ABSTRACT
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.
Subject(s)
Gallbladder Neoplasms , Gastrointestinal Neoplasms , Bile Ducts , Carcinogenesis/pathology , Common Bile Duct/abnormalities , Common Bile Duct/diagnostic imaging , Common Bile Duct/pathology , Female , Gallbladder Neoplasms/etiology , Gallbladder Neoplasms/pathology , Gastrointestinal Neoplasms/pathology , Humans , Middle Aged , Pancreatic Ducts/diagnostic imaging , Pancreatic Ducts/pathologyABSTRACT
(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.
ABSTRACT
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 958â440 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.
ABSTRACT
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.
Subject(s)
Cholangiopancreatography, Endoscopic Retrograde/instrumentation , Cholestasis/therapy , Digestive System Neoplasms/complications , Self Expandable Metallic Stents , Adult , Aged , Aged, 80 and over , Cholangiopancreatography, Endoscopic Retrograde/adverse effects , Cholangiopancreatography, Endoscopic Retrograde/mortality , Cholestasis/diagnostic imaging , Cholestasis/etiology , Cholestasis/mortality , Device Removal , Digestive System Neoplasms/diagnosis , Digestive System Neoplasms/mortality , Female , Foreign-Body Migration/etiology , Foreign-Body Migration/surgery , Humans , Japan , Kaplan-Meier Estimate , Male , Middle Aged , Proportional Hazards Models , Prospective Studies , Prosthesis Design , Recurrence , Risk Factors , Time Factors , Treatment OutcomeABSTRACT
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.
Subject(s)
Carcinoma, Pancreatic Ductal/diagnosis , Carcinoma, Pancreatic Ductal/epidemiology , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/epidemiology , Adult , Aged , Aged, 80 and over , Female , Humans , Japan/epidemiology , Male , Middle Aged , Pancreas/pathology , Pancreatectomy , Retrospective Studies , Pancreatic NeoplasmsABSTRACT
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.
Subject(s)
Common Bile Duct/abnormalities , Gallbladder Diseases/etiology , Gallbladder Neoplasms/diagnosis , Gallbladder/pathology , Pancreatic Ducts/abnormalities , Pancreatic Juice , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Hyperplasia/diagnosis , Japan , Male , Middle Aged , Sphincter of Oddi , United States , Young AdultABSTRACT
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.
Subject(s)
Arteriovenous Fistula/complications , Ascites/etiology , Pancreatic Fistula/complications , Pancreatitis, Chronic/complications , Portal Vein , Aged, 80 and over , Arteriovenous Fistula/diagnostic imaging , Arteriovenous Fistula/therapy , Ascites/diagnostic imaging , Embolization, Therapeutic/methods , Endoscopy, Gastrointestinal , Hepatic Artery/diagnostic imaging , Humans , Male , Pancreatic Fistula/diagnostic imaging , Pancreatic Fistula/therapy , Pancreatitis, Chronic/diagnostic imaging , Portal Vein/diagnostic imaging , Tomography, X-Ray Computed , UltrasonographyABSTRACT
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.
Subject(s)
Adenocarcinoma/diagnostic imaging , Barrett Esophagus/diagnostic imaging , Carcinoma, Squamous Cell/diagnostic imaging , Esophageal Neoplasms/diagnostic imaging , Neoplasms, Multiple Primary/diagnostic imaging , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Aged , Barrett Esophagus/pathology , Barrett Esophagus/surgery , Biopsy , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/therapy , Esophageal Neoplasms/pathology , Esophageal Neoplasms/surgery , Esophageal Neoplasms/therapy , Esophageal Squamous Cell Carcinoma , Esophagus/pathology , Humans , Male , Neoplasms, Multiple Primary/pathology , Neoplasms, Multiple Primary/therapy , Positron Emission Tomography Computed Tomography , Risk FactorsABSTRACT
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.
Subject(s)
Adenocarcinoma/etiology , Adenocarcinoma/pathology , Barrett Esophagus/pathology , Endoscopy, Gastrointestinal , Esophageal Neoplasms/etiology , Esophageal Neoplasms/pathology , Adenocarcinoma/surgery , Aged , Esophageal Neoplasms/surgery , Follow-Up Studies , Humans , Male , Time FactorsABSTRACT
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.
Subject(s)
Adenocarcinoma/pathology , Dissection , Gastric Mucosa/pathology , Homeodomain Proteins/metabolism , Mucin-2/metabolism , Stomach Neoplasms/pathology , Adenocarcinoma/metabolism , Biomarkers, Tumor/metabolism , CDX2 Transcription Factor , Gastric Mucins/metabolism , Gastroscopy , Helicobacter pylori , Humans , Immunohistochemistry , Male , Middle Aged , Stomach Neoplasms/metabolism , Treatment OutcomeABSTRACT
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.
Subject(s)
Autoimmune Diseases/pathology , Bile Ducts/pathology , Pancreas/pathology , Pancreatitis/pathology , Aged , Bile Ducts/diagnostic imaging , Cholangiopancreatography, Endoscopic Retrograde , Cholangitis, Sclerosing/immunology , Cholangitis, Sclerosing/pathology , Constriction, Pathologic/diagnostic imaging , Female , Humans , Immunoglobulin G/immunology , Male , Middle Aged , Pancreas/immunology , Ultrasonography/methodsABSTRACT
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.
Subject(s)
Acetylglucosamine/metabolism , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Barrett Esophagus/metabolism , Barrett Esophagus/pathology , Esophageal Neoplasms/metabolism , Esophageal Neoplasms/pathology , Aged , Aged, 80 and over , Animals , Biomarkers, Tumor/metabolism , CDX2 Transcription Factor , Case-Control Studies , Disease Progression , Female , Homeodomain Proteins/metabolism , Humans , Immunohistochemistry , Male , Mice , Middle Aged , Mucin-6/metabolism , Polysaccharides/metabolismABSTRACT
AIM: To evaluate the differences in the treatment outcomes between the unresectable and recurrent biliary tract cancer patients who received chemotherapy. METHODS: Patients who were treated with gemcitabine and S-1 combination therapy in the previous prospective studies were divided into groups of unresectable and recurrent cases. The tumor response, time-to-progression, overall survival, toxicity, and dose intensity were compared between these two groups. RESULTS: Response rate of the recurrent group was higher than that of the unresectable group (40.0% vs 25.5%; P = 0.34). Median time-to-progression of the recurrent and unresectable groups were 8.7 mo (95%CI), 1.2 mo, not reached) and 5.7 mo (95%CI: 4.0-7.0 mo), respectively (P = 0.14). Median overall survival of the recurrent and the unresectable groups were 16.1 mo (95%CI: 2.0 mo-not reached) and 9.6 mo (95%CI: 7.1-11.7 mo), respectively (P = 0.10). Dose intensities were significantly lower in the recurrent groups (gemcitabine: recurrent group 83.5% vs unresectable group 96.8%; P < 0.01, S-1: Recurrent group 75.9% vs unresectable group 91.8%; P < 0.01). Neutropenia occurred more frequently in recurrent group (recurrent group 90% vs unresectable group 55%; P = 0.04). CONCLUSION: Not only the efficacy but also the toxicity and dose intensity were significantly different between unresectable and recurrent biliary tract cancer.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biliary Tract Neoplasms/drug therapy , Neoplasm Recurrence, Local , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Biliary Tract Neoplasms/mortality , Biliary Tract Neoplasms/pathology , Biliary Tract Neoplasms/surgery , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Disease Progression , Drug Combinations , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Oxonic Acid/administration & dosage , Prospective Studies , Tegafur/administration & dosage , Time Factors , Treatment Outcome , GemcitabineABSTRACT
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.
Subject(s)
Cholangitis, Sclerosing/diagnosis , Immunoglobulin G/blood , Aged , Asian People , Biomarkers/blood , Cholangitis, Sclerosing/classification , Cholangitis, Sclerosing/immunology , Cohort Studies , Diagnosis, Differential , Female , Humans , Male , Middle Aged , ROC Curve , Retrospective Studies , Sensitivity and SpecificityABSTRACT
PURPOSE: In order to confirm the impact of adding S-1 to gemcitabine, we conducted a randomized phase II study to compare the combination therapy of gemcitabine plus S-1 to gemcitabine monotherapy in patients with advanced biliary tract cancer. METHODS: Sixty-two patients with advanced cholangiocarcinoma or gallbladder cancer were randomized to either the combination therapy of gemcitabine and S-1 (gemcitabine 1,000 mg/m(2) on days 1 and 15 and S-1 40 mg/m(2) b.i.d. on days 1-14, repeated every 4 weeks) or gemcitabine monotherapy (gemcitabine 1,000 mg/m(2) on days 1, 8, and 15, repeated every 4 weeks). The primary endpoint of this study was response rate, and the regimen which showed the better response rate was selected as a candidate of phase III study. Tumor response was assessed every two cycles using Response Evaluation Criteria in Solid Tumors criteria version 1.0. RESULTS: The response rates of the combination therapy and the monotherapy were 20.0 and 9.4 %, respectively. The median time-to-progressions and overall survivals of these two treatments were nearly the same (5.6 vs. 4.3 months; 8.9 vs. 9.2 months). Adverse events occurred more frequently in the combination arm. CONCLUSIONS: The combination therapy of gemcitabine and S-1 showed the better response rate, but the superiority of this combination therapy was not clear in total. Because the standard of care changed to the combination therapy with gemcitabine and cisplatin during this study, it is difficult to select this combination therapy with a 4-week regimen as a candidate of phase III study.
Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biliary Tract Neoplasms/drug therapy , Deoxycytidine/analogs & derivatives , Aged , Aged, 80 and over , Antimetabolites, Antineoplastic/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Biliary Tract Neoplasms/mortality , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Deoxycytidine/therapeutic use , Drug Combinations , Female , Humans , Male , Middle Aged , Oxonic Acid/administration & dosage , Oxonic Acid/adverse effects , Patient Compliance , Tegafur/administration & dosage , Tegafur/adverse effects , GemcitabineABSTRACT
BACKGROUND: In patients with unresectable malignant biliary obstruction (MBO), anticancer treatment is often administered. The impact of anticancer treatment on recurrent biliary obstruction in covered self-expandable metallic stents (SEMS) has not been fully elucidated. METHODS: Data on 279 patients enrolled in a multicenter prospective cohort study of two different covered SEMS for distal MBO, WATCH study (141 partially covered WallFlex stents and 138 partially covered Wallstents) were retrospectively analyzed. The rates and causes of recurrent biliary obstruction (stent occlusion or migration) were compared between anticancer treatment group (n = 173) and best supportive care alone (BSC) group (n = 106). Cumulative time and prognostic factors for recurrent biliary obstruction were analyzed, using a proportional hazards model with death without recurrent biliary obstruction as a competing risk. RESULTS: The overall rate (43 vs. 25%, P = 0.002) and the cumulative incidence (16.1 vs. 8.2, 27.9 vs. 18.9 and 44.1 vs. 26.6% at 3, 6 and 12 months, P = 0.030 by Gray's test) of recurrent biliary obstruction were significantly higher in anticancer treatment group compared with BSC group. The multivariate analysis revealed anticancer treatment [subdistribution hazard ratio (SHR) 1.93, P = 0.007) as well as the use of a partially covered WallFlex stent (SHR 0.65, P = 0.049) as prognostic factors. CONCLUSIONS: Anticancer treatment was a risk factor for recurrent biliary obstruction in covered SEMS for distal MBO. The superiority of a partially covered WallFlex stent was again confirmed in this competing risk analysis; UMIN-CTR: UMIN000002293.
Subject(s)
Antineoplastic Agents/adverse effects , Cholestasis/etiology , Digestive System Neoplasms/complications , Stents , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Cholestasis/surgery , Digestive System Neoplasms/drug therapy , Female , Humans , Kaplan-Meier Estimate , Male , Metals , Middle Aged , Palliative Care/methods , Prosthesis Failure , Retrospective Studies , Risk Factors , Secondary Prevention , Stents/adverse effectsABSTRACT
BACKGROUND: IgG4-sclerosing cholangitis (IgG4-SC) patients have an increased level of serum IgG4, dense infiltration of IgG4-positive plasma cells with extensive fibrosis in the bile duct wall, and a good response to steroid therapy. However, it is not easy to distinguish IgG4-SC from primary sclerosing cholangitis, pancreatic cancer, and cholangiocarcinoma on the basis of cholangiographic findings alone because various cholangiographic features of IgG4-SC are similar to those of the above progressive or malignant diseases. METHODS: The Research Committee of IgG4-related Diseases and the Research Committee of Intractable Diseases of Liver and Biliary Tract in association with the Ministry of Health, Labor and Welfare, Japan and the Japan Biliary Association have set up a working group consisting of researchers specializing in IgG4-SC, and established the new clinical diagnostic criteria of IgG4-SC 2012. RESULTS: The diagnosis of IgG4-SC is based on the combination of the following 4 criteria: (1) characteristic biliary imaging findings, (2) elevation of serum IgG4 concentrations, (3) the coexistence of IgG4-related diseases except those of the biliary tract, and (4) characteristic histopathological features. Furthermore, the effectiveness of steroid therapy is an optional extra diagnostic criterion to confirm accurate diagnosis of IgG4-SC. CONCLUSION: These diagnostic criteria for IgG4-SC are useful in practice for general physicians and other nonspecialists.
Subject(s)
Cholangitis, Sclerosing/diagnosis , Immunoglobulin G/blood , Bile Ducts/pathology , Biliary Tract Neoplasms/diagnosis , Cholangitis, Sclerosing/blood , Cholangitis, Sclerosing/pathology , Diagnosis, Differential , Humans , Pancreatic Neoplasms/diagnosisABSTRACT
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.
Subject(s)
Alloys , Cholestasis/therapy , Prosthesis Failure , Stainless Steel , Stents , Adult , Aged , Aged, 80 and over , Bile Duct Neoplasms/complications , Bile Duct Neoplasms/pathology , Cholestasis/etiology , Device Removal , Female , Gallbladder Neoplasms/complications , Gallbladder Neoplasms/pathology , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Pancreatic Neoplasms/complications , Pancreatic Neoplasms/pathology , Proportional Hazards Models , Prosthesis Design , Recurrence , Silicones , Stents/adverse effects , Time FactorsABSTRACT
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.