Toshihiko Arizumi

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.

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.

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.

S-1 Monotherapy in Patients with Advanced Biliary Tract Cancer

Objective: The aim of this study was to evaluate the efficacy and safety of single-agent S-1 in patients with advanced biliary tract cancer. Methods: S-1 was administered orally at a dose of 80 mg/m2 for 28 days, followed by 14 days of rest (1 cycle); treatment was repeated until disease progression, unacceptable toxicity, or patient refusal. Results: Forty-five patients were enrolled between January 2005 and June 2008. Among these, 29 patients received S-1 as first-line chemotherapy and 16 patients received S-1 as second-line chemotherapy. The response rates for first- and second-line chemotherapy were 17.2 and 18.8%, respectively. The median times to progression for the first- and second-line chemotherapy groups were 4.2 and 5.5 months (p = 0.91), respectively. The median overall survival and 1-year survival rate for each group were 8.7 and 8.0 months and 42.2 and 38.2%, respectively (p = 0.62). Only the first-line chemotherapy group experienced grade 3/4 toxicities, including leukopenia (6.9%), neutropenia (10.3%), anemia (6.9%), thrombocytopenia (10.3%) and total bilirubin elevation (3.4%). Conclusion: S-1 monotherapy is a feasible and moderately efficacious treatment for advanced biliary tract cancer, as a first- or second-line chemotherapy regimen.

Incidental pancreatic cysts found by magnetic resonance imaging and their relationship with pancreatic cancer.

Objectives We examined whether the presence of pancreatic cysts could be a risk for pancreatic cancer by comparing the incidence and characteristics of cysts found by magnetic resonance (MR) imaging in patients with and without pancreatic cancer. Methods Half-Fourier rapid acquisition with relaxation enhancement images and MR cholangiopancreatography were performed in 116 patients with pancreatic cancer (PC group) and 1226 with nonpancreatic disease (NP group). Incidence and characteristics of cysts were analyzed. Results Pancreatic cysts were detected in 65 patients (56%) of the PC group and in 123 patients (10%) of the NP group. According to the multivariate analysis, cyst presence was a significant risk factor for pancreatic cancer (odds ratio [OR], 10.27; P < 0.01), especially cysts larger than 10 mm (OR, 4.718; P < 0.01). When the definition of cyst presence in the PC group was restricted to the 33 cases with cysts considered to have existed before the development of cancer, the incidence was still high (OR, 2.976; P < 0.01) and size remained significant (OR, 4.428; P < 0.01). Conclusions Patients with pancreatic cysts, especially larger than 10 mm, were considered to be at an increased risk of pancreatic cancer over the entire pancreas.

Impact of S-1 on the survival of patients with advanced pancreatic cancer.

Objective: The aim of this study was to investigate the effect of S-1 on the prognosis of advanced pancreatic cancer. Methods: In total, 112 patients with pancreatic cancer who received chemotherapy between April 2001 and April 2007 were divided into 2 groups: PreS-1 (53 patients who started chemotherapy before January 2005) and PostS-1 (59 patients who started chemotherapy after February 2005, the time of S-1 introduction). Patient characteristics and clinical outcomes were compared, and prognostic factors were analyzed. Results: Patient characteristics did not significantly differ between the 2 groups. S-1 was administered as a second-line monotherapy in 5.7% of the PreS-1 group and combined with gemcitabine as a first-line therapy in 27.1% or as second-line monotherapy in 23.7% in the PostS-1 group. Both progression-free survival and overall survival improved after introduction of S-1 (median progression-free survival, 4.4 and 5.3 months; P = 0.043; median overall survival, 9.5 and 13.1 months; P = 0.048 in PreS-1 and PostS-1 groups, respectively). Multivariate analysis revealed that the PostS-1 group (hazards ratio, 0.52; P = 0.003), performance status, and carcinoembryonic antigen were significant prognostic factors for survival. Conclusions: Introduction of S-1 may improve the prognosis of Japanese patients with advanced pancreatic cancer.