Fumiaki Sakurai

Biological similarities and differences between pancreatic intraepithelial neoplasias and intraductal papillary mucinous neoplasms

AbstractBackground: Ever since the classification of pancreatic intraepithelial neoplasia (PanIN) was published, studies on the precursor lesions of pancreatic cancer have been advancing along a new directions, using standardized terminology. There are few studies that have examined the biological differences between PanIN and intraductal papillary mucinous neoplasm (IPMN) in detail. Aims: PanIN and IPMN, which are similar in morphology, were compared using various indicators, with the aim of identifying the similarities and differences between the two. Methodology: A total of 46 PanINs and 37 ducts with IPMN were identified in 19 patients with invasive ductal carcinoma and 18 patients with IPMN. These PanINs and IPMNs were examined immunohistologically with respect to the expression patterns of HER2/neu, DPC4/Smad4, Akt/PKB, p53, cyclin A, Ki67, MUC1, and MUC2. Results: Significant differences in the expression of MUC1 and MUC2 were observed between IPMN-adenoma and PanIN-2 and between CIS and PanIN-3 (MUC1: p=0.001 and p=0.005, respectively; MUC2: p=0.002 and p<0.001, respectively). A significant difference in the p53 expression level was also observed between CIS and PanIN-3 (p=0.015). Conclusions: In both IPMN and PanIN, the grade of atypism increased with increasing expression of HER2/neu, DPC4/Smad4, and Akt/PKB, along with progression in the process of multistage carcinogenesis. Although the expression levels of these factors reflected the grade of atypism, they did not reflect any differences in the grade of biological malignancy between IPMN and PanIN. On the other hand, MUC1 and MUC2 may serve as indicators of the direction of differentiation, i.e., either progression to IDAC or IPMN. Positivity for MUC1 was believed to suggest differentiation into IDAC, and positivity for MUC2 appeared to be indicative of differentiation into IPMN. Such indication of the direction of differentiation seemed to appear in PanIN1-2, even before abnormalities of HER2/neu, Akt/PKB, DPC4/Smad4, p53, and cyclin A expression began to be detected.

Expression of MUC5AC and MUC6 in invasive ductal carcinoma of the pancreas and relationship with prognosis.

Aim/Background. MUC5AC and MUC6 are two major types of mucin that are abundantly present in the stomach; both of them form a gel of high viscosity that provides protection and lubrication. Expressions of MUC5AC and MUC6 are seen in pancreatic neoplasms, whereas the relationships between MUC5AC/MUC6 expression and clinicopathological factors and patient prognosis in invasive ductal carcinoma (IDC) of the pancreas have not been investigated. The aim of this study was to investigate MUC5AC and MUC6 expressions in IDC with special reference to clinicopathological factors and patient prognosis.Methods. Tissue samples were taken from 33 patients with IDC of the pancreas after radical surgical treatment. MUC5AC and MUC6 expressions were examined immunohistochemically.Results. The expressions of MUC5AC and MUC6 were observed in the cytoplasm of the tumor cells. MUC5AC and MUC6 immunoreactivities in the cancer tissues were found in 21 (63.6%) and 15 (45.5%) of 33 cases of IDC of the pancreas, respectively. MUC5AC-negative expression was associated significantly with lymphatic invasion, venous invasion, lymph node metastasis, and MUC5AC-positive patients showed significant better survival than those MUC5AC-negative patients. MUC6 expression was significantly related to tumor location, whereas MUC6 expression did not show significant relationship with patient survival.Conclusion. The results indicate that MUC5AC expression plays an important role in impacting tumor progression in IDC of the pancreas. MUC5AC expression is a benefit to better survival of patients with IDC of the pancreas. MUC6 expression is not involved in tumor progression in IDC of the pancreas.

Histopathological study of intraductal papillary mucinous tumor of the pancreas: special reference to the roles of Survivin and p53 in tumorigenesis of IPMT.

AbstractAim. In this study, we investigated the tissue expression of Survivin, p53, and Bcl-2 in intraductal papillary-mucinous tumor (IPMT) of the pancreas to identify their roles in tumorigenesis of IPMT, and examined their correlations with tumor cell apoptosis and proliferation in IPMT. The diagnostic values of the expression of Survivin, p53, and Bcl-2 and the apoptotic index (AI) and Ki-67 labeling index (Ki-67 LI) in IPMT were also examined. Methods. Twenty-two lesions from 17 patients with IPMT, including 12 benign (IPMT Adenoma) and 10 malignant (IPMT Carcinoma In Situ [CIS] (n=4) and Invasive IPMT (n=6) lesions, were immunostained for Survivin, p53, Bcl-2 and Ki-67. The apoptotic cells were detected by the Apop Tag® In Situ Oligo Ligation (ISOL) method. Results. The immunoreactivities for Survivin and p53 significantly increased in the transition from IPMT Adenoma to IPMT CIS (p<0.05 for both). This transition was associated with a significant decrease in tumor cell apoptosis (p<0.001). The expression of Survivin was significantly associated with AI in IPMT (p<0.01), but not with Ki-67 LI. The expressions of Survivin and p53, and AI and Ki-67 LI were also significantly different between benign IPMT and malignant IPMT. Bcl-2 was not expressed in IPMT. Conclusion. These results suggest that Survivin and p53 may play important roles in the transition from IPMT Adenoma to IPMT CIS. This transition is accompanied by a significant decrease in tumor cell apoptosis. Survivin is significantly associated with the change in AI in IPMT. The immunohistochemical detection of Survivin and p53 as well as the determination of the AI and Ki-67 LI have useful roles in the diagnosis of IPMT.

Minute invasive ductal carcinoma of the residual pancreas after distal pancreatectomy for intraductal papillary-mucinous tumor.

SummaryOur report describes a 66-yr-old man who underwent surgical resection of the pancreas twice within a period of 3 yr for primary and recurrent intraductal papillary mucinous tumors (IPMTs). During the second operation, a minute invasive ductal carcinoma (IDC) was accidentally discovered in the resected specimen of the residual pancreas. The similarity and continuity between this IDC and recurrent IPMT were not recognized histologically. A solid tumor was found in the hepatoduodenal ligament 3 mo after the second operation. We performed a third operation, performing laparotomy and intra-operative radiotherapy, but could not extirpate the tumor. A biopsy specimen obtained from the tumor during this third operation revealed adenocarcinoma, and the patient later died because of tumor progression. We immunohistochemically analyzed the expression of HER-2/neu, Smad4, p16, p21, p53, mucin immunophenotypes and the Ki-67 labeling index in this series of pancreatic-duct neoplasias. Overexpression of HER-2/neu and loss of Smad4 were detected in the minute IDC, which was very different from the immunohistochemical features of both the primary and recurrent IPMTs. The IDC also showed a MUC1-positive/MUC2-negative phenotype. Therefore, we suggest that de novo IDC may occur in IPMT patients, especially those with multiple tumor recurrence. The present case may be helpful in understanding the pathogenesis of pancreatic duct lesions.

Microsurgical technique used in right anterior segmentectomy and pancreatoduodenectomy with reconstruction of the right posterior hepatic artery for widespread bile duct cancer involving the hepatic hilus

A microsurgical technique was used in performing anterior hepatic segmentectomy and pancreatoduodenectomy with reconstruction of the posterior hepatic artery in a 64-year-old man with widespread bile duct cancer from the intrapancreatic bile duct over the hepatic hilus. The anterior hepatic artery was obviously involved and the posterior hepatic artery just behind common hepatic duct was very close to the cancer. Microsurgical anastomosis between the remnant gastroduodenal artery and the posterior hepatic artery at the hepatic hilus made it possible to preserve the posterior segment of the liver and to perform a curative resection of the cancer. The patient had pyrexia because of suprahepatic abscess after the operation, but the abscess drained spontaneously. Postoperative arteriogram showed neither obstruction nor kinking of the reconstructed artery. He was discharged 2 months after surgery and has been enjoying a normal quality of life for 10 months since, with no signs of recurrence. It is suggested that a microsurgical technique is useful for performing an accurate anastomosis with good patency that allows not only a safe but also a highly curative operation for advanced bile duct cancer.