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1/5. Biliopancreatic fistula associated with intraductal papillary-mucinous pancreatic cancer: institutional experience and review of the literature.

    Intraductal papillary-mucinous tumour is clinicopathologically characterized by papillary growth and mucin production within the pancreatic duct system. The category includes a wide range of dysplasia, ranging from adenoma to carcinoma, the latter designated as intraductal papillary-mucinous cancer. In general, the tumor renders a favorable prognosis after complete resection. However, intraductal papillary-mucinous tumor with overt invasion outside the gland has been reported to have a poor prognosis, as is the case with the usual type of duct cell cancer of the pancreas. We experienced two cases of intraductal papillary-mucinous cancer with obstructive jaundice due to impaction of thick mucus protruding from the pancreas via a "spontaneous" biliopancreatic fistula. Preoperative examinations of both patients showed a large intraductal papillary-mucinous tumor in the head of the pancreas with fistula formation between the intrapancreatic portion of the common bile duct and the main pancreatic duct. Histopathological investigation of the two resected specimens suggested that the fistula may not have developed from invasion by papillary or tubular adenocarcinoma, but from compression and destruction of the intercalating tissues by abundant mucinous secretion. The first patient died of peritoneal carcinomatosis with clinicopathologic features of pseudomyxoma peritonei 6 years after surgery. The second patient is alive and has been well for 2 years postoperatively. review of the world literature showed that half of the patients with intraductal papillary-mucinous cancer plus biliopancreatic fistula had no stromal invasion around the fistula, indicating that the fistula might have been caused by mechanical pressure. However, the other half of the cases did have stromal invasion around the fistula. Two-thirds of these cases, including our own patients, had foci of mucinous carcinoma in the stroma around the fistulization, implying that mucinous lakes in the stroma may have served as part of the "waterway" from the pancreatic duct to the bile duct, assisted by increased pressure by mucus production. Since intraductal papillary-mucinous cancer with biliopancreatic fistula has a comparatively favorable prognosis, surgical resection should be considered.
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2/5. Mixed ductal-endocrine carcinomas of the pancreas and ductal adenocarcinomas with scattered endocrine cells: characterization of the endocrine cells.

    We compared the histological and immunohistochemical features of mixed ductal-endocrine carcinomas of the pancreas with those of ductal adenocarcinomas (DACs) containing scattered tumor-associated endocrine cells (SECs). Three pancreatic neoplasms fulfilled the WHO criteria for mixed ductal-endocrine carcinomas. Two of them showed moderately to poorly differentiated glandular structures composed of both mucin producing and neuroendocrine cells. The third mixed ductal-endocrine carcinoma was of the composite type showing DAC structures and a solid component with small epithelial cells, most of them of neuroendocrine nature. In 32 of 34 cases of DAC located in the head (30 cases) and body to tail (4 cases) of the pancreas and showing lymph-node metastases, SECs were found, but they were few in number and irregularly distributed in the tumors. In three DACs a few SECs were also detected in lymph-node metastases. Double staining for chromogranin a and the proliferation marker Ki-S5 revealed that all SECs that were not intimately integrated into the neoplastic glandular epithelium failed to show proliferative activity and changes of the expression of tumor suppressor genes (p53 and DPC 4). These findings suggest that only those SECs that belong to the proliferative cell fraction may be of neoplastic origin, while the majority of SECs probably constitute a tumor-associated but non-neoplastic cell population. These features contrast with those of mixed ductal-endocrine carcinomas, in which all endocrine cells are a component of the neoplasm.
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3/5. telomerase gene expression in intraductal papillary-mucinous tumors (IPMT): preliminary findings.

    BACKGROUND AND AIM: The surgical management of IPMT is based upon a preoperative suspicion of malignancy, that is difficult to obtain from the available diagnostic tools. methods: telomerase gene expression was investigated by means of hTERT/RT-PCR on total rna from peripheral blood, tumour and non-tumour pancreatic samples of 2 patients with IPMT. RESULTS: Histological diagnosis was mild-grade dysplasia in the first case and invasive carcinoma in the second. telomerase expression was undetectable in all the samples derived from the first case. blood and tumour samples from the second patient were positive for telomerase mRNA expression, while the pancreatic non-tumour specimen was not. CONCLUSIONS: The following suggestions are made: 1) the telomerase gene expression seems to be implicated in the malignant evolution of IMPT; 2) the malignant transformation may be limited to a single area of the gland; 3) the presence of invasive carcinoma may be preoperatively suspected by peripheral venous blood sample collection. A possible clinical employment of telomerase gene expression determination in the management of IPMT is thus hypothesized.
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4/5. Intraductal papillary mucinous neoplasm of the pancreas in a patient with attenuated familial adenomatous polyposis.

    A 67 year old man with a clinical diagnosis of attenuated familial adenomatous polyposis (AFAP) and a past history of synchronous colon cancers in the transverse colon was also found to have an intraductal papillary mucinous neoplasm (IPMN) of the pancreas. In addition, several foci of heterotopic gastric oxyntic mucosa were noted in the duodenum, interspersed with flat and polypoid adenomas. The duodenal adenomas showed low grade dysplasia, loss of adenomatous polyposis coli (APC) protein expression, but retention of beta catenin staining, localised to the nucleus and cytoplasm. The IPMN in the pancreas showed an identical immunohistochemical profile to the duodenal adenomas. The heterotopic gastric foci in the duodenum were negative for the APC protein, and beta catenin staining was membranous in location. Although the patient did not show germline truncating APC mutations or mutations in the MYH gene, the past history, clinical features, and immunohistochemical profile of the various lesions suggest strongly that the IPMN is part of the spectrum of lesions encountered in AFAP. Whether the heterotopic oxyntic gastric mucosa in the duodenum is also related is unclear, but it may represent a forme fruste of fundic gland polyps.
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5/5. Epidermotropically metastatic pancreatic adenocarcinoma.

    We describe an epidermotropically metastatic pancreatic mucinous ductal adenocarcinoma on the scalp. Neoplastic glandular structures that varied in size and shape containing abundant mucin within the lumens and in the neoplastic cells were present within a seborrheic keratosis and adjacent normal epidermis. Similar neoplastic glandular structures were present in the dermis, some within adnexal epithelium and lymphatic vessels. The patient's history of pancreatic mucinous ductal adenocarcinoma and immunohistochemical staining pattern of carbohydrate antigen 19-9 (CA 19-9) confirmed the diagnosis.
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