BackgroundPancreatic 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 FindingsFormalin-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 SignificanceLow 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.
Endoscopic intervention is considered to be the primary treatment for biliary stricture after adult living donor liver transplantation (LDLT) with duct-to-duct biliary reconstruction. The aim of this study was to investigate the risk factors of biliary stricture and the clinical outcomes and predictors of failure after endoscopic retrograde cholangiography with balloon dilation (ERC-D). We enrolled 239 adult patients who underwent LDLT between 2000 and 2006. Sixty-eight patients (28.4%) developed biliary stricture. Twenty-nine patients with anastomotic biliary stricture were treated with ERC-D and stenting. We retrospectively analyzed the risk factors of biliary stricture and the clinical outcomes of ERC-D. The median follow-up period was 31 months. The risk factors of biliary stricture on multiple logistic regression analysis were a graft with multiple bile ducts, a previous history of bile leakage, and hepatic artery stenosis. The overall success rate of ERC-D was 64.5%. On simple logistic regression, the failure of primary ERC-D was associated with late biliary stricture over 24 weeks and more than 8 weeks between a 2-fold increase of serum alkaline phosphatase from the stable level and ERC-D, even though these were not statistically significant on multiple logistic regression. The relapse rate of stricture after successful ERC-D was 30%. The duration of stenting in the recurrence group was shorter than that in the nonrecurrence group (11.8 Ϯ 5.03 versus 29.0 Ϯ 11.6 weeks, P ϭ 0.004). ERC-D is effective for the management of anastomotic biliary stricture. However, the failure rate of primary ERC-D may be high in patients with late onset and delayed diagnosis of biliary stricture. The recurrence seems to occur frequently in patients with a short duration of stenting. Liver Transpl 15:369-380, 2009.
Although incidental pancreatic cystic neoplasms are being diagnosed with increasing frequency, little is known about the accurate prevalence of pancreatic cysts in the general population. The aims of this study were to evaluate the crude prevalence rate of pancreatic cystic neoplasms in asymptomatic healthy adults, and calculate the age- and sex-adjusted nationwide prevalence rate.A total of 21,745 asymptomatic individuals who underwent abdominal computed tomography (CT) as a health screening examination were enrolled between 2003 and 2013 at the Seoul National University Hospital Healthcare System Gangnam Center. Nationwide population data of 2010 were collected from the National Statistical Office, Korea.Incidental pancreatic cystic neoplasms were found in 457 individuals whose mean age was 58.7 years. The types of neoplasms were reviewed by 2 separate designated radiologists and the final diagnosis was made as follows: intraductal papillary mucinous neoplasm: 376 (82%), serous cystic neoplasm: 19 (4%), mucinous cystic neoplasm: 7 (2%), and indeterminate cysts: 55 (12%). Eight cases underwent operation. The crude prevalence rate was 2.1% and the age- and sex-adjusted expected nationwide prevalence was 2.2%. The prevalence increased with age.Here, we reported the first large-scale study among the healthy population to find out the prevalence rate of pancreatic cystic neoplasms; the age- and sex-adjusted prevalence was 2.2%, and increased with age. Further investigations regarding the clinical implications of incidental pancreatic neoplasms are necessary.
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 firstline 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.
Earlier diagnosis and the less frequent occurrence of pathological factors associated with tumor invasiveness in ampullary carcinoma than in distal extrahepatic cholangiocarcinoma may explain its association with a better prognosis.
Endoscopic ultrasonography-guided ethanol ablation therapy seems to be a safe treatment modality. However, it was only effective in 11% of IPMNs. Therefore, the clinical application should be very limited for certain patients who could not tolerate the surgical treatment.
Background/Aims: 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. Methods: 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 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 χ 2 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. Conclusions: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. (Gut and Liver 2008;2:88-94)
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