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.

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.

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.

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.

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.).

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.

Feasibility study of gemcitabine and cisplatin combination chemotherapy for patients with refractory biliary tract cancer.

Gemcitabine and cisplatin combination chemotherapy have been shown to have promising efficacy for the treatment of advanced biliary tract cancer (BTC) as a first-line chemotherapy. However, this treatment has not been approved for clinical practice in Japan. Oral fluoropyrimidines (e.g., S-1 and capecitabine) are also promising agents that are widely used with or without gemcitabine. Unfortunately, there is no standard chemotherapy for patients refractory to gemcitabine and oral fluoropyrimidine. We conducted a feasibility study of gemcitabine and cisplatin combination chemotherapy for patients with advanced BTC who are refractory to gemcitabine and S-1. Gemcitabine (1,000 mg/m(2)) and cisplatin (25 mg/m(2)) were administered intravenously on days 1 and 8, and this regimen was repeated every 3 weeks. Tumor response was assessed every two cycles using the Response Evaluation Criteria in Solid Tumors version 1.0. Twenty patients with pathologically confirmed BTC were enrolled. Gemcitabine and cisplatin combination chemotherapy was administered as a second-line chemotherapy in thirteen patients and as a third-line chemotherapy in seven patients. Tumor response did not occur in any of the cases. Fourteen patients demonstrated stable diseases, and the disease control rate was 70%. Median overall survival and time-to-progression were 5.9 months (95% CI, 3.9-11.3 months) and 3.6 months (95% CI, 2.2-4.2 months), respectively. Grade 3/4 toxicities included leucopenia (35%), neutropenia (35%), anemia (20%), and thrombocytopenia (15%). Two patients treated for approximately 1 year developed cisplatin-related toxicities. In conclusion, gemcitabine and cisplatin combination chemotherapy produces a limited tumor response in BTC, but may prolong patient's survival.

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.

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.

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.

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 distal malignant biliary obstruction with the ComVi stent, a new covered metallic stent.

BACKGROUND: The covered metallic stent is effective for managing malignant distal biliary obstructions. The most popular covered metallic stent is the covered Wallstent (CWS). This study estimated the efficacy and safety of a new expanded polytetrafluoroethylene (e-PTFE)-covered nitinol metallic stent, the ComVi stent. This covered metallic stent consists of an e-PTFE membrane sandwiched between two uncovered metallic stents with weak axial (straightening) force. Wire is exposed on both the inner and outer surfaces. METHODS: Between May 2005 and April 2007, ComVi stents were placed consecutively in 47 patients with unresectable malignant distal biliary obstruction. The cases involved 35 pancreatic cancers, 8 metastatic nodes, 2 gallbladder cancers, and 2 bile duct cancers. The patients were compared with 47 patients who received CWS placement between August 2001 and May 2005 matched for age, sex, and causative disease from 133 cases. RESULTS: No significant differences in stent patency or patient survival were found. Stent occlusion was observed in 13 patients (27.7%) in the ComVi group and 10 patients (21.3%) in the CWS group. The cause of occlusion in both groups was tumor overgrowth (4.25% vs 4.2%), sludge (8.5% vs 6.3%), impaction of food scraps (14.9% vs 2.1%), and bile duct kinking (0% vs 8.4%). Other complications were migration (2.1% vs 17.0%; p = 0.0304) and cholecystitis (2.1% vs 6.3%), and there were significant differences in the incidence of complications except for occlusion (4.2% vs 24.6%; p = 0.0142). CONCLUSION: The ComVi stent has a patency similar to that of the CWS and a lower incidence of migration. However, early occlusion by food impaction was increased and should be resolved.

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.

A pilot study for combination chemotherapy using gemcitabine and S-1 for advanced pancreatic cancer.

OBJECTIVES: We performed a pilot study of a modified combination chemotherapy regimen with S-1 plus gemcitabine for patients with advanced pancreatic cancer. METHODS: Gemcitabine was administered at a dose of 1,000 mg/m(2) in a 30-min intravenous injection on days 1 and 15. S-1 was administered orally at a dose of 40 mg/m(2) twice daily for 14 consecutive days followed by a 14-day rest. Each cycle was repeated every 28 days. RESULTS: Sixteen patients were enrolled. No complete response was observed and partial response was observed in 5 patients (31.3%), stable disease in 10 patients (62.5%) and progressive disease in 1 patient (6.3%). The median time to progression was 10.0 months (95% CI 4.4-N.A.) and the median survival time was 20.4 months (95% CI 8.6-24.1 months). The major toxicities were grade 3 neutropenia (25.0%) and grade 3 anemia (6.3%). There were no grade 4 toxicities. CONCLUSIONS: Combination therapy with gemcitabine and S-1 using the modified 4-week schedule was well tolerated and efficacious for advanced pancreatic cancer.

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.

Diagnostic utility of biopsy specimens for autoimmune pancreatitis.

BACKGROUND AND AIMS: Infiltration of IgG4-positive plasma cells in the pancreas and other organs is characteristic of autoimmune pancreatitis (AIP). However, it is undetermined whether needle or forceps biopsy of pancreas or other organs is indeed useful for the diagnosis of AIP. We aimed to clarify this point. METHODS: Among 39 AIP patients, tissue sampling without laparotomy was performed in 27. Biopsy of pancreas, gastric mucosa, liver, bile duct, and duodenal papilla was performed in 15, 17, 11, 5 and 7, respectively. The obtained specimens were examined for IgG4-positive plasma cells. We also examined gastric mucosa of 18 patients with pancreatic cancer as controls. When the number of IgG4-positive plasma cells was more than 10 per high-power field, we regarded it as diagnostic. RESULTS: Diagnostic sensitivity in pancreas, gastric mucosa, liver, bile duct, and duodenal papilla was 47% (7/15), 47% (8/17), 36% (4/11), 0% (0/5), and 57% (4/7), respectively. CONCLUSIONS: Sensitivity of IgG4 immunostaining was unsatisfactory when tissue sampling was performed by needle or forceps biopsy. Biopsy of gastric mucosa might be a good subsidiary diagnostic tool.

NOTES and endoscopic pancreatic necrosectomy for the GI endoscopist.

Endoscopists seek to conduct more aggressive surgical procedures that surpass the limitations of existing endoscopic procedures. Endoscopic pancreatic necrosectomy and natural orifice transluminal endoscopic surgery (NOTES) are typical examples of this new trend; both are performed through the gastrointestinal wall without a skin incision. Endoscopic necrosectomy is effective for managing organized pancreatic necrosis and abscesses. The necrotic tissues are removed endoscopically by directly entering the cavity of the organized pancreatic necrosis. NOTES is a possible advance over surgical intervention, as it is a less invasive, more cosmetic, and effective procedure. There are various approaches, including the esophagus, stomach, colon, and vagina; Various procedures are possible using NOTES, such as cholecystectomy, appendectomy, full-thickness stomach resection, splenectomy, gastrointestinal (GI) anastomosis, and peritoneoscopy. The requirements for NOTES include high proficiency in endoscopic techniques, including knowledge of various devices, anatomy, and surgical procedures. Since most GI endoscopists have no surgical background, to increase the usage of NOTES, GI endoscopists should form and lead teams that include various specialists. We believe that endoscopic necrosectomy and NOTES represent a major shift in the treatment paradigm because physicians can treat beyond the gastrointestinal wall and endoscopic procedures will replace surgical treatment.

CA 19-9 response as an early indicator of the effectiveness of gemcitabine in patients with advanced pancreatic cancer.

BACKGROUND: The CA 19-9 decline 8 weeks after gemcitabine administration has been shown to be a useful prognosticator of survival in patients with pancreatic cancer. We assessed the prognostic value of changes in CA 19-9 levels 4 weeks after treatment initiation on overall survival (OS) and time to progression (TTP). METHODS: We evaluated 72 patients who received gemcitabine for advanced pancreatic cancer. The serum CA 19-9 level was measured routinely at baseline (CA 19-9_Pre) and after the first (4 weeks; CA 19-9_A1) and second (8 weeks; CA 19-9_A2) courses. CA 19-9 responses were categorized into quartiles using the proportional change in CA 19-9. RESULTS: The rates of decrease in CA 19-9_A1 and CA 19-9_A2 were strongly correlated with each other (r = 0.8981, p < 0.0001). Multivariate analysis revealed that an early CA 19-9 response was prognostic of OS and TTP in addition to CA 19-9_Pre and performance status. Compared with the first quartile of an early CA 19-9 response, hazard ratios for the second, third and fourth quartiles were 0.91 (95% confidence interval, CI, 0.59-1.34), 0.71 (95% CI, 0.45-1.08), and 0.63 (95% CI, 0.41-0.94) for TTP, respectively (p for trend = 0.002), and 0.98 (95% CI, 0.61-1.49), 0.68 (95% CI, 0.40-1.08) and 0.79 (95% CI, 0.50-1.21) for OS (p for trend = 0.036). CONCLUSION: CA 19-9 response after the first course of gemcitabine was a prognosticator of OS and TTP in patients with advanced pancreatic cancer.