Osamu Togawa

Measurement of radial and axial forces of biliary self-expandable metallic stents

BACKGROUND Efforts to understand the properties of self-expandable metallic stents (SEMSs) through their mechanical properties have progressed. Among them, radial force (RF) is well known as an expanding force, but axial force (AF) has not been measured before. Correlations of these properties to clinical results are not well known. OBJECTIVE We measured RF and AF of 14 different SEMSs and discussed the results in terms of clinical implications. DESIGN Experimental study. SUBJECTS Measurement of RF and AF of 14 different covered and uncovered SEMSs. METHODS RF was measured with an RF measurement machine manufactured by Machine Solution, and AF was measured with in-house equipment. RESULTS Measurements of RF in the process of expansion showed characteristic patterns closely related to the structures and materials of SEMSs. Results of AF measurement can be classified into 3 groups: high, medium, and low AF, depending on the type of SEMS. AF decreased with an increase of the length of stents. A plot of RF against AF revealed 3 distinguished RF/AF combinations and indicated the importance of understanding the properties by not only RF or AF individually but also by RF/AF combination. LIMITATIONS In vitro study using measurement equipment. CONCLUSION It was demonstrated that a combination of RF and AF is more effective than RF or AF individually in understanding the clinical implications of SEMSs. More work is needed to correlate mechanical properties with clinical results by designing model experiments.

Inhibition of renin-angiotensin system affects prognosis of advanced pancreatic cancer receiving gemcitabine.

Background:The renin–angiotensin system (RAS) is thought to have a role in carcinogenesis, and RAS inhibition may prevent tumour growth.Methods:We retrospectively investigated the impact of angiotensin I-converting enzyme inhibitors (ACEIs) and angiotensin II type-1 receptor blockers (ARBs) in 155 patients with pancreatic cancer receiving gemcitabine monotherapy. Patients were divided into three groups: the ACEI/ARB group (27 patients receiving an ACEI or ARB for hypertension (HT)), the non-ACEI/ARB with HT group (25 patients receiving antihypertensive drugs other than ACEIs or ARBs), and the non-HT group (103 patients receiving no antihypertensive drugs).Results:Patient characteristics were not different, except for age and HT medications. Progression-free survival (PFS) was 8.7 months in the ACEI/ARB group, 4.5 months in the non-ACEI/ARB with HT group, and 3.6 months in the non-HT group. Overall survival (OS) was 15.1 months in the ACEI/ARB group, 8.9 months in the non-ACEI/ARB with HT group, and 9.5 months in the non-HT group. The use of ACEIs/ARBs was a significant prognostic factor for both PFS (P=0.032) and OS (P=0.014) in the multivariate analysis.Conclusions:The ACEIs/ARBs in combination with gemcitabine might improve clinical outcomes in patients with advanced pancreatic cancer. Prospective trials are needed to test this hypothesis.

High‐rate pulmonary involvement in autoimmune pancreatitis

Autoimmune pancreatitis (AIP) has extrapancreatic complications such as Sjögrens syndrome, retroperitoneal fibrosis and sclerosing cholangitis. We studied 30 patients with AIP. Of these, we identified pulmonary involvement in four patients during follow up. Among them, two patients had respiratory failure. They showed good response to steroid therapy, but a higher dose of prednisolone was necessary to maintain remission than that required in biliary involvement. Elevation of immunoglobulin G4 and Krebs von den Lungen‐6 levels were characteristic of pulmonary involvement. They may be useful for early detection of pulmonary complication.

A multicentre randomised phase II trial of gemcitabine alone vs gemcitabine and S-1 combination therapy in advanced pancreatic cancer: GEMSAP study.

Background:This randomised phase II trial compared gemcitabine alone vs gemcitabine and S-1 combination therapy in advanced pancreatic cancer.Methods:Patients were randomly assigned to 4-week treatment with gemcitabine alone (1000, mg m−2 gemcitabine by 30-min infusion on days 1, 8, and 15) or gemcitabine and S-1 combination therapy (1000, mg m−2 gemcitabine by 30-min infusion on days 1 and 15 and 40 mg m−2 S-1 orally twice daily on days 1–15). The primary end point was progression-free survival (PFS).Results:Between July 2006 and February 2009, 106 patients were enrolled. The PFS in gemcitabine and S-1 combination arm was significantly longer than in gemcitabine arm (5.4 vs 3.6 months), with a hazard ratio of 0.64 (P=0.036). Overall survival (OS) for gemcitabine and S-1 combination was longer than that for gemcitabine monotherapy (13.5 vs 8.8 months), with a hazard ratio of 0.72 (P=0.104). Overall, grade 3 or 4 adverse events were similar in both arms.Conclusion:Gemcitabine and S-1 combination therapy demonstrated longer PFS in advanced pancreatic cancer. Improved OS duration of 4.7 months was found for gemcitabine and S-1 combination therapy, though this was not statistically significant.

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.

Endoscopic evaluation of factors contributing to intrapancreatic biliary stricture in autoimmune pancreatitis

BACKGROUND Intrapancreatic bile duct stricture in autoimmune pancreatitis (AIP) is usually diagnosed as sclerosing cholangitis even if the stricture is limited to the intrapancreatic area. However, it is not known whether compression caused by pancreatic edema or biliary wall thickening causes such a biliary stricture. OBJECTIVE Our purpose was to clarify the factor that contributes to intrapancreatic biliary stricture in AIP: pancreatic head lesion or biliary wall thickening. DESIGN Single-center retrospective study. SETTING This study was performed in a tertiary care academic medical center. PATIENTS Fifty-six patients with AIP were included. MAIN OUTCOME MEASUREMENTS The relationship between the presence of a pancreatic head lesion and intrapancreatic biliary stricture was examined. In addition, the relationship between the extent of the intrapancreatic biliary stricture and the wall thickening was evaluated. RESULTS Among 44 patients with a pancreatic head lesion, 41 (93%) had intrapancreatic bile duct stricture. Among 12 patients without a pancreatic head lesion, only 2 had such a stricture (P < .0001). Intraductal US showed average intrapancreatic biliary wall thickening with severe stricture of 2.7 +/- 1.0 mm, significantly thicker than that with mild stricture (1.9 +/- 0.35 mm; P = .0200). LIMITATIONS Intraductal US was not performed in all patients. CONCLUSIONS Both pancreatic edema and biliary wall thickening influenced intrapancreatic biliary stricture in AIP. This type of stricture should be differentiated from extrapancreatic biliary stricture that may be caused by biliary wall thickening only.

Management of occluded uncovered metallic stents in patients with malignant distal biliary obstructions using covered metallic stents.

Background Self-expandable metallic stents (EMSs) have been widely used for the palliative treatment of unresectable malignant biliary obstructions, but EMSs are often occluded owing to tumor ingrowth via the wire mesh. Currently, there is no consensus on the management of occluded EMSs. We evaluated the efficacy of a covered EMS as a second endoprosthesis in patients with an occluded EMS. Methods Forty patients with an occluded uncovered EMS (14 men, 26 women; mean age 72 y, range 41 to 89 y) were studied. The patients suffered from the following: pancreatic cancer in 18, bile duct cancer in 11, gallbladder cancer in 5, lymph node metastasis in 4, and papillary cancer in 2. Of these, 26, 7, and 7 were treated with a covered EMS, an uncovered EMS, and a plastic stent (PS), respectively. The second stent was inserted as a stent-in-stent. Results The mean patent period for the covered EMS was 220 days, whereas the mean patent periods for the uncovered EMS and plastic stent were 141 and 58 days, respectively. The cumulative patency of the covered EMS group was significantly higher (P=0.0404) than that of the uncovered EMS group. No significant differences in survival were observed between the covered and uncovered groups. No serious complications occurred. Conclusion Insertion of a covered EMS is an effective and safe treatment for an occluded uncovered EMS.

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.).

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.

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.