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1.  Metastasis to the gallbladder: A single-center experience of 20 cases in South Korea 
AIM: To evaluate the clinicopathologic characteristics of patients with metastases to the gallbladder (MGBs).
METHODS: We performed a single-center retrospective study of 20 patients with MGBs diagnosed pathologically from 1999 to 2007.
RESULTS: Among 417 gallbladder (GB) malignancies, 20 (4.8%) were MGBs. The primary malignancies originated from the stomach (n = 8), colorectum (n = 3), liver (n = 2), kidney (n = 2), skin (n = 2), extrahepatic bile duct (n = 1), uterine cervix (n = 1), and appendix (n = 1). Twelve patients were diagnosed metachronously, presenting with cholecystitis (n = 4), abdominal pain (n = 2), jaundice (n = 1), weight loss (n = 1), and serum CA 19-9 elevation (n = 1); five patients were asymptomatic. The median survival after the diagnosis of MGB was 8.7 mo. On Cox regression analysis, R0 resection was the only factor associated with a prolonged survival [hazard ratio (HR): 0.01, P = 0.002]; presentation with cholecystitis was associated with poor survival (HR: 463.27, P = 0.006).
CONCLUSION: MGBs accounted for 4.8% of all pathologically diagnosed GB malignancies. The most common origin was the stomach. The median survival of MGB was 8.7 mo.
PMCID: PMC2761559  PMID: 19824115
Gallbladder; Neoplasms; Gastrointestinal neoplasms; Neoplasm metastasis; Biliary tract neoplasms
2.  Clobenpropit enhances anti-tumor effect of gemcitabine in pancreatic cancer 
AIM: To evaluate the anti-tumor effect of clobenpropit, which is a specific H3 antagonist and H4 agonist, in combination with gemcitabine in a pancreatic cancer cell line.
METHODS: Three kinds of human pancreatic cancer cell lines (Panc-1, MiaPaCa-2, and AsPC-1) were used in this study. Expression of H3 and H4 receptors in pancreatic cancer cells was identified with Western blotting. Effects of clobenpropit on cell proliferation, migration and apoptosis were evaluated. Alteration of epithelial and mesenchymal markers after administration of clobenpropit was analyzed. An in vivo study with a Panc-1 xenograft mouse model was also performed.
RESULTS: H4 receptors were present as 2 subunits in human pancreatic cancer cells, while there was no expression of H3 receptor. Clobenpropit inhibited cell migration and increased apoptosis of pancreatic cancer cells in combination with gemcitabine. Clobenpropit up-regulated E-cadherin, but down-regulated vimentin and matrix metalloproteinase 9 in real-time polymerase chain reaction. Also, clobenpropit inhibited tumor growth (gemcitabine 294 ± 46 mg vs combination 154 ± 54 mg, P = 0.02) and enhanced apoptosis in combination with gemcitabine (control 2.5%, gemcitabine 25.8%, clobenpropit 9.7% and combination 40.9%, P = 0.001) by up-regulation of E-cadherin and down-regulation of Zeb1 in Panc-1 xenograft mouse.
CONCLUSION: Clobenpropit enhanced the anti-tumor effect of gemcitabine in pancreatic cancer cells through inhibition of the epithelial-mesenchymal transition process.
PMCID: PMC4093704  PMID: 25024609
Clobenpropit; Epithelial-mesenchymal transition; Histamine; Histamine receptors; Pancreatic neoplasm
3.  Non-surgical treatment of post-surgical bile duct injury: Clinical implications and outcomes 
AIM: To investigate the prognostic factors determining the success rate of non-surgical treatment in the management of post-operative bile duct injuries (BDIs).
METHODS: The study patients were enrolled from the pancreatobiliary units of a tertiary teaching hospital for the treatment of BDIs after hepatobiliary tract surgeries, excluding operations for liver transplantation and malignancies, from January 1999 to August 2010. A total of 5167 patients underwent operations, and 77 patients had BDIs following surgery. The primary end point was the treatment success rate according to different types of BDIs sustained using endoscopic or percutaneous hepatic approaches. The type of BDI was defined using one of the following diagnostic tools: endoscopic retrograde cholangiography, percutaneous transhepatic cholangiography, computed tomography scan, and magnetic resonance cholangiography. Patients with a final diagnosis of BDI underwent endoscopic and/or percutaneous interventions for the treatment of bile leak and/or stricture if clinically indicated. Patient consent was obtained, and study approval was granted by the Institutional Review Board in accordance with the legal regulations of the Human Clinical Research Center at the Seoul National University Hospital in Seoul, South Korea.
RESULTS: A total of 77 patients were enrolled in the study. They were divided into three groups according to type of BDI. Among them, 55 patients (71%) underwent cholecystectomy. Thirty-six patients (47%) had bile leak only (type 1), 31 patients had biliary stricture only (type 2), and 10 patients had both bile leak and biliary stricture (type 3). Their initial treatment modalities were non-surgical. The success rate of non-surgical treatment in each group was as follows: BDI type 1: 94%; type 2: 71%; and type 3: 30%. Clinical parameters such as demographic factors, primary disease, operation method, type of operation, non-surgical treatment modalities, endoscopic procedure steps, type of BDI, time to diagnosis and treatment duration were evaluated to evaluate the prognostic factors affecting the success rate. The type of BDI was a statistically significant prognostic factor in determining the success rate of non-surgical treatment. In addition, a shorter time to diagnosis of BDI after the operation correlated significantly with higher success rates in the treatment of type 1 BDIs.
CONCLUSION: Endoscopic or percutaneous hepatic approaches can be used as an initial treatment in type 1 and 2 BDIs. However, surgical intervention is a treatment of choice in type 3 BDI.
PMCID: PMC4051933  PMID: 24944484
Endoscopic retrograde cholangiography; Percutaneous transhepatic cholangiography; Percutaneous transhepatic biliary drainage; Bile duct; Biliary stricture.
4.  Long-Term Outcome of Cystic Lesions in the Pancreas: A Retrospective Cohort Study 
Gut and Liver  2012;6(4):493-500.
The management guidelines for cystic lesions of the pancreas (CLPs) are not yet well established. This study was performed to document the long-term clinical outcome of CLPs and provide guidelines for the management and surveillance of CLPs.
In this retrospective cohort study, an additional follow-up was performed in 112 patients with CLPs enrolled from 1998 to 2004 during a previous study.
During follow-up for the median period of 72.3 months, the size of the CLPs increased in 18 patients (16.1%). Six of these patients experienced growth of their CLPs after 5 years of follow-up. Twenty-six patients underwent surgery during follow-up, and four malignant cysts were detected. The overall rate of malignant progression during follow-up was 3.6%. The presence of mural nodules or solid components was independently associated with the presence of malignant CLPs. Seven patients underwent surgery after 5 years of follow-up. The pathologic findings revealed malignancies in two patients. There was only one pancreas-related death during follow-up.
The majority of CLPs exhibit indolent behavior and are associated with a favorable prognosis. However, long-term surveillance for more than 5 years should be performed because of the potential for growth and malignant transformation in CLPs.
PMCID: PMC3493732  PMID: 23170156
Pancreatic cyst; Natural history; Prognosis
5.  Endoscopic management of occluded metal biliary stents: Metal versus 10F plastic stents 
AIM: To compare the efficacy of self-expandable metal stents (SEMSs) with 10F plastic stents (PSs) in the endoscopic management of occluded SEMSs.
METHODS: We retrospectively reviewed the medical records of 56 patients who underwent SEMS insertion for palliation of unresectable malignant biliary obstruction between 2000 and 2007 and subsequent endoscopic retrograde biliary drainage (ERBD) with SEMS or PS for initial SEMS occlusion between 2000 and 2008.
RESULTS: Subsequent ERBD with SEMS was performed in 29 patients and with PS in 27. The median time to stent occlusion after subsequent ERBD was 186 d in the SEMS group and 101 d in the PS group (P = 0.118). Overall median stent patency was 79 d for the SEMS group and 66 d for the PS group (P = 0.379). The mean number of additional biliary drainage procedures after subsequent ERBD in patients that died (n = 50) during the study period was 2.54 ± 4.12 for the SEMS group and 1.85 ± 1.95 for the PS group (P = 0.457). The mean total cost of additional biliary drainage procedures after the occlusion of subsequent SEMS or PS was $410.04 ± 692.60 for the SEMS group and $630.16 ± 671.63 for the PS group (P = 0.260). Tumor ingrowth as the cause of initial SEMS occlusion was the only factor associated with a shorter time to subsequent stent occlusion (101 d for patients with tumor ingrowth vs 268 d for patients without tumor ingrowth, P = 0.008).
CONCLUSION: Subsequent ERBD with PSs offered similar patency and number of additional biliary drainage procedures compared to SEMSs in the management of occluded SEMS.
PMCID: PMC2980685  PMID: 21072899
Stents; Biliary tract neoplasms; Obstructive jaundice; Endoscopy; Endoscopic retrograde cholangiopancreatography
6.  Secondary Appendiceal Tumors: A Review of 139 Cases 
Gut and Liver  2010;4(3):351-356.
This study evaluated the clinicopathologic characteristics of patients with secondary appendiceal tumors (SATs).
We performed a single-center, retrospective study of patients with pathologically confirmed SATs.
Among 180 cases of appendiceal malignancies diagnosed between 2000 and 2007, 139 cases (77.2%, 46 male) were SATs. The median age at SAT diagnosis was 55 years. The most common primary origin was the ovary. The mode of appendiceal involvement was metastasis in 122 and invasion in 17 patients. Extra-appendiceal involvement was present in 134 patients. The only manifestation that could be attributed to the SAT itself was appendicitis (n=8). Serosal involvement was predominant. The median survival after diagnosis of SAT was 22.6 months. In the Cox regression analysis, chemotherapy included in the treatment was the only factor associated with prolonged survival (hazards ratio, 0.12; 95% confidence interval, 0.06-0.23; p<0.001). Complete resection of the SAT had no influence on survival.
SATs accounted for 77.2% of all pathologically diagnosed appendiceal malignancies. The most common origin was the ovary. SATs were usually associated with widespread disease, and the median survival after SAT diagnosis was 22.6 months. Complete resection of the SAT had no influence on survival.
PMCID: PMC2956347  PMID: 20981212
Neoplasms; Appendix; Secondary
7.  Primary Pancreatic Lymphoma in Korea-A Single Center Experience 
Journal of Korean Medical Science  2010;25(4):536-540.
The aim of this study was to report a single center experience of primary pancreatic lymphoma (PPL) in Korea. We analyzed the clinicopathological data from four PPL patients (three male, median age 36 yr) diagnosed from 1997 to 2007 at Seoul National University Hospital. The diagnoses were: diffuse large B cell lymphoma (n=2), Ki-1 (+) anaplastic large cell lymphoma (n=1), and Burkitt lymphoma (n=1). Presenting symptoms and signs were: abdominal pain (n=4), pancreatitis (n=2), weight loss (n=2) and abdominal mass (n=1). No patient underwent surgery. The Ann Arbor stages of the patients were: IEA (n=1), IIEA (n=1), and IVEB (n=2). Two patients underwent treatment. The stage IEA patient underwent chemotherapy and radiation therapy that resulted in a complete remission. The stage IVEB patient who underwent chemotherapy relapsed. This patient underwent subsequent peripheral blood stem cell transplantation and is alive at 30 months. Two patients (stages IVEB and IIEA) without treatment died at 0.8 and 7.0 months, respectively. For PPL patients, chemotherapy-based treatment, and addition of radiation therapy, if possible, may offer good prognosis.
PMCID: PMC2844603  PMID: 20357994
Pancreas; Lymphoma
8.  Prevalence of clonorchiasis in patients with gastrointestinal disease: A Korean nationwide multicenter survey 
AIM: To investigate prevalence of Clonorchis sinensis in patients with gastrointestinal symptoms, and the relation of the infection to hepatobiliary diseases in 26 hospitals in Korea.
METHODS: Consecutive patients who had been admitted to the Division of Gastroenterology with gastrointestinal symptoms were enrolled from March to April 2005. Of those who had been diagnosed with clonorchiasis, epidemiology and correlation between infection and hepatobiliary diseases were surveyed by questionnaire.
RESULTS: Of 3080 patients with gastrointestinal diseases, 396 (12.9%) had clonorchiasis and 1140 patients (37.2%) had a history of eating raw freshwater fish. Of those with a history of raw freshwater fish ingestion, 238 (20.9%) patients had clonorchiasis. Cholangiocarcinoma was more prevalent in C. sinensis-infected patients than non-infected patients [34/396 (8.6%) vs 145/2684 (5.4%), P = 0.015]. Cholangiocarcinoma and clonorchiasis showed statistically significant positive cross-relation (P = 0.008). Choledocholithiasis, cholecystolithiasis, cholangitis, hepatocellular carcinoma, and biliary pancreatitis did not correlate with clonorchiasis.
CONCLUSION: Infection rate of clonorchiasis was still high in patients with gastrointestinal diseases in Korea, and has not decreased very much during the last two decades. Cholangiocarcinoma was related to clonorchiasis, which suggested an etiological role for the parasite.
PMCID: PMC2653299  PMID: 19115472
Clonorchis sinensis; Epidemiology; Cholangiocarcinoma; Korea; Multicenter study; Clonorchiasis
9.  Management Strategies for Gallbladder Polyps: Is It Possible to Predict Malignant Gallbladder Polyps? 
Gut and Liver  2008;2(2):88-94.
Gallbladder (GB) polyps are commonly encountered in clinical practice, and are found more frequently as the number of medical screening examinations increases. The aim of this study was to determine optimal practice guideline for surgical treatment and follow-up of GB polyps.
Data from healthy subjects of Seoul National University Hospital (SNUH) Health Care System of Gangnam Center were used to investigate the true prevalence of GB polyps. We also enrolled 689 patients with GB polyps diagnosed at SNUH from May 1st, 1988 to April 30th, 2006.
The GB polyp prevalence was 6.1% (7.1% in males and 4.8% in females). The median follow-up duration in the 689 study patients was 60 months, and 139 (20%) of them had polyps ≥10 mm in size. Twenty-five of the 180 patients who underwent cholecystectomy had adenocarcinomas. The χ2 test was used to identify which of the following were risk factors of malignancy: age, sex, symptoms, size, rate of growth, multiplicity, accompanying stones, and shape. Age (≥57 years), presence of symptoms, size (≥10 mm), and shape (sessile) were found to be statistically significant risk factors by univariate analysis. However, multivariate analysis identified only age (≥57 years) and size (≥10 mm) as independent predictors of malignancy.
The present study shows that GB polyps ≥10 mm in size in patients aged ≥57 years are the independent factors predicting malignancy of the GB.
PMCID: PMC2871589  PMID: 20485616
Gallbladder; Polyp; Cholecystectomy
10.  Optimal biliary drainage for inoperable Klatskin's tumor based on Bismuth type 
AIM: To investigate differences in the effects of biliary drainage procedures in patients with inoperable Klatskin’s tumor based on Bismuth type, considering endoscopic retrograde biliary drainage (ERBD), external percutaneous transhepatic biliary drainage (EPTBD) and internal biliary stenting via the PTBD tract (IPTBD).
METHODS: The initial success rate, cumulative patency rate, and complication rate were compared retrospectively, according to the Bismuth type and ERBD, EPTBD, and IPTBD. Patency was defined as the duration for adequate initial bile drainage or to the point of the patient’s death associated with inadequate drainage.
RESULTS: One hundred thirty-four patients (93 men, 41 women; 21 Bismuth type II, 47 III, 66 IV; 34 ERBD, 66 EPTBD, 34 IPTBD) were recruited. There were no differences in demographics among the groups. Adequate initial relief of jaundice was achieved in 91% of patients without a significant difference in the results among different procedures or Bismuth types. The cumulative patency rates for ERBD and IPTBD were better than those for EPTBD with Bismuth type III. IPTBD provided an excellent response for Bismuth type IV. However, there was no difference in the patency rate among drainage procedures for Bismuth type II. Procedure-related cholangitis occurred less frequently with EPTBD than with ERBD and IPTBD.
CONCLUSION: ERBD is recommended as the first-line drainage procedure for the palliation of jaundice in patients with inoperable Klatskin’s tumor of Bismuth type II or III, but IPTBD is the best option for Bismuth type IV.
PMCID: PMC4171166  PMID: 17663508
Klatskin's tumor; Palliation; Drainage; Bile ducts; Intervention
11.  Histologic characteristics of gastric polyps in Korea: Emphasis on discrepancy between endoscopic forceps biopsy and endoscopic mucosal resection specimen 
AIM: To investigate histological characteristics of gastric polyps in the Korean population.
METHODS: We reviewed endoscopic photographs and medical records of patients with gastric polyps who underwent endoscopic mucosal resection from April 1996 through February 2003.
RESULTS: A total of 85 gastric polyps from 74 patients were reviewed. Male-to-female ratio was 1:1.96. Mean age was 59.9 ± 10.8 years. Multiple polyps were observed in 10.8%. Gastric polyps occurred most frequently in the antrum (58.8%). Pathological results on resected specimens were as follows: tubular adenoma 45.9%, hyperplastic polyp 31.8%, inflammatory polyp 9.4%, hamartoma 3.5%, fundic gland polyp 2.4%, tubulovillous adenoma 2.4%, adenocarcinoma 2.4%, dysplasia 1.1%, and mucosal pseudolipomatosis 1.1%. Discrepancy rate between endoscopic biopsy and pathology of resected specimens was 27.1%. There was no relationship between the size of the polyp and concordance rate.
CONCLUSION: There is considerable discrepancy in histologic findings between endoscopic forceps biopsy and resected specimens. Approaches to review of the histology of an entire polyp should be performed, especially when an adenoma is suspected.
PMCID: PMC4087715  PMID: 16810753
Polyp; Gastric; Histology
12.  Risk factors of acute cholecystitis after endoscopic common bile duct stone removal 
AIM: To evaluate the risk factors of acute cholecystitis after endoscopic common bile duct (CBD) stone removal.
METHODS: A total 100 of patients who underwent endoscopic CBD stone removal with gallbladder (GB) in situ without subsequent cholecystectomy from January 2000 to July 2004 were evaluated retrospectively. The following factors were considered while evaluating risk factors for the development of acute cholecystitis: age, gender, serum bilirubin level, GB wall thickening, cystic duct patency, presence of a GB stone, CBD diameter, residual stone, lithotripsy, juxtapapillary diverticulum, presence of liver cirrhosis or diabetes mellitus, a presenting illness of cholangitis or pancreatitis, and procedure-related complications.
RESULTS: During a mean 18-mo follow-up, 28 (28%) patients developed biliary symptoms; 17 (17%) acute cholecystitis and 13 (13%) CBD stone recurrence. Of patients with acute cholecystitis, 15 (88.2%) received laparoscopic cholecystectomy and 2 (11.8%) open cholecystectomy. All recurrent CBD stones were successfully removed endoscopically. The mean time elapse to acute cholecystitis was 10.2 mo (1-37 mo) and that to recurrent CBD stone was 18.4 mo. Of the 17 patients who received cholecystectomy, 2 (11.8%) developed recurrent CBD stones after cholecystectomy. By multivariate analysis, a serum total bilirubin level of
<1.3 mg/dL and a CBD diameter of <11 mm at the time of stone removal were found to predict the development of acute cholecystitis.
CONCLUSION: After CBD stone removal, there is no need for routine prophylactic cholecystectomy. However, patients without a dilated bile duct (<11 mm) and jaundice (<1.3 mg/dL) at the time of CBD stone removal have a higher risk of acute cholecystitis and are possible candidates for prophylactic cholecystectomy.
PMCID: PMC4066164  PMID: 16521227
Sphincterotomy; Choledocholithiasis; Acute cholecystitis; Cholecystectomy
13.  Clinical Significance and Revisiting the Meaning of CA 19-9 Blood Level Before and After the Treatment of Pancreatic Ductal Adenocarcinoma: Analysis of 1,446 Patients from the Pancreatic Cancer Cohort in a Single Institution 
PLoS ONE  2013;8(11):e78977.
Life expectancy of pancreatic ductal adenocarcinoma (PDAC) patients is usually short and selection of the most appropriate treatment is crucial. The aim of this study was to investigate the usefulness of serum CA 19-9 as a surrogate marker under no impress excluding other factors affecting CA 19-9 level other than tumor itself.
We recruited 1,446 patients with PDACs and patients with Lewis antigen both negative or obstructive jaundice were excluded to eliminate the false effects on CA 19-9 level. The clinicopathologic factors were reviewed including initial and post-treatment CA 19-9, and statistical analysis was done to evaluate the association of clinicopathologic factors with overall survival (OS).
The total of 944 patients was enrolled, and205 patients (22%) underwent operation with curative intention and 541 patients (57%) received chemotherapy and/or radiotherapy. The median CA 19-9 levels of initial and post-treatment were 670 IU/ml and 147 IU/ml respectively. The prognostic factors affecting OS were performance status, AJCC stage and post-treatment CA 19-9 level in multivariate analysis. Subgroup analysis was done for the patients who underwent R0 and R1 resection, and patients with normalized post-operative CA 19-9 (≤37 IU/mL) had significantly longer OS and DFS regardless of initial CA 19-9 level; 32 vs. 18 months, P<0.001, 16 vs. 9 months, P = 0.004 respectively.
Post-treatment CA 19-9 and normalized post-operative CA 19-9 (R0 and R1 resected tumors) were independent factors associated with OS and DFS, however, initial CA 19-9 level was not statistically significant in multivariate analysis.
PMCID: PMC3826753  PMID: 24250822
14.  A Multicenter Phase II Trial of Gemcitabine Plus Oxaliplatin in Unresectable Gallbladder Cancer 
Gut and Liver  2013;7(5):594-598.
No standard chemotherapy has been established for advanced gallbladder cancer. The authors studied the activity and tolerability of a gemcitabine and oxaliplatin (GEMOX) combination in unresectable gallbladder cancer (GBC).
Adult patients with pathologically confirmed unresectable GBC were prospectively recruited at three centers. No patient had received prior chemotherapy or radiotherapy. Patients received cycles of gemcitabine at 1,000 mg/m2 on day 1, followed by oxaliplatin at 100 mg/m2 on day 2, every 2 weeks. The primary study endpoint was time to progression.
Forty patients with unresectable GBC were enrolled. The median age was 60 years (range, 38 to 79 years). All patients showed good performance status. Of the 33 analyzable patients, 12 achieved partial response (36%), 17 stable disease (52%), and four progressive disease (12%). No patient achieved a complete response. The tumor control rate was 88%. At a median follow-up of 6.8 months, the median time to progression was 5.3 months (95% confidence interval [CI], 3.7 to 6.9), and median overall survival was 6.8 months (95% CI, 6.1 to 7.5). Nine of the 40 patients (23%) experienced at least a grade-3 adverse event, but no patient experienced a grade-4 adverse event.
GEMOX combination therapy is a feasible option and is well tolerated in unresectable GBC.
PMCID: PMC3782675  PMID: 24073318
Gallbladder neoplasms; Gemcitabine; Oxaliplatin
15.  Clinical Usefulness of Plasma Chromogranin A in Pancreatic Neuroendocrine Neoplasm 
Journal of Korean Medical Science  2013;28(5):750-754.
Chromogranin A (CgA) is widely used as an immunohistochemical marker of neuroendocrine neoplasms and has been measurable in plasma of patients. We assessed the clinical role of plasma CgA in diagnosing pancreatic neuroendocrine neoplasm (PNEN). CgA was checked in 44 patients with pancreatic mass who underwent surgical resection from 2009 through 2011. The cutoff value for diagnosing PNEN and the relationships between CgA and clinicopathologic variables were analyzed. Twenty-six patients were PNENs and 18 patients were other pancreatic disorders. ROC analysis showed a cutoff of 60.7 ng/mL with 77% sensitivity and 56% specificity, and the area under the curve (AUC) was 0.679. Among PNEN group, the sensitivity and specificity of diagnosing metastasis were 100% and 90% respectively when CgA cutoff was 156.5 ng/mL. The AUC was 0.958. High Ki-67 index (160.8 vs 62.1 ng/mL, P = 0.001) and mitotic count (173.5 vs 74.6 ng/mL, P = 0.044) were significantly correlated with plasma CgA, but the tumor size was not. In conclusion, CgA has a little value in diagnosing PNEN. However, the high level of CgA (more than 156.5 ng/mL) can predict the metastasis. Also, plasma CgA level correlates with Ki-67 index and mitotic count which represents prognosis of PNENs.
PMCID: PMC3653089  PMID: 23678268
Pancreatic Neuroendocrine Neoplasm; Chromogranin A; Diagnosis; Pancreatic Neoplasms
16.  A Case of Common Bile Duct Cancer That Completely Responded to Combination Chemotherapy of Gemcitabine and TS-1 
Gut and Liver  2013;7(3):371-376.
Common bile duct (CBD) cancer is a relatively rare malignancy that arises from the biliary epithelium and is associated with a poor prognosis. Here, we report a case of advanced metastatic CBD cancer successfully treated by chemotherapy with gemcitabine combined with S-1 (tegafur+gimeracil+oteracil). A 65-year-old male presented with pyogenic liver abscess. After antibiotic therapy and percutaneous drainage, follow-up computed tomography (CT) showed an enhanced nodule in the CBD. Biopsy was performed at the CBD via endoscopic retrograde cholangiopancreatography, which showed adenocarcinoma. Additional CT and magnetic resonance imaging showed multiple small nodules in the right hepatic lobe, which were confirmed as metastatic adenocarcinoma by sono-guided liver biopsy. The patient underwent combination chemotherapy with gemcitabine and S-1. After nine courses of chemotherapy, the hepatic lesion disappeared radiologically. Pylorus-preserving pancreaticoduodenectomy was performed, and no residual tumor was found in the resected specimen. Three weeks after the operation, the patient was discharged with no complications. Through 3 months of follow-up, no sign of recurrence was observed on CT scan. Gemcitabine combined with S-1 may be a highly effective treatment for advanced cholangiocarcinoma.
PMCID: PMC3661972  PMID: 23710321
Cholangiocarcinoma; Gemcitabine; S-1
17.  Risk Factors of Post Endoscopic Retrograde Cholangiopancreatography Bacteremia 
Gut and Liver  2012;7(2):228-233.
Bacteremia following endoscopic retrograde cholangiopancreatography (ERCP) is a severe complication, but the risk factors for this condition have not yet been clearly determined. Thus, the aim of this study was to investigate the risk factors of post-ERCP bacteremia.
Among patients who underwent ERCP from June 2006 to May 2009, we selected patients without any signs of infection prior to the ERCP procedures. Of these patients, we further selected those who experienced bacteremia after ERCP as well as two-fold age and sex-matched controls who did not experience bacteremia after ERCP procedures. We compared clinical, laboratory and technical aspects between these two groups.
There were 70 patients (3.1%) who developed bacteremia after ERCP. In the multivariate analysis, a history of previous liver transplantation, an elevated serum alkaline phosphatase level and an endoscopic retrograde biliary drainage procedure were independent risk factors of post-ERCP bacteremia (p=0.006, p=0.001, and p=0.004, respectively). The microbiologic analysis revealed the presence of gram-negative organisms in 80% of the cases, and 11 patients had infections with bacteria expressing extended spectrum β-lactamases. Pseudomonas infection was significantly more common in patients who received liver transplantation as compared to patients without transplantation (p=0.014).
A history of liver transplantation, elevated serum alkaline phosphatase levels and endoscopic retrograde biliary drainage procedure were independent risk factors of post-ERCP bacteremia and require additional attention in future studies.
PMCID: PMC3607778  PMID: 23560160
Bacteremia; Endoscopic retrograde cholangiopancreatography; Liver transplantation; Alkaline phosphatase; Endoscopic retrograde biliary drainage
18.  Endoscopic Papillectomy for Benign Ampullary Neoplasms: How Can Treatment Outcome Be Predicted? 
Gut and Liver  2013;7(2):239-245.
Endoscopic papillectomy is increasingly performed with curative intent for benign papillary tumors. This study was performed to identify factors that predict the presence of malignancy and affect endoscopic success.
We retrospectively analyzed the medical records of patients who received an endoscopic papillectomy for papillary adenoma from 2006 to 2009.
A total of 43 patients received endoscopic papillectomy. The pathologic results after papillectomy revealed adenocarcinoma in five patients (12%), and the risk of malignancy was high in cases of large lesions, preprocedural pathology of high-grade dysplasia or high serum alkaline phosphatase. Endoscopic success was observed in 37 patients (86%) at the end of follow-up (mean duration, 10.4±9.6 months). The factor significantly affecting success was a complete resection at the initial papillectomy (p=0.007). Two patients experienced recurrence 10 and 32 months after the complete resection, but both achieved endoscopic success with repeated endoscopic treatment. Six patients with endoscopic failure received surgical resection.
Endoscopic papillectomy is a safe and effective method for the curative resection of benign papillary tumors, especially when complete resection is achieved at the initial papillectomy. Follow-up with surveillance should be performed for at least 3 years because of the possible recurrence of tumors during these periods.
PMCID: PMC3607780  PMID: 23560162
Endoscopic sphincterotomy; Benign papillary tumor; Adenocarcinoma; Endoscopic success
19.  Pancreatic Pseudocyst after Endoscopic Ultrasound-Guided Fine Needle Aspiration of Pancreatic Mass 
Clinical Endoscopy  2012;45(4):431-434.
Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is well known as a safe diagnostic procedure. We report the first case of pancreatic pseudocyst after EUS-FNA of the pancreatic body mass. A 60-year-old male underwent EUS-FNA for incidentally detected pancreatic solid mass which was suspected as neuroendocrine tumor. Two weeks later, the patient visited emergency room with acute abdominal pain and right upper quadrant tenderness; leukocytosis and elevated C-reactive protein, amylase, and lipase levels were noted. Computed tomography discovered newly developed 11.5×9.5 cm sized cystic mass communicating with the main pancreatic duct. Cyst fluid analysis revealed amylase level of 3,423 U/L and fluid culture isolated Streptococcus parasanguinis. The cystic mass corresponds with pancreatic pseudocyst. FNA induced main pancreatic duct injury and fluid leakage may cause it. Endoscopists who perform EUS-FNA must remember that pancreatic main duct injury can occur as one of severe complications and that it could be treated successfully with endoscopic internal drainage.
PMCID: PMC3521949  PMID: 23251895
Pancreatic pseudocyst; Endosonography; Fine-needle biopsy; Complications
20.  Proposal of an endoscopic retrograde cholangiopancreatography-related perforation management guideline based on perforation type 
Consensus for endoscopic retrograde cholangiopancreatography (ERCP) related perforation management is lacking. We aimed to identify candidate patients for conservative management by examining treatment results and to introduce a simple, algorithm-based management guideline.
A retrospective review of 53 patients with ERCP-related perforation between 2000 and 2010 was conducted. Data on perforation site (duodenum lateral wall or jejunum, type I; para-Vaterian, type II), management method, complication, mortality, hospital stay, and hospital cost were reviewed. Comparative analysis was done according to the injury types and management methods.
The outcome was greater in the conservative group than the operative group with shorter hospital stay (20.6 days vs. 29.8 days, P = 0.092), less cost (10.6 thousand United States Dollars [USD] vs. 19.9 thousand USD, P = 0.095), and lower morbidity rate (22.9% vs. 55.6%, P = 0.017). Eighty-one percent (17/21) of type I injuries were operatively managed and 96.9% (31/32) of type II injuries were conservatively managed. Between the types, type II showed better results over type I with shorter hospital stay (19.3 days vs. 30.6 days, P = 0.010), less cost (9.5 thousand USD vs. 20.1 thousand USD, P = 0.028), and lower complication rate (18.8% vs. 57.1%, P = 0.004). There was no difference in mortality.
Type II injuries were conservatively manageable and demonstrated better outcomes than type I injuries. The management algorithm suggests conservative management in type II injuries without severe peritonitis or unsolved problem requires immediate surgical correction, including operative management in type I injuries unless endoscopic intervention is possible. Conservative management offers socio-medical benefits. Conservative management is recommended in well-selected patients.
PMCID: PMC3467388  PMID: 23091794
Endoscopic retrograde cholangiopancreatography; Intestinal perforation; Guideline; Algorithms
21.  Prevalence of Gastric and Duodenal Polyps and Risk Factors for Duodenal Neoplasm in Korean Patients with Familial Adenomatous Polyposis 
Gut and Liver  2011;5(1):46-51.
The prevalence of gastric polyps, duodenal adenoma and duodenal cancer has been reported as being high among familial adenomatous polyposis (FAP) patients, but there have been no reports of this association in Korea. This study evaluated the prevalence of gastric and duodenal polyps and risk factors for duodenal neoplasm in FAP patients in Korea.
We reviewed both initial and follow-up endoscopic results from FAP patients. We also investigated the treatment modality of duodenal adenomas and analyzed the risk factors of duodenal neoplasms by logistic regression analysis.
A total of 148 patients with FAP underwent esophagogastroduodenoscopy (EGD), and the fi ndings were as follows: gastric polyp 39.9% (fundic gland polyp 25.7% and gastric adenoma 14.2%), duodenal adenoma 15.5%, gastric cancer 2.7%, and duodenal cancer 0.7%. There were two cases of gastric cancer that developed from benign gastric polyps. There were progressions of duodenal adenomatosis during follow-up, and some degree of relapse occurred after endoscopic resection. Patients with gastric polyps showed a correlation with the occurrence of duodenal neoplasm (odds ratio, 2.814; p=0.024).
In Korean FAP patients, gastric cancer was detected more frequently, but fundic gland polyps, duodenal adenoma and duodenal cancer were detected less frequently than in Western patients. FAP patients with gastric polyps should undergo regular EGD, particularly for the early detection of duodenal neoplasia.
PMCID: PMC3065092  PMID: 21461071
Familial adenomatous polyposis; Duodenal cancer; Polyps; Adenomas; Gastric cancer
22.  Clinical Features of Metastatic Tumors of the Pancreas in Korea: A Single-Center Study 
Gut and Liver  2011;5(1):61-64.
The purpose of this study was to examine the clinical features of metastatic tumors of the pancreas (MTPs) in Korea.
A total of 53 cases (31 males) of pathologically proven MTPs were collected. Clinicopathological characteristics and patient outcomes were evaluated.
The median age at the diagnosis of the MTP was 60 years. The median interval between the diagnoses of primary malignancy and MTP was 2.2 years. Primary malignancies were renal cell carcinoma (RCC) (n=14), gastric cancer (n=11), colorectal cancer (n=5), lymphoma (n=4), non-small cell lung cancer (n=3), gastrointestinal stromal tumor (n=2), melanoma (n=2), small cell lung cancer (n=2), gallbladder cancer (n=2), hepatocellular carcinoma (n=1), thymic carcinoid (n=1), liposarcoma (n=1), cholangiocarcinoma (n=1), osteosarcoma (n=1), breast cancer (n=1), duodenal cancer (n=1), and ovarian cancer (n=1). The median survival after the diagnosis of MTP was 23.1 months. Multivariate analysis showed that prolonged survival was associated with RCC as the primary malignancy, the patient being asymptomatic upon the diagnosis of MTP, the absence of extrapancreatic involvement, and surgery included in the treatment.
MTPs can occur after a prolonged period from the primary diagnosis. RCC as the primary malignancy, the patient being asymptomatic upon the diagnosis of MTP, the absence of extrapancreatic involvement, and surgery included in the treatment are associated with better prognosis.
PMCID: PMC3065095  PMID: 21461074
Pancreas; Neoplasms; Neoplasm metastasis; Renal cell carcinoma; Stomach neoplasms
23.  Hepatopulmonary Syndrome in Poorly Compensated Postnecrotic Liver Cirrhosis by Hepatitis B Virus in Korea 
Hepatopulmonary syndrome (HPS) refers to the association of hypoxemia, intrapulmonary shunting and chronic liver disease. But there is no clear data about the prevalence of HPS in postnecrotic liver cirrhosis by hepatitis B virus (HBV), the most common cause of liver disease in Korea. The aim of this study was to investigate the prevalence of HPS in poorly compensated postnecrotic liver cirrhosis by HBV, and the correlation of the hepatopulmonary syndrome with clinical aspects of postnecrotic liver cirrhosis by HBV.
Thirty-five patients underwent pulmonary function test, arterial blood gas analysis and contrast-enhanced echocardiography. All patients were diagnosed as HBV-induced Child class C liver cirrhosis and had no evidence of intrinsic cardiopulmonary disease.
Intrapulmonary shunt was detected in 6/35 (17.1%) by contrast-enhanced echocardiography. Two of six patients with intrahepatic shunts had significant hypoxemia (PaO2 < 70 mmHg) and four showed increased alveolar-arterial oxygen gradient over 20 mmHg. Only cyanosis could reliably distinguish between shunt positive and negative patients.
The prevalence of intrapulmonary shunt in poorly compensated postnecrotic liver cirrhosis by HBV was 17.1% and the frequency of hepatopulmonary syndrome was relatively low (5.7%). ‘Subclinical’ hepatopulmonary syndrome (echocardiographically positive intrapulmonary shunt but without profound hypoxemia) exists in 11.4% of cases with poorly compensated postnecrotic liver cirrhosis by HBV. Cyanosis is the only reliable clinical indicator of HPS of HBV-induced poorly compensated liver cirrhosis. Further studies are required to determine if the prevalence and clinical manifestations of HPS varies with etiology or with geographical and racial differences.
PMCID: PMC4531714  PMID: 11590902
Hepatopulmonary syndrome; Contrast echocardiography; Liver cirrhosis; Hepatitis B virus
24.  Association Between Genetic Polymorphisms of the Cytochromes P-450 (1A1, 2D6, and 2E1) and the Susceptibility to Pancreatic Cancer 
Metabolic activation is a prerequisite for the carcinogenic effect of many carcinogens, and considerable interindividual variation exists in the metabolic capacity to activate the carcinogens. The cytochromes P-450 (CYPs) are responsible for the activation mechanism, and polymorphisms of the CYPs (CYP1A1, CYP2D6, and possibly CYP2E1) are known to be related to increased susceptibility to smoking-related Kreyberg type I lung cancer. The aim of this study is to clarify the relationship of genetic polymorphisms of the CYPs to susceptibility to pancreatic cancer, another smoking-related cancer.
We analyzed 45 samples from patients with pancreatic cancer and 53 samples from controls. DNA was isolated from blood samples and the CYP1A1, 2D6 and 2E1 genes were amplified by PCR. Analyzing the genotypes of the CYPs by allele-specific PCR or RFLP analysis, we assessed the allele frequencies for each mutation of the CYPs among the patients with pancreatic cancer and the controls.
The allele frequencies for the mutation in the 3′-flanking region of the CYP1A1 among the cases and the controls were 0.31 and 0.36, respectively. The allele frequencies for the exon 7 mutation of the CYP1A1 were 0.16 and 0.23, respectively, but with no statistical significance. The frequencies for the mutant c2 allele of the CYP2E1 were 0.19 and 0.30, respectively, but with no statistical significance. Two persons homozygous for a gene deletion of the CYP2D6 were observed among control subjects: other mutations were not observed among either the patients or controls.
We could not find any evidence that polymorphisms of the CYPs are associated with increased susceptibility to pancreatic cancer.
PMCID: PMC4531995  PMID: 9439147
Pancreatic cancer; Cytochrome; Polymorphism

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