Christopher R. Pierson

Colloid (mucinous noncystic) carcinoma of the pancreas

In the past, colloid (mucinous noncystic) carcinoma (CC) of the pancreas had been included under the category of ordinary ductal adenocarcinoma, a tumor with a dismal prognosis, or was frequently misdiagnosed as mucinous cystadenocarcinoma. The clinicopathologic features of CC have not yet been well characterized, because most cases on record have been parts of studies on either mucinous cystic neoplasms (MCN) or intraductal papillary mucinous neoplasms (IPMN), with which colloid carcinomas are frequently associated. To determine the clinicopathologic characteristics of CC, 17 pancreatic tumors composed predominantly (>80%) of CC (defined as nodular extracellular mucin lakes with scanty malignant epithelial cells) and in which the invasive carcinoma measured larger than 1 cm were studied. Ten of these were originally classified as mucinous ductal adenocarcinoma and four as mucinous cystadenocarcinoma. The mean age of the patients was 61 years; 9 were men and 8 were women. The mean size of the CC was 5.3 cm (range, 1.2–16 cm). In more than half of the patients, CC represented the invasive component of an IPMN (in nine cases) or MCN (in one case). The tumors were composed of well-defined pools of mucin with sparse malignant cells in various patterns of distribution. Signet-ring cells floating in the mucin (but not as individual cells infiltrating stroma, a characteristic finding of signet-ring cell adenocarcinomas) were commonly identified and were prominent in five cases. Perineurial invasion was noted in six cases and regional lymph node metastases in eight. Mutation in codon 12 of the k-ras gene was detected in only 4 of 12 cases studied and p53 mutation in 2 of 9. Immunohistochemical and histochemical mucin stains suggested luminalization of the basal aspects of the cells. Five-year survival was 57%. At an overall mean follow up of 57 months, 10 patients were alive with no evidence of disease (median, 79 mos), including four with lymph node metastasis, three others with perineurial invasion, and another with vascular invasion. Four patients died of disease (18, 18, 25, and 26 mos), and three died of thromboembolism (with persistent disease) at 2, 5, 10 months. All seven patients who died with or of tumor had undergone incisional biopsy of the tumor either before the operation or intraoperatively, whereas none of the patients who were alive had incisional biopsy. When compared with 82 cases of resectable ordinary ductal adenocarcinoma on whom follow-up and staging information was complete, it was found that the patients with CC present with larger tumors (p = 0.03) but lower stage (p = 0.01). The prognosis of CC is significantly better: 2-year and 5-year survival are 70% versus 28% and 57% versus 12%, respectively (p = 0.001). In conclusion, pancreatic CC may occur with or without an identifiable IPMN and MCN component, and should be distinguished from mucinous cystadenocarcinoma, ordinary ductal adenocarcinoma, and signet-ring cell adenocarcinoma. CC of the pancreas is associated with a significantly better prognosis than ordinary ductal adenocarcinoma. In addition to its distinctive morphologic and clinical characteristics, CC of the pancreas also appears to have a low incidence of mutation in codon 12 of the k-ras gene. In cases with a clinical suspicion of colloid carcinoma, the possibility that an incisional biopsy may contribute to thromboembolic complications or even dissemination of the tumor may need to be considered. The luminalization of the basal aspects of the tumor cells may be the cause of stromal mucin accumulation that characterizes colloid carcinoma and may act as a containing factor.

Impaired glucose tolerance and insulinopenia in the GK‐rat causes peripheral neuropathy

Recent studies indicate that impaired glucose tolerance (IGT) in man is a causative factor in idiopathic sensory neuropathy, and that insulinopenia may contribute substantially to the severity of diabetic peripheral neuropathy. The effect of sustained IGT and progressive insulinopenia in the absence of overt hyperglycemia on peripheral nerve abnormalities was examined in the Goto–Kakizaki (GK)‐rat.

Pulmonary edema complicating prostacyclin therapy in pulmonary hypertension associated with scleroderma: a case of pulmonary capillary hemangiomatosis.

Continuous intravenous infusion of prostacyclin is an effective treatment for primary pulmonary hypertension (PPH), and has recently been shown to be of benefit in PH associated with scleroderma (SSc). Pulmonary capillary hemangiomatosis (PCH) is a rare cause of PPH. Prostacyclin therapy has been complicated by pulmonary edema in cases of PCH. We describe a case of PH associated with limited SSc, where treatment with prostacyclin was complicated by pulmonary edema. Autopsy revealed PCH as the pathologic basis for the PH. There were no clinical features of PCH prior to initiation of vasodilator therapy, illustrating the potential difficulty in establishing the diagnosis. This is the first reported case of PCH in SSc.

Platelet-Type 12-Lipoxygenase Regulates Angiogenesis in Human Prostate Carcinoma

The growth and metastasis of solid tumors are dependent on the ability of tumor cells to induce angiogenesis [1]. Angiogenesis, the formation of new blood vessels from pre-existing ones, involves endothelial cell proliferation, motility, and tubular differentiation. It is known that tumor cells can secrete a variety of angiogenic factors, such as basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), to stimulate angiogenesis. Tumor cells also produce angiogenesis inhibitors such as thrombospondin and angiostatin to control angiogenesis. The balance between angiogenesis stimulators and inhibitors determines the angiogenicity of tumor cells [2]. Acquisition of the ability to stimulate angiogenesis by tumor cells is an integral part of tumorigenesis. Activated oncogenes, such as ras, or inactivated tumor suppressor genes, such as p53, not only increase mitogenesis and prevent apoptosis in tumor cells, but also lead to the development of an angiogenic phenotype [for review,.3].