Emergency endoscopic variceal ligation following variceal rupture in patients with advanced hepatocellular carcinoma and portal vein tumor thrombosis: a retrospective study.

BACKGROUND: The outcomes of treatment of ruptured varices in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) are unclear. We therefore evaluated the long- (rebleeding and death) and short-term (immediate death within 24 h of variceal bleeding diagnosis) outcomes of patients with PVTT who underwent emergency variceal band ligation. METHODS: Data on 62 patients with PVTT and endoscopically proven esophageal or gastric variceal bleeding from 2007 to 2012 were studied. In most cases, the varices were treated using endoscopic variceal band ligation (EVL). We assessed the patients' rebleeding-free and overall survival using the Kaplan-Meier method, and a Cox proportional hazard model was used to analyze effect of independent factors on rebleeding-free and overall survival times. RESULTS: Most patients had decompensated cirrhosis and were classified as Child-Pugh class B (56%) or C (36%). A total of 35 patients (56%) had PVTT in the main portal trunk. Among all patients, 58 (94%) and 4 (6%) had esophageal and gastric variceal bleeding, respectively. Bleeding was managed using EVL in all, but one patient (98%) who was treated with a Sengstaken-Blakemore tube. A total of 24 patients (39.3%) experienced rebleeding, and these patients had a median overall survival time of 36 days. A PVTT in the main portal trunk was predictive of rebleeding (hazard ratio 3.706, p = .0223), and α-fetoprotein-L3 levels <37.4% (hazard ratio 0.464, p = 0.015) and Child-Pugh class A/B (hazard ratio 0.398, p = 0.007) were associated with overall survival. We observed 95 bleeding events in 62 patients. EVL achieved hemostasis in 92 of the 95 bleeding events, whereas seven immediate deaths occurred due to variceal bleeding (7/92, 7.6%). All three bleeding events treated with modalities other than EVL resulted in immediate deaths. CONCLUSIONS: EVL is a safe and effective treatment of variceal ruptures in patients with HCC and PVTT. After successful hemostasis, alleviation of the underlying liver function impairment and tumor control are equally important for a good prognosis.

Intraarterial 5-fluorouracil and interferon therapy is safe and effective for nonresectable biliary tract adenocarcinoma.

PURPOSE: The prognosis in advanced biliary carcinoma has remained poor. The purpose of this study was to investigate the efficacy of intraarterial 5-fluorouracil and interferon therapy against unresectable biliary carcinoma. METHODS: Patients with unresectable biliary carcinoma with performance status 0 or 1 were enrolled between January 2002 and September 2012. They received pegylated interferon-α 2a and intraarterial 5-FU every 4 weeks. The therapy was either terminated at the end of the first cycle for the patients with progressive disease or continued for at least three cycles. Patients' characteristics (physical, laboratory and radiographic) at the time of starting intraarterial 5-FU therapy were investigated. The relationship between the patients' characteristics and outcome, i.e., survival time and radiographic therapeutic evaluation of patients, was statistically analyzed. RESULTS: Tumor sites were the intrahepatic bile ducts in 23 patients and gallbladder in 2 patients. Previous treatment had been administered in ten patients. The overall response rate was 24% (6 partial responses in 25 patients). Stable disease was observed in 13 patients. The median overall survival was 358 days. Among the six partial responses, three patients received surgery, and one patient received radiofrequency ablation because clinical downstaging was obtained. The treatment was well tolerated. The survival analyses revealed that two factors (serum albumin ≥ 3.5 and hypovascular tumor) were significantly associated with overall survival. CONCLUSIONS: Combination therapy with 5-FU and interferon-α was safe and may improve the prognosis of advanced biliary carcinomas.

Endoscopic submucosal dissection to treat ileal high-grade dysplasia after ileoanal anastomosis for familial adenomatous polyposis: report of a case.

Restorative proctocolectomy has become the most common surgical option for familial adenomatous polyposis patients, based on the premise that the technique yields good functional results and reduces colorectal cancer risk. However, several adenomas may develop in the pouch mucosa in later years, and even cancer (at the anastomosis or in the pouch mucosa) has been reported. Endoscopic submucosal dissection (ESD) would then be indicated, even if severe fibrosis extended into the submucosal layer. Endoscopic resection of an ileal tumor from the thin wall of the ileum carries a high-risk of perforation. Our present case demonstrates the successful use of ESD to treat an ileal neoplasm, a technically difficult lesion with a high-risk of complications.

Incidence of malignancies in patients with IgG4-related disease.

OBJECTIVE: It has been discussed whether IgG4-related disease (IgG4-RD), including autoimmune pancreatitis (AIP), is associated with malignancy; however, the issue has not been clarified. METHODS: We analyzed 113 patients with IgG4-RD in whom malignancy was not diagnosed at the time of IgG4-RD onset and the follow-up period was longer than six months. A total of 95 patients had AIP. The mean follow-up period was 73 months. The incidence of the observed malignancies was compared with the expected incidence in an age- and sex-matched general Japanese population based on the Vital Statistics of Japan. RESULTS: There were 15 malignancies (lung cancer in five patients, pancreatic cancer in two patients, gastric cancer in two patients, bile duct cancer in one patient, renal cancer in one patient, breast cancer in one patient, tongue cancer in one patient, malignant melanoma in one patient and acute myeloid leukemia in one patient) in 14 patients during the follow-up period. The calculated standardized incidence rate of the total malignancies was not significant, that is, 1.04 (95% CI 0.57-1.75). CONCLUSION: The incidence of total malignancies in IgG4-RD patients is similar to that observed in the general population. At present, it is reasonable to conclude that IgG4-RD is not associated with an increased incidence of total malignancies.

High single-session success rate of endoscopic bilateral stent-in-stent placement with modified large cell Niti-S stents for malignant hilar biliary obstruction.

BACKGROUND: Endoscopic bilateral self-expandable metallic stent (SEMS) placement in a stent-in-stent method for malignant hilar biliary obstruction is technically challenging. Technical difficulties in the initial placement and reinterventions for stent occlusion are disadvantages inherent to this stent-in-stent method. We previously reported the feasibility of Niti-S large cell D-type biliary stents (LCD). This multicenter prospective consecutive study evaluated the efficacy of bilateral SEMS placement using modified LCD with large and uniform cells, a slimmer delivery system and high radial force. PATIENTS AND METHODS: From July 2010 to June 2011, 26 consecutive patients with unresectable malignant hilar biliary obstruction underwent endoscopic bilateral placement of modified LCD in a stent-in-stent method at three tertiary hospitals. Ten patients had gallbladder cancer, eight had cholangiocarcinoma, four had lymph node metastasis, two had intrahepatic cholangiocarcinoma, and two had liver metastasis. RESULTS: Single-session and final technical success rate was 96% and 100%, respectively. Functional success rate was 89%. Stent occlusion occurred in 11 patients (42%) because of sludge (n = 7) or tumor ingrowth (n = 4). Endoscopic bilateral reintervention was technically easy and successful: six patients had stent clearance by balloon sweeping and five had plastic stent placement. According to Kaplan-Meier analysis, median survival and stent patency were 220 days and 157 days, respectively. CONCLUSIONS: Modified LCD achieved a high technical success rate both in the initial stent-in-stent placement and in bilateral reinterventions in patients with malignant hilar biliary obstruction.

Short- and long-term outcomes of endoscopic papillary large balloon dilation with or without sphincterotomy for removal of large bile duct stones.

OBJECTIVE: Removal of large bile duct stones by endoscopic papillary large balloon dilation (EPLBD) with endoscopic sphincterotomy (EST) has been proven safe and effective. Little evidence supports the benefits of a preceding EST in reducing complications. Recent studies suggest that large bile duct stone removal by EPLBD alone may be safe and effective. MATERIAL AND METHODS: We removed large bile duct stones by EPLBD with EST from March 2008 to February 2010 and without EST from March 2010 to October 2011. Efficacy and safety of EPLBD with or without EST and late biliary complication outcomes were assessed. RESULTS: Forty-two patients (men/women, 27/15; mean age, 76 years) underwent EPLBD: 14 underwent EPLBD with EST and 28 underwent EPLBD without EST. The mean stone size was 14 mm (9-30 mm). Overall complete stone removal rate was 98%, with 83% achieved in 1 session. Complete duct clearance by EPLBD alone was achieved in 79%. Mechanical lithotripsy was required in 4 (10%) patients. Extracorporeal shock wave lithotripsy and electrohydraulic lithotripsy were required in 4 (10%) and 1 (2%) patients, respectively. Pancreatitis and perforation occurred in 2 (5%) and 1 (2%) patients, respectively. Patients treated by EPLBD with EST and by EPLBD alone did not differ in complication outcomes. Six (14%) patients had recurrent bile duct stones, with a significant correlation to dilated common bile duct (p = 0.0351). CONCLUSIONS: EPLBD is safe and effective in patients with large bile duct stones. Preceding EST may be unnecessary.

Feasibility of a new self-expandable metallic stent for patients with malignant colorectal obstruction.

AIM: Stent migration due to peristalsis of the colon is one of the unresolved complications of colonic self-expandable metallic stent (SEMS) placement. Axial force (AF), a recovery force of the stent to a straight position after bending, has been considered a factor influencing the conformability of the digestive tract. An uncovered SEMS (Niti-S Enteral Colonic Uncovered Stent, D-type; Taewoong, Inc., Gimpo, South Korea) with improved conformability is considered to decrease migration. METHODS: Thirty three consecutive patients with symptomatic colorectal obstruction between March 2006 and December 2011 underwent endoscopic stent placement for palliation to estimate the efficacy and safety of Niti-S stents prospectively in four tertiary referral centers. RESULTS: Technical and clinical success rates were 100% and 97%, respectively. Seventeen patients had the following complications: ingrowth (n = 6), overgrowth (n = 1), collapse of the SEMS (n = 1), stool impaction (n = 2), migration (n = 1), bleeding (n = 3), and tenesmus (n = 3). The patient with migration had no recurrent symptoms until death. Of these 17 patients, 10 required re-interventions. Seven patients underwent an additional SEMS implantation. One patient underwent surgery for stoma creation. Two patients had stool impaction, and they underwent endoscopic cleaning. The median duration of patency was 347.0 ± 65.5 days. The mean survival time after stent insertion was 240.1 ± 39.9 days. CONCLUSION: The new SEMS effectively relieves malignant colorectal obstruction. Good conformability, according to the very low AF, may contribute to the low incidence of migration.

Management of dysfunctional covered self-expandable metallic stents in patients with malignant distal biliary obstruction.

BACKGROUND: Endoscopic placement of covered self-expandable metallic stents (CSEMSs) is effective for distal malignant biliary obstruction. However, management of dysfunctional CSEMSs has not been established. METHODS: Between March 1998 and July 2007, a total of 74 patients who underwent endoscopic re-interventions for CSEMS dysfunction were analyzed. Second stent insertion (CSEMS or plastic stent) or mechanical cleaning of the occluded CSEMS was performed endoscopically. The period between second stent insertion and stent dysfunction or patient death (time to dysfunction; TTD) was calculated. The cleaned initial CSEMSs were analyzed as second stents. RESULTS: Dysfunction of the second stent occurred in 17 of 37 patients (45.9%) in the CSEMS group, 16 of 20 (80.0%) in the plastic stent group, and 13 of 17 (76.5%) in the cleaning group. The median TTD of each group was 176, 57, and 46 days, respectively. The cumulative TTD was significantly higher in the CSEMS group than in the plastic stent and cleaning groups (P = 0.08). From the multivariate analysis, sludge occlusion of the first CSEMS was identified as a significant risk factor for second stent dysfunction (HR, 2.51; 95% CI, 1.19-5.46), and placement of the second CSEMS significantly reduced the risk of dysfunction (HR, 0.39; 95% CI, 0.18-0.79). CONCLUSIONS: Insertion of a new CSEMS should be considered as the treatment of choice for the management of dysfunctional CSEMSs.

The results of the Tokyo trial of prevention of post-ERCP pancreatitis with risperidone (Tokyo P3R): a multicenter, randomized, phase II, non-placebo-controlled trial.

BACKGROUND: A previous study suggested that ulinastatin effectively prevented post-ERCP pancreatitis (PEP) and hyperenzymemia (PEH) in patients at average risk. In experimental models, risperidone, a selective serotonin 2A antagonist, ameliorated acute pancreatitis. We assessed the effect of risperidone combined with ulinastatin for the prevention of PEP in high-risk patients. METHODS: In a multicenter, randomized, controlled, phase II trial, patients undergoing therapeutic ERCP were randomly assigned to receive ulinastatin (150000 U) with or without risperidone (1 mg). A risperidone tablet was taken orally 30-60 min before ERCP and ulinastatin was administered intravenously for 10 min immediately prior to ERCP. The primary end point was the incidence of PEP; secondary end points were PEH severity and enzyme levels (amylase, pancreatic amylase, lipase). RESULTS: A total of 226 patients (113 per group) were included in the study. Six patients in the risperidone + ulinastatin group and ten patients in the ulinastatin group developed pancreatitis (5.3 vs. 8.8 %, p = 0.438). The incidence of moderate/severe PEP was lower in the risperidone + ulinastatin group (1.8 %) than in the ulinastatin group (4.4 %), but this difference was not significant. Although the incidence of PEH did not differ significantly, post-ERCP levels of all pancreatic enzymes were significantly lower in the risperidone + ulinastatin group. CONCLUSIONS: Prophylactic oral risperidone administration in combination with ulinastatin did not reduce the incidence and severity of PEP in high-risk patients as compared with ulinastatin alone. However, risperidone showed an additive effect with ulinastatin, reducing serum pancreatic enzyme levels.

Predictive factors of solid food intake in patients with malignant gastric outlet obstruction receiving self-expandable metallic stents for palliation.

AIM: As for self-expandable metallic stents (SEMS) for malignant gastric outlet obstruction (GOO), some predictive factors of stent patency have been reported, although re-canalization of GOO by SEMS does not necessarily lead to favorable food intake. Therefore, we analyzed the predictive factors of oral food intake following SEMS placement. METHODS: A total of 97 consecutive patients in whom SEMS were placed for malignant GOO in five hospitals were included in this retrospective study. Clinical outcomes and predictive factors influencing solid food intake were analyzed. RESULTS: The technical and clinical success rates were 97.9% and 87.6%, respectively. The mean gastric outlet obstruction scoring system (GOOSS) improved from 0.39 to 2.24 after SEMS placement (P<0.01). The median eating period was 2.1 months (95% CI, 1.1-3.0 months), and the median survival time was 3.1 months (95% CI, 2.0-4.2 months). A Karnofsky performance status of ≤ 50 (odds ratio, 3.65; 95% CI, 1.17-13.1; P=0.03) and ascites (odds ratio, 3.28; 95% CI, 1.23-9.05; P=0.02) were identified as statistically significant independent poor predictive factors of solid food intake. CONCLUSION: SEMS is an effective treatment for patients with malignant GOO. Ascites and a poor performance status were poor predictive factors of solid food intake.

Long-term prognosis of autoimmune pancreatitis in terms of glucose tolerance.

OBJECTIVE: Glucose intolerance is often observed in autoimmune pancreatitis (AIP), although its long-term prognosis after steroid treatment (ST) is still unclear. METHODS: A total of 47 patients with AIP were enrolled. On the basis of the change in hemoglobin A1c (HbA1c) and the use of diabetic medication, prognosis was classified into 3 categories, namely, "improved," "aggravated," and "unchanged." The relation between the result of an initial glucagon tolerance test (ΔCPR) and the later use of insulin during maintenance ST was examined in 20 patients. The transitions of homeostasis model assessment ß cell and insulin resistance (HOMA-ß and HOMA-R) were analyzed in 16 patients. RESULTS: Glucose tolerance was improved in 6 patients (13%), aggravated in 9 patients (19%), and unchanged in 32 patients (68%). All patients with ΔCPR less than 0.6 ng/mL were obliged to use insulin even after long-term observation, whereas all patients with ΔCPR more than 1.0 ng/mL were free from insulin therapy. Moreover, HOMA-ß showed significant improvement after ST (43.9% → 56.0% in median, P = 0.030), and HOMA-R showed significant aggravation (1.30 → 1.78, P = 0.039). CONCLUSIONS: Glucose tolerance that is too severely damaged may not recover fully even after ST. Thus, ST should be performed to preserve insulin secretion at the early stage of AIP.

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.).

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.

Acoustic radiation force impulse elastography for noninvasive assessment of chronic pancreatitis.

BACKGROUND: Endoscopic ultrasonography or real-time elastography has been applied for the diagnosis of chronic pancreatitis. Acoustic radiation force impulse (ARFI) imaging is another tissue strain imaging technology, and recent technological advances have enabled quantification of the stiffness of some tissues by measuring the shear wave velocity (SWV) during routine B-mode ultrasonography. METHODS: ARFI elastography was performed in 52 healthy volunteers and 46 patients with chronic pancreatitis. SWV was measured in the head, body, and tail of the pancreas. The diagnostic performance was assessed using receiver-operating characteristic (ROC) curves. RESULTS: SWV in patients with chronic pancreatitis was significantly higher than that in healthy volunteers in each part of the pancreas, although the measurement was difficult in the tail of the pancreas. The area under the ROC curve was 0.78 in the body of the pancreas, with an optimal cut-off value of 1.40 m/s, and the sensitivity, specificity, positive predictive value, and negative predictive value were 75, 72, 69, and 78%, respectively. In the patients with chronic pancreatitis, alcoholic etiology and decreased body mass index (BMI) were associated with high SWV. CONCLUSIONS: ARFI elastography of the pancreas showed high elasticity in chronic pancreatitis compared to findings in the normal pancreas. This modality is feasible to use for the diagnosis of chronic pancreatitis.

Fever-based antibiotic therapy for acute cholangitis following successful endoscopic biliary drainage.

BACKGROUND: The current management of acute cholangitis consists of antibiotic therapy in combination with biliary drainage. However, the optimal duration of antibiotic therapy after the resolution of clinical symptoms by biliary drainage is unclear. We aimed to evaluate whether discontinuing antibiotic therapy for acute cholangitis immediately after the resolution of clinical symptoms, achieved by endoscopic biliary drainage, was safe and effective. METHODS: This prospective study included patients with moderate and severe acute cholangitis. Cefmetazole sodium and meropenem hydrate were used as initial antibiotic therapy for patients with moderate and severe acute cholangitis, respectively. All patients underwent endoscopic biliary drainage within 24 h of diagnosis. When the body temperature of < 37 ° C was maintained for 24 h, administration of antibiotics was stopped. The primary endpoint was the recurrence of acute cholangitis within 3 days after the withdrawal of antibiotic therapy. RESULTS: Eighteen patients were subjected to the final analysis. The causes of cholangitis were bile duct stone (n = 17) and bile duct cancer (n = 1). The severity of acute cholangitis was moderate in 14 patients and severe in 4. Body temperature of < 37 ° C was achieved in all patients after a median of 2 days (range 1-6) following endoscopic biliary drainage. Antibiotic therapy was administered for a median duration of 3 days (range 2-7). None of the patients developed recurrent cholangitis within 3 days after the withdrawal of antibiotics. CONCLUSIONS: Fever-based antibiotic therapy for acute cholangitis is safe and effective when resolution of fever is achieved following endoscopic biliary drainage.

A large volume of visceral adipose tissue leads to severe acute pancreatitis.

BACKGROUND: Obesity plays an important role in acute pancreatitis. Assuming that the volume of visceral adipose tissue (VAT) directly influences the severity of acute pancreatitis, we investigated the relationship between VAT and acute pancreatitis. METHODS: Data were collected consecutively from 124 patients who were diagnosed with acute pancreatitis. Body mass index (BMI) was calculated from the database. Computed tomography was performed in all patients, and VAT, subcutaneous adipose tissue (SAT), and waist circumference (WC) were measured at the level of the intervertebral disk between L2 and L3. Atlanta criteria were adopted to define severe acute pancreatitis. Clinical courses were investigated, and the Ranson and acute physiology and chronic health evaluation II (APACHE II) scores were calculated for all patients. RESULTS: Forty-eight patients had severe acute pancreatitis (38.7%), and 76 were mild cases. BMI, VAT, SAT, and WC were correlated with the severity of acute pancreatitis in a univariate analysis, but only VAT had a strong correlation with severe acute pancreatitis in the multivariate analysis. In a trend analysis, not only severity but also the presence of pseudocysts (local complication) and prognostic factors (Ranson and APACHE II scores) were significantly related to VAT volume. In particular, the presence of a pancreatic pseudocyst was strongly related to VAT volume (p < 0.001). CONCLUSION: In acute pancreatitis, peripancreatic VAT has a stronger correlation with severe acute pancreatitis than BMI or WC. VAT volume is strongly correlated with the formation of a pseudocyst and with systemic inflammatory response syndrome in patients with acute pancreatitis and high VAT volume may lead to severe acute pancreatitis.

Duodenal invasion is a risk factor for the early dysfunction of biliary metal stents in unresectable pancreatic cancer.

BACKGROUND: Although the placement of self-expandable metal stents (SEMSs) has been widely accepted as palliation for distal malignant biliary obstruction, the risk factors for their early dysfunction remain unclear. OBJECTIVE: To identify risk factors for early (<3 months) SEMS dysfunction in unresectable pancreatic cancer. DESIGN: A multicenter retrospective study. SETTING: Five tertiary referral centers. PATIENTS: Patients were included who underwent first-time SEMS placement for distal malignant biliary obstruction caused by pancreatic cancer between April 1994 and August 2010. MAIN OUTCOME MEASUREMENTS: Rates and causes of early dysfunction were evaluated, and risk factors were analyzed. RESULTS: In all, 317 eligible patients were identified. Covered SEMSs were placed in 82% of patients. Duodenal invasion was observed endoscopically in 37%. The median time to dysfunction was 170 days. The rates of all and early SEMS dysfunction were 55% and 31%, respectively. The major causes of SEMS dysfunction were food impaction and nonocclusion cholangitis (21% each) in early dysfunction and sludge (29%) in nonearly dysfunction. The rate of early dysfunction was 42% with duodenal invasion and 24% without duodenal invasion (P = .001). Early dysfunction caused by food impaction was more frequent in patients with duodenal invasion (10% and 4%, P = .053). Duodenal invasion was a risk factor (odds ratio 2.35; 95% CI, 1.43-3.90; P = .001) in a multiple logistic regression model. LIMITATIONS: A retrospective design. CONCLUSIONS: Duodenal invasion is a risk factor for early SEMS dysfunction in patients with pancreatic cancer.

Gemcitabine and oxaliplatin combination chemotherapy for patients with refractory pancreatic cancer.

OBJECTIVE: The aim of this study was to investigate the effect of gemcitabine and oxaliplatin combination chemotherapy on refractory pancreatic cancer. METHODS: Patients with advanced pancreatic cancer refractory to gemcitabine and S-1 were treated with gemcitabine 1,000 mg/m² over 30 min and oxaliplatin 85 mg/m² over 120 min on days 1 and 15. Treatment was repeated every 4 weeks and tumor response was assessed every two cycles by RECIST version 1.0. RESULTS: Twenty-two patients with pathologically confirmed pancreatic cancer were enrolled. The treatment was administered as a second-line chemotherapy in eighteen patients (82%) and as a third-line chemotherapy in four patients (18%). Tumor response did not occur in any of the cases. Thirteen patients demonstrated stable diseases, and the disease control rate was 59%. Median overall survival and time to progression were 6.8 months (95% CI, 2.8-11.5) and 2.6 months (95% CI, 1.5-3.8), respectively. Median overall survival from the first-line chemotherapy was 22.7 months (95% CI, 14.8-24.4). The major grade 3/4 adverse events included neutropenia (14%), anorexia (23%), and peripheral neuropathy (14%). CONCLUSIONS: Gemcitabine and oxaliplatin combination chemotherapy was tolerable but had limited activity in patients with advanced pancreatic cancer in a refractory setting.

Impact of introduction of wire-guided cannulation in therapeutic biliary endoscopic retrograde cholangiopancreatography.

BACKGROUND AND AIM: Wire-guided cannulation (WGC) might increase the biliary cannulation rate and decrease the risk of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). We assessed the learning curve for WGC in therapeutic biliary ERCP (study 1) and compared WGC and conventional contrast-assisted cannulation (CC) by a matched case-control study (study 2). METHODS: Prospectively collected data of 500 therapeutic biliary ERCP cases (250 consecutive cases of WGC and 250 matched controls of CC) were retrospectively studied. Rate and time of biliary cannulation, total procedure time, PEP, and hyperamylasemia were analyzed. RESULTS: In study 1, biliary cannulation by WGC was successful in 96% of the first 50 cases, with a median time to cannulation of 3 min. Rates of hyperamylasemia were within 10% after 100 WGC. In study 2, there were no significant differences in the overall cannulation rate and PEP between WGC and CC, but the total procedure time was shorter in WGC (30 vs 35 min, P = 0.059). Rates of hyperamylasemia and the change in serum amylase levels was lower (9% vs 14%, P = 0.069, and + 62.8 U/L vs+ 169.5 U/L, P = 0.043) in WGC, which was more prominent in experienced endoscopists (9% vs 17%, P = 0.025, and + 68.9 U/L vs+ 229.3 U/L, P = 0.014). CONCLUSIONS: The introduction of WGC was effective in the first 50 cases and did not increase the rate of PEP in biliary therapeutic ERCP.

New method of covered wallstents for distal malignant biliary obstruction to reduce early stent-related complications based on characteristics.

AIM: We previously reported a low occlusion rate with covered Wallstents for malignant biliary obstruction, but stent-related complications other than occlusion posed a problem. A modified covered Wallstent insertion method based on stent characteristics was evaluated to reduce stent-related complications. METHODS: A total of 138 patients with distal malignant biliary obstruction received covered Wallstent placement. From October 2001 to October 2003, 69 patients received covered Wallstent placement (Group 1). Thereafter, we modified our stent insertion method and 69 patients received stent placement using this modified method from November 2003 to January 2007 (Group 2). The modified insertion method consists of endoscopic sphincterotomy carried out in patients without pancreatic duct invasion and longer stent placement with the center of the stent located in the center of the biliary stricture to prevent pancreatitis, kinking of the bile duct, and stent dislocation. A comparative analysis was carried out using prospectively collected data in these two cohorts. RESULTS: Tumor ingrowth was not observed, and stent occlusion rate was 18.8% in Group 1 and 23.2% in Group 2. The overall rates of stent-related complications did not differ (39.1% in Group 1 and 30.4% in Group 2), but stent-related complications within 3months decreased from 22 episodes in Group 1 to 13 episodes in Group 2. Median event-free survival was prolonged by modified stent insertion method (125days in Group 1 and 268days in Group 2, P=0.020), although cumulative survival and stent patency were not significantly different. CONCLUSIONS: Our modified method of covered Wallstent placement showed improved event-free survival.