Risk factors of poor prognosis and impairment of activities of daily living in patients with hemorrhagic gastroduodenal ulcers.

BACKGROUND: Impairment of activities of daily living (ADL) due to hemorrhagic gastroduodenal ulcers (HGU) has rarely been evaluated. We analyzed the risk factors of poor prognosis, including mortality and impairment of ADL, in patients with HGU. METHODS: In total, 582 patients diagnosed with HGU were retrospectively analyzed. Admission to a care facility or the need for home adaptations during hospitalization were defined as ADL decline. The clinical factors were evaluated: endoscopic features, need for interventional endoscopic procedures, comorbidities, symptoms, and medications. The risk factors of outcomes were examined with multivariate analysis. RESULTS: Advanced age (> 75 years) was a significant predictor of poor prognosis, including impairment of ADL. Additional significant risk factors were renal disease (odds ratio [OR] 3.43; 95% confidence interval [CI] 1.44-8.14) for overall mortality, proton pump inhibitor (PPIs) usage prior to hemorrhage (OR 5.80; 95% CI 2.08-16.2), and heart disease (OR 3.05; 95% CI 1.11-8.43) for the impairment of ADL. Analysis of elderly (> 75 years) subjects alone also revealed that use of PPIs prior to hemorrhage was a significant predictor for the impairment of ADL (OR 8.24; 95% CI 2.36-28.7). CONCLUSION: In addition to advanced age, the presence of comorbidities was a risk of poor outcomes in patients with HGU. PPI use prior to hemorrhage was a significant risk factor for the impairment of ADL, both in overall HGU patients and in elderly patients alone. These findings suggest that the current strategy for PPI use needs reconsideration.

Incidence and risk factors of contrast-induced nephropathy after transcatheter arterial chemoembolization in hepatocellular carcinoma.

BACKGROUND: Transcatheter arterial chemoembolization (TACE) is widely used for unresectable hepatocellular carcinoma (HCC). The purpose of this study was to investigate incidence and risk factors of contrast-induced nephropathy (CIN) after TACE in patients with HCC. METHODS: In this single-center retrospective study, we examined 461 consecutive TACE sessions in 260 patients between January 2003 and October 2015. CIN was defined as an increase in serum creatinine levels by ≥ 0.5 mg/dl or ≥ 25% from baseline within 72 h after TACE. We calculated incidence rate of CIN and tried to identify its risk factors by logistic regression analysis. RESULTS: Twenty-one cases of CIN (5%) were observed in 461 TACE sessions. One patient required subsequent hemodialysis transiently. In univariate analysis, tumor size > 5 cm [odds ratio (OR) 5.76, 95% confidence interval (CI) 2.34-14.14, p < 0.001], chronic kidney disease (OR 2.54, 95% CI 1.05-6.14, p = 0.04), serum hemoglobin level [OR 0.79 (per 1 g/dl increase), 95% CI 0.64-0.98, p = 0.03] and serum albumin level [OR 0.44 (per 1 g/dl increase), 95% CI 0.19-1.02, p = 0.05] were associated with the development of CIN. Stepwise logistic regression methods showed that tumor size > 5 cm (OR 7.81, 95% CI 2.99-20.46, p < 0.001) and serum albumin [OR 0.29 (per 1 g/dl increase), 95% CI 0.11-0.75, p = 0.01] were risk factors of CIN. CONCLUSIONS: In this study, HCC tumor size and lower serum albumin level were independent predictors of CIN after TACE.

Multicenter study of endoscopic preoperative biliary drainage for malignant hilar biliary obstruction: E-POD hilar study.

BACKGROUND AND AIM: Endoscopic nasobiliary drainage (ENBD) is often recommended in preoperative biliary drainage (PBD) for hilar malignant biliary obstruction (MBO), but endoscopic biliary stent (EBS) is also used in the clinical practice. We conducted this large-scale multicenter study to compare ENBD and EBS in this setting. METHODS: A total of 374 cases undergoing PBD including 281 ENBD and 76 EBS for hilar MBO in 29 centers were retrospectively studied. RESULTS: Extrahepatic cholangiocarcinoma (ECC) accounted for 69.8% and Bismuth-Corlette classification was III or more in 58.8% of the study population. Endoscopic PBD was technically successful in 94.6%, and adverse event rate was 21.9%. The rate of post-endoscopic retrograde cholangiopancreatography pancreatitis was 16.0%, and non-endoscopic sphincterotomy was the only risk factor (odds ratio [OR] 2.51). Preoperative re-intervention was performed in 61.5%: planned re-interventions in 48.4% and unplanned re-interventions in 31.0%. Percutaneous transhepatic biliary drainage was placed in 6.4% at the time of surgery. The risk factors for unplanned procedures were ECC (OR 2.64) and total bilirubin ≥ 10 mg/dL (OR 2.18). In surgically resected cases, prognostic factors were ECC (hazard ratio [HR] 0.57), predraiange magnetic resonance cholangiopancreatography (HR 1.62) and unplanned re-interventions (HR 1.81). EBS was not associated with increased adverse events, unplanned re-interventions, or a poor prognosis. CONCLUSIONS: Our retrospective analysis did not demonstrate the advantage of ENBD over EBS as the initial PBD for resectable hilar MBO. Although the technical success rate of endoscopic PBD was high, its re-intervention rate was not negligible, and unplanned re-intervention was associated with a poor prognosis in resected hilar MBO.

Gemcitabine and S-1 versus gemcitabine and cisplatin treatment in patients with advanced biliary tract cancer: a multicenter retrospective study.

Objective This study aimed to compare the safety and efficacy of the combination therapy of gemcitabine and S-1 (GS) versus gemcitabine and cisplatin (GC) in patients with advanced biliary tract cancer (BTC). Methods In this multicenter retrospective cohort study, a total of 212 patients with advanced BTC receiving GS (n = 125) or GC (n = 87) between July 2006 and August 2015 were analyzed. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), objective tumor response, and safety. Results Patient characteristics were well balanced between the two groups, except for tumor size (the baseline sum of the largest diameter of the tumor: 6.3 cm in the GS group vs. 8.6 cm in the GC group, p = 0.01). Although the response rate was higher in the GS group than in the GC group (28.8% vs. 10.3%, p = 0.01), the median PFS and OS were comparable between the two groups (PFS of 5.6 vs. 7.6 months, p = 0.74; OS of 12.4 vs. 9.2 months, p = 0.20, respectively). Stomatitis and skin rash were more frequently observed in the GS group, whereas anemia, thrombocytopenia, nausea, and renal toxicity were more commonly observed in the GC group. Conclusion This study demonstrates that GS and GC are similar with regard to their safety and efficacy in patients with advanced BTC. GS could serve as an alternative treatment for advanced BTC as a first-line chemotherapy.

Outcome of Long-term Maintenance Steroid Therapy Cessation in Patients With Autoimmune Pancreatitis: A Prospective Study.

OBJECTIVE: To predict the duration of steroid maintenance therapy required to achieve good prognosis in patients with autoimmune pancreatitis. PATIENTS AND METHODS: The study sample comprised 21 patients with autoimmune pancreatitis who met the following criteria: (1) they received steroid therapy (ST) for at least 3 years without clinical relapse; and (2) immunoglobulin (Ig) G<1600 mg/dL was observed in the past year with a prednisolone maintenance dose ≤5 mg. All patients could be diagnosed with international consensus diagnostic criteria. Patients were prospectively followed up after tapering and cessation of steroids. Clinical relapse was defined as the need to resume ST. Serological relapse was defined as having an IgG level of >1600 mg/dL. RESULTS: During the 43-month (range, 19 to 48 mo) follow-up period, clinical relapse occurred in 10 patients: pancreatic lesion in 4; coronary lesion in 2; submandibular lesion in 1; both pulmonary and renal lesions in 1; pulmonary, retroperitoneal, and submandibular lesions in 1; and bronchial asthma in 1. Serological relapse was observed in 12 patients. Although clinical and serological relapse occurred concomitantly in 3 patients, serological relapse preceded clinical relapse in 4 patients. Five patients experienced serological relapse alone, and no clinical or serological relapse occurred in 6 patients. According to Cox proportional hazard analysis, the duration of ST before tapering was a significant predictive parameter (hazard ratio, 0.969/month; 95% confidence interval, 0.940-0.998; P=0.038). CONCLUSIONS: ST cessation resulted in a high rate of clinical relapses, even in patients with long-term maintenance therapy. Therefore, it appears desirable to continue steroid maintenance therapy for a period >3 years to prevent relapse.

Risk Factors for Aspiration Pneumonia After Endoscopic Hemostasis.

BACKGROUND: Although all types of endoscopic procedures harbor risk of aspiration, little is understood about risk factors for aspiration pneumonia developing after endoscopic hemostasis. AIMS: The present study aimed to identify risk factors for aspiration pneumonia after endoscopic hemostasis. METHODS: Charts from consecutive patients with upper gastrointestinal bleeding that had been treated by endoscopic hemostasis at a single center between January 2004 and January 2015 were retrospectively reviewed. Patient information and clinical characteristics including cause of hemorrhage, established prognostic scales, laboratory data, comorbidities, medications, duration of endoscopic hemostasis, vital signs, sedative use, and the main operator during the procedure were compared between patients who developed aspiration pneumonia and those who did not. RESULTS: Aspiration pneumonia developed in 24 (4.8%) of 504 patients after endoscopic hemostasis. Endotracheal intubation was required for three of them, and one died of the complication. Multivariate analysis revealed that age >75 years (odds ratio (OR) 4.4; 95% confidence interval (CI) 1.5-13.6; p = 0.0073), procedural duration >30 min (OR 5.6; 95% CI 1.9-18.2; p = 0.0023), hemodialysis (OR 3.6; 95% CI 1.2-11; p = 0.024), and a history of stroke (OR 3.8; 95% CI 1-14; p = 0.041) were independent risk factors for developing aspiration pneumonia. CONCLUSIONS: Specific risk factors for aspiration pneumonia after endoscopic hemostasis were identified. Endoscopists should carefully consider aspiration pneumonia when managing older patients who are on hemodialysis, have a history of stroke, and undergo a longer procedure.

Early use of double-guidewire technique to facilitate selective bile duct cannulation: the multicenter randomized controlled EDUCATION trial.

BACKGROUND AND STUDY AIMS: There are no guidelines for the timing of conversion from a single-guidewire to a double-guidewire technique to facilitate selective bile duct cannulation and reduce post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP), when using wire-guided cannulation. We investigated whether early conversion to the double-guidewire method, at first unintentional insertion of a guidewire into the pancreatic duct, facilitated selective bile duct cannulation and reduced PEP compared with repeated single-guidewire attempts. PATIENTS AND METHODS: A multicenter prospective randomized controlled trial included 274 patients with a naive papilla, undergoing endoscopic retrograde cholangiography (ERC) using wire-guided cannulation in whom there was unintentional insertion of the guidewire into the pancreatic duct. With the guidewire still in the duct, patients were randomly assigned to undergo the double-guidewire technique or repeated single-wire cannulation. Main outcomes were success rates for selective bile duct cannulation and PEP frequency. RESULTS: Success rates for selective bile duct cannulation within 10 attempts and 10 minutes were 75 % and 70 %, respectively, for the early double-guidewire (EDG) and repeated single-guidewire (RSG) cannulation groups (relative rate 1.07, 95 % confidence interval [95 %CI] 0.93 - 1.24, P = 0.42). Corresponding final selective bile duct cannulation rates were 98 % and 97 % (relative rate 1.01, 95 %CI 0.97 - 1.05, P = 1.00). PEP rates were 20 % and 17 %, respectively, for the EDG and RSG cannulation groups (relative risk 1.17, 95 %CI 0.71 - 1.94, P = 0.53). Double-guidewire cannulation was more effective in patients with malignant biliary stricture (relative rate 1.36, 95 %CI 1.05 - 1.77, P = 0.02). CONCLUSIONS: During therapeutic ERC using wire-guided cannulation, converting to a double-guidewire technique neither facilitated selective bile duct cannulation nor decreased PEP incidence compared with repeated use of a single-wire technique.

Clinical outcomes of secondary gastroduodenal self-expandable metallic stent placement by stent-in-stent technique for malignant gastric outlet obstruction.

BACKGROUND AND AIM: To evaluate the efficacy and safety of secondary gastroduodenal stent placement after first stent dysfunction for malignant gastric outlet obstruction. METHODS: We conducted a retrospective analysis to investigate the efficacy and safety of secondary stent-in-stent gastroduodenal stent placement. RESULTS: Among 260 patients who had been treated with first gastroduodenal stent placement for malignant gastric outlet obstruction, 29 patients (11.2%) were treated with secondary gastroduodenal stent placement because of first stent dysfunction. Pancreatic cancer was the major primary cancer (55.2%). A WallFlex duodenal stent was the most frequently inserted stent both as a first stent (75.9%) and as a secondary stent (62.1%). There were 22 patients (75.9%) that received gastroduodenal stents at the bending site (supraduodenal angle or infraduodenal angle). Technical and clinical success rates were 100% and 86.2%, respectively. Median eating period was 3.0 months, and median survival time was 3.5 months. As for related complications, gastrointestinal perforation, insufficient stent expansion, tumor ingrowth, tumor overgrowth, and cholangitis were experienced in 13.8% (four cases), 6.9% (two cases), 6.9% (two cases), 3.4% (one case), and 3.4% (one case), respectively. CONCLUSION: Secondary gastroduodenal stent placement might be effective for managing first stent dysfunction in malignant gastric outlet obstruction. However, gastrointestinal perforation was the major complication.

Sofosbuvir plus ribavirin in Japanese patients with chronic genotype 2 HCV infection: an open-label, phase 3 trial.

Genotype 2 hepatitis C virus (HCV) accounts for up to 30% of chronic HCV infections in Japan. The standard of care for patients with genotype 2 HCV - peginterferon and ribavirin for 24 weeks - is poorly tolerated, especially among older patients and those with advanced liver disease. We conducted a phase 3, open-label study to assess the efficacy and safety of an all-oral combination of the NS5B polymerase inhibitor sofosbuvir and ribavirin in patients with chronic genotype 2 HCV infection in Japan. We enrolled 90 treatment-naïve and 63 previously treated patients at 20 sites in Japan. All patients received sofosbuvir 400 mg plus ribavirin (weight-based dosing) for 12 weeks. The primary endpoint was sustained virologic response at 12 weeks after therapy (SVR12). Of the 153 patients enrolled and treated, 60% had HCV genotype 2a, 11% had cirrhosis, and 22% were over the aged 65 or older. Overall, 148 patients (97%) achieved SVR12. Of the 90 treatment-naïve patients, 88 (98%) achieved SVR12, and of the 63 previously treated patients, 60 (95%) achieved SVR12. The rate of SVR12 was 94% in patients with cirrhosis and in those aged 65 and older. No patients discontinued study treatment due to adverse events. The most common adverse events were nasopharyngitis, anaemia and headache. Twelve weeks of sofosbuvir and ribavirin resulted in high rates of SVR12 in treatment-naïve and previously treated patients with chronic genotype 2 HCV infection. The treatment was safe and well tolerated by patients, including the elderly and those with cirrhosis.

Estimation and comparison of cumulative incidences of biliary self-expandable metallic stent dysfunction accounting for competing risks.

BACKGROUND: Self-expandable metallic stent (SEMS) placement is widely carried out for distal malignant biliary obstruction, and survival analysis is used to evaluate the cumulative incidences of SEMS dysfunction (e.g. the Kaplan-Meier [KM] method and the log-rank test). However, these statistical methods might be inappropriate in the presence of 'competing risks' (here, death without SEMS dysfunction), which affects the probability of experiencing the event of interest (SEMS dysfunction); that is, SEMS dysfunction can no longer be observed after death. A competing risk analysis has rarely been done in studies on SEMS. PATIENTS AND METHODS: We introduced the concept of a competing risk analysis and illustrated its impact on the evaluation of SEMS outcomes using hypothetical and actual data. Our illustrative study included 476 consecutive patients who underwent SEMS placement for unresectable distal malignant biliary obstruction. RESULTS: A significant difference between cumulative incidences of SEMS dysfunction in male and female patients via theKM method (P = 0.044 by the log-rank test) disappeared after applying a competing risk analysis (P = 0.115 by Gray's test). In contrast, although cumulative incidences of SEMS dysfunction via the KM method were similar with and without chemotherapy (P = 0.647 by the log-rank test), cumulative incidence of SEMS dysfunction in the non-chemotherapy group was shown to be significantly lower (P = 0.031 by Gray's test) in a competing risk analysis. CONCLUSION: Death as a competing risk event needs to be appropriately considered in estimating a cumulative incidence of SEMS dysfunction, otherwise analytical results may be biased.

Results of the Tokyo trial of prevention of post-ERCP pancreatitis with risperidone-2: a multicenter, randomized, placebo-controlled, double-blind clinical trial.

BACKGROUND: Our previous study suggested that a combination of ulinastatin and risperidone reduced post-ERCP pancreatitis (PEP) compared with ulinastatin alone. OBJECTIVE: The aim of this study was to evaluate the efficacy of risperidone alone for prevention of PEP. DESIGN: A multicenter, randomized, placebo-controlled, double-blind clinical trial. SETTING: Two academic hospitals and 5 referral hospitals in Tokyo and Saitama, Japan. PATIENTS: Patients undergoing therapeutic or interventional-diagnostic ERCP. INTERVENTION: The patients were randomized to receive 2 mg of oral risperidone or oral placebo at 0.5 to 2 hours before ERCP. MAIN OUTCOME MEASUREMENTS: The primary endpoint was the incidence of PEP. Secondary endpoints were the incidence of hyperenzymemia and enzyme levels (amylase, pancreatic amylase, lipase). Risk factors for PEP were evaluated. RESULTS: We initially enrolled 500 patients in the study (250 in the risperidone group and 250 in the placebo group), but 17 (11 in the risperidone and 6 in the placebo group) were excluded after randomization. PEP developed in 24 patients (10.0%) in the risperidone group and 21 patients (8.6%) in the placebo group (P = .587). Serum amylase levels at 3 hours after ERCP were lower in the risperidone group (P = .007 in a single test of hypothesis, significance removed by Bonferroni correction for multiple testing). In multivariate analysis, a small papilla of Vater, total procedure time ≥40 minutes, and stenosis of the intrahepatic duct were significantly associated with PEP. LIMITATIONS: Multiplicity of study centers and a relatively wide time range of drug administration time. CONCLUSION: Risperidone did not show a benefit in prevention of PEP in this trial. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT000004592.).

Duodenal metal stent placement is a risk factor for biliary metal stent dysfunction: an analysis using a time-dependent covariate.

BACKGROUND: Although the combination of biliary and duodenal self-expandable metal stents (SEMS) is useful, the exacerbating effect of duodenal SEMS placement on biliary SEMS has not been documented. We conducted a multicenter retrospective study to evaluate the effect of duodenal SEMS placement on biliary SEMS. METHODS: Patients who underwent first-time biliary SEMS placement for a distal malignant biliary obstruction between September 1994 and November 2010 were included. Time to dysfunction of biliary SEMS was analyzed to identify risk factors for biliary SEMS dysfunction. Duodenal SEMS placement was analyzed as a time-dependent covariate. RESULTS: In total, 410 eligible patients were identified. Duodenal SEMS were placed in 33 patients (8 %). The median time to dysfunction of biliary SEMS was 170 days. Male gender (hazard ratio 1.37, 95 % confidence interval 1.03-1.83, P = 0.029) and duodenal SEMS placement (hazard ratio 2.00, 95 % confidence interval 1.16-3.45, P = 0.013) were risk factors in the multivariate Cox model. In patients undergoing duodenal SEMS, biliary SEMS dysfunction was observed in 17 (52 %) with a median time to dysfunction of 64 days after duodenal SEMS placement. As many as 60 % of the patients with biliary SEMS dysfunction after duodenal SEMS placement needed permanent percutaneous transhepatic biliary external drainage. CONCLUSIONS: Duodenal SEMS placement is a risk factor for biliary SEMS dysfunction. Alternative methods for biliary drainage should be considered for better biliary drainage in patients with a gastric outlet obstruction.

AA amyloid nephropathy with predominant vascular deposition in Crohn's disease.

A 44-year-old man with a 17-year history of Crohn's disease (CD) was referred to our nephrology department on suspicion of drug-induced nephrotoxicity. Over the preceding 18 months, he had slowly progressive renal insufficiency with slight urinary abnormalities. His disease activity had been well controlled up to that point with 5-aminosalicylic acid and azathiopurine. Laboratory examination revealed slight proteinuria without hematuria and an elevated serum creatinine level of 1.4 mg/dl. Pathological examination revealed amyloid A (AA) deposition in the kidney, predominantly in the arterial and arteriolar walls with little to none in the glomerular capillaries. AA amyloidosis is typically accompanied by glomerular amyloid deposition and massive proteinuria. In the present case, however, vascular amyloid deposition was predominant, and the renal function was deteriorated with slight urinary abnormalities. The present case confirmed the importance of conducting a definitive pathological diagnosis of renal insufficiency in CD patients.

A retrospective study of gemcitabine and cisplatin combination therapy as second-line treatment for advanced biliary tract cancer.

BACKGROUND: To evaluate the treatment outcome of gemcitabine and cisplatin combination therapy as second-line treatment for advanced biliary tract cancer. PATIENTS AND METHODS: Patients with advanced biliary tract cancer who were refractory to gemcitabine-based first-line chemotherapy were treated with gemcitabine and cisplatin combination therapy. Gemcitabine (1,000 mg/m(2)) and cisplatin (25 mg/m(2)) were administered intravenously on days 1 and 8, repeated every 3 weeks. RESULTS: Sixty patients were included. The tumor response and disease control rates were 1.7 and 58.3%, respectively. The median overall survival and time to progression were 6.7 months (95% CI 4.9-8.1) and 3.5 months (95% CI 2.5-5.0), respectively. Grade 3/4 toxicities included leucopenia (20%), neutropenia (25%), anemia (23%), thrombocytopenia (17%), nausea (2%), anorexia (2%), and liver dysfunction (2%). CONCLUSIONS: Gemcitabine and cisplatin combination therapy showed moderate efficacy and safety as second-line treatment for advanced biliary tract cancer that is refractory to gemcitabine-based first-line chemotherapy.

Japanese multicenter estimation of WallFlex duodenal stent for unresectable malignant gastric outlet obstruction.

AIM: This retrospective study estimated the efficacy and safety of the WallFlex duodenal stent for malignant gastric outlet obstruction (GOO) in Japan. METHODS: Forty-two consecutive patients with symptomatic malignant GOO were treated using WallFlex duodenal stents between January 2010 and October 2010. RESULTS: The technical and clinical success rates were 100% and 83.3%, respectively.The median gastric outlet obstruction scoring system increased significantly, from 0 to 2, after stent placement (P < 0.01).The median survival time was 3.3 months (95% confidence interval (CI), 1.8-6.0 months), and the median eating period was 3.0 months (95% CI, 1.1-4.3 months). Re-intervention was required in 11 patients (26.2%). The complication rate was 26.2%. The major complication was stent occlusion (23.8%) by tumor ingrowth, which occurred in nine (21.4%) patients, and tumor overgrowth, which occurred in one (2.4%) patient. Stentmigration, perforation, and food impaction without stent occlusion were not observed.The median survival time of the patients with stent occlusion was 11.7 months (95% CI, 2.2 months - not reached), and the median stent patency of these patients was 4.0 months (95% CI, 0.8-4.7 months).These patients were successfully treated with additional stent insertion using a stent-in-stent procedure. CONCLUSION: Duodenal stent placement using a WallFlex duodenal stent was safe and effective for managing malignant GOO.This stent is an uncovered metallic stent, and the major problem was stent occlusion due to tumor ingrowth. However, the occluded stent could be corrected by inserting an additional duodenal stent.

Anti-nuclear matrix protein 2 antibody-positive dermatomyositis with gastrointestinal ulcers: A case report.

Gastrointestinal manifestations are a very rare complication of dermatomyositis (DM) and are much less frequent in adult cases than in juvenile cases. Only a few previous papers have reported adult patients who had DM with anti-nuclear matrix protein 2 (anti-NXP2) antibodies and who developed gastrointestinal ulcers. Herein, we report a similar case of a 50-year-old man who had DM with anti-NXP2 antibodies followed by relapsing multiple gastrointestinal ulcers. Even after the administration of prednisolone, his muscle weakness and myalgia deteriorated and gastrointestinal ulcers relapsed. In contrast, intravenous immunoglobulin and azathioprine improved his muscle weakness and gastrointestinal ulcers. Based on the parallel disease activity of the muscular and gastrointestinal symptoms, we considered that his gastrointestinal ulcers were a complication of DM with anti-NXP2 antibodies. We also propose that early intensive immunosuppressive therapy would be required for the muscular and gastrointestinal symptoms in DM with anti-NXP2 antibodies.

Lower incidence of biliary carcinoma in patients with primary sclerosing cholangitis and high serum levels of immunoglobulin E.

BACKGROUND & AIMS: High serum levels of immunoglobulin (Ig)E often are detected in patients with primary sclerosing cholangitis (PSC), but the clinical significance is not known. METHODS: We analyzed data from 44 patients with PSC and known serum levels of IgE. They were divided into groups called high IgE (>170 IU/mL; n = 17) or normal IgE (n = 27). We compared occurrence of biliary carcinoma including cholangiocellular and gallbladder carcinoma, liver transplantation, and death between groups. RESULTS: The high IgE group had a later age of onset of PSC than the normal IgE group (54 ± 20 y vs 39 ± 16 y; P = .010); they also had a higher serum level of IgG (2078 ± 638 vs 1517 ± 475 mg/dL; P = .002) and IgG4 (104 ± 102 vs 38 ± 16 mg/dL; P = .002). Association with inflammatory bowel disease did not differ significantly between groups (5 of 17 vs 11 of 27; P = .661). No patient had biliary carcinoma in the high IgE group, but biliary carcinoma was observed during the follow-up period in 8 patients in the normal IgE group (0 of 17 vs 8 of 27; P = .016). The occurrence of biliary carcinoma, liver transplantation, or death did not differ between groups (4 of 17 vs 13 of 27; P = .124). CONCLUSIONS: High serum levels of IgE often are observed in older patients with PSC and are associated with a reduced incidence of biliary carcinoma.

Multicenter phase II study of S-1 monotherapy as second-line chemotherapy for advanced biliary tract cancer refractory to gemcitabine.

Gemcitabine is widely used for the treatment of advanced biliary tract cancer (BTC) as first-line chemotherapy. However, there is no standard chemotherapy for patient with advanced BTC refractory to gemcitabine. We conducted a multicenter phase II study of S-1 monotherapy as second-line chemotherapy for patients with advanced BTC that were refractory to gemcitabine. S-1 was administered orally at a dose of 80 mg/m(2) for 28 days, followed by 14 days of rest. This regimen was repeated every 6 weeks. Tumor response was assessed every two cycles using the Response Evaluation Criteria in Solid Tumors version 1.0. Twenty-two patients were enrolled between March 2007 and January 2010, with 14 patients (64%) representing cases of recurrence after surgery. The overall response rate was 22.7%, and the overall disease control rate was 50.0%. The median overall survival time was 13.5 months (95% CI, 7.1-23.1 months) and the median time-to-progression was 5.4 months (95% CI, 2.6-17.2 months). Grade 3/4 toxicities included neutropenia (5%) and anemia (5%). The most common non-hematological toxicities were nausea (27%), anorexia (55%), and pigmentation (32%). In conclusion, S-1 monotherapy is feasible and moderately efficacious second-line chemotherapy for advanced BTC.

Management of malignant gastric outlet obstruction with a modified triple-layer covered metal stent.

BACKGROUND: A high incidence of migration with covered metal stents has been reported in malignant gastric outlet obstruction (GOO). A newly modified, partially covered, triple-layer nitinol stent was developed that has a longer uncovered portion (5-15 mm) to prevent stent migration. OBJECTIVE: To estimate the efficacy and safety of the modified covered, triple-layer metal stent. DESIGN: Multicenter, prospective cohort study. SETTING: Three tertiary referral centers. PATIENTS: Fifty consecutive patients (26 with pancreatic carcinoma, 14 with gastric carcinoma, 9 with cholangiocarcinoma, 1 with a metastatic node) who presented with symptomatic unresectable malignant GOO between April 2007 and March 2010. INTERVENTIONS: Endoscopic placement of the modified covered, triple-layer metal stent. MAIN OUTCOME MEASUREMENTS: The primary endpoint was to improve the GOO scoring system (GOOSS) score. Secondary endpoints were success rate, patency, and complications. RESULTS: The median GOOSS score improved significantly (P < .0001) after stenting (from 0 to 3). The technical and clinical success rates were 100% and 90%, respectively. Stent occlusion by tumor overgrowth or ingrowth at the uncovered portion developed in 5 patients (10%). Asymptomatic stent migration occurred in 3 patients (6%) receiving chemotherapy at 95, 230, and 553 days after stent placement, but these patients tolerated solid food 68, 260, and 142 days after stent migration, respectively. Other complications occurred in 1 patient with insufficient expansion, cholangitis, and pancreatitis. No procedure-related deaths occurred. LIMITATIONS: A single-arm study in tertiary-care centers. CONCLUSIONS: The modified covered, triple-layer metal stent was effective and safe for managing malignant GOO and can prevent tumor ingrowth and stent migration. ( CLINICAL TRIAL REGISTRATION NUMBER: UMIN000004566.).

Comparison of partially covered nitinol stents with partially covered stainless stents as a historical control in a multicenter study of distal malignant biliary obstruction: the WATCH study.

BACKGROUND: Covered self-expandable metal stents (CSEMSs) were developed to prevent tumor ingrowth, but stent migration is one of the problems with CSEMSs. OBJECTIVE: To evaluate a new, commercially available CSEMS with flared ends and low axial force compared with a commercially available CSEMS without the anti-migration system and high axial force. DESIGN: Multicenter, prospective study with a historical cohort. SETTING: Twenty Japanese referral centers. PATIENTS: This study involved patients with unresectable distal malignant biliary obstruction. INTERVENTION: Placement of a new, commercially available, partially covered SEMS. MAIN OUTCOME MEASUREMENTS: Recurrent biliary obstruction rate, time to recurrent biliary obstruction, stent-related complications, survival. RESULTS: Between April 2009 and March 2010, 141 patients underwent partially covered nitinol stent placement, and between May 2001 and January 2007, 138 patients underwent placement of partially covered stainless stents as a historical control. The silicone cover of the partially covered nitinol stents prevented tumor ingrowth. There were no significant differences in survival (229 vs 219 days; P = .250) or the rate of recurrent biliary obstruction (33% vs 38%; P = .385) between partially covered nitinol stents and partially covered stainless stents. Stent migration was less frequent (8% vs 17%; P = .019), and time to recurrent biliary obstruction was significantly longer (373 vs 285 days; P = .007) with partially covered nitinol stents. Stent removal was successful in 26 of 27 patients (96%). LIMITATIONS: Nonrandomized, controlled trial. CONCLUSION: Partially covered nitinol stents with an anti-migration system and less axial force demonstrated longer time to recurrent biliary obstruction with no tumor ingrowth and less stent migration.