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1.  Systematic review on the surgical treatment for T1 gallbladder cancer 
AIM: To evaluate the efficacy of simple and extended cholecystectomy for mucosa (T1a) or muscularis (T1b) gallbladder (GB) cancer.
METHODS: Original studies on simple and extended cholecystectomy for T1a or T1b GB cancer were searched from MEDLINE (PubMed), Cochrane Library, EMBase, and CancerLit using the search terms of GB, cancer/carcinoma/tumor/neoplasm.
RESULTS: Twenty-nine out of the 2312 potentially relevant publications met the eligibility criteria. Of the 1266 patients with GB cancer included in the publications, 706 (55.8%) and 560 (44.2%) had T1a and T1b GB cancer, respectively. Simple cholecystectomy for T1a and T1b GB cancer was performed in 590 (83.6%) and 375 (67.0%) patients, respectively (P < 0.01). In most series, the treatment of choice was simple cholecystectomy for T1a GB cancer patients with a 5-year survival rate of 100%. Lymph node metastasis was detected in 10.9% of the T1b GB cancer patients and in 1.8% of the T1a GB cancer patients, respectively (P < 0.01). Eight patients (1.1%) with T1a GB cancer and 52 patients (9.3%) with T1b GB cancer died of recurrent GB cancer (P < 0.01).
CONCLUSION: Simple cholecystectomy represents the adequate treatment of T1a GB cancer. There is no definite evidence that extended cholecystectomy is advantageous over simple cholecystectomy for T1b GB cancer.
PMCID: PMC3020370  PMID: 21245989
Gallbladder; Cancer; Cholecystectomy; Simple; Extended
2.  Role of resection for Bismuth type IV hilar cholangiocarcinoma and analysis of determining factors for curative resection 
Extended liver resection may provide long-term survival in selected patients with Bismuth type IV hilar cholangiocarcinoma (HCCA). The purpose of this study was to identify anatomical factors that predict curative-intended resection.
Thirty-three of 159 patients with Bismuth type IV HCCA underwent major hepato-biliary resection with curative intent (CIR) between 2000 and 2010. Disease extent and anatomical variations were analyzed as factors enabling CIR.
CIR ratio with hilar trifurcation bile duct variation (13/16) was significantly higher than that with other bile duct variation types (18/25). Hilum to left second bile duct confluence and tumor infiltration over left second bile duct confluence lengths in right-sided CIR were significantly shorter than those lengths in left-sided CIR (10.8 ± 4.9 and 2.7 ± 0.8 mm vs. 16.5 ± 8.4 and 7.0 ± 5.3 mm, respectively). Left-sided CIR patients had a marginally higher proportion of tumors invading ≤5 mm over the right second confluence than that in right-sided CIR patients (13/17 vs. 6/16; P = 0.061). The 3-year survival rate after CIR (28%) was significantly higher than after non-CIR (6.1%).
We recommend the criteria of CIR as bile duct variation type, length of hilum to contralateral second bile duct confluence, and extent of tumor infiltration over the second confluence for Bismuth type IV HCCA.
PMCID: PMC4127903  PMID: 25114888
Klatskin's tumor; Bismuth type IV; Surgery; Anatomy
3.  Which method of pancreatic surgery do medical consumers prefer among open, laparoscopic, or robotic surgery? A survey 
The consumers' preferences are not considered in developing or implementing new medical technologies. Furthermore, little efforts are made to investigate their demands. Therefore, their preferred surgical method and the factors affecting that preference were investigated in pancreatic surgery.
Six-hundred subjects including 100 medical personnel (MP) and 500 lay persons (LP) were surveyed. Questionnaire included basic information on different methods of distal pancreatectomy; open surgery (OS), laparoscopic surgery (LS), and robotic surgery (RS). Assuming they required the operation, participants were told to indicate their preferred method along with a reason and an acceptable cost for both benign and malignant conditions.
For benign disease, the most preferred method was LS. Limiting the choice to LS and RS, LS was preferred for cost and well-established safety and efficacy. OS was favored in malignant disease for the concern for radicality. Limiting the choice to LS and RS, LS was favored for its better-established safety and efficacy. The majority thought that LS and RS were both overpriced. Comparing MP and LP responses, both groups preferred LS in benign and OS in malignant conditions. However, LP more than MP tended to prefer RS under both benign and malignant conditions. LP thought that LS was expensive whereas MP thought the cost reasonable. Both groups felt that RS was too expensive.
Though efforts for development of novel techniques and broadening indication should be encouraged, still more investments and research should focus on LS and OS to provide optimal management and satisfaction to the patients.
PMCID: PMC3994613  PMID: 24761401
Pancreas; Surgery; Consumer satisfaction; Survey
4.  Changes in Demographic Features of Gallstone Disease: 30 Years of Surgically Treated Patients 
Gut and Liver  2013;7(6):719-724.
The aim of this study was to investigate changes in the clinical and demographical characteristics of gallstone disease in Korea, based on 30 years of surgically treated patients at a single institute.
In total, 7,949 gallstone patients who underwent surgery between 1981 and 2010 were analyzed. Patients were divided into six time periods: period I (1981 to 1985, n=831), period II (1986 to 1990, n=888), period III (1991 to 1995, n=1,040), period IV (1996 to 2000, n=1,261), period V (2001 to 2005, n=1,651) and period VI (2006 to 2010, n=2,278).
The total number and mean age of the patients gradually increased, and the male/female ratio decreased. The proportion of gallbladder (GB)-stone cases increased, whereas the proportions of common bile duct (CBD)- and intrahepatic duct (IHD)-stone cases decreased. Differences in patient geographical origins also decreased. Based on the relationship between changes in the prevalence of gallstone disease and socioeconomic status, the prevalence of CBD stones showed a strong correlation with Engel's coefficient (p<0.001).
Our study indicates that although the total number of cases and the mean age of gallstone patients have continuously increased, there are trends of increasing GB-stone cases and decreasing CBD- and IHD-stone cases.
PMCID: PMC3848536  PMID: 24312714
Cholelithiasis; Epidemiology; Surgery
5.  Cancer cells with p53 deletion detected by fluorescent in situ hybridization in peritoneal drainage fluid is correlated with early peritoneal seeding in resectable pancreatic cancer 
Free tumor cells in peritoneal fluid in patients with pancreatic cancer may have prognostic significance but there are few reports on methods for the effective detection of free tumor cells. The aims of this study were to identify free cancer cells in peritoneal fluid with fluorescent in situ hybridization (FISH) technique and to investigate its prognostic significance.
Twenty-eight patients with resectable pancreatic cancer who underwent surgical resection were included. Peritoneal washing and peritoneal drainage fluid were examined by FISH for p53 deletion.
Among the study subjects, the R0 resection rate was 75%. None of the patients had positive cytology with Papanicolaou's method. p53 deletion was detected in 9 peritoneal washings (32.1%) and in 5 peritoneal drainage fluids (17.9%). After a median of 18 months of follow-up, 25 patients (89.3%) experienced recurrence and 14 patients (50.0%) had peritoneal seeding. Patients with p53 deletion detected in the peritoneal drainage fluid had positive radial margin (60.0% vs. 17.4%, P = 0.046) more frequently and a lower peritoneal metastasis free survival (median, 11.1 months vs. 30.3 months; P = 0.030). Curative resection (P < 0.001) and p53 deletion in peritoneal drainage fluid (P = 0.030) were independent risk factors of peritoneal metastasis free survival after multivariate analysis.
FISH technique detects free cancer cells with higher sensitivity compared to Papanicolaou's method. p53 deletion detected in peritoneal drainage fluid is correlated with positive radial resection margin and results in early peritoneal seeding. Patients with p53 deletion in peritoneal drainage fluid need more aggressive adjuvant treatment.
PMCID: PMC3616274  PMID: 23577315
Pancreatic neoplsms; Peritoneal fluid; Fluorescent in situ hybridization; p53 gene
6.  CD24 expression predicts distant metastasis in extrahepatic bile duct cancer 
AIM: To evaluate the prognostic significance of CD24 expression in patients undergoing adjuvant chemoradiotherapy for extrahepatic bile duct (EHBD) cancer.
METHODS: Eighty-four patients with EHBD cancer who underwent curative resection followed by adjuvant chemoradiotherapy were enrolled in this study. Postoperative radiotherapy was delivered to the tumor bed and regional lymph nodes up to a median of 40 Gy (range: 40-56 Gy). All patients also received fluoropyrimidine chemotherapy for radiosensitization during radiotherapy. CD24 expression was assessed with immunohistochemical staining on tissue microarray. Clinicopathologic factors as well as CD24 expression were evaluated in multivariate analysis for clinical outcomes including loco-regional recurrence, distant metastasis-free and overall survival.
RESULTS: CD24 was expressed in 36 patients (42.9%). CD24 expression was associated with distant metastasis, but not with loco-regional recurrence nor with overall survival. The 5-year distant metastasis-free survival rates were 55.1% and 29.0% in patients with negative and positive expression, respectively (P = 0.0100). On multivariate analysis incorporating N stage, histologic differentiation and CD24 expression, N stage was the only significant factor predicting distant metastasis-free survival (P = 0.0089), while CD24 expression had borderline significance (P = 0.0733). In subgroup analysis, CD24 expression was significantly associated with 5-year distant metastasis-free survival in node-positive patients (38.4% with negative expression vs 0% with positive expression, P = 0.0110), but not in node-negative patients (62.0% with negative expression vs 64.0% with positive expression, P = 0.8599).
CONCLUSION: CD24 expression was a significant predictor of distant metastasis for patients undergoing curative resection followed by adjuvant chemoradiotherapy especially for node-positive EHBD cancer.
PMCID: PMC3602503  PMID: 23539485
CD24; Tissue microarray; Extrahepatic bile duct cancer; Adjuvant chemoradiotherapy; Distant metastasis
7.  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
8.  Comparison of Clinical Outcome and Cost-Effectiveness after Various Preoperative Biliary Drainage Methods in Periampullary Cancer with Obstructive Jaundice 
Journal of Korean Medical Science  2012;27(4):356-362.
The aim of this study was to compare the clinical outcome and cost-effectiveness of preoperative biliary drainage (BD) methods in periampullary cancer, and to suggest guidelines for selecting the appropriate preoperative BD method. Between October 2004 and August 2010, 211 patients underwent pancreatoduodenectomy after preoperative BD. Clinical outcome and cost-effectiveness of the preoperative BD methods were compared based on the final drainage method used and on intention-to-treat analysis. There was no significant difference in drainage duration between percutaneous transhepatic biliary drainage (PTBD) and endoscopic BD groups (14.2 vs 16.6 days, respectively; P = 0.121) but daily diminution of serum bilirubin level was higher in the PTBD group (0.7 vs 0.6 mg/dL/day, respectively; P = 0.041). Based on intention-to-treat analysis, drainage duration was shorter (13.2 vs 16.5 days, respectively; P = 0.049), daily diminution of serum bilirubin level was higher (0.7 vs 0.6 mg/dL/day, respectively; P = 0.041). Medical care cost was lower (14.2 vs 15.7 × 103 USD, respectively; P = 0.040) in the PTBD group than in the endoscopic BD group. When selecting the preoperative BD method, practitioners should consider that PTBD is more cost-effective and safer than endoscopic BD.
PMCID: PMC3314846  PMID: 22468097
Drainage; Biliary Cancer; Jaundice; Preoperative; Pancreatoduodenectomy
9.  Determination of Malignant and Invasive Predictors in Branch Duct Type Intraductal Papillary Mucinous Neoplasms of the Pancreas: A Suggested Scoring Formula 
Journal of Korean Medical Science  2011;26(6):740-746.
Prediction of malignancy or invasiveness of branch duct type intraductal papillary mucinous neoplasm (Br-IPMN) is difficult, and proper treatment strategy has not been well established. The authors investigated the characteristics of Br-IPMN and explored its malignancy or invasiveness predicting factors to suggest a scoring formula for predicting pathologic results. From 1994 to 2008, 237 patients who were diagnosed as Br-IPMN at 11 tertiary referral centers in Korea were retrospectively reviewed. The patients' mean age was 63.1 ± 9.2 yr. One hundred ninty-eight (83.5%) patients had nonmalignant IPMN (81 adenoma, 117 borderline atypia), and 39 (16.5%) had malignant IPMN (13 carcinoma in situ, 26 invasive carcinoma). Cyst size and mural nodule were malignancy determining factors by multivariate analysis. Elevated CEA, cyst size and mural nodule were factors determining invasiveness by multivariate analysis. Using the regression coefficient for significant predictors on multivariate analysis, we constructed a malignancy-predicting scoring formula: 22.4 (mural nodule [0 or 1]) + 0.5 (cyst size [mm]). In invasive IPMN, the formula was expressed as invasiveness-predicting score = 36.6 (mural nodule [0 or 1]) + 32.2 (elevated serum CEA [0 or 1]) + 0.6 (cyst size [mm]). Here we present a scoring formula for prediction of malignancy or invasiveness of Br-IPMN which can be used to determine a proper treatment strategy.
PMCID: PMC3102866  PMID: 21655058
Branch Duct Type Intraductal Papillary Mucinous Neoplasm (IPMN); Cyst Size; Mural Nodule; CEA; Malignancy; Invasive Carcinoma
10.  Clinicopathologic Features of Polypoid Lesions of the Gallbladder and Risk Factors of Gallbladder Cancer 
Journal of Korean Medical Science  2009;24(3):481-487.
It is difficult to differentiate benign and malignancy in polypoid lesions of the gallbladder (PLG) by solely depending on imaging studies. Therefore clinicopathologic features of benign and malignant polyps are compared in an attempt to identify the risk factors of malignant polypoid lesions. The medical records of 291 patients who were confirmed to have PLG through cholecystectomy were reviewed and analyzed for age, sex, symptom, associated gallstone, morphology of PLG, size of PLG, number of PLG, and preoperative tumor markers. Benign PLG was found in 256 patients (88.0%) and malignant PLG in 35 patients (12.0%). Compared with benign group, the malignant group were older (61.1 yr vs. 47.1 yr, P<0.001), more often accompanied with symptoms (62.9% vs. 28.9%, P<0.001). Malignant PLG tended to be sessile (60.0% vs. 10.5%, P<0.001), larger (28.0 mm vs. 8.6 mm, P<0.001) and single lesion (65.7% vs. 44.1%, P<0.016). Age over 60 yr (P=0.021, odds ratio [OR], 8.16), sessile morphology (P<0.001, OR, 7.70), and size over 10 mm (P=0.009, OR, 8.87) were identified as risk factors for malignant PLG. Careful decision making on therapeutic plans should be made with consideration of malignancy for patients over 60 yr, with sessile morphology of PLG, and with PLG size of over 10 mm.
PMCID: PMC2698196  PMID: 19543513
Gallbladder; Polyps; Gallbladder Neoplasms; Risk Factors
11.  Pancreatic fistula after pancreaticoduodenectomy: A comparison between the two pancreaticojejunostomy methods for approximating the pancreatic parenchyma to the jejunal seromuscular layer: Interrupted vs continuous stitches 
AIM: The purpose of this study is to find a better operative technique by comparing interrupted stitches with continuous stitches for the outer layer of the pancreaticojejunostomy, i.e., the stitches between the stump parenchyma of the pancreas and the jejunal seromuscular layer, and other risk factors for the incidence of pancreatic leakage.
METHODS: During the period January 1997 to October 2004, 133 patients have undergone the end-to-side and duct-to-mucosa pancreaticojejunostomy reconstruction after pancreaticoduodenectomy with interrupted suture for outer layer of the pancreaticojejunostomy and 170 patients with a continuous suture at our institution by one surgeon.
RESULTS: There were no significant differences between the two groups in the diagnosis, texture of the pancreas, use of octreotide and pathologic stage. Pancreatic fistula occurred in 14 patients (11%) among the interrupted suture cases and in 10 (6%) among the continuous suture cases (P = 0.102). Major pancreatic leakage developed in three interrupted suture patients (2%) and zero continuous suture patients (P = 0.026). In multivariate analysis, soft pancreatic consistency (odds ratio, 5.5; 95% confidence interval 2.3-13.1) and common bile duct cancer (odds ratio, 3.7; 95% CI 1.6-8.5) were predictive of pancreatic leakage.
CONCLUSION: Pancreatic texture and pathology are the most important factors in determining the fate of pancreaticojejunal anastomosis and our continuous suture method was performed with significantly decreased occurrence of major pancreatic fistula. In conclusion, the continuous suture method is more feasible and safer in performing duct-to-mucosa pancreaticojejunostomy.
PMCID: PMC4171325  PMID: 17879405
Pancreaticoduodenectomy; Pancreati-cojejunostomy; Pancreatic fistula
12.  Intraductal papillary mucinous carcinoma with atypical manifestations: Report of two cases 
Intraductal papillary mucinous neoplasms (IPMNs) are a well-characterized group of mucin-producing cystic neoplasms of the clear malignant potential type. We report here two cases of intraductal papillary mucinous carcinoma (IPMC) with atypical manifestations. In one case, we discussed a pseudomyxoma peritonei caused by a ruptured IPMC. In the other case we discussed the fistulization of IPMC into the stomach and duodenum. These two cases suggest that IPMN can either spontaneously rupture causing mucinous materials to spill into the free abdominal cavity or directly invade adjacent organs resulting in fistula development.
PMCID: PMC4146910  PMID: 17461460
Intraductal papillary mucinous neoplasm; Intraductal papillary mucinous carcinoma; Pseudomyxoma peritonei; Fistula
13.  Presence of CCK-A, B receptors and effect of gastrin and cholecystokinin on growth of pancreatobiliary cancer cell lines 
AIM: To investigate the effects of gastrin and cholecystokinin (CCK) and their specific antagonists on the growth of pancreatic and biliary tract cancer cell lines.
METHODS: Five pancreatic and 6 biliary cancer cell lines with 2 control cells were used in this study. Cell proliferation study was done using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) test and direct cell count method. Reverse transcription-polymerase chain reaction (RT-PCR) and slot blot hybridization were performed to examine and quantify the expression of hormonal receptors in these cell lines.
RESULTS: SNU-308 showed a growth stimulating effect by gastrin-17, as did SNU-478 by both gastrin-17 and CCK-8. The trophic effect of these two hormones was completely blocked by specific antagonists (L-365, 260 for gastrin and L-364, 718 for CCK). Other cell lines did not respond to gastrin or CCK. In RT-PCR, the presence of CCK-A receptor and CCK-B/gastrin receptor mRNA was detected in all biliary and pancreatic cancer cell lines. In slot blot hybridization, compared to the cell lines which did not respond to hormones, those that responded to hormones showed high expression of receptor mRNA.
CONCLUSION: Gastrin and CCK exert a trophic action on some of the biliary tract cancers.
PMCID: PMC4250587  PMID: 15682471
Bile duct cancer; Gallbladder cancer; Pancreatic cancer; Gastrin; Cholecystokinin
14.  Identifying molecular subtypes related to clinicopathologic factors in pancreatic cancer 
BioMedical Engineering OnLine  2014;13(Suppl 2):S5.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal tumors and usually presented with locally advanced and distant metastasis disease, which prevent curative resection or treatments. In this regard, we considered identifying molecular subtypes associated with clinicopathological factor as prognosis factors to stratify PDAC for appropriate treatment of patients.
In this study, we identified three molecular subtypes which were significant on survival time and metastasis. We also identified significant genes and enriched pathways represented for each molecular subtype. Considering R0 resection patients included in each subtype, metastasis and survival times are significantly associated with subtype 1 and subtype 2.
We observed three PDAC molecular subtypes and demonstrated that those subtypes were significantly related with metastasis and survival time. The study may have utility in stratifying patients for cancer treatment.
PMCID: PMC4304250  PMID: 25560450
15.  Reconstruction of portal vein and superior mesenteric vein after extensive resection for pancreatic cancer 
Tumor invasion to the portal vein (PV) or superior mesenteric vein (SMV) can be encountered during the surgery for pancreatic cancer. Venous reconstruction is required, but the optimal surgical methods and conduits remain in controversies.
From January 2007 to July 2012, 16 venous reconstructions were performed during surgery for pancreatic cancer in 14 patients. We analyzed the methods, conduits, graft patency, and patient survival.
The involved veins were 14 SMVs and 2 PVs. The operative methods included resection and end-to-end anastomosis in 7 patients, wedge resection with venoplasty in 2 patients, bovine patch repair in 3 patients, and interposition graft with bovine patch in 1 patient. In one patient with a failed interposition graft with great saphenous vein (GSV), the SMV was reconstructed with a prosthetic interposition graft, which was revised with a spiral graft of GSV. Vascular morbidity occurred in 4 cases; occlusion of an interposition graft with GSV or polytetrafluoroethylene, segmental thrombosis and stenosis of the SMV after end-to-end anastomosis. Patency was maintained in patients with bovine patch angioplasty and spiral vein grafts. With mean follow-up of 9.8 months, the 6- and 12-month death-censored graft survival rates were both 81.3%.
Many of the involved vein segments were repaired primarily. When tension-free anastomosis is impossible, the spiral grafts with GSV or bovine patch grafts are good options to overcome the size mismatch between autologous vein graft and portomesenteric veins. Further follow-up of these patients is needed to demonstrate long-term patency.
PMCID: PMC3671003  PMID: 23741692
Portal vein; Superior mesenteric vein; Reconstruction; Pancreaticoduodenectomy
16.  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
17.  Clinical Implications of Immunohistochemically Demonstrated Lymph Node Micrometastasis in Resectable Pancreatic Cancer 
Journal of Korean Medical Science  2011;26(7):881-885.
The purpose of this study was to determine the clinical significance of nodal micrometastasis detected by immunohistochemistry in patients that had undergone curative surgery for pancreatic cancer. Between 2005 and 2006, a total of 208 lymph nodes from 48 consecutive patients with pancreatic cancer that had undergone curative resection were immunostained with monoclonal antibody against pan-ck and CK-19. Micrometastasis was defined as metastasis missed by a routine H&E examination but detected during an immunohistochemical evaluation. Relations between immunohistochemical results and clinical and pathologic features and patient survival were examined. Nodal micrometastases were detected in 5 (29.4%) patients of 17 pN0 patients. Nodal micrometastasis was found to be related to tumor relapse (P = 0.043). Twelve patients without overt nodal metastasis and micrometastasis had better prognosis than 5 patients with only nodal micrometastasis (median survival; 35.9 vs 8.6 months, P < 0.001). The Cox proportional hazard model identified nodal micrometastasis as significant prognostic factors. Although the number of patients with micrometastasis was so small and further study would be needed, our study suggests that the lymph node micrometastasis could be the predictor of worse survival and might indicate aggressive tumor biology among patients undergoing curative resection for pancreas cancer.
PMCID: PMC3124717  PMID: 21738340
Pancreas; Adenocarcinoma; Lymph Nodes; Micrometastasis; Prognosis
18.  Small Rice Bowl-Based Meal Plan for Energy and Marcronutrient Intake in Korean Men with Type 2 Diabetes: A Pilot Study 
Diabetes & Metabolism Journal  2011;35(3):273-281.
Koreans eat rice, which is usually served in a rice bowl. We investigated the effect of a meal plan using small rice bowls on the total energy intake (TEI) and the marcronutrient intake in Korean men with type 2 diabetes.
A total of 62 men with type 2 diabetes were divided by body mass index (BMI) (normal weight [NW], BMI<23 kg/m2; overweight [OW], 23≤BMI<25 kg/m2; obese [OB], BMI≥25 kg/m2) and proportions of carbohydrate intake to TEI (PCI) (low carbohydrate intake [LC], <55%; recommended carbohydrate intake [RC], ≥55% and ≤60%; high carbohydrate intake [HC], >60%). The 3-day dietary records were analyzed for TEI and proportions of macronutrients, before and 2 weeks after a small-sized (300 mL) rice bowl based education was given.
There were no significant differences in the age and BMI within the sub-groups by BMI and PCI groups. In baseline, the ratio of TEI to recommended total energy intake (RTR) of OW and OB were higher than that of NW. The PCI of HC was higher than that of LC and alcohol intake of HC was lower than that of LC. After education, the reduction of RTREI in OB was higher than that in OW and NW. The reduction of PCI in HC was higher than that of LC.
A small rice bowl based meal plan was effective for the reduction of energy intake and control of marcronutrient intake in Korean obese men with type 2 diabetes consuming a high carbohydrate diet.
PMCID: PMC3138099  PMID: 21785748
Carbohydrate-restrict; Diabetes mellitus, type 2; Diabetic diet; Men
19.  Diagnostic performance of contrast enhanced CT and 18F-FDG PET/CT in suspicious recurrence of biliary tract cancer after curative resection 
BMC Cancer  2011;11:188.
Because of the late clinical presentation of biliary tract cancer (BTC), only 10% of patients are eligible for curative surgery. Even among those patients who have undergone curative surgery, most patients develop recurrent cancer. This study is to determine the clinical role of 18F-FDG PET/CT during post-operative surveillance of suspected recurrent BTC based on symptoms, laboratory findings and contrast-enhanced CT (ceCT) findings.
We consecutively enrolled 50 patients with BTC who underwent curative surgery. An 18F-FDG PET/CT was obtained for assessment of recurrence based on clinical suspicion during post-operative surveillance. The final confirmation of recurrence was determined pathologically or clinically. When a pathologic confirmation was impossible or inconclusive, a clinical confirmation was used by radiologic correlation with subsequent follow-up ceCT at a minimum of 3-month intervals. Diagnostic efficacy was evaluated by comparing the results of ceCT and 18F-FDG PET/CT with the final diagnosis.
Among the 50 patients, 34(68%) were confirmed to have a recurrence. PET/CT showed higher sensitivity (88% vs. 76%, p = 0.16) and accuracy (82% vs. 66%, p = 0.11) for recurrence compared to ceCT, even though the difference was not significant. The positive (86% vs. 74%, p = 0.72) and negative predictive values for recurrence (73% vs. 47%, p = 0.55) were not significantly different between PET/CT and ceCT. However, an additional PET/CT on ceCT significantly improved the sensitivity than did a ceCT alone (94% [32/34] for PET/CT on ceCT vs. 76% [26/34] for ceCT alone, p = 0.03) without increasing the specificity, positive predictive value, and negative predictive value.
18F-FDG PET/CT alone is not more sensitive or specific than ceCT in the detection of recurrent BTC after curative surgery. These results do not reach statistical significance, probably due to the low number of patients. However, an additional 18F-FDG PET/CT on ceCT significantly improves the sensitivity of detecting recurrences.
PMCID: PMC3120804  PMID: 21599995
18F-FDG PET/CT; biliary tract cancer; surveillance; recurrence
20.  Identification and Validation of Src and Phospho-Src Family Proteins in Circulating Mononuclear Cells as Novel Biomarkers for Pancreatic Cancer1 
Translational Oncology  2011;4(2):83-91.
There is an urgent need to develop novel markers of pancreatic cancer to facilitate early diagnosis. Pancreatic carcinoma is characterized by marked stroma formation with a high number of infiltrating tumor-associated macrophages (TAMs) that originate from circulating mononuclear cells (MNCs). We hypothesized that differential analysis of protein expression and phosphorylation in circulating MNCs from healthy nude mice and nude mice bearing orthotopic human pancreatic cancer would identify a surrogate marker of pancreatic cancer. These differences were analyzed by two-dimensional gel electrophoresis followed by Western blot analysis using antibody against phosphorylated tyrosine proteins (pY). Protein and phosphorylated protein spots of interest were identified by mass spectrometry and validated by Western blot analysis as candidate markers for pancreatic cancer. We found that the expression and phosphorylation of Src family proteins were significantly higher in circulating MNCs from mice bearing pancreatic cancer than in circulating MNCs from healthy mice. TAMs in mice with pancreatic tumors also had higher Src family protein expression and phosphorylation than resident macrophages in the pancreas of healthy mice. The expression and phosphorylation of Src family proteins were correlated with tumor weight; however, increased Src expression and phosphorylation also occurred in MNCs from mice with chronic pancreatitis. This is the first report to explore novel pancreatic tumor markers in circulating MNCs. Although the specificity of the marker for pancreatic cancer was low, it could be used to monitor the disease or to select high-risk patients with chronic pancreatitis.
PMCID: PMC3069651  PMID: 21461171
21.  Coffee intake can promote activity of antioxidant enzymes with increasing MDA level and decreasing HDL-cholesterol in physically trained rats 
Nutrition Research and Practice  2010;4(4):283-289.
This study investigated the effect of coffee intake and exercise on the antioxidative activity and plasma cholesterol profile of physically trained rats while they were exercising. Forty eight rats were under either the control diet with water (C) or control diet with coffee (CF) and at the same time they were given physical training for 4 weeks. In terms of physical training, the rats were exercised on a treadmill for 30 minutes everyday. At the end of 4 weeks, animals in each dietary group were subdivided into 3 groups: before-exercise (BE); during-exercise (DE); after-exercise (AE). Animals in the DE group were exercised on a treadmill for one hour, immediately before being sacrificed. Animals in the AE group were allowed to take a rest for one hour after exercise. TG levels were significantly high in coffee intake group than in control group. Also TG level of AE group was significantly higher than that of BE group. Exercise and coffee-exercise interaction effects were significant in total cholesterol (P = 0.0004, 0.0170). The AE of coffee intake group showed highest total cholesterol levels. HDL-cholesterol was significantly lower in coffee intake group than in control group. Coffee, exercise, and coffee-exercise interaction effects were significant in SOD (P = 0.0001, 0.0001, and 0.0001). The AE and BE of coffee intake group showed higher SOD levels than the other four groups. Catalase activities were significantly higher in coffee intake group than control group. No significant main effect was found in GSH/GSSG. Coffee, exercise, and coffee-exercise interaction effects were significant in MDA levels (P = 0.0464, 0.0016, and 0.0353). The DE and AE of coffee intake group and the DE of control group showed higher MDA levels than the BE of control group. Therefore, coffee intake can promote activities of antioxidant enzyme but it also increases MDA and decreases HDL-cholesterol in physically trained rats.
PMCID: PMC2933445  PMID: 20827343
Freeze dried instant coffee; antioxidant enzymes; MDA; cholesterol; physical training
22.  A case of gangliocytic paraganglioma in the ampulla of Vater 
Duodenal gangliocytic paraganglioma is an extremely rare tumor and few cases have been reported to date.
Case presentation
The authors report a case of gangliocytic paraganglioma verified by post-op pathology after pancreaticoduodenectomy for a tumor in the ampulla of Vater. The 56-year-old male patient concerned visited our emergency room with melena that started one week prior to hospitalization. The patient was diagnosed to have a tumor in the ampulla of Vater with bleeding on its surface. However post-op, he was diagnosed as having gangliocytic paraganglioma by immunohistochemistry.
This tumor has precise clinical implications, and if continuous follow up is conducted after careful diagnosis and surgical treatment, invasive major operations, such as, radical pancreaticoduodenectomy can be avoided.
PMCID: PMC2887868  PMID: 20497533
23.  Clinical Efficacy of Organ-Preserving Pancreatectomy for Benign or Low-Grade Malignant Potential Lesion 
The clinical usefulness of organ-preserving pancreatectomy is not well established due to technical difficulty and ambiguity of functional merit. The purpose of this study is to evaluate the clinical efficacy of organ-preserving pancreatectomy such as duodenum-preserving resection of the head of the pancreas (DPRHP), pancreatic head resection with segmental duodenectomy (PHRSD), central pancreatectomy (CP) and spleen-preserving distal pancreatectomy (SPDP). Between 1995 and 2007, the DPRHP were performed in 14 patients, the PHRSD in 16 patients, the CP in 13 patients, and the SPDP in 45 patients for preoperatively diagnosed benign lesions or tumors with low-grade malignant potential. The clinical outcomes including surgical details, postoperative complications and long-term functional outcomes were compared between organ-preserving pancreatectomy and conventional pancreatectomy group. Major postoperative complications constituted the following: bile duct stricture (7.1% [1/14]) in DPRHP, delayed gastric emptying (31.2% [5/16]) in PHRSD, pancreatic fistula (21.4% [3/14]) in CP. There were no significant differences in postoperative complications and long-term functional outcomes between two groups. Organ-preserving pancreatectomy is associated with tolerable postoperative complications, and good long-term outcome comparing to conventional pancreatectomy. Organ-preserving pancreatectomy could be alternative treatment for benign or low-grade malignant potential lesion of the pancreas or ampullary/parapapillary duodenum.
PMCID: PMC2800014  PMID: 20052354
Pancreatectomy; Organ-Preserving; Low-Grade Malignant
24.  Adjuvant concurrent chemoradiation therapy (CCRT) alone versus CCRT followed by adjuvant chemotherapy: Which is better in patients with radically resected extrahepatic biliary tract cancer?: a non-randomized, single center study 
BMC Cancer  2009;9:345.
There is currently no standard adjuvant therapy for patients with curatively resected extrahepatic biliary tract cancer (EHBTC). The aim of this study was to analyze the clinical features and outcomes between patients undergoing adjuvant concurrent chemoradiation therapy (CCRT) alone and those undergoing CCRT followed by adjuvant chemotherapy after curative resection.
We included 120 patients with EHBTC who underwent radical resection and then received adjuvant CCRT with or without further adjuvant chemotherapy between 2000 and 2006 at Seoul National University Hospital.
Out of 120 patients, 30 received CCRT alone, and 90 received CCRT followed by adjuvant chemotherapy. Baseline characteristics were comparable between the two groups. Three-year disease-free survival (DFS) rates for CCRT alone and CCRT followed by adjuvant chemotherapy were 26.6% and 45.2% (p = 0.04), respectively, and 3-year overall survival (OS) rates were 30.8% and 62.6% (p < 0.01), respectively. CCRT followed by adjuvant chemotherapy showed longer survival than did CCRT alone, especially in R1 resection (microscopically positive margins) or negative lymph node.
Adjuvant CCRT followed by adjuvant chemotherapy prolonged DFS and OS, compared with CCRT alone in patients with curatively resected EHBTC. Adjuvant chemotherapy deserves to consider after adjuvant CCRT. In the future, a randomized prospective study will be needed, with the objective of investigating the role of adjuvant chemotherapy.
PMCID: PMC2761944  PMID: 19781103
25.  Clinical Comparison of Distal Pancreatectomy with or without Splenectomy 
Journal of Korean Medical Science  2008;23(6):1011-1014.
The spleen may be preserved during distal pancreatectomy (DP) for benign disease. The aim of this study was to compare the perioperative and postoperative courses of patients with conventional DP and spleen-preserving distal pancreatectomy (SPDP) for benign lesions or tumors with low-grade malignant potential occurred at the body or tail of the pancreas. A retrospective analysis was performed for the hospital records of all the patients undergoing DP and SPDP between January 1995 and April 2006. One-hundred forty-three patients underwent DP and 37 patients underwent SPDP. There were no significant differences in age, sex, indications of operation, estimated blood loss, operative time, and postoperative hospital stay between the two groups. Pancreatic fistula occurred in 21 (13.3%) patients following DP and in 3 (8.1%) following SPDP without a significant difference (p=0.081). Portal vein thrombosis occurred in 4 patients after DP. Splenic infarction occurred in one patient after SPDP. Overwhelming postosplenectomy infection was observed in one patient after DP. SPDP can be achieved with no increase in complication rate, operative time, or length of postoperative hospitalization as compared to conventional DP. Additionally, it has the advantage of reducing the risk of overwhelming postsplenectomy infection and postoperative venous thrombosis.
PMCID: PMC2610636  PMID: 19119445
Pancreatectomy; Spleen; Organ Preservation

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