Pancreatobiliary Maljunction-associated Gallbladder Cancer Is as Common in the West, Shows Distinct Clinicopathologic Characteristics and Offers an Invaluable Model for Anatomy-induced Reflux-associated Physio-chemical Carcinogenesis.

OBJECTIVE: To determine the associations of pancreatobiliary maljunction (PBM) in the West. BACKGROUND: PBM (anomalous union of common bile duct and pancreatic duct) is mostly regarded as an Asian-only disorder, with 200X risk of gallbladder cancer (GBc), attributed to reflux of pancreatic enzymes. Methods: Radiologic images of 840 patients in the US who underwent pancreatobiliary resections were reviewed for PBM and contrasted with 171 GBC cases from Japan. RESULTS: Eight % of the US GBCs (24/300) had PBM (similar to Japan; 15/ 171, 8.8%), in addition to 1/42 bile duct carcinomas and 5/33 choledochal cysts. None of the 30 PBM cases from the US had been diagnosed as PBM in the original work-up. PBM was not found in other pancreatobiliary disorders. Clinicopathologic features of the 39 PBM-associated GBCs (US:24, Japan:15) were similar; however, comparison with non-PBM GBCs revealed that they occurred predominantly in females (F/M = 3); at younger (<50-year-old) age (21% vs 6.5% in non-PBM GBCs; P = 0.01); were uncommonly associated with gallstones (14% vs 58%; P < 0.001); had higher rate of tumor-infiltrating lymphocytes (69% vs 44%; P = 0.04); arose more often through adenoma-carcinoma sequence (31% vs 12%; P = 0.02); and had a higher proportion of nonconventional carcinomas (21% vs 7%; P = 0.03). Conclusions: PBM accounts for 8% of GBCs also in the West but is typically undiagnosed. PBM-GBCs tend to manifest in younger age and often through adenoma-carcinoma sequence, leading to unusual carcinoma types. If PBM is encountered, cholecystectomy and surveillance of bile ducts is warranted. PBM-associated GBCs offer an invaluable model for variant anatomy-induced chemical (reflux-related) carcinogenesis.

Multicenter study of early pancreatic cancer in Japan.

BACKGROUND/OBJECTIVES: The diagnosis of early-stage pancreatic ductal adenocarcinoma (PDAC) is still challenging. We conducted a multicenter study to clarify the clinical features of early-stage PDAC in Japan. METHODS: We collected patients with stage 0 and stage I PDAC according to the sixth edition of the Japanese Classification of Pancreatic Carcinoma. We retrospectively analyzed the clinical profiles including opportunities for medical examination, imaging modalities and findings, methods of cytological diagnosis, and prognosis according to the stages at diagnosis. RESULTS: Two hundred cases with Stage 0 and stage I PDAC were reported from 14 institutions, which accounted for approximately 0.7% and 3% of all PDAC cases, respectively. Overall, 20% of the early-stage PDAC cases were symptomatic. Indirect imaging findings such as dilatation of the main pancreatic duct were useful to detect early-stage PDAC. In particular, local fatty changes may be specific to early-stage PDAC. For preoperative pathologic diagnosis, cytology during endoscopic retrograde cholangiopancreatography was more commonly applied than endoscopic ultrasound fine-needle aspiration. Although the overall prognosis was favorable, new PDAC lesions developed in the remnant pancreas in 11.5% cases. CONCLUSIONS: This multicenter study revealed several key points concerning the diagnosis and management of early-stage PDAC, including screening of asymptomatic cases, importance of indirect imaging findings, application of cytology during endoscopic retrograde cholangiopancreatography, and the risk of carcinogenesis in the remnant pancreas.

A Prospective Multicenter Study of a Fully Covered Metal Stent in Patients with Distal Malignant Biliary Obstruction: WATCH-2 Study.

BACKGROUND: Both fully covered (FC) and partially covered (PC) self-expandable metal stents (SEMSs) are now commercially available for distal malignant biliary obstruction (MBO). While FCSEMS can be easily removed at the time of re-interventions, it is theoretically prone to migration. However, few comparative data between FC and PC SEMSs have been reported. AIMS: The aim of this study was to compare clinical outcomes of FCSEMS with those of PCSEMS. METHODS: This was a multicenter, prospective study of FCSEMS for unresectable distal MBO with a historical control of PCSEMS, which was previously reported as the WATCH study. The primary outcome was recurrent biliary obstruction (RBO), and secondary outcomes were stent migration, stent removal, stent-related adverse events, and survival. RESULTS: A total of 151 cases with unresectable distal MBO undergoing FCSEMS placement were enrolled and compared with a historical cohort of 141 cases undergoing PCSEMS placement. No significant differences were found in the rate of RBO (29 vs. 33%; P = 0.451), time to RBO (318 vs. 373 days; P = 0.382), and survival (229 vs. 196 days; P = 0.177) between FCSEMS and PCSEMS. The rate of stent migration also did not differ significantly between the two groups (14 vs. 8%; P = 0.113). The removal of FCSEMSs was successful in all 24 attempted cases (100%). CONCLUSIONS: FCSEMSs appeared comparable to PCSEMSs in terms of RBO without a significant increase in stent migration rate in patients with unresectable distal MBO. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000007131.

Case of Barrett's adenocarcinoma with marked endoscopic morphological changes in Barrett's esophagus over a long follow-up period of 15 years.

The natural history of Barrett's esophagus (BE) is unclear. We herein describe a case of Barrett's adenocarcinoma (BAC) in which we could closely observe marked morphological changes in BE over a long follow-up period of 15 years. A man in his seventies received routine esophagogastroduodenoscopy (EGD) and was diagnosed as having reflux esophagitis and short-segment BE. The BE gradually became elongated, and BAC was detected 9 years following the initial EGD examination with continued administration of a proton pump inhibitor. We witnessed that BE elongated sporadically over time and mucosal breaks of reflux esophagitis were detectable several years before elongation. The patient underwent endoscopic submucosal dissection for BAC and has been monitored by EGD every year thereafter. These remarkable morphological changes may be representative of the natural history of BE and aid in deciding long-term disease management.

Reduced expression of αGlcNAc in Barrett's oesophagus adjacent to Barrett's adenocarcinoma--a possible biomarker to predict the malignant potential of Barrett's oesophagus.

AIMS: Gastric gland mucin contains O-glycans exhibiting terminal α1,4-linked N-acetylglucosamine residues (αGlcNAc). Recently we demonstrated that mice deficient in αGlcNAc in gastric gland mucin develop gastric adenocarcinoma spontaneously, indicating that αGlcNAc is a tumour suppressor for gastric cancer. However, the role of αGlcNAc in Barrett's oesophagus (BO) remains unknown. In this study, we investigated whether reduced αGlcNAc expression in BO is associated with development of Barrett's adenocarcinoma (BAC). METHODS AND RESULTS: Thirty-five BO lesions adjacent to BAC were examined by immunohistochemistry for αGlcNAc, MUC6 and CDX2. As controls, 35 BO lesions without BAC obtained from patients with oesophageal squamous cell carcinoma were also analysed. Expression of αGlcNAc relative to its scaffold MUC6 in BO adjacent to BAC was reduced significantly compared to control BO. Decreased αGlcNAc expression in BO adjacent to BAC was particularly significant in patients with smaller tumour size (<20 mm) and minimal invasion of tumour cells to the superficial muscularis mucosae. There was also a significant inverse correlation between αGlcNAc and CDX2 expression in BO adjacent to BAC. CONCLUSIONS: Decreased expression of αGlcNAc compared with MUC6 in BO is a possible hallmark in predicting BAC development.

Establishment of a serum IgG4 cut-off value for the differential diagnosis of IgG4-related sclerosing cholangitis: a Japanese cohort.

BACKGROUND AND AIM: IgG4-related sclerosing cholangitis (IgG4-SC) must be precisely distinguished from primary sclerosing cholangitis and cholangiocarcinoma (CC) because the treatments are completely different. However, the pathological diagnosis of IgG4-SC is difficult. Therefore, highly specific non-invasive criteria such as serum IgG4 should be established. This study established a cut-off for serum IgG4 to differentiate IgG4-SC from respective controls using serum IgG4 levels measured in Japanese centers. METHODS: A total of 344 IgG4-SC patients were enrolled in this study. As controls, 245, 110, and 149 patients with pancreatic cancer, primary sclerosing cholangitis, and CC, respectively, were enrolled. IgG4-SC patients were classified into three groups: type 1 (stenosis only in the lower part of the common bile duct), type 2 (stenosis diffusely distributed throughout the intrahepatic and extrahepatic bile ducts), and types 3 and 4 (stenosis in the hilar hepatic region) with 246, 56, and 42 patients, respectively. Serum IgG4 levels were compared, and the cut-offs were established. RESULTS: The cut-off obtained from receiver operator characteristic curves showed similar sensitivity and specificity to that of 135 mg/dL when all IgG4-SC and controls were compared. However, a new cut-off value was established when subgroups of IgG4-SC and controls were compared. A cut-off of 182 mg/dL can increase the specificity to 96.6% (4.7% increase) for distinguishing types 3 and 4 IgG4-SC from CC. A cut-off of 207 mg/dL might be useful for completely distinguishing types 3 and 4 IgG4-SC from all CC. CONCLUSIONS: Serum IgG4 is useful for the differential diagnosis of IgG4-SC and controls.

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.

Results of a Japanese multicenter, randomized trial of endoscopic stenting for non-resectable pancreatic head cancer (JM-test): Covered Wallstent versus DoubleLayer stent.

BACKGROUND: No study has compared covered metallic stents with Tannenbaum stents. We evaluated the efficacy of the DoubleLayer stent (DLS) and Covered Wallstent (CWS) in patients with pancreatic head cancer (PHC). PATIENTS & METHODS: This was a multicenter, prospective randomized study. Between October 2005 and December 2007, we enrolled 113 patients (58 DLS, 55 CWS) with unresectable PHC with distal biliary obstructions and observed them for at least 6 months. RESULTS: No significant difference in patient survival was found between groups, with a median survival of 231 and 248 days in the DLS and CWS groups, respectively. The cumulative stent patency was significantly higher (P = 0.0072) in the CWS group. The respective mean and median stent patency was 202 and 133 days in the DLS group and 285 and 419 days in the CWS group. The incidence of DLS occlusion (53.5%) was significantly higher than that of CWS (23.6%; P = 0.0019). The respective causes of occlusion were tumor overgrowth (0, 1), ingrowth (0, 2), sludge (24, 2), food impaction (3, 5), kinking bile duct (2, 0), and other (2, 3). Other complications were cholecystitis (0, 4), pancreatitis (0, 1), migration (1, 5), liver abscess (2, 0), and other (1, 2). No significant difference in the incidence of complications between groups was observed. CONCLUSION: CWS had significantly longer patency than DLS for the management of PHC with obstructive jaundice. The incidence of complications other than stent occlusion was higher in CWS, but this difference did not reach significance.

[A case of metachronous invasive ductal carcinoma concomitant with intraductal papillary-mucinous neoplasm (IPMN) of the pancreas, which could not be detected in contrast-enhanced CT scan performed 3 months ago].

A 61-year-old man had been followed up in another hospital under diagnosis of branch duct type IPMN for 4 years. Contrast-enhanced CT scan for regular check performed 3 months ago revealed no increase of IPMN and no pancreatic tumor. However, he complained of back pain after that, MRI was performed. It revealed a solid tumor in size of 25mm diameter at the head of pancreas. The tumor was apparent from IPMN in several imaging modalities. Pancreatoduodenectomy was performed under diagnosis of invasive ductal carcinoma concomitant with IPMN. Post-operative pathological findings revealed IPMN was adenoma with mild atypia, and solid tumor was diagnosed invasive ductal carcinoma with solitary minute liver metastasis.

Unilateral versus Bilateral Endoscopic Nasobiliary Drainage and Subsequent Metal Stent Placement for Unresectable Malignant Hilar Obstruction: A Multicenter Randomized Controlled Trial.

(1) Background: Endoscopic management of hilar biliary obstruction is still challenging. Compared with unilateral drainage, bilateral drainage could preserve larger functional liver volume and potentially improve clinical outcomes. To evaluate the effectiveness of bilateral drainage, we conducted this multicenter randomized controlled study. (2) Methods: Patients with unresectable malignant hilar biliary obstruction were assigned to unilateral or bilateral group. At first, patients underwent endoscopic nasobiliary drainage (ENBD), and subsequently underwent self-expandable metallic stent (SEMS) deployment. Primary outcomes were the functional success rate of ENBD and time to recurrent biliary obstruction (TRBO) after SEMS deployment. (3) Results: During the study period, 38 and 39 patients were enrolled in the unilateral and bilateral groups. The functional success rate was similar in the uni- and bi-ENBD group (57% vs. 56%; p = 0.99), but the rate of additional drainage was higher in uni-ENBD group. Although TRBO and overall survival time after SEMS deployment were not different between the groups (p = 0.11 and 0.78, respectively), the incidence of early adverse events tended to be higher in the bi-SEMS group (5.3% vs. 28%; p = 0.11). (4) Conclusions: Our study failed to demonstrate the superiority of bilateral over unilateral biliary drainage in terms of functional success rate and TRBO.

Long-term outcomes after endoscopic sphincterotomy versus endoscopic papillary balloon dilation for bile duct stones.

OBJECTIVE: Endoscopic sphincterotomy (ES) is a well-established standard method for treating common bile duct stones. However, biliary sphincter function is impaired after the treatment, and this may influence the long-term outcomes. In this study, we aimed to compare the long-term outcomes after ES with those after endoscopic papillary balloon dilation (EPBD) because the latter procedure is expected to preserve biliary sphincter function better than ES. DESIGN: A prospective follow-up of the original cohort in a previously randomized, controlled trial to compare the early outcomes after ES and EPBD. SETTING: Eleven centers, including 6 clinical practices and 5 academic institutions. PATIENTS: A total of 282 patients with common bile duct stones were randomly selected to undergo ES (n = 144) or EPBD (n = 138) in the previous study. INTERVENTIONS: ES or EPBD. MAIN OUTCOME MEASUREMENTS: Complications after ES or EPBD occurring during long-term follow-up. RESULTS: The patients were followed up annually after the treatment. The median duration of the follow-up was 6.7 years. Morbidity was observed in 36 (25.0%) and 14 (10.1%) of the patients who underwent ES and EPBD, respectively (P = .0016). Kaplan-Meier analysis revealed a significantly higher incidence of biliary complications in the ES group than in the EPBD group (P = .0011). Multivariate analysis showed that ES, periampullary diverticulum, and in situ gallbladder stones were independent risk factors for stone recurrence. CONCLUSIONS: During long-term follow-up, patients who underwent ES had significantly more biliary complications than those who underwent EPBD. The biliary sphincter dysfunction after ES results in additional late complications.

IgG4-related disease in the Japanese population: a genome-wide association study.

BACKGROUND: IgG4-related disease is a newly recognised immunopathological entity that includes autoimmune pancreatitis, IgG4-related sialadenitis, and IgG4-related kidney disease. To understand the genetic landscape of IgG4-related disease, we did a genome-wide association study. METHODS: We did a genome-wide association study of Japanese individuals, initially screening 857 patients with IgG4-related disease at 50 Japanese research institutions and DNA samples from 2082 healthy control participants from the Nagahama Prospective Genome Cohort for the Comprehensive Human Bioscience. From Oct 27, 2008, to July 22, 2014, we enrolled 835 patients and used data from 1789 healthy participants. Only patients with confirmed diagnosis of IgG4-related disease according to the international diagnostic criteria were included. Genotyping was done with the Infinium HumanOmni5Exome, HumanOmni2.5Exome, or HumanOmni2.5 Illumina arrays, and genomic distributions were compared between case and control samples for 958 440 single nucleotide polymorphisms. The HLA region was extensively analysed using imputation of HLA alleles and aminoacid residues. Fine mapping of the FCGR2B region was also done. Associations between clinical manifestations of disease and the genetic variations identified in these two genes were examined. FINDINGS: We identified the HLA-DRB1 (p=1·1×10-11) and FCGR2B (p=2·0×10-8) regions as susceptibility loci for IgG4-related disease. We also identified crucial aminoacid residues in the ß domain of the peptide-binding groove of HLA-DRB1, in which the seventh aminoacid residue showed the strongest association signal with IgG4-related disease (p=1·7×10-14), as has been reported with other autoimmune diseases. rs1340976 in FCGR2B showed an association with increased FCGR2B expression (p=2·7×10-10) and was in weak linkage disequilibrium with rs1050501, a missense variant of FCGR2B previously associated with systemic lupus erythematosus. Furthermore, rs1340976 was associated with the number of swollen organs at diagnosis (p=0·011) and IgG4 concentration at diagnosis (p=0·035). INTERPRETATION: Two susceptibility loci for IgG4-related disease were identified. Both FCGR2B and HLA loci might have important roles in IgG4-related disease development. Common molecular mechanisms might underlie IgG4-related disease and other immune-related disorders FUNDING: The Japanese Ministry of Health, Labour, and Welfare, the Japanese Agency of Medical Research and Development, and Kyoto University Grant for Top Global University Japan Project.

Massive ascites caused by intra-pancreatic arterioportal fistula: a rare complication of chronic pancreatitis.

An 86-year-old man with a long-term habit of ethanol consumption was admitted due to massive transudate ascites and leg edema. Abdominal computed tomography revealed a dilated main pancreatic duct and atrophied pancreatic parenchyma, leading to the diagnosis of chronic pancreatitis. Moreover, the portal vein was enhanced in the early arterial phase, which indicated the presence of an arterioportal fistula. The fistula was located between the posterior superior pancreaticoduodenal artery and the portal vein near a pancreatic retention cyst. Transarterial coil embolization dramatically improved the ascites. Arterioportal fistula and ensuing ascites should be recognized as a complication of chronic pancreatitis.

Reflux-Associated Cholecystopathy: Analysis of 76 Gallbladders From Patients With Supra-Oddi Union of the Pancreatic Duct and Common Bile Duct (Pancreatobiliary Maljunction) Elucidates a Specific Diagnostic Pattern of Mucosal Hyperplasia as a Prelude to Carcinoma.

Pancreaticobiliary maljunction (PBM) is the anomalous union of the main pancreatic duct and common bile duct outside the Oddi-sphincter, allowing the reflux of pancreatic juice to the gallbladder. There is only limited awareness and understanding of the pathologic correlates of this condition, mostly from Japan; this entity is largely unrecognized in the West. In this study, 76 gallbladders from patients with PBM (64 from Japan; 12 from the United States) were analyzed and contrasted with 66 from non-PBM patients. These were predominantly females (54 vs. 22), mean age, 53 (range: 14 to 81). Cholelithiasis was uncommon (16% vs. 80% in non-PBM, P<0.01) whereas cholesterolosis was more common (49% vs. 29%, P=0.02) suggesting an altered chemical milieu. There was a distinctive diffuse mucosal hyperplasia (82% vs. 42%, P<0.01) with markedly elongated folds (mean: 1.1 vs. 0.7 mm, P<0.01) composed of compact villoglandular proliferation, often showing broad-based pushing into muscle, accompanied by prominent and more complex Rokitansky-Aschoff sinus formation (2.0 vs. 1.0/cm, P<0.01) at the base. At the tips, this villiform hyperplasia displayed frequent horizontal bridging of the folds (68% vs. 47%, P=0.01), bulbous dilatation (52% vs. 21%, P<0.01) as well as deposition of a peculiar amyloid-like hyaline material (56% vs. 15%, P<0.01). Despite paucity of inflammation and gallstones, findings attributed to mucosal injury were common including: pyloric gland metaplasia (70% vs. 48%, P=0.01) and intestinal metaplasia (24% vs. 6%, P<0.01). Invasive gallbladder carcinoma was present in 22 (29%) of the cases with 6 of these (27%) arising in association with intracholecystic papillary tubular neoplasm. Five cases had bile duct carcinoma at the time of cholecystectomy and 1 developed it 4 years after. In conclusion, gallbladders with patients with PBM display a distinctive pattern of mucosal hyperplasia with distinguishing features, which in constellation render it a microscopically diagnosable specific entity. We propose to refer to this entity as "reflux-associated cholecystopathy." Recognition of the pathologic characteristics of this entity is important so that investigation for, as well as treatment and prevention of, PBM-associated complications (biliary tract cancers and pancreatitis) can be instituted. This group also offers a distinct model of carcinogenesis (chemical rather than inflammatory) in the gallbladder for cancer researchers to scrutinize.

Assessment of treatment efficacy in radiofrequency ablation for hepatocellular carcinoma: Comparison between multiplanar reconstruction by multi-detector row CT and contrast-enhanced ultrasonography by Truagent detection mode.

PURPOSE: We compared the image of multiplanar reconstruction (MPR) by multi-detector row CT (MDCT) and contrast-enhanced ultrasonography (CEUS) by Truagent Detection Modetrade mark after radiofrequency ablation (RFA) for hepatocellular carcinoma to assess treatment efficacy. METHODS: We examined 16 nodules in 15 patients who underwent CEUS just before and on the day following RFA, and then CT-MPR by MDCT 5 or 6 days after RFA. We measured the lengths of the major and minor axes at the maximal necrotic area, which were thought to correspond to similarly shaped images on both CT-MPR and CEUS. RESULTS: There are significant positive correlations in the lengths of the major and minor axes at the maximal necrotic area as measured on CT-MPR and CEUS. The differences in the lengths of the major and minor axes between CT-MPR and the parenchymal phase of CEUS were smaller than those between CT-MPR and the late vascular phase of CEUS. CONCLUSION: Our study showed a non-enhanced area of CT-MPR 5 or 6 days after RFA was similar to that of the parenchymal phase of CEUS on the day following RFA, and so it is possible to assess the treatment efficacy by CEUS on the day following RFA.

A case of simultaneous esophageal squamous cell carcinoma and Barrett's adenocarcinoma.

A 77-year-old male with a long history of alcohol consumption and smoking was admitted for hoarseness and dysphagia. Computed tomography revealed thickening of the middle intrathoracic esophageal wall and multiple mediastinal lymph node swellings. Esophagogastroduodenoscopic examination disclosed an advanced-stage squamous cell carcinoma lesion in the middle intrathoracic esophagus with synchronous early stage Barrett's adenocarcinoma. The patient underwent endoscopic submucosal dissection for the adenocarcinoma followed by chemoradiation therapy for the squamous cell carcinoma. In spite of their common risk factors, the simultaneous manifestation of esophageal squamous cell carcinoma and Barrett's adenocarcinoma is extremely rare and requires further study.

[Survey of gemcitabine treatment for advanced pancreatic cancer in 20 hospitals of Nagano Prefecture].

To establish an effective therapy for pancreatic cancer, we made a retrospective survey of gemcitabine treatment performed at 20 hospitals in Nagano Prefecture. We analyzed data of 106 patients (64 men and 42 women, median age 66 years (33-83 years old)), half of whom had stage IV disease. Gemcitabine was administered for 3 consecutive weeks with one week rest in 57 patients, biweekly in 30 patients, initially for 3 weeks with 1 week rest and switched to biweekly schedule to 15 patients, and with another regimen to 4 patients. Analysis of the results of gemcitabine treatment between the 3 weeks with 1-week-rest regimen and the biweekly regimen revealed no differences between regimens in growth inhibition and symptom alleviation. However, we found less occurrence of blood toxicity in the biweekly regimen (40%) than in the 3 weeks with 1 week-rest regimen (59%). Median survival time for the biweekly regime was 9.7 months, only slightly longer than that of the 3 weeks with 1-week-rest regimen (8.5 months). The present study showed that a biweekly regimen for gemcitabine administration may be equivalent to the standard regime of 3 weeks with 1-week-rest regimen. Moreover, the biweekly regimen has advantages over the 3 weeks with 1-week rest regimen both economically and in terms of convenience for outpatient treatment. Therefore, the present results should be confirmed in future prospective studies, with the hope of developing a new standard treatment regimen for pancreatic cancer.

Helicobacter pylori-negative Differentiated Adenocarcinoma of the Stomach.

A 58-year-old Japanese man was diagnosed with differentiated adenocarcinoma of the stomach. Histological findings of the resected specimen revealed well- to moderately-differentiated tubular adenocarcinoma (tub1, tub2), 13 mm in diameter, which invaded into the submucosa (SM1, 300 µm) and lymphovascular lumen (ly1). Serum antibody against Helicobacter pylori (Hp) and the (13)C-urea breath test were negative, and there were no atrophic changes in the tumor-adjacent mucosa. The immunohistochemical analysis showed that gastric mucin (MUC5AC) was strongly positive and intestinal mucin (MUC2) was weakly and partially positive. According to these results, the final diagnosis of Hp-negative well-differentiated early gastric cancer was made.

[Clinical problems in gemcitabine treatment for unresectable pancreatic cancer in the elderly--a multicentric retrospective study of 53 cases].

In Gemcitabine treatment, elderly patients with unresectable pancreatic cancer are more likely to suffer from haematological and non-haematological adverse effects than non-elderly patients. Forty percent of the elderly patients were dropped from the initial protocol due to the adverse effects, mainly because of non-haematological events or symptoms. To avoid adverse effects, the administration schedule for Gemcitabine tended to be less often and at a lower dose for elderly patients among members of the Nagano Pancreatic Cancer Study Group. However, the fact that some cases showed a limited effect from this administration schedule albeit without adverse effect, might suggest that the frequency of ordinary administration schedule should be maintained, although the Gemcitabine dose could be decreased in unresectable pancreatic cancer patients in poor condition.

Mechanisms of lower bile duct stricture in autoimmune pancreatitis.

OBJECTIVES: We attempted to clarify the mechanism underlying lower bile duct stricture in autoimmune pancreatitis. METHODS: Imaging and histologic finding of the bile duct were assessed for 73 patients with autoimmune pancreatitis to clarify whether IgG4-related biliary inflammation or pancreatic head swelling is associated with lower bile duct stricture. RESULTS: Lower bile duct stricture was found in 59 (81%) patients. Pancreatic head swelling was significantly more frequent among patients with lower bile duct stricture than those patients without lower bile duct stricture (53 [90%] vs 4 [29%]; P < 0.01). Intraductal ultrasonography findings revealed lower bile duct wall thickening in 21 (95%) of the 22 patients with lower bile duct stricture, and the lower bile duct wall of the patients with pancreatic head swelling was significantly thicker than those patients without pancreatic head swelling (P = 0.028). Among the 38 patients with lower bile duct biopsies, 14 (37%) exhibited abundant IgG4-bearing plasma cell infiltration. Among the patients with lower bile duct stricture, an IgG4-related inflammation seemed to exert a dominant effect under limited conditions, including concomitant middle bile duct stricture and neither pancreatic swelling nor pancreatic duct stricture in the head region. CONCLUSIONS: Both pancreatic head swelling and IgG4-related biliary inflammation affect lower bile duct stricture, which may be included in IgG4-related sclerosing cholangitis. Pancreatic head swelling affects IgG4-related biliary wall thickening.