Naminatsu Takahara

Preliminary report on a new, fully covered, metal stent designed for the treatment of pancreatic fluid collections

BACKGROUND Endoscopic transluminal treatment of pancreatic fluid collections (PFC) has been reported as an effective alternative approach to surgical treatment. A wide, short stent with an anti-migration system has been developed. OBJECTIVE To evaluate a newly developed, fully covered, self-expandable metal stent (FCSEMS) customized for cystogastrostomy. DESIGN Retrospective case series. SETTING Tertiary-care academic medical centers and affiliated hospitals. PATIENTS Nine patients who underwent endoscopic treatment of PFCs (5 with pseudocysts and 4 with walled-off pancreatic necrosis). INTERVENTION Stent deployment after endoscopic US-guided puncture. Irrigation and necrosectomy were performed at the discretion of the endoscopist. MAIN OUTCOME MEASUREMENTS Technical and clinical success rate, complications, and removability. RESULTS The FCSEMS was inserted successfully in all cases (9/9, 100%). Clinical success was achieved in 7 of 9 cases (77.8%). No early complications associated with the procedure were observed. Late complications were observed in 2 cases (bleeding and asymptomatic migration). The FCSEMS was removed without any complications in all 6 cases where it was attempted after the procedure had been completed (100%). LIMITATIONS This was a retrospective evaluation of a small number of cases. The FCSEMS was always inserted via the transgastric route. Follow-up duration was short. CONCLUSION The endoscopic approach that uses this new FCSEMS is feasible for the treatment of PFCs. However, further evaluation is required.

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.

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

Abstract 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.

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

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.

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 (&Dgr;CPR) and the later use of insulin during maintenance ST was examined in 20 patients. The transitions of homeostasis model assessment &bgr; cell and insulin resistance (HOMA-&bgr; 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 &Dgr;CPR less than 0.6 ng/mL were obliged to use insulin even after long-term observation, whereas all patients with &Dgr;CPR more than 1.0 ng/mL were free from insulin therapy. Moreover, HOMA-&bgr; 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. Abbreviations ST - steroid treatment CPR - C-peptide response HOMA-&bgr; - homeostasis model assessment &bgr; cell HOMA-R - homeostasis model assessment insulin resistance DM - diabetes mellitus GTT - glucagon tolerance test OHA - oral hypoglycemic agent HbA1c - hemoglobin A1c

Prognostic nomogram for nonresectable pancreatic cancer treated with gemcitabine-based chemotherapy

Background:A nomogram is progressively being used as a useful predictive tool for cancer prognosis. A nomogram to predict survival in nonresectable pancreatic cancer treated with chemotherapy has not been reported.Methods:Using prospectively collected data on patients with nonresectable pancreatic cancer receiving gemcitabine-based chemotherapy at five Japanese hospitals, we derived a predictive nomogram and internally validated it using a concordance index and calibration plots.Results:In total, 531 patients were included between June 2001 and February 2013. The American Joint Committee on Cancer (AJCC) TNM stages were III and IV in 204 and 327 patients, respectively. The median survival time of the total cohort was 11.3 months. A nomogram was generated to predict survival probabilities at 6, 12, and 18 months and median survival time, based on the following six variables: age; sex; performance status; tumour size; regional lymph node metastasis; and distant metastasis. The concordance index of the present nomogram was higher than that of the AJCC TNM staging system at 12 months (0.686 vs 0.612). The calibration plots demonstrated good fitness of the nomogram for survival prediction.Conclusions:The present nomogram can provide valuable information for tailored decision-making early after the diagnosis of nonresectable pancreatic cancer.

Risk for mortality from causes other than pancreatic cancer in patients with intraductal papillary mucinous neoplasm of the pancreas.

Objectives The long-term prognosis in patients with intraductal papillary mucinous neoplasm (IPMN) has not been determined. The aim of this study was to elucidate the risk for nonpancreatic cancer–specific mortality in patients with IPMN. Methods Seven hundred ninety-three patients with IPMN who were followed up more than 1 year were included in this study. Fine and Gray competing risk regression was used to assess the risk for mortality unrelated to pancreatic cancer. A comorbidity score at diagnosis was assigned using the Adult Comorbidity Evaluation 27. Results After a median follow-up of 50 months, a high comorbidity score and age at diagnosis were significantly associated with a risk for mortality unrelated to pancreatic cancer. Adjusted hazards ratio and 95% confidence interval of each comorbidity burden were as follows: none, 1; mild, 2.68 (0.76–9.45; P = 0.124); moderate, 10.9 (3.19–37.1; P < 0.001); and severe, 32.0 (9.41–108.8; P < 0.001). Comorbidity burden did not affect the risk for pancreatic cancer–specific mortality. Conclusions Comorbidity and age at diagnosis was significantly related to mortality unrelated to pancreatic cancer in patients with IPMN. For patients at high risk for nonpancreatic cancer mortality, a follow-up management may be more reasonable than surgery.

High Alcohol Consumption Increases the Risk of Pancreatic Stone Formation and Pancreatic Atrophy in Autoimmune Pancreatitis

Objectives This study aimed to investigate risk factors for pancreatic stones and atrophy in autoimmune pancreatitis (AIP). Methods Seventy-one patients with AIP observed for more than 1 year were enrolled. The frequency of pancreatic stone development and atrophy on computed tomography as well as their risk factors were examined. Results Pancreatic stones and atrophy were observed in 13 and 43 patients, respectively. Alcohol consumption of greater than 50 g/d was the only significant risk factor for pancreatic atrophy in univariate analysis. Alcohol intake of greater than 50 g/d was observed in 6 of 13 patients with stones and 10 of 58 patients without stones (46% vs 17%, P = 0.059). Alcohol intake of greater than 50 g/d was observed in 14 of 43 patients with atrophy and 2 of 28 patients without atrophy (33% vs 7.1%, P = 0.018). In multivariate analysis, alcohol consumption was a significant risk factor both for pancreatic stone formation (odds ratio [OR], 7.47; P = 0.040) and atrophy (OR 6.24; P = 0.034). Higher age at onset was another significant risk factor for pancreatic atrophy (OR 1.07 per year; P = 0.029). Conclusions Alcohol consumption of greater than 50 g/d increases the risk of pancreatic stone development and atrophy in patients with AIP.

Clinical utility of single-operator cholangiopancreatoscopy using a SpyGlass probe through an endoscopic retrograde cholangiopancreatography catheter

Background and Aim:  A single‐operator cholangiopancreatoscopy was developed to overcome a problem in conventional peroral cholangiopancreatoscopy. The aim of this pilot study was to clarify the clinical utility of single‐operator cholangiopancreatoscopy using a SpyGlass probe through an endoscopic retrograde cholangiopancreatography (ERCP) catheter.

Multicenter Phase II Study of Intravenous and Intraperitoneal Paclitaxel With S-1 for Pancreatic Ductal Adenocarcinoma Patients With Peritoneal Metastasis.

Objective: To evaluate the clinical efficacy and tolerability of intravenous (i.v.) and intraperitoneal (i.p.) paclitaxel combined with S-1, “an oral fluoropyrimidine derivative containing tegafur, gimestat, and otastat potassium” in chemotherapy-naive pancreatic ductal adenocarcinoma (PDAC) patients with peritoneal metastasis. Background: PDAC patients with peritoneal metastasis (peritoneal deposits and/or positive peritoneal cytology) have an extremely poor prognosis. An effective treatment strategy remains elusive. Methods: Paclitaxel was administered i.v. at 50 mg/m2 and i.p. at 20 mg/m2 on days 1 and 8. S-1 was administered at 80 mg/m2/d for 14 consecutive days, followed by 7 days of rest. The primary endpoint was 1-year overall survival (OS) rate. The secondary endpoints were antitumor effect and safety (UMIN000009446). Results: Thirty-three patients who were pathologically diagnosed with the presence of peritoneal dissemination (n = 22) and/or positive peritoneal cytology (n = 11) without other organ metastasis were enrolled. The tumor was located at the pancreatic head in 7 patients and the body/tail in 26 patients. The median survival time was 16.3 (11.47–22.57) months, and the 1-year survival rate was 62%. The response rate and disease control rate in assessable patients were 36% and 82%, respectively. OS in 8 patients who underwent conversion surgery was significantly higher than that of nonsurgical patients (n = 25, P = 0.0062). Grade 3/4 hematologic toxicities occurred in 42% of the patients and nonhematologic adverse events in 18%. One patient died of thrombosis in the superior mesenteric artery. Conclusions: This regimen has shown promising clinical efficacy with acceptable tolerability in chemotherapy-naive PDAC patients with peritoneal metastasis.