Shomei Ryozawa

A comparison of DNA copy number changes detected by comparative genomic hybridization in malignancies of the liver, biliary tract and pancreas.

Tumors arising from the liver, biliary tract and pancreas, which originate in the foregut and are in close anatomical proximity to each other, sometimes show similar histological features. No studies have focused on genetic similarities and differences between tumors of these organs. To elucidate the similarities and differences in DNA copy number alterations between tumors of these organs, we applied comparative genomic hybridization (CGH) to cancers of the liver (31 cases), biliary tract (42 cases) and pancreas (27 cases). Some alterations were common to tumors of all three organs, and some were preferential in certain types of tumor. Gains of 1q and 8q and losses of 8p and 17p were common to all tumors. In contrast, 13q14 and 16q losses were detected exclusively in hepatocellular carcinomas (HCCs; p < 0.01). The incidence of 17q21 gain and 5q loss was higher in biliary tract cancers than in the other two types (p < 0.05). Pancreatic cancers exhibited higher incidence of 5q14-q23 gain and 19p loss than tumors of other organs (p < 0.01). Gains of 7p, 7q, 12p and 20q and losses of 3p, 6q, 9p and 18q were frequent in both biliary tract and pancreatic cancers but rare in HCCs (p < 0.05). The present results suggest that although genes located at 1q, 8p, 8q and 17p are frequently involved in HCC, biliary tract and pancreatic cancer, at least some of the genes implicated in carcinogenesis are different between these three types. It is also suggested that CGH analysis is useful as a potential adjunct for the diagnosis and management of these tumors of organs that are anatomically close to one another.

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).

A multicenter, prospective, randomized study of selective bile duct cannulation performed by multiple endoscopists: the BIDMEN study

BACKGROUND Wire-guided cannulation (WGC) with a sphincterotome (S) for selective bile duct cannulation (SBDC) has been reported to have a higher success rate and lower incidence of post-ERCP pancreatitis (PEP) than conventional methods in some randomized, controlled trials (RCTs) that were both single center and limited to only a few endoscopists. OBJECTIVE To estimate the difference in SBDC according to the method and catheter used in a multicenter and multiendoscopist study. DESIGN A prospective, multicenter RCT with a 2 × 2 factorial design. SETTING Fifteen referral endoscopy units. PATIENTS In total, 400 consecutive patients with naive papillae who were candidates for ERCP were enrolled and randomized. INTERVENTIONS Patients were assigned to 4 groups according to combined catheter (S or catheter [C]) and method (with/without guidewire [GW]). MAIN OUTCOME MEASUREMENTS Success rate of SBDC performed in 10 minutes, SBDC time, fluoroscopy time, and incidence of complications. RESULTS There was no significant difference in the SBDC success rate between the groups with and without GW, between C and S, or among the 4 groups (C+GW, C, S+GW, S). WGC had a tendency to significantly shorten cannulation and fluoroscopy times only in approximately 70% of patients in this study in whom SBDC was achieved in 10 minutes or less (P = .036 and .00004, respectively). All 4 groups resulted in similar outcomes in PEP (4%, 5.9%, 2%, and 2.1%, respectively). LIMITATIONS Non-double-blind study. CONCLUSIONS WGC appears to significantly shorten cannulation and fluoroscopy times. However, neither the method nor type of catheter used resulted in significant differences in either SBDC success rate or incidence of PEP in this RCT. ( CLINICAL TRIAL REGISTRATION NUMBER UMIN000002572.).

UNILATERAL VERSUS BILATERAL DRAINAGE USING SELF-EXPANDABLE METALLIC STENT FOR UNRESECTABLE HILAR BILIARY OBSTRUCTION

Background:  There is no consensus on the choice of either unilateral or bilateral drainage in stent placement for patients with unresectable hilar biliary obstruction. The aim of the present study was to clarify which drainage method is superior.

Usefulness of endoscopic ultrasound-guided fine-needle aspiration biopsy for the diagnosis of pancreatic cancer.

BackgroundEndoscopic ultrasonography-guided fine-needle aspiration biopsy (EUS-FNAB) has come into widespread use, mainly in Western countries, as an efficient and safe method for the cytologic or histologic diagnosis of pancreatic cancer. However, it still has received relatively little attention in Japan. To evaluate the clinical status of EUS-FNAB in Japan, we retrospectively analyzed the results with regard to the ability of EUS-FNAB to diagnose pancreatic cancer, as well as its safety.MethodsA total of 52 patients (37 male, 15 female; mean age, 62.5 years; range, 33–85 years) with focal pancreatic lesions underwent EUS-FNAB at our group of hospitals in one region of Japan. Final diagnosis was confirmed by histologic examination of surgical specimens or clinical follow-up.ResultsThe final diagnoses were malignant tumors in 32 patients and benign ones in 20. Insertion of the needle into the lesion was successful in 50 of the 52 patients (96.2%). Adequate specimens were obtained by EUS-FNAB from 47 of the 50 pancreatic lesions (94.0%). With five false-negative and no false-positive results, the accuracy, sensitivity, specificity, and positive and negative predictive values were 89.4%, 82.1%, 100%, 100%, and 79.2%, respectively. No complications occurred.ConclusionsEUS-FNAB is an efficient and safe method for the histologic diagnosis of pancreatic cancer. It should be considered as one of the indispensable modalities for the histological diagnosis of pancreatic cancer in Japan, as it is in Western countries.

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.

TOKYO criteria 2014 for transpapillary biliary stenting

It is difficult to carry out meta‐analyses or to compare the results of different studies of biliary stents because there is no uniform evaluation method. Therefore, a standardized reporting system is required. We propose a new standardized system for reporting on biliary stents, the ‘TOKYO criteria 2014’, based on a consensus among Japanese pancreatobiliary endoscopists. Instead of stent occlusion, we use recurrent biliary obstruction, which includes occlusion and migration. The time to recurrent biliary obstruction was estimated using Kaplan–Meier analysis with the log–rank test. We can evaluate both plastic and self‐expandable metallic stents (uncovered and covered). We also propose specification of the cause of recurrent biliary obstruction, identification of complications other than recurrent biliary obstruction, indication of severity, measures of technical and clinical success, and a standard for clinical care. Most importantly, the TOKYO criteria 2014 allow comparison of biliary stent quality across studies. Because blocked stents can be drained not only using transpapillary techniques but also by an endoscopic ultrasonography‐guided transmural procedure, we should devise an evaluation method that includes transmural stenting in the near future.

Comparative genomic hybridization analysis for pancreatic cancer specimens obtained by endoscopic ultrasonography-guided fine-needle aspiration.

BackgroundComparative genomic hybridization (CGH) analysis of pancreatic cancer has been done exclusively for surgical and autopsy specimens, because of the difficulty of tissue sampling without surgery. To overcome this difficulty, we applied CGH technology to cells obtained by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA).MethodsIn the present study, we performed EUS-FNA for 17 patients with pancreatic cancer before surgery. Tumor cells were selected by microdissection. DNA was extracted from the cells and amplified by degenerate oligonucleotide-primed polymerase chain reaction (DOP-PCR). Then CGH was carried out.ResultsIn the 15 patients with tubular adenocarcinoma, the most common loci of gains (including amplification) were 5p, 8q, and 20q (60% of the patients); and 1q, 7p, and 12p (27%). The most frequent losses were 17p (73%); 9p, 18q, and 19p (47%); and 8p (33%). These findings were similar to our previously reported data. Both of the patients with acinar cell carcinoma showed gains of 2q and 5p, and losses of 1p, 9p, 9q, 11p, 11q, 14q, 17p, 17q, and 18q.ConclusionsThe results of this study suggest that comprehensive genetic analysis is possible for EUS-FNA biopsy specimens, with a combination of microdissection and DOP-PCR. This analytical strategy will enable us to evaluate the biological characteristics of pancreatic cancer before treatment.

DOUBLE BALLOON ENDOSCOPE FACILITATES ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY IN ROUX-EN-Y ANASTOMOSIS PATIENTS

Endoscopic retrograde cholangiopancreatography (ERCP) is the gold standard for the treatment of patients with pancreaticobiliary disorders, but endoscopic therapy is very difficult to carry out in patients with a Roux‐en‐Y anastomosis. We herein present the results of ERCP for patients with a Roux‐en‐Y anastomosis using a double‐balloon endoscope. Six patients (six men with a mean age of 69 years) who had undergone prior gastric resection with Roux‐en‐Y reconstruction were enrolled in the present study and underwent ERCP and associated procedures. ERCP was carried out with a double balloon endoscope, which has one balloon attached to the tip of the endoscope and another attached to the distal end of the soft overtube. In all patients, entering the Y loop was successfully accomplished, and the papilla of Vater was also reached in all cases (100%). Cannulation was successful in four patients (66.7%). The final diagnosis was choledocholithiasis in two patients, biliary fistula in one patient and pancreatic cancer in one patient. A needle‐knife precut papillotomy was carried out after placement of a bile duct stent in two patients, and injection of N‐butyl‐2‐cyanoacrylate into a biliary fistula was carried out in one patient. None of the patients suffered from any complications. A double balloon endoscope is therefore considered to be useful for carrying out ERCP and associated procedures in patients with a Roux‐en‐Y anastomosis.

ERCP using double-balloon endoscopes in patients with Roux-en-Y anastomosis

INTRODUCTION Endoscopic retrograde cholangiopancreatography (ERCP) and associated procedures are difficult to perform in patients with a Roux-en-Y reconstruction. Therefore, at present, at many institutions, ERCP is not generally performed for those with a Roux-en-Y anastomosis. METHODS However, double-balloon endoscopes (DBEs) have dramatically changed this situation. RESULTS The use of a DBE enables an endoscopic approach into the deeply situated small intestine, which has been difficult with a conventional endoscope. Therefore, ERCP for patients with a Roux-en-Y anastomosis has been attempted using a DBE, and good results have been reported. CONCLUSION The development of DBEs has created the possibility of performing ERCP for patients with Roux-en-Y reconstruction in whom an endoscopic approach has conventionally been believed to be difficult.