摘要:

This article summarizes the proceedings of the 1996 Comfort Symposium on Pancreatic Carcinogenesis that took place at the Mayo Clinic in Rochester, Minnesota, September 11–13, 1996. The annual series of Comfort lectures are aimed at discussing leading theories and advanced technological developments in the area of pancreatic research. The goals of this year's symposium were to summarize epidemiologic and experimental findings in the field of pancreatic cancer research, to foster communications among scientists studying this disease, and to identify areas of research that are likely to bridge the gaps between basic science and patient care. The topics discussed included (i) current algorithms for the diagnosis of early pancreatic cancer, (ii) animal and cellular models of pancreatic carcinogenesis, (iii) mechanisms of pain in pancreatic cancer, (iv) the role of signaling cascades and transcription factors in the regulation of pancreatic cell growth and differentiation, (v) methods to study genetic alterations associated with neoplastic diseases, and (vi) recent developments in genetargeting techniques. The lectures and discussions during the symposium successfully achieved the goals outlined above and resulted in the identification of novel areas of research that may increase our understanding of the etiology and pathogenesis, and lead to early diagnosis and treatment of pancreatic cancer.

ISSN:0885-3177    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Mutation of the p53 tumor suppressor gene is found in a large number of exocrine pancreatic tumors. The majority of these tumors is of the ductal cell phenotype. We examined 12 human acinar cell carcinomas and 42 transgenic mouse carcinomas (including 36 acinar cell tumors, four islet cell tumors, and two liver metastases of primary acinar cell tumors) for evidence ofp53 mutation. Immunohistochemistry was used to identifyp53 protein in tumor sections. To evaluatep53 exons 5–8, heteroduplex analysis was used on formalin-fixed, paraffin-embedded human tumor DNA, and single-strand conformation polymorphism analysis was used on frozen mouse tumor DNA. No molecular evidence of p53 mutation was found in any of the tumor DNAs and immunohistochemical data were regarded as negative. This study provides evidence that acinar cell carcinogenesis in both humans and transgenic mice is independent ofp53 mutation.

ISSN:0885-3177    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The effects of α-carotene, β-carotene, palm carotene, and green tea polyphenols (GTP) on the progression stage of pancreatic carcinogenesis after rapid production of ductal lesions were studied in Syrian hamsters. Dose threshold inhibitory effects were noted for β-carotene, 25 ppm, and palm carotene, 40 ppm, which includes 24 ppm β-carotene reducing the numbers of putative preneoplastic lesions of duct epithelial hyperplasia and atypical hyperplasia, as well as carcinoma in situ and invasive carcinomas. GTP at doses of 500 and 5000 ppm, but not 100 ppm, also significantly decreased the numbers of hyperplasia and total duct lesions. Combined administration of 40 ppm palm carotene, and 50 ppm GTP similarly inhibited the lesion development. α-Carotene, however, did not affect pancreatic carcinogenesis. The results suggest that chemopreventive effects are exerted by β-carotene and GTP above critical doses and that combined administration of palm carotene and GTP might be a candidate chemoprevention strategy for pancreatic cancer in humans.

ISSN:0885-3177    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Adenocarcinoma of the pancreas is currently the fifth leading cause of death in the United States. It remains generally incurable by available treatment modalities. We report here on the characterization of a permanent pancreatic cell line (KCI-MOHl), established as a xenograft in severe combined immune deficient (SCID) mice, from a 74 year-old African American male patient diagnosed with pancreatic cancer. Sections from paraffin-embedded tumors excised from SCID mice revealed typical adenocarcinoma of the pancreas. Karyotypic analysis of cultured cells derived from tumors grown in SCID mice revealed a male karyotype with multiple clonal aberrations: 42, XY, add (3)(p11.2), der(7) t(7;12) (p22;q12), -10, -12, add (14)(p11), -18, add (20)(q13)-22/84, idemx2. Immunostaining of KCI-MOH1 tissues shows strong expression of p53 and p21 proteins. The xenograft model was established by transplanting the KCI-MOHI cells subcutaneously (sc) in SCID mice. When the sc tumor was transplanted in vivo to other SCID mice, the success rate was 100%, with a doubling time of 8.5 days. The SCID mouse xenograft model was used to test the efficacy of selected standard chemotherapeutic drugs (taxol, gemcitabine, 5-fluorouracil, and Ara-C) and novel biological agents (Bryostatin 1 and Auristatin-PE). Results show that gemcitabine, Ara-C, and Bryostatin I were active against KCI-MOH1. The xenograft described herein can be used as an animal model to facilitate the development of novel therapeutic agents against human pancreatic cancers.

ISSN:0885-3177    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

We describe our experience with color Doppler ultrasonography (CDU) in the preoperative staging of pancreatic cancer and, particularly, in detecting the involvement of the portal-mesenteric trunk (PMT). Of the 54 patients studied, 43 (79.6%) underwent surgery and 11 (20.4%) did not because of evident infiltration of the PMT. Of the 43 patients operated on, the CDU study was normal in 8 cases (1 8.6%), abnormal in 33 (76.7%), and not possible in the remaining 2 cases (4.7%). Results of the CDU were confirmed intraoperatively in 39 cases (diagnostic accuracy, 95.1%). In only two cases (4.9%) did the CDU not show involvement of the PMT, which was, instead, demonstrated by intraoperative ultrasonography (false negatives). Of the 11 nonoperated patients, all showed morphological alterations at CDU, while only 7 showed hematic flow changes. The sensitivity of CDU was 94.2% and the specificity 100%. The positive predictive value was 100%; the negative predictive value, 75%. The results indicate that CDU may be the first imaging technique for preoperative assessment of PMT involvement in pancreatic cancer.

ISSN:0885-3177    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Thirty-six patients with pancreatic head carcinoma entered a protocol, but only 20 were suitable for resection and evaluation of long-term survival. They were nine males and 11 females, with a mean age of 64.3 years. Following surgical resection, 10 Gy was delivered to the tumor bed intraoperatively. Postoperative radiotherapy was performed 4–6 weeks after surgery: patients were treated with 50.4 Gy (1.8 Gy/day, 5 daydweek) to the tumor and nodal bed. Since 1991, 10 patients have also received preoperative short-course radiotherapy (5 Gy) of the liver and pancreas. Postoperative morbidity was 25%; two postoperative deaths were observed in patients with locally advanced neoplasms, in whom a vascular resection was also performed. Only 14 patients started postoperative radiotherapy, which was interrupted in two cases. At present, 14 patients are dead and four are alive and disease free. The local recurrence rate was 11.1% and distant metastases were observed in 66.7% of cases. The median actuarial survival was 11.9 months, but it was 18.5 months in patients with disease-free resection margins. A significantly better survival was also observed in patients submitted to short-course preoperative radiotherapy. These preliminary results show that intraoperative and perioperative radiotherapy is feasible and may improve local control of disease. Unfortunately, these results are not matched by a significant improvement in survival due to the high incidence of intraabdominal metastases. Thus, new therapeutic modalities, including preoperative radiotherapy (with or without chemotherapy), should be tested.

ISSN:0885-3177    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Seven cases of pancreatic serous cystadenoma were examined immunohistochemically and molecular biologically. Six were benign tumors and one was clinically malignant. Immunohistochemical studies were performed with the avidin-biotin peroxidase complex technique on paraffinembedded tumor tissue and were stained with antibody to carcinoembryonic antigen (CEA), CA19-9, and p53 protein. Twostage polymerase chain reaction-restriction fragment length polymorphism analysis was used to detect K-ras oncogene mutation at codon 12. No tumor cells were stained with anti-CEA and anti-p53 protein, but two cases were stained focally with anti-CA19-9. One case was benign and one was clinically malignant. In the anti-CA19-9 staining, tumor cells of the benign case were positive only on the apical membrane and supranuclear cytoplasm of the cells, whereas those of the clinically malignant case were positive over the entire surface and cytoplasm of the cells. All seven cases were without K-rasgene mutation. So the features of serous cystadenoma of the pancreas suggest a tumor genesis different from that of ductal adenocarcinoma. They also suggest a relationship between immunohistochemical localizations of CA 19-9 in the tumor cells and the biological behavior of the tumor itself.

ISSN:0885-3177    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The clinical value of amylase and lipase measurement for the diagnosis of acute pancreatitis was evaluated in 253 patients presenting with acute abdominal pain. Acute pancreatitis was detected in 32 patients by computed tomography or ultrasound. In the serum samples collected on days 0–1 after the onset of symptoms, lipase was elevated in 100% and amylase in 95%. A 95% sensitivity/specificity was reached at a lipase cutoff near twofold above normal. The receiveroperating characteristics (ROC) showed similar curves for both enzymes, lipase being slightly superior to amylase. The ROC curves from days 2–3 demonstrated a much lower sensitivity/specificity of both enzymes. Lipase, however, was notably superior to amylase: at a sensitivity of 85% the specificity of lipase (amylase) was 82% (68%). In samples from days 4–5 the accuracy of the enzyme assays was even worse; at a sensitivity of 60% the specificity did not increase above 70%. The diagnostic value of simultaneous measurement of amylase and lipase was tested at different cutoffs in two groups: the OR group, in which one of the two parameters had to be elevated, and the AND group, in which both parameters had to be above normal. Combination of both parameters mainly improved the specificity of the assay (from 91 to 98% on days 2–3 and from 93 to 97% on day 4–5) but only when, in the OR group, twofold elevated amylase was combined with lipase. We conclude that the simultaneous determination of serum lipase and amylase marginally improved the diagnosis of acute pancreatitis in patients with acute abdominal pain, however, the sensitivity of the assay with samples collected 4–5 days after onset of the disease remained low.

ISSN:0885-3177    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

In view of the reported association of insulin-dependent diabetes mellitus (IDDM) with viral infections, (non-) islet-specific immune changes, and partial immunodeficiencies, we used immunonephelometry to measure circulating levels of IgM, IgG, and IgA in a registry-based group of IDDM patients under age 40 years at clinical onset (n= 397) and in age-matched nondiabetic siblings (n= 316) and control subjects (n= 322). Overall, IgM and IgA concentrations were higher, and IgG concentrations lower, in patients than in control subjects or siblings (P<0.001). In siblings, IgM concentrations were higher than in control subjects (P<0.001). Using age-adjusted reference intervals, abnormal Ig concentrations were noted in 27% of the patients at onset versus only 10% of the siblings and 7% of the control subjects (P<0.001). For onset between 20 and 40 years (n= 220), 30% of the patients presented either increased IgM levels (21 %) or decreased IgG levels (11 %). Both independent phenomena occurred regardless of diabetes-associated immune and genetic markers. In patients and siblings, IgM levels were positively correlated with pancreatic lipase activity. In diabetic children (0–9 years;n= 65), a subgroup presented increased IgA levels (15%) in association with the highest HLA DQ-linked genetic risk and elevated IgM levels. The changes in total Ig concentrations at onset were largely reversed under insulin therapy. They may reflect exposure to environmental triggers, such as viral infections, or to (relative) insulinopenia prior to clinical disease onset. Whatever their cause, different serum Ig levels exist in different age groups of recent-onset IDDM patients.

ISSN:0885-3177    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

We evaluated, from 96 postmortem angiographs, the main feeding arteries and degree of vascularity of the pancreas to discover to what extent atherosclerosis affects pancreatic blood supply in subjects with and without non-insulin-dependent diabetes mellitus (NIDDM). Patients with NIDDM more often showed intrapancreatic arteries with irregularities in the body-tail of the pancreas (p= 0.050) and more frequently demonstrated decreased vascularity in both the body-tail and the head of the pancreas (p<0.001) than did the controls. When the arterial system from the aorta to the intrapancreatic branches was examined as a whole, 26 (58%) of the NIDDM patients and 10 (20%) of the controls 0, = 0.0001) showed one or more of the following: >50% stenosis in the celiac or splenic artery, two or more irregular intrapancreatic branches, or a distinctly decreased degree of vascularity in the body-tail portion of the pancreas, the region responsible for most insulin secretion. Only 1 NIDDM patient, compared to 10 controls, showed a totally normal angiogram. In conclusion, vascular disease in the feeding arteries of the pancreas is more common in NIDDM patients than age- and gender-matched controls.

ISSN:0885-3177    

出版商:OVID    

年代:1998

数据来源: OVID