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1.  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.
doi:10.3748/wjg.v13.i40.5351
PMCID: PMC4171325  PMID: 17879405
Pancreaticoduodenectomy; Pancreati-cojejunostomy; Pancreatic fistula
2.  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.
doi:10.3748/wjg.v13.i10.1622
PMCID: PMC4146910  PMID: 17461460
Intraductal papillary mucinous neoplasm; Intraductal papillary mucinous carcinoma; Pseudomyxoma peritonei; Fistula
3.  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.
doi:10.3748/wjg.v11.i6.803
PMCID: PMC4250587  PMID: 15682471
Bile duct cancer; Gallbladder cancer; Pancreatic cancer; Gastrin; Cholecystokinin
4.  Changes in Demographic Features of Gallstone Disease: 30 Years of Surgically Treated Patients 
Gut and Liver  2013;7(6):719-724.
Background/Aims
The aim of this study was to investigate changes in the clinical and demographical characteristics of gallstone disease in Korea, based on 30 years of surgically treated patients at a single institute.
Methods
In total, 7,949 gallstone patients who underwent surgery between 1981 and 2010 were analyzed. Patients were divided into six time periods: period I (1981 to 1985, n=831), period II (1986 to 1990, n=888), period III (1991 to 1995, n=1,040), period IV (1996 to 2000, n=1,261), period V (2001 to 2005, n=1,651) and period VI (2006 to 2010, n=2,278).
Results
The total number and mean age of the patients gradually increased, and the male/female ratio decreased. The proportion of gallbladder (GB)-stone cases increased, whereas the proportions of common bile duct (CBD)- and intrahepatic duct (IHD)-stone cases decreased. Differences in patient geographical origins also decreased. Based on the relationship between changes in the prevalence of gallstone disease and socioeconomic status, the prevalence of CBD stones showed a strong correlation with Engel's coefficient (p<0.001).
Conclusions
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.
doi:10.5009/gnl.2013.7.6.719
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 
Purpose
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.
Methods
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.
Results
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.
Conclusion
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.
doi:10.4174/jkss.2013.84.4.209
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.
doi:10.3748/wjg.v19.i9.1438
PMCID: PMC3602503  PMID: 23539485
CD24; Tissue microarray; Extrahepatic bile duct cancer; Adjuvant chemoradiotherapy; Distant metastasis
7.  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.
doi:10.3346/jkms.2011.26.7.881
PMCID: PMC3124717  PMID: 21738340
Pancreas; Adenocarcinoma; Lymph Nodes; Micrometastasis; Prognosis
8.  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.
doi:10.3748/wjg.v17.i2.174
PMCID: PMC3020370  PMID: 21245989
Gallbladder; Cancer; Cholecystectomy; Simple; Extended
9.  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.
doi:10.3346/jkms.2010.25.1.97
PMCID: PMC2800014  PMID: 20052354
Pancreatectomy; Organ-Preserving; Low-Grade Malignant
10.  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.
doi:10.3346/jkms.2008.23.6.1011
PMCID: PMC2610636  PMID: 19119445
Pancreatectomy; Spleen; Organ Preservation
11.  Role of resection for Bismuth type IV hilar cholangiocarcinoma and analysis of determining factors for curative resection 
Purpose
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.
Methods
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.
Results
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%).
Conclusion
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.
doi:10.4174/astr.2014.87.2.87
PMCID: PMC4127903  PMID: 25114888
Klatskin's tumor; Bismuth type IV; Surgery; Anatomy
12.  Which method of pancreatic surgery do medical consumers prefer among open, laparoscopic, or robotic surgery? A survey 
Purpose
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.
Methods
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.
Results
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.
Conclusion
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.
doi:10.4174/astr.2014.86.1.7
PMCID: PMC3994613  PMID: 24761401
Pancreas; Surgery; Consumer satisfaction; Survey
13.  Reconstruction of portal vein and superior mesenteric vein after extensive resection for pancreatic cancer 
Purpose
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.
Methods
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.
Results
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%.
Conclusion
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.
doi:10.4174/jkss.2013.84.6.346
PMCID: PMC3671003  PMID: 23741692
Portal vein; Superior mesenteric vein; Reconstruction; Pancreaticoduodenectomy
14.  Proposal of an endoscopic retrograde cholangiopancreatography-related perforation management guideline based on perforation type 
Purpose
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.
Methods
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.
Results
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.
Conclusion
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.
doi:10.4174/jkss.2012.83.4.218
PMCID: PMC3467388  PMID: 23091794
Endoscopic retrograde cholangiopancreatography; Intestinal perforation; Guideline; Algorithms
15.  Long-Term Outcome of Cystic Lesions in the Pancreas: A Retrospective Cohort Study 
Gut and Liver  2012;6(4):493-500.
Background/Aims
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.5009/gnl.2012.6.4.493
PMCID: PMC3493732  PMID: 23170156
Pancreatic cyst; Natural history; Prognosis
16.  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.
doi:10.3346/jkms.2012.27.4.356
PMCID: PMC3314846  PMID: 22468097
Drainage; Biliary Cancer; Jaundice; Preoperative; Pancreatoduodenectomy
17.  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.
doi:10.3346/jkms.2011.26.6.740
PMCID: PMC3102866  PMID: 21655058
Branch Duct Type Intraductal Papillary Mucinous Neoplasm (IPMN); Cyst Size; Mural Nodule; CEA; Malignancy; Invasive Carcinoma
18.  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.
Background
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1186/1471-2407-11-188
PMCID: PMC3120804  PMID: 21599995
18F-FDG PET/CT; biliary tract cancer; surveillance; recurrence
19.  Clinical Features of Metastatic Tumors of the Pancreas in Korea: A Single-Center Study 
Gut and Liver  2011;5(1):61-64.
Background/Aims
The purpose of this study was to examine the clinical features of metastatic tumors of the pancreas (MTPs) in Korea.
Methods
A total of 53 cases (31 males) of pathologically proven MTPs were collected. Clinicopathological characteristics and patient outcomes were evaluated.
Results
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.
Conclusions
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.
doi:10.5009/gnl.2011.5.1.61
PMCID: PMC3065095  PMID: 21461074
Pancreas; Neoplasms; Neoplasm metastasis; Renal cell carcinoma; Stomach neoplasms
20.  A case of gangliocytic paraganglioma in the ampulla of Vater 
Background
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.
Conclusion
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.
doi:10.1186/1477-7819-8-42
PMCID: PMC2887868  PMID: 20497533
21.  Identification of MicroRNA-21 as a Biomarker for Chemoresistance and Clinical Outcome Following Adjuvant Therapy in Resectable Pancreatic Cancer 
PLoS ONE  2010;5(5):e10630.
Background
Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. The high risk of recurrence following surgical resection provides the rationale for adjuvant therapy. However, only a subset of patients benefit from adjuvant therapy. Identification of molecular markers to predict treatment outcome is therefore warranted. The aim of the present study was to evaluate whether expression of novel candidate biomarkers, including microRNAs, can predict clinical outcome in PDAC patients treated with adjuvant therapy.
Methodology/Principal Findings
Formalin-fixed paraffin embedded specimens from a cohort of 82 resected Korean PDAC cases were analyzed for protein expression by immunohistochemistry and for microRNA expression using quantitative Real-Time PCR. Cox proportional hazards model analysis in the subgroup of patients treated with adjuvant therapy (N = 52) showed that lower than median miR-21 expression was associated with a significantly lower hazard ratio (HR) for death (HR = 0.316; 95%CI = 0.166–0.600; P = 0.0004) and recurrence (HR = 0.521; 95%CI = 0.280–0.967; P = 0.04). MiR-21 expression status emerged as the single most predictive biomarker for treatment outcome among all 27 biological and 9 clinicopathological factors evaluated. No significant association was detected in patients not treated with adjuvant therapy. In an independent validation cohort of 45 frozen PDAC tissues from Italian cases, all treated with adjuvant therapy, lower than median miR-21 expression was confirmed to be correlated with longer overall as well as disease-free survival. Furthermore, transfection with anti-miR-21 enhanced the chemosensitivity of PDAC cells.
Conclusions Significance
Low miR-21 expression was associated with benefit from adjuvant treatment in two independent cohorts of PDAC cases, and anti-miR-21 increased anticancer drug activity in vitro. These data provide evidence that miR-21 may allow stratification for adjuvant therapy, and represents a new potential target for therapy in PDAC.
doi:10.1371/journal.pone.0010630
PMCID: PMC2871055  PMID: 20498843
22.  Techniques of biliary drainage for acute cholecystitis: Tokyo Guidelines 
The principal management of acute cholecystitis is early cholecystectomy. However, percutaneous transhepatic gallbladder drainage (PTGBD) may be preferable for patients with moderate (grade II) or severe (grade III) acute cholecystitis. For patients with moderate (grade II) disease, PTGBD should be applied only when they do not respond to conservative treatment. For patients with severe (grade III) disease, PTGBD is recommended with intensive care. Percutaneous transhepatic gallbladder aspiration (PTGBA) is a simple alternative drainage method with fewer complications; however, its clinical usefulness has been shown only by case-series studies. To clarify the clinical value of these drainage methods, proper randomized trials should be done. This article describes techniques of drainage for acute cholecystitis.
doi:10.1007/s00534-006-1155-8
PMCID: PMC2784517  PMID: 17252296
Acute cholecystitis; Cholecystostomy; Drainage; Percutaneous; Endoscopy; Acalculous cholecystitis; Guidelines
23.  Diagnostic criteria and severity assessment of acute cholangitis: Tokyo Guidelines 
Because acute cholangitis sometimes rapidly progresses to a severe form accompanied by organ dysfunction, caused by the systemic inflammatory response syndrome (SIRS) and/or sepsis, prompt diagnosis and severity assessment are necessary for appropriate management, including intensive care with organ support and urgent biliary drainage in addition to medical treatment. However, because there have been no standard criteria for the diagnosis and severity assessment of acute cholangitis, practical clinical guidelines have never been established. The aim of this part of the Tokyo Guidelines is to propose new criteria for the diagnosis and severity assessment of acute cholangitis based on a systematic review of the literature and the consensus of experts reached at the International Consensus Meeting held in Tokyo 2006. Acute cholangitis can be diagnosed if the clinical manifestations of Charcot’s triad, i.e., fever and/or chills, abdominal pain (right upper quadrant or epigastric), and jaundice are present. When not all of the components of the triad are present, then a definite diagnosis can be made if laboratory data and imaging findings supporting the evidence of inflammation and biliary obstruction are obtained. The severity of acute cholangitis can be classified into three grades, mild (grade I), moderate (grade II), and severe (grade III), on the basis of two clinical factors, the onset of organ dysfunction and the response to the initial medical treatment. “Severe (grade III)” acute cholangitis is defined as acute cholangitis accompanied by at least one new-onset organ dysfunction. “Moderate (grade II)” acute cholangitis is defined as acute cholangitis that is unaccompanied by organ dysfunction, but that does not respond to the initial medical treatment, with the clinical manifestations and/or laboratory data not improved. “Mild (grade I)” acute cholangitis is defined as acute cholangitis that responds to the initial medical treatment, with the clinical findings improved.
doi:10.1007/s00534-006-1156-7
PMCID: PMC2784515  PMID: 17252297
Cholangitis; Diagnosis; Severity of illness index; Guidelines
24.  Flowcharts for the diagnosis and treatment of acute cholangitis and cholecystitis: Tokyo Guidelines 
Diagnostic and therapeutic strategies for acute biliary inflammation/infection (acute cholangitis and acute cholecystitis), according to severity grade, have not yet been established in the world. Therefore we formulated flowcharts for the management of acute biliary inflammation/infection in accordance with severity grade. For mild (grade I) acute cholangitis, medical treatment may be sufficient/appropriate. For moderate (grade II) acute cholangitis, early biliary drainage should be performed. For severe (grade III) acute cholangitis, appropriate organ support such as ventilatory/circulatory management is required. After hemodynamic stabilization is achieved, urgent endoscopic or percutaneous transhepatic biliary drainage should be performed. For patients with acute cholangitis of any grade of severity, treatment for the underlying etiology, including endoscopic, percutaneous, or surgical treatment should be performed after the patient’s general condition has improved. For patients with mild (grade I) cholecystitis, early laparoscopic cholecystectomy is the preferred treatment. For patients with moderate (grade II) acute cholecystitis, early laparoscopic or open cholecystectomy is preferred. In patients with extensive local inflammation, elective cholecystectomy is recommended after initial management with percutaneous gallbladder drainage and/or cholecystostomy. For the patient with severe (grade III) acute cholecystitis, multiorgan support is a critical part of management. Biliary peritonitis due to perforation of the gallbladder is an indication for urgent cholecystectomy and/or drainage. Delayed elective cholecystectomy may be performed after initial treatment with gallbladder drainage and improvement of the patient’s general medical condition.
doi:10.1007/s00534-006-1153-x
PMCID: PMC2784508  PMID: 17252294
Cholangitis; Acute cholecystitis; Cholecystec-tomy; Laparoscopic cholecystectomy; Biliary; Drainage; Guidelines
25.  Need for criteria for the diagnosis and severity assessment of acute cholangitis and cholecystitis: Tokyo Guidelines 
The Tokyo Guidelines formulate clinical guidance for healthcare providers regarding the diagnosis, severity assessment, and treatment of acute cholangitis and acute cholecystitis. The Guidelines were developed through a comprehensive literature search and selection of evidence. Recommendations were based on the strength and quality of evidence. Expert consensus opinion was used to enhance or formulate important areas where data were insufficient. A working group, composed of gastroenterologists and surgeons with expertise in biliary tract surgery, supplemented with physicians in critical care medicine, epidemiology, and laboratory medicine, was selected to formulate draft guidelines. Several other groups (including members of the Japanese Society for Abdominal Emergency Medicine, the Japan Biliary Association, and the Japanese Society of Hepato-Biliary-Pancreatic Surgery) have reviewed and revised the draft guidelines. To build a global consensus on the management of acute biliary infection, an international expert panel, representing experts in this area, was established. Between April 1 and 2, 2006, an International Consensus Meeting on acute biliary infections was held in Tokyo. A consensus was determined based on best available scientific evidence and discussion by the panel of experts. This report describes the highlights of the Tokyo International Consensus Meeting in 2006. Some important areas focused on at the meeting include proposals for internationally accepted diagnostic criteria and severity assessment for both clinical and research purposes.
doi:10.1007/s00534-006-1151-z
PMCID: PMC2784506  PMID: 17252292
Evidence-based medicine; Practice guidelines; Acute cholecystitis; Acute cholangitis

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