Clinical Characteristics and Treatment Outcomes of Patients with Hepatitis C Virus and Human Immunodeficiency Virus Coinfection: Experience at a Single Center in Korea.

BACKGROUND: Because of the very low incidence of human immunodeficiency virus (HIV) coinfection in Korea, data on hepatitis C virus (HCV)/HIV coinfection are limited. This study aimed to investigate the clinical characteristics and treatment outcomes of patients with HCV/HIV coinfection in Korea. METHODS: We performed a retrospective cohort study of all HCV-monoinfected and HCV/HIV-coinfected patients treated with antivirals at National Medical Center in Seoul, Korea, between January 2009 and March 2020. RESULTS: We enrolled 220 HCV-monoinfected and 23 HCV/HIV-coinfected patients treated with antivirals. The HCV/HIV-coinfected patients were younger (HCV vs. HCV/HIV: 57.3 ± 11.3 vs. 40.7 ± 10.1 years, P < 0.001) and had a higher proportion of men (HCV vs. HCV/HIV: 54.5% [n = 120] vs. 91.3% [n = 21], P < 0.001) than the HCV-monoinfected patients. Genotype 1b and 2 were most common in both HCV monoinfection and HCV/HIV coinfection groups. HCV-monoinfected patients had a higher incidence of genotype 1b and 2 than HCV/HIV-coinfected patients (HCV vs. HCV/HIV: 95.4% [n = 210] vs. 73.9% [n = 17], P < 0.001), while the HCV/HIV-coinfected patients had genotype 1a (HCV vs. HCV/HIV: 1.8% [n = 4] vs. 21.7% [n = 5], P < 0.001). The fibrosis-4 index was significantly lower in the HCV/HIV-coinfected patients than in the HCV-monoinfected patients (HCV vs. HCV/HIV: 3.81 ± 3.38 vs. 1.66 ± 1.10, P < 0.001). Among the direct-acting antivirals (DAA)-treated patients, the sustained viral response (SVR) rate did not differ significantly between both groups (HCV vs. HCV/HIV: 94.9% [93/99] vs. 90.9% [10/11], P = 0.480). CONCLUSION: In Korea, the HCV/HIV-coinfected patients who received antiviral treatment were younger, had higher proportion of men and incidence of genotype 1a, and had less advanced fibrosis than the HCV-monoinfected patients. In actual clinical settings, HCV/HIV-coinfected patients show excellent SVR to DAA treatment, similar to HCV-monoinfected patients.

Clobenpropit enhances anti-tumor effect of gemcitabine in pancreatic cancer.

AIM: To evaluate the anti-tumor effect of clobenpropit, which is a specific H3 antagonist and H4 agonist, in combination with gemcitabine in a pancreatic cancer cell line. METHODS: Three kinds of human pancreatic cancer cell lines (Panc-1, MiaPaCa-2, and AsPC-1) were used in this study. Expression of H3 and H4 receptors in pancreatic cancer cells was identified with Western blotting. Effects of clobenpropit on cell proliferation, migration and apoptosis were evaluated. Alteration of epithelial and mesenchymal markers after administration of clobenpropit was analyzed. An in vivo study with a Panc-1 xenograft mouse model was also performed. RESULTS: H4 receptors were present as 2 subunits in human pancreatic cancer cells, while there was no expression of H3 receptor. Clobenpropit inhibited cell migration and increased apoptosis of pancreatic cancer cells in combination with gemcitabine. Clobenpropit up-regulated E-cadherin, but down-regulated vimentin and matrix metalloproteinase 9 in real-time polymerase chain reaction. Also, clobenpropit inhibited tumor growth (gemcitabine 294 ± 46 mg vs combination 154 ± 54 mg, P = 0.02) and enhanced apoptosis in combination with gemcitabine (control 2.5%, gemcitabine 25.8%, clobenpropit 9.7% and combination 40.9%, P = 0.001) by up-regulation of E-cadherin and down-regulation of Zeb1 in Panc-1 xenograft mouse. CONCLUSION: Clobenpropit enhanced the anti-tumor effect of gemcitabine in pancreatic cancer cells through inhibition of the epithelial-mesenchymal transition process.

Non-surgical treatment of post-surgical bile duct injury: clinical implications and outcomes.

AIM: To investigate the prognostic factors determining the success rate of non-surgical treatment in the management of post-operative bile duct injuries (BDIs). METHODS: The study patients were enrolled from the pancreatobiliary units of a tertiary teaching hospital for the treatment of BDIs after hepatobiliary tract surgeries, excluding operations for liver transplantation and malignancies, from January 1999 to August 2010. A total of 5167 patients underwent operations, and 77 patients had BDIs following surgery. The primary end point was the treatment success rate according to different types of BDIs sustained using endoscopic or percutaneous hepatic approaches. The type of BDI was defined using one of the following diagnostic tools: endoscopic retrograde cholangiography, percutaneous transhepatic cholangiography, computed tomography scan, and magnetic resonance cholangiography. Patients with a final diagnosis of BDI underwent endoscopic and/or percutaneous interventions for the treatment of bile leak and/or stricture if clinically indicated. Patient consent was obtained, and study approval was granted by the Institutional Review Board in accordance with the legal regulations of the Human Clinical Research Center at the Seoul National University Hospital in Seoul, South Korea. RESULTS: A total of 77 patients were enrolled in the study. They were divided into three groups according to type of BDI. Among them, 55 patients (71%) underwent cholecystectomy. Thirty-six patients (47%) had bile leak only (type 1), 31 patients had biliary stricture only (type 2), and 10 patients had both bile leak and biliary stricture (type 3). Their initial treatment modalities were non-surgical. The success rate of non-surgical treatment in each group was as follows: BDI type 1: 94%; type 2: 71%; and type 3: 30%. Clinical parameters such as demographic factors, primary disease, operation method, type of operation, non-surgical treatment modalities, endoscopic procedure steps, type of BDI, time to diagnosis and treatment duration were evaluated to evaluate the prognostic factors affecting the success rate. The type of BDI was a statistically significant prognostic factor in determining the success rate of non-surgical treatment. In addition, a shorter time to diagnosis of BDI after the operation correlated significantly with higher success rates in the treatment of type 1 BDIs. CONCLUSION: Endoscopic or percutaneous hepatic approaches can be used as an initial treatment in type 1 and 2 BDIs. However, surgical intervention is a treatment of choice in type 3 BDI.

Clinical factors associated with accuracy of EUS-FNA for pancreatic or peripancreatic solid mass without on-site cytopathologists.

BACKGROUND AND AIMS: Endoscopic ultrasound-guided fine needle aspiration (EUSFNA) is a safe and effective technique for tissue diagnosis in patients with pancreatic or peripancreatic solid masses. However, the procedure is difficult to accomplish without an on-site cytopathologist. The aims of this study were to examine the outcomes of EUS-FNA for pancreatic or peripancreatic solid masses without an on-site cytopathologist and to determine the factors associated with diagnostic accuracy. METHODS: From December 2005 to November 2011, 230 patients with pancreatic or peripancreatic solid masses had 240 EUS-FNAs performed without an on-site cytopathologist. The medical records of the 230 patients from a single tertiary center were retrospectively reviewed. RESULTS: Among the 230 patients who underwent EUS-FNA, 201 patients (88%) had malignancy, which included 171 adenocarcinomas (74%). Assuming that the cytopathological malignancy was positive or suspicious for malignant cells with cytology, the accuracy without an on-site cytopathologist was 67.9%. However, the accuracy increased from 40.0% for the first 30 cases (from 2006 to 2008) to 83.3% for the last 30 cases (in 2011) and was constantly over 80.0% starting from the sixth octile onwards for every 30 cases (in 2011). From the analysis of factors associated with the accuracy of the diagnosis using logistic regression analysis, the number of needle passes and the experience of endosonographer were statistically associated with the diagnostic accuracy. CONCLUSIONS: In the case of performing EUS-FNA for pancreatic or peripancreatic solid masses without an on-site cytopathologist, the experience of the endosonographer, and the number of needle passes were associated with the diagnostic accuracy.

Hedgehog signaling between cancer cells and hepatic stellate cells in promoting cholangiocarcinoma.

BACKGROUND: Aberrant Hedgehog (HH) signaling activation is important in cancer growth and mediates the interaction between cancer cells and the surrounding stromal cells. This study investigated the role of HH signaling on the growth of cholangiocarcinoma (CC), focusing on the interaction of CC cells with stromal cells. METHODS: To evaluate the interaction between human CC cells (SNU-1196, SNU-246, SNU-308, SNU-1079, and HuCCT-1) and stromal cells (hepatic stellate cell line, Lx-2), co-culture proliferation, migration, and invasion assays were performed. In vivo nude mice experiments were conducted using two groups-HuCCT-1 single implant xenograft (SX) and co-implant xenograft (CX) with HuCCT-1 and Lx-2. RESULTS: When HuCCT-1 cells were co-cultured with Lx-2 cells, the expression of HH signaling-related proteins increased in both HuCCT-1 and Lx-2 cells. Co-culture with Lx-2 cells stimulated the proliferation, migration, and invasion of CC cells, and these effects were mediated by HH signaling. Co-culture of HuCCT-1 and Lx-2 cells increased the secretion of several cytokines. In an ectopic xenograft model, Lx-2 co-implantation increased CC tumor growth and stimulated angiogenesis. Cyclopamine attenuated tumor growth in the CX group, but not in the HuCCT-1 mono-implant (SX) group. Cyclopamine treatment decreased CC cell proliferation, suppressed microvessel density, and increased tumor necrosis in the CX group, but not in the SX group. CONCLUSION: Hepatic stellate cells stimulate the proliferation, migration, and invasion of CC cells, promote angiogenesis through HH signaling activation, and render CC more susceptible to necrosis by HH inhibitor.

Clinical significance and revisiting the meaning of CA 19-9 blood level before and after the treatment of pancreatic ductal adenocarcinoma: analysis of 1,446 patients from the pancreatic cancer cohort in a single institution.

BACKGROUND: Life expectancy of pancreatic ductal adenocarcinoma (PDAC) patients is usually short and selection of the most appropriate treatment is crucial. The aim of this study was to investigate the usefulness of serum CA 19-9 as a surrogate marker under no impress excluding other factors affecting CA 19-9 level other than tumor itself. METHODS: We recruited 1,446 patients with PDACs and patients with Lewis antigen both negative or obstructive jaundice were excluded to eliminate the false effects on CA 19-9 level. The clinicopathologic factors were reviewed including initial and post-treatment CA 19-9, and statistical analysis was done to evaluate the association of clinicopathologic factors with overall survival (OS). RESULTS: The total of 944 patients was enrolled, and205 patients (22%) underwent operation with curative intention and 541 patients (57%) received chemotherapy and/or radiotherapy. The median CA 19-9 levels of initial and post-treatment were 670 IU/ml and 147 IU/ml respectively. The prognostic factors affecting OS were performance status, AJCC stage and post-treatment CA 19-9 level in multivariate analysis. Subgroup analysis was done for the patients who underwent R0 and R1 resection, and patients with normalized post-operative CA 19-9 (≤37 IU/mL) had significantly longer OS and DFS regardless of initial CA 19-9 level; 32 vs. 18 months, P<0.001, 16 vs. 9 months, P = 0.004 respectively. CONCLUSIONS: Post-treatment CA 19-9 and normalized post-operative CA 19-9 (R0 and R1 resected tumors) were independent factors associated with OS and DFS, however, initial CA 19-9 level was not statistically significant in multivariate analysis.

A Multicenter Phase II Trial of Gemcitabine Plus Oxaliplatin in Unresectable Gallbladder Cancer.

BACKGROUND/AIMS: No standard chemotherapy has been established for advanced gallbladder cancer. The authors studied the activity and tolerability of a gemcitabine and oxaliplatin (GEMOX) combination in unresectable gallbladder cancer (GBC). METHODS: Adult patients with pathologically confirmed unresectable GBC were prospectively recruited at three centers. No patient had received prior chemotherapy or radiotherapy. Patients received cycles of gemcitabine at 1,000 mg/m(2) on day 1, followed by oxaliplatin at 100 mg/m(2) on day 2, every 2 weeks. The primary study endpoint was time to progression. RESULTS: Forty patients with unresectable GBC were enrolled. The median age was 60 years (range, 38 to 79 years). All patients showed good performance status. Of the 33 analyzable patients, 12 achieved partial response (36%), 17 stable disease (52%), and four progressive disease (12%). No patient achieved a complete response. The tumor control rate was 88%. At a median follow-up of 6.8 months, the median time to progression was 5.3 months (95% confidence interval [CI], 3.7 to 6.9), and median overall survival was 6.8 months (95% CI, 6.1 to 7.5). Nine of the 40 patients (23%) experienced at least a grade-3 adverse event, but no patient experienced a grade-4 adverse event. CONCLUSIONS: GEMOX combination therapy is a feasible option and is well tolerated in unresectable GBC.

Natural history and malignant risk factors of solid pseudopapillary tumors of the pancreas.

BACKGROUND AND AIM: Solid pseudopapillary tumors (SPTs) of the pancreas are unusual neoplasms of uncertain prognosis. Most patients with SPTs have a good prognosis after undergoing surgical resection, but there are rare cases in which a locally infiltrative growth pattern and metastatic variety are exhibited, or recurrence of the disease after surgery occurs; these cases have been reported with very poor clinical outcomes. Our study investigated the natural history of SPTs and delineated the clinicopathologic features that may predict the malignancy potential of the disease. METHODS: A total of 100 patients with suspected SPTs were enrolled in our study and 77 patients underwent surgical resection. A resulting 60 tumors were pathologically proven to be SPTs and the affected patients were followed-up regularly after surgery. Clinical and pathologic data for all 100 patients were analyzed. RESULTS: Of the 60 total patients with histologically positive SPTs, 55 (92%) were women and 5 (8%) were men. The median patient age was 34 years (range, 13-77 years). Among the 60 patients, 9 had malignant SPTs and 51 had benign SPTs. Deep parenchymal invasion into the surrounding tissue was the most frequent pathologic feature suggesting malignancy (75%) among the 60 patients who underwent surgical resection. Patient clinicopathologic characteristics and demographic factors were compared between those who had benign SPTs and those who had malignant SPTs. There were no significant differences in the various patient features between the 2 groups, including age, sex, symptoms, tumor size, tumor location, internal tumor composition, pattern of tumor calcification, tumor necrosis, hemorrhage, and immunohistochemical tumor tissue patterns. There were 2 patients who had distant metastasis; 1 presented with distal metastasis in the liver and the other patient had recurrence of cancer with a peritoneal mass after surgery. Metastasectomy was performed on the 2 patients and there was no mortality or disease progression during the follow-up period (median, 143 months; range, 53-319 months). CONCLUSION: Solid pseudopapillary tumors are low-grade tumors that have a generally good prognosis. However, the clinical development and malignancy potential of SPTs are neither fully understood nor predictable, even with histologically benign tumors. Further investigations in tumor biology, along with long-term patient follow-up, may provide insight into the disease process and clinical development of SPTs.

Palliative treatment of unresectable hepatocellular carcinoma with obstructive jaundice using biliary drainage with subsequent transarterial chemoembolization.

BACKGROUND: Nonsurgical biliary drainage is considered as a priority for obstructive jaundice associated with unresectable hepatocellular carcinoma (HCC). Successful drainage allows the patient to receive antitumor therapy, such as transarterial chemoembolization (TACE). However, only limited data are available on clinical outcomes in patients who treated biliary drainage with subsequent TACE. OBJECTIVE: This study evaluated the clinical outcome of biliary drainage with subsequent TACE in unresectable HCC patients with obstructive jaundice. DESIGN: This was a retrospective study. SETTING/SUBJECTS: A total of 60 patients received endoscopic biliary drainage (ERBD) or percutaneous transhepatic biliary drainage (PTBD) in two tertiary care referral centers. MEASUREMENTS: Successful drainage and survival were measured. RESULTS: Successful drainage was achieved in 39 (65%) patients. The median survival of 39 patients in whom successful drainage was achieved, regardless of which procedure was performed, was much longer than that of 21 patients without successful drainage (147 days versus 38 days, respectively, P<.001). In particular, the median survival was longer in 17 patients who underwent TACE after achieving successful drainage than in 22 patients who were treated conservatively after achieving successful drainage (410 days versus 77 days, respectively, P<.001). Multivariable analysis in 39 patients in the successful drainage group showed that TACE (hazard ratio 0.15; 95% confidence interval 0.05-0.45, P=.001) was an independent predictive factor of a favorable outcome. CONCLUSIONS: Effective palliation by successful biliary drainage with subsequent TACE might prolong the survival in patients with obstructive jaundice caused by unresectable HCC.

Clinical usefulness of plasma chromogranin a in pancreatic neuroendocrine neoplasm.

Chromogranin A (CgA) is widely used as an immunohistochemical marker of neuroendocrine neoplasms and has been measurable in plasma of patients. We assessed the clinical role of plasma CgA in diagnosing pancreatic neuroendocrine neoplasm (PNEN). CgA was checked in 44 patients with pancreatic mass who underwent surgical resection from 2009 through 2011. The cutoff value for diagnosing PNEN and the relationships between CgA and clinicopathologic variables were analyzed. Twenty-six patients were PNENs and 18 patients were other pancreatic disorders. ROC analysis showed a cutoff of 60.7 ng/mL with 77% sensitivity and 56% specificity, and the area under the curve (AUC) was 0.679. Among PNEN group, the sensitivity and specificity of diagnosing metastasis were 100% and 90% respectively when CgA cutoff was 156.5 ng/mL. The AUC was 0.958. High Ki-67 index (160.8 vs 62.1 ng/mL, P = 0.001) and mitotic count (173.5 vs 74.6 ng/mL, P = 0.044) were significantly correlated with plasma CgA, but the tumor size was not. In conclusion, CgA has a little value in diagnosing PNEN. However, the high level of CgA (more than 156.5 ng/mL) can predict the metastasis. Also, plasma CgA level correlates with Ki-67 index and mitotic count which represents prognosis of PNENs.

Presence of coronary artery disease increases the risk of biliary events in patients with asymptomatic gallstones.

BACKGROUND AND AIM: Propensity score indicates a probability of having a confounding factor. It is used to match each patient with the closest propensity score between two groups, which is known as propensity score matching. This study aimed to evaluate the gallstone-related biliary events, defined as biliary colic and acute cholecystitis between coronary artery disease (CAD) and non-CAD patients using propensity score matching. METHODS: This retrospective cohort study evaluated 267 asymptomatic gallstone patients with CAD and 459 asymptomatic gallstone patients without CAD from March 2003 to December 2009 at two tertiary teaching hospitals in the Republic of Korea. After propensity score matching, total 378 patients, including 126 in study group (with CAD) and 252 in control group (without CAD), were evaluated. RESULTS: During a median follow-up of 47 months, overall gallstone-related biliary event rate was 33.5% in the study group and 27.5% in the control group. The 5-year cumulative rates were 25.3% versus 17.7% in gallstone-related biliary event and 10.9% versus 1.6% in acute cholecystitis (study versus control group). After propensity score adjustment, the risk of gallstone-related biliary events in the CAD patients significantly increased (hazard ratio 2.11, 95% confidence interval 1.14-3.90, P = 0.017 in matched patients). CONCLUSION: In patients with asymptomatic gallstones, the coexistence of CAD can increase the risk of gallstone-related biliary events, particularly acute cholecystitis. Therefore, gallstone patients with CAD should be carefully monitored, even if they are asymptomatic.

A Case of Common Bile Duct Cancer That Completely Responded to Combination Chemotherapy of Gemcitabine and TS-1.

Common bile duct (CBD) cancer is a relatively rare malignancy that arises from the biliary epithelium and is associated with a poor prognosis. Here, we report a case of advanced metastatic CBD cancer successfully treated by chemotherapy with gemcitabine combined with S-1 (tegafur+gimeracil+oteracil). A 65-year-old male presented with pyogenic liver abscess. After antibiotic therapy and percutaneous drainage, follow-up computed tomography (CT) showed an enhanced nodule in the CBD. Biopsy was performed at the CBD via endoscopic retrograde cholangiopancreatography, which showed adenocarcinoma. Additional CT and magnetic resonance imaging showed multiple small nodules in the right hepatic lobe, which were confirmed as metastatic adenocarcinoma by sono-guided liver biopsy. The patient underwent combination chemotherapy with gemcitabine and S-1. After nine courses of chemotherapy, the hepatic lesion disappeared radiologically. Pylorus-preserving pancreaticoduodenectomy was performed, and no residual tumor was found in the resected specimen. Three weeks after the operation, the patient was discharged with no complications. Through 3 months of follow-up, no sign of recurrence was observed on CT scan. Gemcitabine combined with S-1 may be a highly effective treatment for advanced cholangiocarcinoma.

The optimal duration of preoperative biliary drainage for periampullary tumors that cause severe obstructive jaundice.

BACKGROUND: Despite routine preoperative biliary drainage (PBD) with periampullary cancer, its optimal duration has not been established. The objective of this study was to investigate PBD in severely jaundiced patients. METHODS: A total of 120 patients with periampullary tumors who underwent surgery with intent to cure after PBD for severe obstructive jaundice were enrolled. According to the duration of PBD, 66 and 54 patients were classified into the long-term (≥2 weeks) and short-term (<2 weeks) groups. RESULTS: PBD-related complications occurred in 6 (9.1%) and 14 (25.9%) patients in the short-term and long-term groups, respectively (P = .014). Rates of surgery-related complications and mortalities were not significantly different between the 2 groups. The R0 resection rate tended to be lower (P = .054) and the mean length of hospital stay was significantly longer (P = .039) in the long-term group. CONCLUSIONS: PBD duration <2 weeks is more appropriate in severely jaundiced patients with periampullary cancer.

Risk factors of post endoscopic retrograde cholangiopancreatography bacteremia.

BACKGROUND/AIMS: Bacteremia following endoscopic retrograde cholangiopancreatography (ERCP) is a severe complication, but the risk factors for this condition have not yet been clearly determined. Thus, the aim of this study was to investigate the risk factors of post-ERCP bacteremia. METHODS: Among patients who underwent ERCP from June 2006 to May 2009, we selected patients without any signs of infection prior to the ERCP procedures. Of these patients, we further selected those who experienced bacteremia after ERCP as well as two-fold age and sex-matched controls who did not experience bacteremia after ERCP procedures. We compared clinical, laboratory and technical aspects between these two groups. RESULTS: There were 70 patients (3.1%) who developed bacteremia after ERCP. In the multivariate analysis, a history of previous liver transplantation, an elevated serum alkaline phosphatase level and an endoscopic retrograde biliary drainage procedure were independent risk factors of post-ERCP bacteremia (p=0.006, p=0.001, and p=0.004, respectively). The microbiologic analysis revealed the presence of gram-negative organisms in 80% of the cases, and 11 patients had infections with bacteria expressing extended spectrum ß-lactamases. Pseudomonas infection was significantly more common in patients who received liver transplantation as compared to patients without transplantation (p=0.014). CONCLUSIONS: A history of liver transplantation, elevated serum alkaline phosphatase levels and endoscopic retrograde biliary drainage procedure were independent risk factors of post-ERCP bacteremia and require additional attention in future studies.

Endoscopic papillectomy for benign ampullary neoplasms: how can treatment outcome be predicted?

BACKGROUND/AIMS: Endoscopic papillectomy is increasingly performed with curative intent for benign papillary tumors. This study was performed to identify factors that predict the presence of malignancy and affect endoscopic success. METHODS: We retrospectively analyzed the medical records of patients who received an endoscopic papillectomy for papillary adenoma from 2006 to 2009. RESULTS: A total of 43 patients received endoscopic papillectomy. The pathologic results after papillectomy revealed adenocarcinoma in five patients (12%), and the risk of malignancy was high in cases of large lesions, preprocedural pathology of high-grade dysplasia or high serum alkaline phosphatase. Endoscopic success was observed in 37 patients (86%) at the end of follow-up (mean duration, 10.4±9.6 months). The factor significantly affecting success was a complete resection at the initial papillectomy (p=0.007). Two patients experienced recurrence 10 and 32 months after the complete resection, but both achieved endoscopic success with repeated endoscopic treatment. Six patients with endoscopic failure received surgical resection. CONCLUSIONS: Endoscopic papillectomy is a safe and effective method for the curative resection of benign papillary tumors, especially when complete resection is achieved at the initial papillectomy. Follow-up with surveillance should be performed for at least 3 years because of the possible recurrence of tumors during these periods.

Stent patency using competing risk model in unresectable pancreatic cancers inserted with biliary self-expandable metallic stent.

BACKGROUND AND AIM: Biliary self-expandable metallic stents (SEMS) play an important role in the quality of life and palliative treatment in unresectable pancreatic cancer patients. We aimed to determine the factors affecting the patency of biliary SEMS and the survival in unresectable pancreatic cancer with obstructive jaundice. METHODS: Considering the competing risk and survival, we retrospectively evaluated the patency in 107 unresectable pancreatic cancer patients with obstructive jaundice who were successfully treated with biliary SEMS from January 2000 to April 2010. RESULTS: There were 107 incidents of biliary drainage that were clinically successful and the overall survival period was a median of 133 days. Stent occlusion before death was observed in 36 (33.6%) of 107 patients. Cumulative stent obstruction rates were 4.7%, 16.8%, and 24.4% at 1, 3, and 6 months, respectively. Lower cancer stage (<5 month's hazard ratio [HR] = 2.327, >5 month's HR = 0.108) was only associated with the longer patency of the stents in a multivariable analysis using a Fine and Gray model that considered competing risk. In multivariable analysis, lower cancer stage, uncovered stent and normalized serum bilirubin level were associated with a longer survival period (HR = 2.335, 1.906 and 1.795 respectively, P < 0.05). CONCLUSION: The patency of biliary SEMS in unresectable pancreatic cancers might be affected by the stage. Lower cancer stage and normalized bilirubin are associated with longer survival.

Inflexinol reduces severity of acute pancreatitis by inhibiting nuclear factor-κB activation in cerulein-induced pancreatitis.

OBJECTIVES: To examine the effect of inflexinol on the development of acute pancreatitis (AP) and to investigate the mechanisms responsible for the protective effect against AP. METHODS: Acute pancreatitis was induced in mice by intraperitoneal injection of cerulein. Inflexinol was administered intraperitoneally 4 times every 6 hours from 1 hour before the first cerulein injection. Serum amylase activity and histology of the pancreas were measured. Determination of pancreatic nuclear factor-κB (NF-κB) p65 expression was conducted by Western blotting and immunohistochemistry to investigate the mechanisms responsible for the inflexinol effects. RESULTS: Serum amylase activity in the cerulein group was significantly higher than that in the control group (P < 0.05). Pancreatic histology revealed marked inflammatory changes in the cerulein group such as interstitial edema, vacuolization, necrosis, and infiltration of inflammatory cells; and Western blotting and immunohistochemistry showed marked NF-κB p65 expression. Treatment with inflexinol significantly attenuated the inflammatory changes in pancreatic histology at 24, 48, and 72 hours (P < 0.05). Pancreatic NF-κB p65 expression decreased significantly after inflexinol treatment (P < 0.05). CONCLUSION: Inflexinol reduced the severity of cerulein-induced AP by inhibiting NF-κB activation.

Long-term clinical outcomes of biliary cast syndrome in liver transplant recipients.

Biliary cast syndrome (BCS) is an uncommon complication of orthotopic liver transplantation (OLT), so the long-term treatment outcomes of BCS are not well characterized. The purpose of this study was to evaluate the long-term treatment outcomes and prognosis of BCS after OLT. The medical records of 1097 patients who underwent OLT from January 2000 to September 2009 were reviewed. Those patients who had BCS were evaluated with respect to the treatment method, overall survival and relapse rates, and relapse-free time. Twenty-three patients (2.1%) were diagnosed with BCS with a mean overall follow-up of 59.9 months. All the patients had benign biliary strictures and repeatedly underwent balloon dilatation by an endoscopic or percutaneous approach. Primary biliary cast removal was tried with the endoscopic method from 11 patients and with the percutaneous methods from 12 patients. Casts were completely removed by repetitive procedures in 22 patients, but BCS relapsed in 12 patients (55%). Persistent biliary strictures were significantly associated with the BCS relapse frequency (0.37 versus 0.05 times per year, P = 0.006). The 5-year overall survival rate for BCS patients after OLT was 87%. The risk factors associated with early relapse were female sex, hepatic artery stenosis, and acute cellular rejection. In a multivariate analysis, acute cellular rejection was the only significant risk factor for early relapse (hazard ratio = 11.1, 95% confidence interval = 1.9-63.2, P = 0.007). In conclusion, patients with BCS frequently relapse, and multiple interventions and the treatment of biliary strictures are needed. Acute cellular rejection after OLT is a significant risk factor for early relapse.

Pancreatic pseudocyst after endoscopic ultrasound-guided fine needle aspiration of pancreatic mass.

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is well known as a safe diagnostic procedure. We report the first case of pancreatic pseudocyst after EUS-FNA of the pancreatic body mass. A 60-year-old male underwent EUS-FNA for incidentally detected pancreatic solid mass which was suspected as neuroendocrine tumor. Two weeks later, the patient visited emergency room with acute abdominal pain and right upper quadrant tenderness; leukocytosis and elevated C-reactive protein, amylase, and lipase levels were noted. Computed tomography discovered newly developed 11.5×9.5 cm sized cystic mass communicating with the main pancreatic duct. Cyst fluid analysis revealed amylase level of 3,423 U/L and fluid culture isolated Streptococcus parasanguinis. The cystic mass corresponds with pancreatic pseudocyst. FNA induced main pancreatic duct injury and fluid leakage may cause it. Endoscopists who perform EUS-FNA must remember that pancreatic main duct injury can occur as one of severe complications and that it could be treated successfully with endoscopic internal drainage.