Yumi Izumisato

Coexpression of Matrilysin and Laminin-5 γ2 Chain May Contribute to Tumor Cell Migration in Colorectal Carcinomas

We attempted to examine the correlation between matrilysin and laminin-5 γ2 chain expression with reference to the number of dedifferentiation units along the entire invasive front (tumor budding). Immunostaining for hMMP-7 and laminin-5 γ2 chain was performed in 50 T1 colorectal carcinomas, and immunoreactivity was evaluated at the invasive front of the tumor. On hematoxylin–eosin sections, the number of tumor budding was counted. The localization of matrilysin tended to be widespread compared with that of laminin-5 γ2 chain. Matrilysin and laminin-5 γ2 chain expression were positive in 28 (56%) and 15 (30%) tumors respectively. There was a significant correlation between matrilysin and laminin-5 γ2 chain expression (P = 0.02). Matrilysin(+)/laminin-5 γ2 chain(+) tumors had a significantly greater amount of tumor budding than matrilysin(−)/laminin-5 γ2 chain(−) tumors (P = 0.003) or matrilysin(+)/laminin-5 γ2 chain(−) tumors (P = 0.03). In conclusions, coexpression of matrilysin and laminin-5 γ2 chain may contribute to tumor cell migration in colorectal carcinomas.

Diagnostic significance of high mobility group I(Y) protein expression in intraductal papillary mucinous tumors of the pancreas

Introduction Overexpression of the high mobility group I(Y), [HMGI(Y)], gene/proteins has been demonstrated in many types of human malignancies, suggesting that HMGI(Y) may play a vital role in the oncogenic transformation of cells. Aims To analyze HMGI(Y) expression in intraductal papillary mucinous tumor (IPMT) of the pancreas to verify whether determination of the HMGI(Y) expression level could provide any diagnostic advantages in the pathological diagnosis of IPMT. Methodology Thirty-three different lesions from 25 patients with IPMT, including 20 with mild dysplasia, 7 with moderate dysplasia, and 6 with carcinoma, were analyzed immunohistochemically with use of an HMGI(Y)-specific antibody. Results Immunohistochemical analysis revealed that, although no significant immunoreactivity was found in cases of normal pancreatic duct or mild dysplasia, 28.6% (2/7) of moderate dysplasia showed multifocal immunoreactivity with moderate intensity. In contrast, in 50% (3/6) of the cases of carcinoma, intense multifocal or diffuse immunoreactivity occurred, almost equivalent to that observed in cases of duct cell carcinoma, whereas in the remaining 3 cases of carcinoma only a faint focal immunoreactivity occurred. Histologic examination revealed that these HMGI(Y)-positive carcinomas had an invasive growth pattern, whereas the HMGI(Y)-negative carcinomas were either carcinomas in situ or tumors with minimal invasion. Thus, an increased expression level of HMGI(Y) proteins was closely associated with the malignant phenotype in IPMT. Conclusion On the basis of these findings, we propose that HMGI(Y) proteins could play an important role(s) in a multistage process of carcinogenesis of IPMT and that the HMGI(Y) protein level could serve as a potential diagnostic marker, which may enable the identification of tumor cells with potential to be biologically malignant.

High mobility group A1 is expressed in metastatic adenocarcinoma to the liver and intrahepatic cholangiocarcinoma, but not in hepatocellular carcinoma: its potential use in the diagnosis of liver neoplasms

BackgroundAn increased level of high mobility group A (HMGA) gene/protein expression has been demonstrated to be associated with many human neoplasms originating from a variety of tissues. However, HMGA1 expression has not yet been studied in hepatic tumors. In this study, we analyzed HMGA1 expression in hepatic primary and metastatic tumors in order to verify whether determination of the HMGA1 expression level could provide any diagnostic advantages in the pathological diagnosis of hepatic tumors.MethodsTwenty samples of hepatocellular carcinoma, 5 samples of intrahepatic cholangiocarcinoma, and 21 samples of metastatic adenocarcinoma to the liver (15 metastatic tumors from colorectal carcinoma and 6 metastatic tumors from pancreatic carcinoma) were analyzed immunohistochemically using an HMGA1-specific antibody.ResultsWhile no significant nuclear immunoreactivity was found in hepatocytes of non-neoplastic liver tissue, 40% (2/5) of intrahepatic cholangiocarcinomas, 53.3% (8/15) of metastatic lesions from colorectal carcinoma, and 100% (6/6) of metastatic lesions from pancreatic carcinoma showed positive immunoreactivity. In contrast, all 20 samples of hepatocellular carcinoma were negative for HMGA1 nuclear immunoreactivity. Thus, hepatocellular carcinoma represents the first case of malignant neoplasia in which HMGA1 expression is not induced, which presents a striking contrast to several previous studies demonstrating the significance of increased HMGA gene/protein levels in carcinogenesis and/or tumor progression.ConclusionsBased on these findings, we conclude that the HMGA1 protein level could serve as a potential diagnostic marker that may enable the differential diagnosis between hepatocellular carcinoma and intrahepatic cholangiocarcinoma or metastatic adenocarcinoma to the liver.

Laminin-5 γ2 Chain Expression as a Possible Determinant of Tumor Aggressiveness in T1 Colorectal Carcinomas

This study was undertaken to clarify the associations between laminin-5 γ2 chain expression, and tumor budding and lymph node metastasis or local recurrence (locoregional failure) of 50 T1 colorectal carcinomas immunohistochemically. Fifteen (30%) of 50 lesions were positive for laminin-5 γ2 chain expression. By univariate analysis, less histological differentiation (P = 0.02), nonpolypoid growth pattern (P = 0.03) and tumor budding (P < 0.001) were associated with laminin-5 γ2 chain positivity. By multivariate analysis, tumor budding alone was significantly associated with laminin-5 γ2 chain positivity (P = 0.006), and correlation between nonpolypoid growth pattern and laminin-5 γ2 chain positivity lost its significance (P = 0.09). Tumor budding (P = 0.004) and laminin-5 γ2 chain expression (P = 0.001) were significantly associated with locoregional failure. Laminin-5 γ2 chain expression may contribute to the formation of budding tumor cells at the invasive front, and immunostaining of this adhesion molecule may be useful in identifying high-risk patients for locoregional failure in T1 colorectal carcinomas.

Biliopancreatic reflux via anomalous pancreaticobiliary junction

A PREVIOUSLY HEALTHY 32-YEAR-OLD WOMAN experienced an attack of mild acute pancreatitis manifested by right upper quadrant abdominal pain and hyperamylasemia (1676 IU/L; normal range, 50 to 240 IU/L). The patient had no history of excessive alcohol intake or jaundice. Conservative treatment improved the acute pancreatitis. Endoscopic retrograde cholangiopancreatography showed a long (11 mm) common channel, a dilated (48 mm) extrahepatic bile duct with gallstones, and nondilated normal pancreatic ducts (Fig 1). These findings represented anomalous pancreaticobiliary junction (APBJ) associated with choledochal cyst (Todani’s type I).1 Drip infusion cholangiography (DIC)-multidetector row computed tomography (MDCT) was performed using Aquilion (Toshiba Medical System, Tokyo, Japan) with four high-resolution detectors. After intravenous injection of a 100-mLdose of iotroxate meglumine (Biliscopin DIC 50; ScheringAG, Berlin, Germany),maximum intensity projection (MIP) images obtained by DIC-MDCT showed a long common channel, a dilated extrahepatic bile duct, and a proximalmain pancreatic duct (of the pancreatic head) (Fig 2). At 30minutes after ingestion of 4 g of dried egg yolk (Molyork; Toho Chemical Co, Osaka, Japan), DIC-MDCT demonstrated the main pancreatic duct more distally (Fig 3). Axial images revealed yolk-induced contraction of the nonopacified gallbladder. This patient underwent excision of the extrahepatic bile duct and gallbladder followed by

Clinical utility of grading criteria for submucosal invasion in the prognosis of T1 colorectal carcinomas

Background: The clinical utility of relative and absolute grading criteria for submucosal invasion in T1 colorectal carcinomas has been controversial. Methods: In 51 T1 colorectal carcinomas, depth of submucosal invasion was graded either according to a modified Haggitts classification (a relative criterion) or by direct measurement using a micrometer (an absolute criterion), and immunostaining for E-cadherin, α-catenin, β-catenin, matrilysin, and CD44 variant 6 was performed on formalin-fixed, paraffin-embedded sections. The associations between lymph node metastasis or local recurrence (locoregional failure) and tumor budding, and clinicopathologic parameters and immunoreactivity were examined statistically. Results: By univariate analysis, tumor budding, histology, and the co-expression pattern of nuclear β-catenin and CD44 variant 6 were significantly associated with locoregional failure. The relative and absolute grading of submucosal invasion were not significantly associated with locoregional failure. Multivariate analysis showed that tumor budding alone was significantly associated with locoregional failure, and the association between the co-expression pattern of nuclear β-catenin and CD44 variant 6, and locoregional failure was marginally significant (P = 0.0502). Lymphatic invasion and absolute grading of depth and width of submucosal invasion were significantly associated with tumor budding, and the associations between tumor budding, and histologic differentiation and membranous α-catenin expression were marginally significant (P = 0.06; P = 0.08), whereas, a relative grading of submucosal invasion was not significant (P = 0.58). Analysis of variance showed that histologic differentiation and lymphatic invasion were independently and significantly associated with tumor budding (P = 0.005; P < 0.001). Conclusions: These results suggest that the grading of submucosal invasion, either relative or absolute, may not be a useful risk factor for lymph node metastasis or local recurrence in T1 colorectal carcinomas.

Pancreatic transection using ultrasonic dissector in pancreatoduodenectomy

BACKGROUND Pancreatoenterostomic leakage after pancreatoduodenectomy may be caused partly by pancreatic juice leakage from transected branch pancreatic ducts on the pancreatic cut surface that do not drain into the main pancreatic duct after pancreatectomy. METHODS We devised a new technique of pancreatic transection using an ultrasonic dissector followed by duct-to-mucosa pancreatojejunostomy, in order to prevent pancreatoenterostomic leakage after pancreatoduodenectomy in patients with a soft pancreas and a small main pancreatic duct. During pancreatic transection, branch pancreatic ducts and blood vessels are adequately skeletonized and securely ligated. The pancreatic duct is anastomosed to the full thickness of the jejunum with four to six interrupted sutures. RESULTS Ten patients with a nondilated pancreatic duct (2 to 3 mm) underwent pancreatoduodenectomy by the present method. During pancreatic transection, 24 to 35 ducts including the pancreatic ducts and blood vessels were skeletonized and ligated. Postoperatively, no patients developed pancreatojejunostomic leakage. The present method may prevent pancreatoenterostomic leakage after pancreatoduodenectomy.

Pancreatic carcinoma that completely obstructs the Wirsung duct without dilatation of the main pancreatic duct

Background and Aim:  Pancreatic carcinomas in which the main pancreatic duct (MPD) is completely obstructed are almost always associated with dilatation of the upstream MPD. However, some carcinomas are not associated with MPD dilatation despite complete MPD obstruction. This paradoxical phenomenon has not been well documented.

Management of unsuspected common bile duct stones found during laparoscopic cholecystectomy by means of transcystic catheter placement and papillary dilation

BACKGROUND The optimal treatment strategy for treatment of bile duct stones first diagnosed during laparoscopic cholecystectomy has not been established. We prospectively treated unsuspected bile duct stones by means of intraoperative placement of a transcystic catheter followed by postoperative pharmacologic papillary dilation or endoscopic papillary balloon dilation. METHODS In 17 patients with bile duct stones first found at laparoscopic cholecystectomy, a catheter was introduced via the cystic duct into the bile duct. If postoperative cholangiography via a transcystic catheter showed stones 5 mm or less in diameter, glyceryl trinitrate was infused via the catheter into the bile duct. Patients in whom medical dilation was unsuccessful or who had larger stones underwent endoscopic papillary balloon dilation. RESULTS Stone diameter measured 3 to 11 mm (mean 6.4 mm). Postoperative cholangiography revealed spontaneous passage in four patients. After pharmacologic papillary dilation, two of five patients with stones 5 mm or less in diameter had stone clearance. The remaining 11 patients underwent successful endoscopic papillary balloon dilation with stone clearance. In two patients, a guidewire introduced via a transcystic catheter through the papilla facilitated selective biliary cannulation. One early minor complication occurred. All patients remained without symptoms for a mean follow-up of 13 months. CONCLUSION For unsuspected bile duct stones (usually small ones), this strategy is a simple and effective alternative to laparoscopic bile duct exploration and postoperative sphincterotomy and may minimize early and late complications. Transcystic catheterization ensures access to the bile duct, thereby avoiding endoscopic treatment failures.

Cavernous pancreatic ductal ectasia with smooth muscle proliferation causing recurrent acute pancreatitis.

SummaryBackground. Pancreatic cystic lesions have various etiologies, including pseudocyst (inflammatory cyst), retention cyst, congenital cyst, and neoplastic cyst. Results. This report describes a previously unreported, unique pancreatic cyst-like lesion causing recurrent acute pancreatitis. A 23-yr-old man had an 8×5×3-cm pancreatic head mass which contained multiple 3–7-mm cysts communicating with the main pancreatic duct on imaging studies. Pancreatoduodenectomy with mass excision prevented further attacks of acute pancreatitis. Pathological examination showed multiple cystic dilatations of branch pancreatic ducts surrounded by proliferating smooth muscle tissue, probably associated with hamartomatous changes. Conclusion. We consider the present lesion to represent cavernous pancreatic ductal ectasia with smooth muscle proliferation because of its striking cholangiopancreatographic similarity to Caroli disease.