The role of p21ras in pancreatic neoplasia and chronic pancreatitis.

K-ras mutations have been detected in both ductal cell carcinoma and intraductal papillary mucinous tumor (IPMT) of pancreas. The frequency of this mutation in ductal cell carcinoma is high, whereas in IPMT, it is variable. It has been suggested that the relatively high frequency of this mutation in ductal cell carcinomas compared with IPMT may account for the differences in biological behavior between these tumor types. More recently, the significance of K-ras mutations in pancreatic tissue has been questioned with the demonstration of this mutation in nonneoplastic pancreata. The current study aims to estimate the relative frequency and evaluate the biological significance of K-ras gene mutations in these neoplasms by performing polymerase chain reaction (PCR) assays of microdissected areas of IPMT, ductal cell carcinomas, and resected chronic pancreatitis. The study also investigates whether alterations of p21ras occur in K-ras mutation-negative cases by using immunohistochemical staining for K-, N- and H-ras. K-ras codon 12 mutations were found almost as frequently in IPMT (71%) as in ductal cell carcinomas (78%). They were also associated with the earliest morphological lesion, flat mucinous change. This mutation also was detected in 42% of cases of chronic pancreatitis. Expression of p21ras was found to correlate closely with K-ras mutation status in IPMT and ductal cell carcinoma. Negative staining for pan-ras, H-ras, and N-ras in cases with wild-type K-ras genes suggests that alternative routes of ras gene alteration are not operative in IPMT or ductal carcinoma. The findings suggest that K-ras activation is frequently associated with both IPMT and ductal cell carcinoma. Its high prevalence in nonneoplastic pancreata suggests that it is also associated with self-limited morphological lesions of the pancreas that do not progress to malignancy.

Response of normal aorta to endovascular grafting: a serial histopathological study.

OBJECTIVE: To examine the histological changes caused by the presence of the endovascular stented graft in the native aorta. DESIGN AND INTERVENTION: Case series. Twenty Western crossbred adult male sheep underwent endovascular placement of an infrarenal aortic stented graft, using the Bard aortic aneurysm repair device catheter delivery system (Bard Vascular Systems, Dovermill, Mass). Six self-expanding wire hooks at the proximal anchor allow fixation to the aorta. After 1 month (n=6), 3 months (n=6), and 6 months (n=8), the animals underwent repeated angiography and intravascular ultrasonography to study the aorta and the graft. The aorta was explanted en bloc with the left renal artery, pressure perfused with a formalin gluteraldehyde solution, and then underwent histological examination with hematoxylin-eosin, trichrome, and elastic tissue staining. MAIN OUTCOME MEASURES: Description of histological changes at various intervals after endovascular stented graft placement. RESULTS: Significant histological findings include (1) complete incorporation of the grafts into the aortic wall, with a pseudointima of smooth muscle cells and collagen; (2) a foreign-body reaction around the graft; (3) an organized blood clot noted between the graft and the aortic wall, without evidence of recent blood flow through the perigraft space or the lumbar vessels; and (4) focal replacement by collagen of the inner one third to one half of the media at the proximal anchor sites. CONCLUSION: There was good incorporation of the graft without evidence of pressure necrosis, bleeding around the graft, or flow in the occluded lumbar vessels.

An unusual case of Behçet's syndrome: triggered by typhoid vaccination?

A case of Behçet's syndrome in a 32-year-old woman occurring shortly after her third vaccination against typhoid fever is described. Scleritis and pyoderma gangrenosum were unusual manifestations of BS that occurred in this case. Treatment benefit was provided by mycophenolate mofetil and etanercept. As bacterial antigens have been proposed as potential triggers for the onset of BS, it is possible that the syndrome was precipitated by typhoid vaccination in this patient.

Percentages of cervical cytologic diagnoses as a quality assurance method.

OBJECTIVE: To demonstrate empirically that the efficiency of rescreening to discover false negative cytologic diagnoses is greatly enhanced by prospectively stratifying accessions according to risk level. STUDY DESIGN: We stratified accessions from 11 clinical sources and established the rate of diagnoses according to three categories: (1) "within normal limits"/"benign cellular changes" (WNL/BCC), (2) "atypical squamous/glandular cells of undetermined significance" (ASCUS/AGCUS) and (3) "squamous intraepithelial lesion/invasive carcinoma" (SIL/CA). We then prospectively rescreened all negative smears from sources with rates of positive diagnoses (ASCUS/AGCUS and SIL/CA) in excess of 20% and 5% of negative smears from sources with rates of positive diagnoses < 20%. We compared the detection rates of false negatives on rescreening target groups with random rescreening of 10% of all negative smears. RESULTS: The rates of SIL/CA, ASCUS/AGCUS and WNL/BCC varied from 0 to 43%, 4% to 14% and 46% to 94%, respectively. Rescreening 10% of all negative smears revealed a false negative fraction of 3%; rescreening target groups revealed a false negative fraction of 5.9%. CONCLUSION: The yield of prospectively detected false negative diagnoses was significantly increased by targeting high-risk accession groups. When cytology laboratories serve diverse populations, stratifying accessions by risk to permit increased sampling from the proportionately higher risk categories is a simple and effective device to maximize the yield and benefit from rescreening.