Kazuto Nakamura

Differential diagnosis of pancreatic tumors using ultrasound contrast imaging

BackgroundThe development of equipment and contrast agents for ultrasound imaging has contributed to major breakthroughs in the diagnosis of pancreatic tumors. We aimed to determine the diagnostic effectiveness of contrast ultrasound with Levovist, using the Agent Detection Imaging (ADI) technique, in 50 patients with pancreatic tumors.MethodsWe studied 50 cases of histologically proven pancreatic disease; 39 carcinomas, 2 endocrine tumors, 4 intraductal papillary mucinous carcinomas (IPMCs), and 5 cases of tumor-forming pancreatitis (TFP). Vascular and perfusion images of contrast-enhanced ultrasound (CE-US) were used for the evaluation of tumor vascularity and parenchymal perfusion of the tumor, respectively. The hemodynamics of the tumor, and the diagnostic capacity of CE-US were compared with those shown by computed tomography (CT). The histological diagnosis in all cases was made from either biopsy or surgical specimens.ResultsThirty-four cases of pancreatic carcinoma (87%) showed a hypovascular and hypoperfusion pattern. The endocrine tumors showed a heterogeneous hypervascular and hyperperfusion pattern. All IPMC cases showed hypervascularity of the nodules inside the tumors. TFP showed an isovascular and homogeneous isoperfusion pattern. When tumors showing a hypovascular or hypoperfusion pattern on CE-US were diagnosed as carcinomas, 34 of the 39 carcinomas (87%) fit this criterion, with a 95% confidence interval (CI) of 73%–96%, whereas, on CT, 31 of the 39 were diagnosed as carcinoma; (sensitivity, 79%). The sensitivity and accuracy of CT were inferior to those of CE-US. Results of comparison between the CE-US findings and the histological diagnosis were as follows. The one papillary adenocarcinoma showed a hypervascular and hyperperfusion pattern; the 32 well or moderately differentiated adenocarcinomas showed a hypovascular and hypoperfusion pattern; and in the poorly differentiated adenocarcinomas, 2 cases of scirrhous type showed a hypovascular and hypoperfusion pattern, and the 4 cases of medullary type showed an isovascular and isoperfusion pattern.ConclusionsThe differences in vascularity of pancreatic carcinomas depicted by CE-US were associated well with differences in histology. CE-US, by the ADI technique, is useful for the diagnosis of pancreatic tumors.

Assessment of occult pancreatobiliary reflux in patients with pancreaticobiliary disease by ERCP.

BackgroundThe aim of this study was to evaluate the degree of occult pancreatobiliary reflux by measuring the biliary amylase levels in the common bile duct (CBDA) and gallbladder (GBA) at endoscopic retrograde cholangiopancreatography (ERCP).MethodsEligible patients included 86 consecutive cases of pancreaticobiliary disease with prospective implementation of bile collection during an ERCP procedure. Patients with pancreatobiliary maljunction (PBM) were excluded. Nineteen cases of eligible patients had simultaneous collection of gallbladder bile. Bile was further collected by cholecystectomy in 8 cases.ResultsTwenty-two cases (26%) revealed a CBDA level higher than serum amylase (high bile amylase level, HBA group) and 64 cases exhibited a CBDA level lower than serum (LBA group). The mean values of CBDA in the HBA and LBA groups were 5502 IU/l and 29 IU/l, respectively. The rate of HBA was significantly higher in patients who were elderly, had a dilated common bile duct, and those with choledocholithiasis (P < 0.05). Three cases (16%) showed a CBDA greater than twice the GBA. Eleven cases (58%) exhibited a GBA higher than the CBDA. The values of GBA obtained during ERCP and cholecystectomy were consistent.ConclusionsThese findings suggest that even non-PBM cases can exhibit occult pancreatobiliary reflux, which can thereby cause biliary disease.

Nuclear cyclin D1 overexpression is a critical event associated with cell proliferation and invasive growth in gallbladder carcinogenesis.

Abstract: Cyclin D1 overexpression is remarkably frequent in several human carcinomas and is believed to be a critical event in oncogenesis. We examined cyclin D1 expression, p53 expression, and the Ki-67 labeling index by immunostaining in human gallbladder mucosa in conditions varying from normal to malignant tissue. We also examined K-ras codon 12 mutations in these tissues with a two-step polymerase chain reaction. Nuclear cyclin D1 overexpression was observed in 48% of carcinomas occurring independently of adenoma, but not in adenomas, carcinomas arising in adenomas, or nonneoplastic lesions. Cytoplasmic cyclin D1 overexpression was observed in about 15% of abnormal specimens, irrespective of the type of epithelial abnormality. Carcinomas showing nuclear cyclin D1 overexpression had significantly higher Ki-67 labeling indexes than those with no overexpression. Moderately to poorly differentiated adenocarcinomas showed a higher incidence of nuclear cyclin D1 overexpression than papillary to well differentiated carcinomas. Specimens with cyclin D1 overexpression showed a high incidence of lymph permeation, venous permeation, and lymph node metastasis. We conclude that nuclear cyclin D1 overexpression is a critical event importantly associated with cell proliferation and invasive growth in gallbladder carcinogenesis, and that cyclin D1 immunostaining may become a useful marker for evaluating gallbladder carcinomas.

A novel technique for endoscopic sphincterotomy when using a percutaneous transhepatic cholangioscope in patients with an endoscopically inaccessible papilla.

BACKGROUND Endoscopic sphincterotomy is difficult and sometimes impossible in patients who have undergone gastrectomy or partial gastrectomy with Billroth II reconstruction. For such patients, a novel technique was developed in which endoscopic sphincterotomy is performed via percutaneous transhepatic cholangioscopy. This report describes an initial experience with this technique. METHODS After dilation of the percutaneous fistula, a cholangioscope with a push-type sphincterotome attached was inserted into the bile duct via the fistula and then through the papilla into the duodenum. The tip of the instrument then was retroverted to obtain a frontal view of the papilla. Then, a sphincterotomy incision was extended to the proximal, orad margin of the papillary eminence. OBSERVATIONS Percutaneous transhepatic biliary drainage was performed in 3 patients with obstructive jaundice and bile duct stones. In all patients, percutaneous transhepatic cholangioscopic sphincterotomy was performed successfully, without procedure-related complication. Thereafter, all stones and stone fragments cleared from the duct by spontaneous migration. CONCLUSIONS Endoscopic sphincterotomy via percutaneous transhepatic cholangioscopy potentially is an innovative technique for endoscopic sphincterotomy in patients with an endoscopically inaccessible papilla.

IMPROVEMENT OF CHOLEDOCHOSCOPY: CHROMOENDOCHOLEDOCHOSCOPY, AUTOFLUORESCENCE IMAGING, OR NARROW‐BAND IMAGING

Past and present results concerning assessment of choledochoscopy using chromoendoscopy, autofluorescence imaging (AFI), or narrow‐band imaging (NBI) are summarized herein. On chromoendocholedochoscopy using methylene blue, cancer was stained dark blue. Interestingly, normal bile duct had dimple signs that are a significant feature of non‐neoplastic mucosa. First‐generation AFI (laser‐induced fluorescence endoscopy–gastrointestine system) and system of autofluorescence endoscopy made it possible to detect neoplastic lesions as dark green–black lesions, although the image was insufficient. The sensitivity, specificity and diagnostic accuracy of white light illumination and AFI were 88.0%, 87.5%, 87.7%, and 100%, 52.5%, 70.8%, respectively. In contrast, the recently developed NBI system made it possible to emphasize the imaging of certain features such as mucosal structures and mucosal microvessels. NBI showed not only clear neoplastic findings such as irregular mucosa or tortuous tumor vessel, but also non‐neoplastic findings such as smooth surface mucosa or dimple sign. In conclusion, the diagnostic power of chromoendoscopy and AFI were low, but NBI is expected to become the new‐generation diagnostic tool for biliary tract diseases.

Endoscopic removal of a dislocated covered wallstent using a wire‐loop technique

Background:  Self‐expandable metallic stents (SEMS) and covered‐SEMS (cSEMS) are used for patients with unresectable malignant biliary strictures. Occasionally, there are cases where stent migration can easily occur.

SALVAGE THERAPY IN PATIENTS WITH UNRESECTABLE HILAR CHOLANGIOCARCINOMA

We describe our methods and outcomes of multidisciplinary treatments in patients with unresectable hilar cholangiocarcinoma. Fifty‐seven patients with a known outcome were enrolled. Thirty‐four of 57 patients were treated and evaluated by salvage therapy. For salvage therapy, we used internal and external radiotherapy, photodynamic therapy, YAG laser therapy and microwave coagulation therapy. The median survival time was 548 days for the group receiving salvage therapy and 198 days for the group not receiving this treatment. In conclusion, although no randomization of the patients was performed in this retrospective study, our present data provide convincing evidence that salvage therapy is a useful therapeutic approach for unresectable hilar cholangiocarcinomas.

Extraction of uncovered biliary metallic stent using percutaneous transhepatic cholangioscopy

In this study, we describe the successful removal of a biliary nitinol metallic stent during percutaneous transhepatic cholangioscopy (PTCS) after lithotripsy of stones caused by obstruction of a metallic stent placed to alleviate stenosis of the choledochoduodenal anastomotic site in a case of benign biliary disease. Using serrated‐edge forceps, one third of the metallic stent was removed in piecemeal sections and then the remaining portion of the stent was removed in one piece through the percutaneous transhepatic fistula. The endoscope was not damaged because all stent materials were removed through the PTCS fistula, not the channel of the endoscope. There were no procedural complications excluding minor bleeding seen endoscopically and no residual stent wires on cholangiograms. In conclusion, this technique is a useful method for metal stent removal from patients in whom it is to extract metallic stent by peroral endoscopic treatment.

Assessment of Occult Pancreatobiliary Reflux by Biliary Amylase Levels in Patients with Pancreaticobiliary Disease

Assessment of Occult Pancreatobiliary Reflux by Biliary Amylase Levels in Patients with Pancreaticobiliary Disease Takao Itoi, Kazuto Nakamura, Atsushi Sofuni, Fumihide Itokawa, Kazuhiro Kakimi, Jun Sanada, Fuminori Moriyasu Objectives: Pancreatobiliary maljunction (PBM) is a high risk factor for biliary tract cancer. Carcinogenesis by PBMhas yet to be completely clarified; however, it has been suggested that the mixing of pancreatic juice and bile could activate pancreatic enzymes. Recently, however, several investigators reported existence of pancreatobiliary reflux in patients with a normal pancreaticobiliary junction. The aim of this study was to prospectively examine pancreatobiliary reflux in patients with a normal pancreaticobiliary junction by measuring the amylase level in bile obtained during ERCP. Methods: Eligible patients included 86 consecutive cases of pancreaticobiliary disease with prospective implementation of bile collection during an ERCP procedure. Patients with PBM were excluded. Nineteen cases of eligible patients had simultaneous collection of gallbladder bile. Bile was further collected by cholecystectomy in eight cases. Results: Twenty-two cases (26%) revealed a common bile duct higher than serum amylase (high bile amylase level HBA group) and sixty-six cases exhibited a common bile duct amylase level lower than serum (LBA group). The mean values of common bile duct amylase level in the HBA and LBA groups were 5,502 IU/L and 29 IU/L, respectively. The rate of HBA was significantly higher in patients who were elderly, had a dilated common bile duct, and with choledocholithiasis (p<0.05). Three cases (16%) showed a common bile duct amylase level greater than twice the gallbladder amylase level. Eleven cases (58%) exhibited a gallbladder amylase level higher than the common bile duct amylase level. The values of gallbladder amylase level obtained during ERCP and cholecystectomy were consistent. Conclusions: In conclusion, the data in our study suggested that non-PBMpatients with pancreaticobiliary disease that shows a normal pancreaticobiliary junction might have occult pancreatobiliary reflux under physiological conditions, thereby possibly leading to biliary diseases. *T1442 Importance of Real Time Interpretation (INTERP) of ERCP Films Over Conventional Static Images: Medicolegal Implications Miriam Thomas, Joseph E. Geenen, Marc F. Catalano ERCP is a complex procedure requiring technical skill, careful attention to endoscopic and radiographic (INTERP) that frequently requires evaluation of both real time & hard film copies. Although ERCP X-Rays are reviewed & formally reported by radiologist (RAD), gastroenterologist (GE) perform the studies & interpret fluoroscopic images. Differences in INTERP could lead to medicolegal liability. METHOD: ERCP records of 154 consecutive pts were prospectively evaluated.GE INTERP of ERCP films using real time&hard copies were documented & compared with available text documentation by RAD. Components of each exam were assessed for differences in final INTERP between GE andRAD. Biliary &pancreatic cases were reviewed for documentation of duct diameter, duct INTERP, strictures, stones, cytology, dilatation & stone removal. RESULT: Bile duct (BD) INTERP byGE&RADwere ABN&NL in 64%, 36% compared to 56%, 44% respectively. PD INTERP by GE was documented to be ABN in 63%, NL in 38% compared to 53% & 46% respectively by RAD. There was significant disagreement between GE & RAD regarding ductal INTERP (P<0.05). For the presence of BD stones, PD stones, BD stricture, PD stricture there was an agreement of 52%, 73%, 79% & 84% respectively. In therapeutic cases agreement between RAD & GE of BD cytology, duct dilation, stone removal, PD cytology, PDdilatation, PD stone removal was present in 73%, 50%, 32%, 53%, 44%, & 42% respectively. When compared to GE documentation RAD failed to document the CBD & PD diameter, 27% of BD cytology cases, 50% of biliary dilatation, 68% of BD stone removal, 47% of PD cytology, 55% of PD dilatation & 58%of PD stone removal. Under INTERP of findings frequently occurred in RAD dictated report when compared to GE. CONCLUSION: Many important aspects of the ERCP findings are under documented when interpreting findings using hard copies only. This could be due to lack of adequate film documentation of the procedure. The extent of documentation carries clinical & medicolegal importance. Careful reviews of both real time images & hard film copies are essential to ensure accurate final INTERP.