFIRINOX. Baseline SMI has an impact on prognosis in patients who undergoing second-line chemotherapy for pancreatic cancer. Skeletal muscle mass may warrant consideration as a predictive factor with which to identify candidates for second-line chemotherapy for advanced pancreatic cancer.
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http://dx.doi.org/10.1080/01635581.2019.1597906DOI Listing
June 2020

KML001, an arsenic compound, as salvage chemotherapy in refractory biliary tract cancers: A prospective study.

Hepatobiliary Pancreat Dis Int 2019 Feb 28;18(1):62-66. Epub 2018 Dec 28.

Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea. Electronic address:

Background: Sodium meta-arsenite (NaAsO, KML001) is a potential oral anticancer agent acting on telomerase and telomere length. This prospective study evaluated its safety, tolerability, and effectiveness as salvage chemotherapy in patients with advanced biliary tract cancer (BTC) resistant to gemcitabine-based chemotherapy.

Methods: Forty-four patients (21 women and 23 men) with advanced BTC and failure history of gemcitabine-based chemotherapy, performance status (PS) 0-2, normal cardiac, hepatic, and renal function were enrolled. Daily dose of KML001 (7.5 mg. p.o.) was administered to eligible subjects for 24 weeks divided into six treatment cycles. Response was evaluated bimonthly using CT.

Results: After an average of 1.5 months of treatment (range: 0.5-10.0), 3 patients (6.8%) obtained progression-free status, 23 patients (52.3%) had disease progression, and 18 patients (40.9%) dropped out before evaluation. One patient (2.3%) completed six treatment cycles without progression. During the treatment, morphine dosage kept the same or decreased in 20 patients (47.6%). Nine patients (20.5%) experienced grade-3 adverse events (AEs), while no patient experienced grade-4 AEs. The most common AEs were liver enzyme elevation (11/44, 25%) and anemia (10/44, 22.7%). KML001 was discontinued in six patients (13.6%) due to AEs, including liver toxicity (n = 3), QTc prolongation (n = 2), and abdominal pain (n = 1).

Conclusions: KML001 did not have enough anticancer effect on patients with advanced BTC resistant to gemcitabine. However, KML001 was safe and well-tolerable in terms of AEs and pain control when used as salvage therapy. Further studies are needed to establish arsenic agents as a reliable treatment option in patients with BTC.
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http://dx.doi.org/10.1016/j.hbpd.2018.12.009DOI Listing
February 2019

Comparison of efficacy and safety between standard-dose and modified-dose FOLFIRINOX as a first-line treatment of pancreatic cancer.

World J Gastrointest Oncol 2018 Nov;10(11):421-430

Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seodaemun-gu, Seoul 03722, South Korea.

Aim: To directly compare the efficacy and toxicity of standard-dose FOLFIRINOX (sFOLFIRINOX) and modified-dose FOLFIRINOX (mFOLFIRINOX, 75% of standard-dose) for pancreatic cancer.

Methods: One hundred and thirty pancreatic cancer patients who received sFOLFIRINOX ( = 88) or mFOLFIRINOX ( = 42) as their first-line chemotherapy from January 2013 to July 2017 were retrospectively reviewed. For efficacy analysis, the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were evaluated and compared using Pearson's chi-square test, Kaplan-Meier plot and log-rank test. The adverse events (AEs) were evaluated, and severe (≥ grade 3) AEs rates of the two groups were compared for toxicity analysis.

Results: The mFOLFIRINOX group included more female patients (30.7% 57.1%; = 0.004) and older patients [age (median), 57 63.5; = 0.018] than the sFOLFIRINOX group. In the efficacy analysis, the ORR and DCR were not significantly different between the two groups (ORR: 39.8% 35.7%; = 0.656; DCR: 80.7% 83.3%; = 0.716). The median PFS and OS were also not different between the groups (PFS: 8.7 mo 8.1 mo, = 0.272; OS: 13.9 mo 13.7 mo, = 0.476). In the safety analysis with severe AEs, the rates of neutropenia (83.0% 66.7%; = 0.044), anorexia (48.9% 28.6%; = 0.029) and diarrhea (13.6% 0.0%; = 0.009) were markedly lower in the mFOLFIRINOX group.

Conclusion: mFOLFIRINOX showed comparable efficacy but better safety compared to sFOLFIRINOX. If clinically necessary, initiating FOLFIRINOX with 75% of the standard-dose can alleviate toxicity concerns without compromising efficacy.
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http://dx.doi.org/10.4251/wjgo.v10.i11.421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6247105PMC
November 2018

Efficacy and treatment-related adverse events of gemcitabine plus nab-paclitaxel for treatment of metastatic pancreatic cancer "in a Korean" population: A single-center cohort study.

Semin Oncol 2017 Dec 12;44(6):420-427. Epub 2018 Jan 12.

Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea. Electronic address:

Pancreatic cancer has poor prognosis because of its rapid progression and treatment resistance. Based on the results of the Metastatic Pancreatic Adenocarcinoma Clinical Trial (MPACT), a combination regimen of gemcitabine with nab-paclitaxel is currently used as standard therapy for the treatment of metastatic pancreatic cancer. However, because studies in Asian populations are lacking, we investigated the treatment efficacy and safety of this combination therapy in Korean population. Patients with metastatic pancreatic cancer (n=81) treated with gemcitabine and nab-paclitaxel (1,000 and 125 mg/m, respectively) as the first-line chemotherapy from January 2016 were identified using the Severance Hospital Pancreatic Cancer Cohort Registry. Treatment efficacy and treatment-related adverse events (AEs) were analyzed. The median follow-up period was 10.7 months (range, 1.5-23.3 months). Median overall survival, progression-free survival, and objective response rates were 12.1 months (95% confidence interval [CI], 10.7-not estimable), 8.4 months (95% CI, 5.0-11.8), and 46.9%, respectively. The incidence of grade ≥3 neurotoxicity and neutropenia were 18.5% and 46.9%, respectively. Febrile neutropenia and grade ≥3 gastrointestinal AEs occurred in 13 (16.0%) and 16 (19.8%) patients, respectively. Dose reductions because of AEs were required in 60.5% of patients. The combination of gemcitabine with nab-paclitaxel is an effective anti-cancer regimen in Korean population of patients with metastatic pancreatic adenocarcinoma. However, careful monitoring and management are required because of occurrence of treatment-related AEs.
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http://dx.doi.org/10.1053/j.seminoncol.2018.01.001DOI Listing
December 2017

Oncologic outcomes after radical surgery for periampullary cancer in octogenarians.

Ann Hepatobiliary Pancreat Surg 2018 May 30;22(2):128-135. Epub 2018 May 30.

Department of Hepatobiliary and Pancreatic Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.

Backgrounds/aims: Interest in treatments for elderly patients has increased with life expectancy, and various studies have reported on the safety and feasibility of radical surgery in elderly patients with cancer. Here, we investigated oncologic outcomes of periampullary cancer in octogenarians.

Methods: We retrospectively reviewed medical records of 68 patients over 80 years of age who were diagnosed with periampullary cancer and were eligible for surgery; we analyzed overall survival (OS) and immediate postoperative complications and mortality.

Results: There were no significant differences in mean age, disease type, oncologic features, comorbidities, or nutritional status between the patients who had surgery and those who did not. Five patients (20.0%) had major postoperative complications, but there was no immediate postoperative mortality. Patients who had surgery (n=25) had better OS (29.3 months; 95% confidence interval [CI]: 5.6-53.0) than did those who did not (n=43, OS: 7.6 months; 95% CI: 3.2-12.0 months; <0.001). Similarly, patients with distal common bile duct cancer who underwent surgery had better OS than those who did not (surgery group: n=13, OS: 29.3 months, 95% CI: 8.9-49.7; non-surgery group: n=15, OS: 5.7 months, 95% CI: 4.2-7.2 months; =0.002).

Conclusions: Radical surgery for octogenarian patients with periampullary cancer is safe, feasible, and expected to result in better survival outcomes, especially for patients with common bile duct cancer.
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http://dx.doi.org/10.14701/ahbps.2018.22.2.128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5981142PMC
May 2018

Combined use of CEMIP and CA 19-9 enhances diagnostic accuracy for pancreatic cancer.

Sci Rep 2018 02 21;8(1):3383. Epub 2018 Feb 21.

Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

Carbohydrate antigen (CA) 19-9 is the only diagnostic marker used in pancreatic cancer despite its limitations. Here, we aimed to identify the diagnostic role of CEMIP (also called KIAA1199) combined with CA 19-9 in patients with pancreatic cancer. A retrospective analysis of prospectively collected patient samples was performed to determine the benefit of diagnostic markers in the diagnosis of pancreatic cancer. We investigated CEMIP and CA 19-9 levels in 324 patients with pancreatic cancer and 49 normal controls using serum enzyme-linked immunosorbent assay. Median CA 19-9 and CEMIP levels were 410.5 U/ml (40.8-3342.5) and 0.67 ng/ml (0.40-1.08), respectively, in patients with pancreatic cancer. The AUROC for CA 19-9 and CEMIP were 0.847 (95% confidence interval [CI]: 0.806-0.888) and 0.760 (95% CI: 0.689-0.831), respectively. Combination of CA 19-9 with CEMIP showed markedly improved AUROC over CA 19-9 alone in pancreatic cancer diagnosis (0.94 vs. 0.89; P < 0.0001). CEMIP showed a diagnostic yield of 86.1% (68/79) in CA 19-9 negative pancreatic cancer. Combined use with CEMIP showed significantly improved diagnostic value compared with CA 19-9 alone in pancreatic cancer. Especially, CEMIP may be a complementary marker in pancreatic cancer patients with normal CA 19-9 levels.
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http://dx.doi.org/10.1038/s41598-018-21823-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5821821PMC
February 2018

Urgent endoscopic retrograde cholangiopancreatography is not superior to early ERCP in acute biliary pancreatitis with biliary obstruction without cholangitis.

PLoS One 2018 5;13(2):e0190835. Epub 2018 Feb 5.

Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.

Acute pancreatitis is a common diagnosis worldwide, with gallstone disease being the most prevalent cause (50%). The American College of Gastroenterology recommends urgent endoscopic retrograde cholangiopancreatography (ERCP) (within 24 h) for patients with biliary pancreatitis accompanied by cholangitis. Most international guidelines recommend that ERCP be performed within 72 h in patients with biliary pancreatitis and a bile duct obstruction without cholangitis, but the optimal timing for endoscopy is controversial. We investigated the optimal timing for ERCP in patients with biliary pancreatitis and a bile duct obstruction without cholangitis, and whether performing endoscopy within 24 h is superior to performing it after 24 h. We analyzed the clinical data of 505 patients with newly diagnosed acute pancreatitis, from January 1, 2005 to December 31, 2014. We divided the patients into two groups according to the timing of ERCP: < 24 h (urgent) and 24-72 h (early).Among the 505 patients, 73 were diagnosed with biliary pancreatitis and a bile duct obstruction without cholangitis. The mean age of the patients was 55 years (range: 26-90 years). Bile duct stones and biliary sludge were identified on endoscopy in 45 (61.6%) and 11 (15.0%) patients, respectively. The timing of ERCP within 72 h was not associated with ERCP-related complications (P = 0.113), and the total length of hospital stay was not different between urgent and early ERCP (5.9 vs. 5.7 days, P = 0.174). No significant differences were found in total length of hospitalization or procedural-related complications, in patients with biliary pancreatitis and a bile duct obstruction without cholangitis, according to the timing of ERCP (< 24 h vs. 24-72 h).
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0190835PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5798765PMC
March 2018

Clinical Value of Contrast-Enhanced Harmonic Endoscopic Ultrasonography in the Differential Diagnosis of Pancreatic and Gallbladder Masses.

Clin Endosc 2018 Jan 20;51(1):80-88. Epub 2017 Sep 20.

Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

Background/aims: Recent studies have revealed that contrast-enhanced harmonic endoscopic ultrasonography (CEH-EUS) is beneficial in the differential diagnosis of malignant neoplasms of the pancreas and gallbladder from benign masses, in terms of the evaluation of microvasculature and real-time perfusion. In this study, we aimed to prove the clinical value of CEH-EUS in the differential diagnosis of pancreatic and gallbladder masses by direct comparison with that of conventional EUS.

Methods: We reviewed the sonographic images and medical information of 471 patients who underwent conventional EUS and CEH-EUS for the diagnosis of pancreatic and gallbladder masses at a single medical center (Severance Hospital, Seoul, Korea) between March 2010 and March 2016.

Results: The enhancement pattern of CEH-EUS of the pancreatic solid masses showed higher sensitivity and specificity in differentiating pancreatic adenocarcinoma and neuroendocrine tumors (82.0% and 87.9% for pancreatic adenocarcinoma and 81.1% and 90.9% for neuroendocrine tumors, respectively), and the area under the receiver operating characteristic curves was higher than that of conventional EUS. The enhancement texture of CEH-EUS of the gallbladder masses showed a higher sensitivity in differentiating malignant masses than that of conventional EUS; however, the difference between the areas under the receiver operating characteristic curves was not statistically significant.

Conclusions: CEH-EUS can complement conventional EUS in the diagnosis of pancreatic and gallbladder masses, in terms of the limitations of the latter.
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http://dx.doi.org/10.5946/ce.2017.044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5806916PMC
January 2018

Combination Therapy with Capecitabine and Cisplatin as Second-Line Chemotherapy for Advanced Biliary Tract Cancer.

Chemotherapy 2017 26;62(6):361-366. Epub 2017 Aug 26.

Division of Gastroenterology, Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Republic of Korea.

Background/aims: Palliative chemotherapy is the main treatment for advanced biliary tract cancer (BTC). However, there is a lack of established second-line chemotherapy to treat disease progression after first-line chemotherapy. We examined combination therapy with capecitabine and cisplatin for advanced BTC as a second-line regimen.

Methods: We analyzed the medical records of 40 patients diagnosed with BTC who received palliative second-line chemotherapy with capecitabine and cisplatin.

Results: The median overall survival from the start of second-line chemotherapy was 6.3 months. The median overall survival from diagnosis was 17.9 months. The median progression-free survival during second-line chemotherapy was 2.3 months. Nine (30%) patients experienced adverse events of grade ≥3. Eastern Cooperative Oncology Group performance score was an independent predictor of adverse events.

Conclusions: Combination therapy with capecitabine and cisplatin may be an option for second-line chemotherapy in some of patients with advanced BTC.
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http://dx.doi.org/10.1159/000479425DOI Listing
March 2018

Assessment of the Risk of Colorectal Cancer Survivors Developing a Second Primary Pancreatic Cancer.

Gut Liver 2017 Sep;11(5):728-732

Division of Gastroenterology, Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.

Background/aims: We aimed to investigate the incidence of second primary pancreatic cancer (PC) after colorectal cancer (CRC) and to identify risk factors associated with subsequent PC.

Methods: The observed incidence of a subsequent PC in patients with CRC was standardized using a population with CRC from the Korean Central Cancer Registry (KCCR). The expected incidence rate of PC was obtained by assuming that the select group experienced the same cancer incidence as the corresponding general population in the KCCR.

Results: The registry included 4,822 patients with CRC aged 45 to 74 years, representing 16,725.1 person-years of follow-up. Thirteen patients (0.3%) were diagnosed with a subsequent PC, and the overall age-adjusted incidence of second primary PC was 269.6 per 100,000 cases. In contrast, the overall incidence of primary PC in the general population was 18.68 per 100,000 individuals. The standardized incidence ratio of subsequent PC was 14.44, which was significantly higher in patients with CRC than in the general population. Sex, diabetes mellitus, smoking, body mass index, and a history of receiving chemotherapy as a treatment for CRC did not increase the risk of subsequent development of PC.

Conclusions: The risk of a second primary PC was higher in patients with CRC. Further studies are needed to identify the risk factors and generate a screening strategy for cancer survivors.
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http://dx.doi.org/10.5009/gnl16526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5593336PMC
September 2017

Clinical characteristics of second primary pancreatic cancer.

PLoS One 2017 26;12(6):e0179784. Epub 2017 Jun 26.

Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.

Purpose: Several studies reported the increased risk of second primary pancreatic ductal adenocarcinoma (2nd PDAC) in cancer survivors. However, data on the characteristics of 2nd PDAC are insufficient.

Methods: This retrospective cohort study included 1759 patients with PDAC. They were classified as having 2nd PDAC or first primary PDAC (1st PDAC) according to a prior diagnosed cancer of different origin, at least 6 months before PDAC diagnosis.

Results: There were 110 patients (6.4%) with 2nd PDAC and 1606 (93.6%) patients with 1st PDAC. Patients with 2nd PDAC presented with older age (66.5 vs. 62.2 years, p < 0.001) and higher rate of resectability (26.4% vs. 15.9%, p = 0.004) at diagnosis than those with 1st PDAC. Multivariate analysis without considering resectable status showed that 2nd PDAC (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.56-0.94, p = 0.016) was associated with better overall survival. After adjusting for resectable status, however, 2nd PDAC (HR 0.85, 95% CI 0.66-1.09, p = 0.198) was no longer associated with overall survival. When subgroups were separately analyzed according to initial treatment modality, the effectiveness of surgery and chemotherapy were similar between 2nd and 1st PDAC (33.1 vs. 28.5 months, p = 0.860 and 10.8 vs. 10.7 months, p = 0.952).

Conclusions: The proportion of resectable cases was significantly higher in 2nd PDAC. When surgery with curative aim was possible, the overall survival was increased even in patients with 2nd PDAC. These results suggest the importance of screening for second primary cancer in cancer survivors.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0179784PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5484482PMC
September 2017

Benefit of neoadjuvant concurrent chemoradiotherapy for locally advanced perihilar cholangiocarcinoma.

World J Gastroenterol 2017 May;23(18):3301-3308

Jang Han Jung, Division of Gastroenterology, Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, 7, Keunjaebong-gil, Hwaseong-si, Gyeonggi-do 18450, South Korea.

Aim: To clarify the role of neoadjuvant concurrent chemoradiotherapy (NACCRT) followed by surgical resection for localized or locally advanced perihilar cholangiocarcinoma (CCA).

Methods: We retrospectively reviewed 57 patients who underwent surgical resection with or without NACCRT for perihilar CCA; 12 patients received NACCRT and 45 patients did not received NACCRT. Patients with locally advanced perihilar CCA requiring NACCRT were defined as follows: (1) a mass involving unilateral branches of the portal vein or hepatic artery with insufficient volume of the anticipated remnant lobe; or (2) an infiltrating mass in the main portal vein that was too long for reconstruction, identified at preoperative staging.

Results: The median disease-free survival (DFS) durations of the neoadjuvant and non-neoadjuvant CCRT groups were 26.0 and 15.1 mo, respectively ( = 0.91). The median overall survival (OS) durations of the neoadjuvant and non-neoadjuvant CCRT groups were 32.9 and 27.1 mo, respectively ( = 0.26). The NACCRT group showed a downstaging tendency compared to the non-NACCRT group as compared with the tumor stage confirmed by histological examination after surgery and the tumor stage confirmed by imaging test at the time of diagnosis ( = 0.01).

Conclusion: NACCRT does not prolong DFS and OS in localized or locally advanced perihilar CCA. However, NACCRT may allow tumor downstaging and improve tumor resectability.
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http://dx.doi.org/10.3748/wjg.v23.i18.3301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5434436PMC
May 2017

A randomized, multicenter, phase III study of gemcitabine combined with capecitabine versus gemcitabine alone as first-line chemotherapy for advanced pancreatic cancer in South Korea.

Medicine (Baltimore) 2017 Jan;96(1):e5702

Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu Department of Internal Medicine, Dong-A University College of Medicine, Busan Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine Department of Internal Medicine, Korea University College of Medicine Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul Department of Internal Medicine, Keimyung University School of Medicine Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu Digestive Disease Center and Research Institute, Department of Internal Medicine, Soon Chun Hyang University School of Medicine, Bucheon and Seoul Department of Internal Medicine, Pusan National University Hospital, Busan. Departments of Internal Medicine, Pusan National University Hospital, Yangsan Department of Internal Medicine, Digestive Disease Centre, Konkuk University School of Medicine, Seoul Departments of Internal Medicine, Hanyang University College of Medicine, Seoul Department of Internal Medicine, School of Medicine, Wonkwang University, Iksan Department of Internal Medicine, The Catholic University of Korea College of Medicine, St. Mary's Hospital Biostatistics Collaboration Unit, Medical Research Center, Yonsei University College of Medicine, Seoul, Korea.

Background: This phase III trial compared the efficacy and safety of gemcitabine plus capecitabine (GemCap) versus single-agent gemcitabine (Gem) in advanced pancreatic cancer as first-line chemotherapy.

Methods: A total of 214 advanced pancreatic cancer patients were enrolled from 16 hospitals in South Korea between 2007 and 2011. Patients were randomly assigned to receive GemCap (oral capecitabine 1660 mg/m plus Gem 1000 mg/m by 30-minute intravenous infusion weekly for 3 weeks followed by a 1-week break every 4 weeks) or Gem (by 30-minute intravenous infusion weekly for 3 weeks every 4 weeks).

Results: Median overall survival (OS) time, the primary end point, was 10.3 and 7.5 months in the GemCap and Gem arms, respectively (P = 0.06). Progression-free survival was 6.2 and 5.3 months in the GemCap and Gem arms, respectively (P = 0.08). GemCap significantly improved overall response rate compared with Gem alone (43.7% vs 17.6%; P = 0.001). Overall frequency of grade 3 or 4 toxicities was similar in each group. Neutropenia was the most frequent grade 3 or 4 toxicity in both groups.

Conclusion: GemCap failed to improve OS at a statistically significant level compared to Gem treatment. This study showed a trend toward improved OS compared to Gem alone. GemCap and Gem both exhibited similar safety profiles.
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http://dx.doi.org/10.1097/MD.0000000000005702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5228666PMC
January 2017