145 results on '"Cleary, K. R."'
Search Results
2. Metastatic behavior and cell surface properties of HT-29 human colon carcinoma variant cells selected for their differential expression of sialyl-dimeric Lex antigen
- Author
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Matsushita, Y., Hoff, S. D., Nudelman, E. D., Otaka, M., Hakomori, S., Ota, D. M., Cleary, K. R., and Irimura, T.
- Published
- 1991
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3. Survival following pancreaticoduodenectomy with resection of the superior mesenteric-portal vein confluence for adenocarcinoma of the pancreatic head
- Author
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LEACH, S. D., LEE, J. E., CHARNSANGAVEJ, C., CLEARY, K. R., LOWY, A. M., FENOGLIO, C. J., PISTERS, P. W. T., and EVANS, D. B.
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- 1998
4. Intraductal papillary mucinous neoplasm of the pancreas: Importance of accurate histologic evaluation
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Raut, C. P., Cleary, K. R., Pisters, P. W., Vauthey, J. N., Lee, J. E., and Evans, D. B.
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- 2004
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5. Arterial Therapy in the Management of Resectable and Nonresectable Metastatic Colorectal Cancer in the Liver
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Patt, Y. Z., primary, Boddie, A. W., additional, Charnsangavej, C., additional, Mavligit, G. M., additional, Cleary, K. R., additional, Soski, M., additional, Claghorn, L., additional, and Wallace, S., additional
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- 1988
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6. Multiparametric in situ mRNA hybridization analysis to predict disease recurrence in patients with colon carcinoma
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Kitadai, Y., Ellis, L. M., Tucker, S. L., Greene, G. F., Bucana, C. D., Cleary, K. R., Takahashi, Y., Tahara, E., and Fidler, I. J.
- Subjects
Predictive Value of Tests ,Recurrence ,Carcinoma ,Colonic Neoplasms ,Humans ,RNA, Messenger ,RNA, Neoplasm ,In Situ Hybridization ,Research Article - Abstract
We examined the expression level of several genes that regulate different steps of metastasis in formalin-fixed, paraffin-embedded archival specimens of primary human colon carcinomas from patients with at least 5 years of follow-up. The expression of epidermal growth factor receptor, basic fibroblast growth factor, type IV collagenase, E-cadherin, and multidrug resistance (mdr-1) was examined by a colorimetric in situ mRNA hybridization technique concentrating on reactivity at the periphery of the neoplasms. The in situ hybridization technique revealed inter- and intratumor heterogeneity for expression of the metastasis-related genes. The expression of basic fibroblast growth factor, collagenase type IV, epidermal growth factor receptor, and mdr-1 mRNA was higher in Dukes's stage D than in Dukes' stage B tumors. Among the 22 Dukes' stage B neoplasms, 5 specimens exhibited a high expression level of epidermal growth factor receptor, basic fibroblast growth factor, and collagenase type IV. Clinical outcome data (5-year follow-up) revealed that all 5 patients with Dukes' stage B tumors developed distant metastasis (recurrent disease), whereas the other 17 patients with Dukes' stage B tumors expressing low levels of the metastasis-related genes were disease-free. Multivariate analysis identified high levels of expression of collagenase type IV and low levels of expression of E-cadherin as independent factors significantly associated with metastasis or recurrent disease. More specifically, metastatic or recurrent disease was associated with a high ratio (> 1.35) of expression of collagenase type IV to E-cadherin (specificity of 95%). Collectively, the data show that multiparametric in situ hybridization analysis for several metastasis-related genes may predict the metastatic potential, and hence the clinical outcome, of individual lymph-node-negative human colon cancers.
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- 1996
7. Loci for efficient detection of microsatellite instability in hereditary non-polyposis colorectal cancer.
- Author
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Frazier, M L, primary, Sinicrope, F A, additional, Amos, C I, additional, Cleary, K R, additional, Lynch, P M, additional, Levin, B, additional, and Luthra, R, additional
- Published
- 1999
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8. Rapid-fractionation preoperative chemoradiation, pancreaticoduodenectomy, and intraoperative radiation therapy for resectable pancreatic adenocarcinoma.
- Author
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Pisters, P W, primary, Abbruzzese, J L, additional, Janjan, N A, additional, Cleary, K R, additional, Charnsangavej, C, additional, Goswitz, M S, additional, Rich, T A, additional, Raijman, I, additional, Wolff, R A, additional, Lenzi, R, additional, Lee, J E, additional, and Evans, D B, additional
- Published
- 1998
- Full Text
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9. An Unusual Metastasis to the Thumb in a Laryngectomized Tracheoesophageal Speaker
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Lewin, J. S., primary, Cleary, K. R., additional, and Eicher, S. A., additional
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- 1997
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10. Preoperative and postoperative chemoradiation strategies in patients treated with pancreaticoduodenectomy for adenocarcinoma of the pancreas.
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Spitz, F R, primary, Abbruzzese, J L, additional, Lee, J E, additional, Pisters, P W, additional, Lowy, A M, additional, Fenoglio, C J, additional, Cleary, K R, additional, Janjan, N A, additional, Goswitz, M S, additional, Rich, T A, additional, and Evans, D B, additional
- Published
- 1997
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11. Platelet-Derived Endothelial Cell Growth Factor in Human Colon Cancer Angiogenesis: Role of Infiltrating Cells
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Takahashi, Y., primary, Bucana, C. D., additional, Liu, W., additional, Yoneda, J., additional, Kitadai, Y., additional, Cleary, K. R., additional, and Ellis, L. M., additional
- Published
- 1996
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12. Letters to the editor
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Lehrer, Steven, primary, Levine, Eva, additional, Savoretti, Penny, additional, Cropley, Joan, additional, Song, Hee Kyung, additional, Mandell, Lynda R., additional, Shank, Brenda, additional, Heffner, Dennis K., additional, Mc, Cap T., additional, Seider, M. J., additional, Cleary, K. R., additional, Fuller, L. M., additional, Clark, R. M., additional, Pasquier, Basile, additional, Marc'Hadour, Francois Le, additional, Dieny, Anne, additional, and Pasquier, Dominique, additional
- Published
- 1991
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13. The Association of Shiga Toxin and Other Cytotoxins with the Neurologic Manifestations of Shigellosis
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Ashkenazi, S., primary, Cleary, K. R., additional, Pickering, L. K., additional, Murray, B. E., additional, and Cleary, T. G., additional
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- 1990
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14. Plasma cell granuloma of the nasal cavity treated by radiation therapy.
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Seider, Michael J., Frias, Antonio, Fuller, Lillian M., Cleary, Karen R., Van Tassel, Pamela, Alexanian, Raymond, Schantz, Stimson P., Seider, M J, Cleary, K R, van Tassel, P, Alexanian, R, Schantz, S P, Frias, A, and Fuller, L M
- Published
- 1991
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15. Sarcomatoid carcinoma of the stomach. A report of three cases with immunohistochemical and ultrastructural observations.
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Robey-Cafferty, Susan S., Grignon, David J., Ro, Jae Y., Cleary, Karen R., Ayala, Alberto G., Ordonez, Nelson G., Mackay, Bruce, Robey-Cafferty, S S, Grignon, D J, Ro, J Y, Cleary, K R, Ayala, A G, Ordonez, N G, and Mackay, B
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- 1990
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16. Adjuvant perioperative hepatic arterial mitomycin C and floxuridine combined with surgical resection of metastatic colorectal cancer in the liver.
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Patt, Yehuda Z., McBride, Charles M., Ames, Frederick C., Claghorn, Laura J., Cleary, Karen R., Boddie, Arthur W., Charnsangavej, Chusilp, Mavligit, Giora M., Patt, Y Z, McBride, C M, Ames, F C, Claghorn, L J, Cleary, K R, Boddie, A W, Charnsangavej, C, and Mavligit, G M
- Published
- 1987
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17. Overexpression of elongation factor-1gamma protein in colorectal carcinoma.
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Mathur, Sandip, Cleary, Karen R., Inamdar, Nikhil, Kim, Yeul Hong, Steck, Peter, Frazier, Marsha L., Mathur, S, Cleary, K R, Inamdar, N, Kim, Y H, Steck, P, and Frazier, M L
- Published
- 1998
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18. Preoperative Chemoradiation for Adenocarcinoma of the Pancreas: Excessive Toxicity of Prophylactic Hepatic Irradiation
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Evans, D. B., Abbruzzese, J. L., Cleary, K. R., Buchholz, D. J., Fenoglio, C. J., Collier, C., and Rich, T. A.
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- 1995
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19. Vessel counts and vascular endothelial growth factor expression in pancreatic adenocarcinoma
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Ellis, L. M., Takahashi, Y., Fenoglio, C. J., Cleary, K. R., Bucana, C. D., and Evans, D. B.
- Published
- 1998
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20. Preoperative Chemoradiation, Pancreaticoduodenectomy, and Intraoperative Radiation Therapy for Adenocarcinoma of the Pancreatic Head
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Staley, C. A., Lee, J. E., Cleary, K. R., Abbruzzese, J. L., Fenoglio, C. J., Rich, T. A., and Evans, D. B.
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- 1996
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21. Neoadjuvant Chemoradiation for Extrahepatic Cholangiocarcinoma
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McMasters, K. M., Tuttle, T. M., Leach, S. D., Rich, T., Cleary, K. R., Evans, D. B., and Curley, S. A.
- Published
- 1997
- Full Text
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22. Traumatic neuroma of the bile duct causing cholangitis and atrophy of the right hepatic lobe.
- Author
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SHUMATE, CHARLES R., CURLEY, STEVEN A., CLEARY, KAREN R., AMES, FREDERICK C., Shumate, C R, Curley, S A, Cleary, K R, and Ames, F C
- Published
- 1992
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23. Thin-Section Contrast-Enhanced Computed Tomography Accurately Predicts the Resectability of Malignant Pancreatic Neoplasms
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Fuhrman, G. M., Charnsangavej, C., Abbruzzese, J. L., and Cleary, K. R.
- Published
- 1994
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24. Induction of ductal and stromal hyperplasia by basic fibroblast growth factor produced by human pancreatic carcinoma.
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Kuniyasu H, Abbruzzese JL, Cleary KR, and Fidler IJ
- Subjects
- Adenocarcinoma surgery, DNA Primers chemistry, DNA Probes, Fibroblast Growth Factor 2 genetics, Fibrosis, Humans, Hyperplasia, In Situ Hybridization, Mitotic Index, Neoplasm Staging, Pancreatic Ducts metabolism, Pancreatic Neoplasms surgery, Proliferating Cell Nuclear Antigen metabolism, RNA, Messenger metabolism, Stromal Cells metabolism, Tumor Cells, Cultured pathology, Adenocarcinoma metabolism, Fibroblast Growth Factor 2 metabolism, Pancreatic Ducts pathology, Pancreatic Neoplasms metabolism, Stromal Cells pathology
- Abstract
A histopathology study of 22 pancreatic adenocarcinoma cases revealed that 13 of the patients presented with hyperplastic lesions (atypical and non-atypical hyperplasia, mucous cell hypertrophy, focal epithelial hyperplasia, and ductal papillary hyperplasia), and 9 exhibited fibrosis adjacent to the carcinoma. All lesions expressed high levels of epidermal growth factor receptor (EGF-R) (p<0.0001 and p=0.0008, respectively) as compared with normal ductal epithelium. Non-atypical and atypical hyperplastic lesions also had a higher proliferating cell nuclear antigen (PCNA) labeling index (p<0.001 and p=0.0008, respectively) than normal ductal epithelium. A gradient in PCNA+ nuclei was found in acinar cells adjacent to the tumors. In 16 cases with marked fibrosis, we observed a significant increase of PCNA+ nuclei in stromal fibroblasts (p=0.0041) and significant upregulation of basic fibroblast growth factor (bFGF) mRNA expression in adjacent tumor cells (p=0.0213). These data suggest that the production of bFGF by pancreatic cancer cells induces ductal and stromal hyperplasia of the pancreas.
- Published
- 2001
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25. Neoadjuvant chemoradiotherapy for adenocarcinoma of the pancreas: treatment variables and survival duration.
- Author
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Breslin TM, Hess KR, Harbison DB, Jean ME, Cleary KR, Dackiw AP, Wolff RA, Abbruzzese JL, Janjan NA, Crane CH, Vauthey JN, Lee JE, Pisters PW, and Evans DB
- Subjects
- Adenocarcinoma mortality, Adenocarcinoma surgery, Antineoplastic Agents therapeutic use, Chemotherapy, Adjuvant, Combined Modality Therapy methods, Deoxycytidine administration & dosage, Deoxycytidine analogs & derivatives, Female, Fluorouracil administration & dosage, Humans, Male, Middle Aged, Multivariate Analysis, Neoplasm Recurrence, Local epidemiology, Paclitaxel administration & dosage, Pancreatectomy adverse effects, Pancreatic Neoplasms mortality, Pancreatic Neoplasms surgery, Radiotherapy Dosage, Radiotherapy, Adjuvant, Survival Analysis, Treatment Outcome, Gemcitabine, Adenocarcinoma drug therapy, Adenocarcinoma radiotherapy, Pancreatic Neoplasms drug therapy, Pancreatic Neoplasms radiotherapy
- Abstract
Background: For patients with potentially resectable pancreatic cancer, the poor outcome associated with resection alone and the survival advantage demonstrated for combined-modality therapy have stimulated interest in preoperative chemoradiotherapy. The goal of this study was to analyze the effects of different preoperative chemoradiotherapy schedules, intraoperative radiation therapy, patient factors. and histopathologic variables on survival duration and patterns of treatment failure in patients who underwent pancreaticoduodenectomy for adenocarcinoma of the pancreatic head., Methods: Data on 132 consecutive patients who received preoperative chemoradiation followed by pancreaticoduodenectomy for adenocarcinoma of the pancreatic head between June 1990 and June 1999 were retrieved from a prospective pancreatic tumor database. Patients received either 45.0 or 50.4 Gy radiation at 1.8 Gy per fraction in 28 fractions or 30.0 Gy at 3.0 Gy per fraction in 10 fractions with concomitant infusional chemotherapy (5-fluorouracil, paclitaxel, or gemcitabine). If restaging studies demonstrated no evidence of disease progression, patients underwent pancreaticoduodenectomy. All patients were evaluated with serial postoperative computed tomography scans to document first sites of tumor recurrence., Results: The overall median survival from the time of tissue diagnosis was 21 months (range 19-26, 95%CI). At last follow-up, 41 patients (31%) were alive with no clinical or radiographic evidence of disease. The survival duration was superior for women (P = .04) and for patients with no evidence of lymph node metastasis (P = .03). There was no difference in survival duration associated with patient age, dose of preoperative radiation therapy, the delivery of intraoperative radiotherapy, tumor grade, tumor size, retroperitoneal margin status, or the histologic grade of chemoradiation treatment effect., Conclusion: This analysis supports prior studies which suggest that the survival duration of patients with potentially resectable pancreatic cancer is maximized by the combination of chemoradiation and pancreaticoduodenectomy. Furthermore, there was no difference in survival duration between patients who received the less toxic rapid-fractionation chemoradiotherapy schedule (30 Gy, 2 weeks) and those who received standard-fractionation chemoradiotherapy (50.4 Gy, 5.5 weeks). Short-course rapid-fractionation preoperative chemoradiotherapy combined with pancreaticoduodenectomy, when performed on accurately staged patients, maximizes survival duration and is associated with a low incidence of local tumor recurrence.
- Published
- 2001
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26. Phase I study of preoperative oral uracil and tegafur plus leucovorin and radiation therapy in rectal cancer.
- Author
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Hoff PM, Janjan N, Saad ED, Skibber J, Crane C, Lassere Y, Cleary KR, Benner S, Randolph J, Abbruzzese JL, and Pazdur R
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- Administration, Oral, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Combined Modality Therapy, Drug Administration Schedule, Female, Humans, Leucovorin administration & dosage, Leucovorin adverse effects, Male, Middle Aged, Postoperative Care, Preoperative Care, Rectal Neoplasms drug therapy, Rectal Neoplasms radiotherapy, Rectal Neoplasms surgery, Surgical Procedures, Operative, Tegafur administration & dosage, Tegafur adverse effects, Uracil administration & dosage, Uracil adverse effects, Antineoplastic Combined Chemotherapy Protocols adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Rectal Neoplasms therapy
- Abstract
Purpose: Preoperative combined-modality therapy for rectal cancer may allow for sphincter preservation, while decreasing recurrence rates and improving the overall prognosis. Oral chemotherapy with uracil and tegafur (UFT) plus leucovorin (LV) may reduce costs and complications associated with protracted infusions of fluorouracil. Our goal was to evaluate the safety of UFT plus LV combined with preoperative radiation and determine the maximum-tolerated dose (MTD) and dose-limiting toxicity (DLT) of UFT plus LV in this setting., Patients and Methods: Patients with tumor-node-metastasis stage II or III rectal cancer received escalating doses of UFT (starting at 250mg/m(2)/d, with 50-mg/m(2)/d increments between consecutive cohorts) and fixed doses of LV (90 mg/d). The UFT and LV combination was given 5 days per week concurrently with a 5-week course of preoperative radiation totaling 45 Gy (1.8 Gy/fraction). Surgery was performed 4 to 6 weeks after radiation and was followed by four 35-day cycles of fixed doses of UFT and LV (28 days of therapy each cycle)., Results: Fifteen patients were treated, and 13 received the full preoperative chemotherapy. All planned radiation was delivered successfully. The MTD of UFT with radiation was 350 mg/m(2)/d with 90 mg/d of LV. Diarrhea was the DLT. Sphincter-preserving surgery was performed in 12 of 14 patients. One patient had progressive disease before surgery. Pathologic evaluation of 14 resected specimens showed a complete response in three cases., Conclusion: Preoperative chemoradiation with oral UFT plus LV is feasible and well tolerated and should be further investigated.
- Published
- 2000
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27. Human pancreatic ribonuclease 1: expression and distribution in pancreatic adenocarcinoma.
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Peracaula R, Cleary KR, Lorenzo J, de Llorens R, and Frazier ML
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- Adenocarcinoma pathology, Adult, Aged, Antibodies, Carcinoma, Pancreatic Ductal pathology, Chronic Disease, Female, Humans, Immunohistochemistry, In Situ Hybridization, Liver Neoplasms enzymology, Liver Neoplasms secondary, Lymphatic Metastasis, Male, Middle Aged, Pancreas enzymology, Pancreatic Neoplasms pathology, Pancreatitis enzymology, Ribonuclease, Pancreatic biosynthesis, Ribonuclease, Pancreatic immunology, Risk Factors, Adenocarcinoma enzymology, Carcinoma, Pancreatic Ductal enzymology, Pancreatic Neoplasms enzymology, Ribonuclease, Pancreatic metabolism
- Abstract
Background: Human pancreatic ribonuclease (RNase 1) is a pancreatic enzyme that is present at high levels in the serum of most patients with pancreatic adenocarcinoma. For this reason, the authors studied its patterns of expression at the single-cell level in pancreatic adenocarcinoma tissues by immunohistochemical analysis and in situ hybridization (ISH)., Methods: Immunohistochemical analysis with polyclonal antibodies against RNase 1 and by ISH with digoxigenin-labeled RNase 1 probe were used to detect RNase 1 in the neoplastic cells of ductal type pancreatic adenocarcinomas., Results: Fifteen of 18 carcinoma samples were positive for RNase 1, demonstrating that the expression of ribonuclease that the authors observed previously in human pancreatic adenocarcinoma cell lines was not an artifact of cell culture. The authors also found RNase 1 in some of the metaplastic ducts and atrophic islets in 4 of 6 chronic pancreatitis samples, and they observed RNase 1 immunostaining in hyperplastic ducts adjacent to one of the well-differentiated adenocarcinomas., Conclusions: The expression levels of RNase 1 by tumor cells from pancreatic adenocarcinomas are consistent with the high RNase 1 levels found in the serum of most patients with pancreatic adenocarcinoma. This expression of RNase 1, which is an acinar protein, demonstrates that the patterns of gene expression in pancreatic adenocarcinoma are distinct from those of normal pancreatic duct cells. Conversely, RNase 1 expression levels in altered ductal cells from some chronic pancreatitis tissues and hyperplastic ducts from carcinoma tissues suggest that abnormal expression levels may be an early event in pancreatic tumorigenesis., (Copyright 2000 American Cancer Society.)
- Published
- 2000
28. Reduced expression of cyclooxygenase 2 proteins in hereditary nonpolyposis colorectal cancers relative to sporadic cancers.
- Author
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Sinicrope FA, Lemoine M, Xi L, Lynch PM, Cleary KR, Shen Y, and Frazier ML
- Subjects
- Adenomatous Polyposis Coli enzymology, Blotting, Western, Cyclooxygenase 2, Cyclooxygenase 2 Inhibitors, Cyclooxygenase Inhibitors pharmacology, Humans, Immunohistochemistry, Isoenzymes drug effects, Isoenzymes immunology, Membrane Proteins, Mutation, Prostaglandin-Endoperoxide Synthases drug effects, Prostaglandin-Endoperoxide Synthases immunology, Receptors, Transforming Growth Factor beta genetics, Tumor Cells, Cultured, Colorectal Neoplasms, Hereditary Nonpolyposis enzymology, Isoenzymes analysis, Prostaglandin-Endoperoxide Synthases analysis
- Abstract
Background & Aims: Cyclooxygenase (COX) enzymes catalyze the conversion of arachidonic acid to prostaglandins. Evidence suggests that nonsteroidal anti-inflammatory drugs reduce the risk of colorectal cancer (CRC) and that this effect is mediated through COX inhibition. We analyzed and compared expression of the inducible COX-2 isoform in colorectal neoplasms from patients with hereditary nonpolyposis colorectal cancer (HNPCC), familial adenomatous polyposis (FAP), and sporadic CRC. Given that COX-2 is induced by transforming growth factor (TGF)-beta and that TGF-beta type II receptor (RII) mutations are found in HNPCCs, we determined the relationship between RII status and COX-2 expression., Methods: COX-2 protein expression was determined in colorectal epithelia using immunohistochemistry and Western blotting. Patients with HNPCC had known mutations in hMLH1 or hMSH2 genes and/or met the Amsterdam criteria. In CRCs from HNPCC cases, mutations were sought in the coding region of the RII gene using the polymerase chain reaction., Results: COX-2 was detected in adenomas from 2 of 3 HNPCC, 6 of 7 FAP, and 5 of 8 sporadic cases. In CRCs, COX-2 staining was found in 16 of 24 (67%) HNPCC vs. 24 of 26 (92%) sporadic cases (P = 0.035) and in 2 of 2 FAP cases. Staining intensity was reduced in HNPCCs compared with sporadic CRCs (P = 0.035). Staining localized to the cytoplasm of neoplastic cells; normal epithelial cells were negative for COX-2. Overexpression of COX-2 in CRCs relative to normal mucosa was confirmed by Western blotting. TGF-beta RII mutations were detected in 12 of 14 HNPCCs examined, including 3 of 4 COX-2-negative and 9 of 10 COX-2-positive cancers., Conclusions: The frequency and intensity of COX-2 expression was significantly reduced in HNPCCs relative to sporadic CRCs, and was not a consequence of RII mutations. Given that many HNPCCs express COX-2, inhibition of this enzyme may be an important strategy to prevent CRC in these patients.
- Published
- 1999
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29. Tumor downstaging and sphincter preservation with preoperative chemoradiation in locally advanced rectal cancer: the M. D. Anderson Cancer Center experience.
- Author
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Janjan NA, Khoo VS, Abbruzzese J, Pazdur R, Dubrow R, Cleary KR, Allen PK, Lynch PM, Glober G, Wolff R, Rich TA, and Skibber J
- Subjects
- Adult, Aged, Aged, 80 and over, Antimetabolites, Antineoplastic therapeutic use, Combined Modality Therapy, Disease-Free Survival, Female, Fluorouracil therapeutic use, Humans, Lymphatic Metastasis pathology, Male, Middle Aged, Neoplasm, Residual, Radiotherapy Dosage, Rectal Neoplasms mortality, Rectal Neoplasms pathology, Rectal Neoplasms surgery, Anal Canal, Neoplasm Staging, Rectal Neoplasms drug therapy, Rectal Neoplasms radiotherapy
- Abstract
Purpose: To evaluate the rates of tumor downstaging after preoperative chemoradiation for locally advanced rectal cancer., Materials and Methods: Preoperative chemoradiotherapy (CTX/XRT) that delivered 45 Gy in 25 fractions over 5 weeks with continuous infusion 5-fluorouracil (300 mg/m2/day) was given to 117 patients. The pretreatment stage distribution, as determined by endorectal ultrasound (u), included uT2N0 in 2%, uT3N0 in 47%, uT3N1 in 49%, and uT4N0 in 2% of cases; endorectal ultrasound was not performed in 13% of cases (15 patients). Approximately 6 weeks after completion of CTX/XRT, surgery was performed., Results: The pathological tumor stages were Tis-2N0 in 26%, T2N1 in 5%, T3N0 in 21%, T3N1 in 15%, T4N0 in 5%, and T4NI in 1%; a complete response (CR) to preoperative CTX/XRT was pathologically confirmed in 32 (27%) of patients. Tumor downstaging occurred in 72 (62%) cases. Only 3% of cases had pathologic evidence of progressive disease. Pretreatment tumor size (< 5 cm vs. > or = 5 cm) was the only factor predictive of tumor downstaging (p < 0.04). A decrease of > 1 T-stage level was accomplished in 45% of those downstaged. Overall, a sphincter-saving (SP) procedure was possible in 59% of patients and an abdominoperineal resection (APR) was required in 41 % of cases. Factors predictive of SP included downstaging (p < 0.03), age > 40 years (p < 0.007), pretreatment tumor distance, 3 to 6 cm from the anal verge (p < 0.00001), tumor size <6 cm (p < 0.02), mobility (p < 0.004), tumor stage
6 cm from the anal verge, SP was performed in 14 of the 15 (93%) patients with a CR and 32 of 33 (97%) of patients with residual disease (p < 0.00004)., Conclusions: Significant tumor downstaging results from preoperative chemoradiation allowing sphincter sparing surgery in over 40% of patients whose tumors were located < 6 cm from the anal verge and who otherwise would have required colostomy. - Published
- 1999
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30. Prognostic factors in resectable pancreatic cancer: p53 and bcl-2.
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Bold RJ, Hess KR, Pearson AS, Grau AM, Sinicrope FA, Jennings M, McConkey DJ, Bucana CD, Cleary KR, Hallin PA, Chiao PJ, Abbruzzese JL, and Evans DB
- Subjects
- Adenocarcinoma pathology, Analysis of Variance, Apoptosis genetics, Cell Cycle genetics, Cell Nucleus ultrastructure, Coloring Agents, Combined Modality Therapy, Female, Forecasting, Gene Expression Regulation, Neoplastic genetics, Genes, bcl-2 genetics, Genes, p53 genetics, Humans, Immunohistochemistry, Male, Middle Aged, Multivariate Analysis, Neoplasm Staging, Pancreatic Neoplasms pathology, Pancreaticoduodenectomy, Prognosis, Prospective Studies, Proto-Oncogene Mas, Survival Rate, Adenocarcinoma surgery, Biomarkers, Tumor analysis, Pancreatic Neoplasms surgery, Proto-Oncogene Proteins c-bcl-2 analysis, Tumor Suppressor Protein p53 analysis
- Abstract
The p53 tumor suppressor gene and the Bcl-2 proto-oncogene regulate cell cycle progression and apoptosis. We evaluated the expression of these molecular markers with standard pathologic prognostic variables in patients who received multimodality therapy for resectable adenocarcinoma of the pancreas to study the effect of p53 and Bcl-2 on survival duration. Immunohistochemical staining of archival material was performed to determine levels of expression of p53 and Bcl-2 proteins in 70 patients with adenocarcinoma of pancreatic origin. All patients underwent a potentially curative pancreaticoduodenectomy and standardized pathologic analysis of resected specimens. Potential pathologic and molecular prognostic variables were assessed for their effect on survival duration. Nuclear staining for p53 was observed in 33 (47%) of 70 specimens. Immunostaining for Bcl-2 was observed in 23 specimens (33%). A trend toward improved survival duration was seen in patients whose tumors stained positive for either p53 or Bcl-2. Negative staining for both markers predicted short survival (P = 0.01). By univariate and multivariate analyses, no single pathologic factor was associated with survival duration. Immunohistochemical staging using both p53 and Bcl-2 significantly predicted survival duration by univariate and multivariate analysis; patients whose tumors stained positively for p53 and/or overexpressed Bcl-2 had a significantly longer survival than those whose tumors stained negative for both proteins.
- Published
- 1999
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31. Expression of interferon-beta is associated with growth arrest of murine and human epidermal cells.
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Bielenberg DR, McCarty MF, Bucana CD, Yuspa SH, Morgan D, Arbeit JM, Ellis LM, Cleary KR, and Fidler IJ
- Subjects
- Animals, Antibodies pharmacology, Calcium physiology, Carcinoma, Squamous Cell metabolism, Carcinoma, Squamous Cell pathology, Cell Differentiation, Cell Division physiology, Cells, Cultured, Fluorescent Antibody Technique, Humans, Immunohistochemistry, Interferon-beta immunology, Interferon-beta pharmacology, Interferon-beta physiology, Keratin-14, Keratinocytes cytology, Keratinocytes metabolism, Keratins biosynthesis, Membrane Proteins biosynthesis, Mice, Mice, Inbred BALB C, Mice, Transgenic, Skin Neoplasms metabolism, Skin Neoplasms pathology, Time Factors, Epidermal Cells, Epidermis metabolism, Interferon-beta biosynthesis
- Abstract
The cytokine interferon-beta is a regulator of cell replication and function, including invasion and induction of angiogenesis. The goal of this study was to determine whether the expression of interferon-beta by cells in the epidermis correlated with terminal differentiation. In situ hybridization analysis and immunohistochemical staining of formalin-fixed, paraffin-embedded specimens of normal human and murine epidermis and human and murine skin tumors of epithelial origin revealed that only differentiated, nondividing cells of the epidermis expressed interferon-beta protein. Keratinocyte cultures established from the epidermis of 3 d old mice were maintained under conditions permitting continuous cell division or induction of differentiation. Continuously dividing cells did not produce interferon-beta whereas nondividing differentiated cells expressing keratin 1 did. Growth-arrested, undifferentiated keratinocytes also expressed interferon-beta protein. Neutralizing interferon-beta in the culture medium inhibited differentiation, but the addition of exogenous interferon-beta did not stimulate differentiation. These data indicate that interferon-beta is produced by growth-arrested, terminally differentiated keratinocytes.
- Published
- 1999
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32. Major vascular resection as part of pancreaticoduodenectomy for cancer: radiologic, intraoperative, and pathologic analysis.
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Bold RJ, Charnsangavej C, Cleary KR, Jennings M, Madray A, Leach SD, Abbruzzese JL, Pisters PW, Lee JE, and Evans DB
- Subjects
- Adenocarcinoma diagnostic imaging, Adenocarcinoma pathology, Adenocarcinoma surgery, Carcinoma, Neuroendocrine diagnostic imaging, Carcinoma, Neuroendocrine pathology, Carcinoma, Neuroendocrine surgery, Contrast Media, Female, Forecasting, Hepatic Artery pathology, Hepatic Artery surgery, Humans, Intraoperative Care, Male, Mesenteric Artery, Superior pathology, Mesenteric Artery, Superior surgery, Mesenteric Veins pathology, Mesenteric Veins surgery, Middle Aged, Neoadjuvant Therapy, Neoplasm Invasiveness, Pancreas pathology, Pancreatic Neoplasms diagnostic imaging, Pancreatic Neoplasms pathology, Portal Vein pathology, Portal Vein surgery, Radiographic Image Enhancement, Survival Rate, Tomography, X-Ray Computed, Vena Cava, Inferior pathology, Vena Cava, Inferior surgery, Pancreas blood supply, Pancreatic Neoplasms surgery, Pancreaticoduodenectomy methods, Vascular Surgical Procedures
- Abstract
Intraoperative assessment is inaccurate in defining the relationship of a pancreatic head neoplasm to adjacent vascular structures. We evaluated the ability of preoperative contrast-enhanced CT to predict the need for vascular resection during pancreaticoduodenectomy and examined the resected vessels for histologic evidence of tumor invasion. During a 7-year period, 63 patients underwent pancreaticoduodenectomy with en bloc resection of adjacent vascular structures for a presumed pancreatic head malignancy. Clinical, radiologic, operative, and pathologic data were reviewed and analyzed. Fifty-six patients underwent resection of the superior mesenteric-portal vein confluence, three patients required inferior vena cava resection, and the hepatic artery was resected and reconstructed in eight patients. The operative mortality rate was 1.6%, and the overall complication rate was 22%. CT predicted the need for resection of the superior mesenteric or portal veins in 84% of patients. Pathologic analysis revealed tumor invasion of the vein wall in 71% of resected specimens. Tumor invasion of vascular structures adjacent to the pancreas can be predicted with preoperative CT and should alert the surgeon that vascular resection may be required. Histologic evidence of tumor cell infiltration of vessel walls was present in the majority of the resected specimens.
- Published
- 1999
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33. Sarcoidosis after surgically induced remission of Cushing's disease.
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Maldonado M, Orlander P, Roshan SY, McCutcheon IE, Cleary KR, and Friend KE
- Abstract
Objective: To describe a rare case of sarcoidosis diagnosed after surgical resection of an adenoma in a patient with Cushing's disease., Methods: We present a case report and discuss the only other similar case identified from the published medical literature., Results: In a 33-year-old woman with symptoms of cortisol excess (including progressive weight gain, proximal muscle weakness, ecchymoses, and amenorrhea), laboratory studies showed serum cortisol values consistent with Cushing's syndrome. After inferior petrosal sinus sampling, the patient underwent surgical resection of an adenoma in the right aspect of the anterior pituitary gland. Maintenance corticosteroid therapy was implemented, and the signs and symptoms of Cushing's disease began to resolve. Five months postoperatively, multiple erythematous lesions developed on the patient's arms and legs. Skin biopsy specimens demonstrated noncaseating granulomas, and sarcoidosis was diagnosed. Two months later, the lesions resolved spontaneously without therapy other than continued corticosteroid replacement., Conclusion: Physicians should be aware that unusual postoperative symptoms in a patient who has undergone successful treatment of Cushing's syndrome may be attributable to the emergence of another corticosteroid-responsive disease such as sarcoidosis.
- Published
- 1999
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34. The nuclear factor-kappa B RelA transcription factor is constitutively activated in human pancreatic adenocarcinoma cells.
- Author
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Wang W, Abbruzzese JL, Evans DB, Larry L, Cleary KR, and Chiao PJ
- Subjects
- Adenocarcinoma genetics, Adult, Amino Acid Sequence, Animals, Cricetinae, DNA, Neoplasm metabolism, Gene Expression Regulation, Neoplastic, Genes, ras, Humans, Immunohistochemistry, Mesocricetus, Molecular Sequence Data, Pancreatic Neoplasms genetics, Point Mutation, Transcription Factor RelA, Tumor Cells, Cultured, Adenocarcinoma metabolism, NF-kappa B metabolism, Pancreatic Neoplasms metabolism
- Abstract
Pancreatic adenocarcinoma is a leading cause of adult cancer mortality in the United States. Recent studies have revealed that point mutation of the K-ras oncogene is a common event in pancreatic cancer, and oncogenesis mediated by Ras may also involve activation of Rel/nuclear factor (NF)-kappa B transcription factors. Furthermore, the c-rel member of Rel/NF-kappa B transcription factor family was first identified as a cellular homologue of the v-rel oncogene, suggesting that other members of the Rel/NF-kappa B family are potentially oncogenes. We therefore investigated the possibility that Rel/NF-kappa B transcription factors are activated in pancreatic cancer. Immunohistochemical analysis, Western blot and Northern blot analysis, electrophoretic mobility shift assays, and chloramphenicol acetyltransferase assays were performed to determine RelA activity in human pancreatic adenocarcinomas and normal tissues and nontumorigenic or tumorigenic cell lines. RelA, the p65 subunit of NF-kappa B, was constitutively activated in approximately 67% (16 of 24) of pancreatic adenocarcinomas but not in normal pancreatic tissues. Constitutive RelA activity was also detected in 9 of 11 human pancreatic tumor cell lines but not in nontumorigenic Syrian golden hamster cell lines. I kappa B alpha, a previously identified NF-kappa B-inducible gene, was overexpressed in human pancreatic tumor tissues and cell lines, and RelA activation could be inhibited by curcumin and dominant-negative mutants of I kappa B alpha, raf, and MEKK1. This is the first report demonstrating constitutive activation of RelA in nonlymphoid human cancer. These data are consistent with the possibility that RelA is constitutively activated by the upstream signaling pathway involving Ras and mitogen-activated protein kinases in pancreatic tumor cells. Constitutive RelA activity may play a key role in pancreatic tumorigenesis through activation of its downstream target genes.
- Published
- 1999
35. Predictors of recurrence after local excision and postoperative chemoradiation therapy of adenocarcinoma of the rectum.
- Author
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Bouvet M, Milas M, Giacco GG, Cleary KR, Janjan NA, and Skibber JM
- Subjects
- Adenocarcinoma pathology, Adenocarcinoma surgery, Adult, Aged, Aged, 80 and over, Chemotherapy, Adjuvant, Disease-Free Survival, Female, Follow-Up Studies, Humans, Male, Middle Aged, Multivariate Analysis, Neoplasm Recurrence, Local pathology, Neoplasm Staging, Prognosis, Radiotherapy, Adjuvant, Rectal Neoplasms pathology, Rectal Neoplasms surgery, Risk Factors, Time Factors, Adenocarcinoma diagnosis, Neoplasm Recurrence, Local diagnosis, Postoperative Care, Rectal Neoplasms diagnosis
- Abstract
Background: Local excision of rectal cancer preserves anal continence, bladder function, and normal sexual function. However, local recurrence after excision remains a significant problem. To further define the indications for local excision, we analyzed possible factors predictive of recurrence after local excision of rectal cancer., Methods: The charts of all patients undergoing local excision of adenocarcinoma of the rectum between 1985 and 1995 at a single institution were reviewed. Patients with metastatic disease at the time of excision and patients treated preoperatively with chemoradiation therapy were excluded. All available slides were reviewed by a single pathologist, who assessed the depth of invasion; the presence or absence of vascular invasion, lymphatic invasion, perineural invasion, and lymphocytic infiltrate; the mucinous status; and the degree of differentiation. Using the log-rank test and Cox proportional hazards model, univariate and multivariate analyses were performed to identify predictors of recurrence., Results: Ninety patients underwent local excision, 46 transanally and 44 using a Kraske approach. The breakdown of patients by tumor stage was as follows: Tis, 13%; T1, 41%; T2, 30%; T3, 15%; and Tx, 1%. Sixty-eight percent of patients with T1 tumors were treated with postoperative radiotherapy; all patients with T2 or T3 tumors were treated postoperatively with or without 5-fluorouracil. The median duration of follow-up was 51 months. The median tumor diameter was 2.5 cm (range, 0.4 to 7 cm), and the median distance of the tumor from the anal verge was 4.5 cm (range, 1 to 10 cm). The 4-year actuarial local disease-free survival rate broken down by tumor stage was as follows: Tis, 100%; T1, 95%; T2, 80%; and T3, 73%. The median time to local recurrence was 23 months (range, 7 to 61 months). Multivariate analysis showed that only tumor stage and margin status were predictors of local recurrence., Conclusions: Local excision and postoperative radiotherapy result in adequate local control of early stage (Tis and T1) adenocarcinoma of the rectum. Higher rates of recurrence were seen in patients with T2 and T3 tumors, especially in those with positive margins.
- Published
- 1999
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36. Relative expression of E-cadherin and type IV collagenase genes predicts disease outcome in patients with resectable pancreatic carcinoma.
- Author
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Kuniyasu H, Ellis LM, Evans DB, Abbruzzese JL, Fenoglio CJ, Bucana CD, Cleary KR, Tahara E, and Fidler IJ
- Subjects
- Adenocarcinoma enzymology, Adenocarcinoma metabolism, Adenocarcinoma pathology, Cadherins genetics, Collagenases genetics, Gene Expression Regulation, Neoplastic, Humans, In Situ Hybridization, Matrix Metalloproteinase 9, Pancreatic Neoplasms enzymology, Pancreatic Neoplasms metabolism, Pancreatic Neoplasms pathology, Predictive Value of Tests, Prognosis, Adenocarcinoma genetics, Cadherins biosynthesis, Collagenases biosynthesis, Pancreatic Neoplasms genetics
- Abstract
We examined the expression level of several genes that regulate distinct steps of metastasis in formalin-fixed, paraffin-embedded, archival specimens of primary human pancreatic carcinomas from patients undergoing curative surgery. The expression of epidermal growth factor receptor, E-cadherin, type IV collagenase [matrix metalloproteinase (MMP) 2 and MMP-9), basic fibroblast growth factor, vascular endothelial growth factor/vascular permeability factor, and interleukin 8 was examined by a colorimetric in situ mRNA hybridization technique. Down-regulation of E-cadherin and up-regulation of type IV collagenase (MMP-9 and MMP-2) at the periphery of the neoplasms (P = 0.0167, 0.0102, and 0.0349, respectively) had significant prognostic value. The ratio of type IV collagenase expression (mean of the expression of MMP-2 and MMP-9) to E-cadherin expression (MMP:E-cadherin ratio) at the periphery of the tumors was significantly higher in patients with recurrent disease (4.7 +/- 2.1) than in patients who were disease free (2.3 +/- 1.7; P = 0.0008). Death from pancreatic cancer was significantly associated with a high MMP:E-cadherin ratio (>3.0) by overall survival analysis (P < 0.0002), whereas a low MMP:E-cadherin ratio (<3.0) was found in seven of eight patients alive 28-64 months after surgery. Multivariate analysis of overall survival showed that the MMP:E-cadherin ratio was a significant independent prognostic factor, whereas stage, nodal metastasis, and histological type were not. These data show that multiparametric analysis for several metastasis-related genes may allow physicians to assess the metastatic potential and hence predict the clinical outcome of individual patients with resectable pancreatic carcinoma.
- Published
- 1999
37. Experience implementing a DICOM 3.0 multivendor teleradiology network.
- Author
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Levine BA, Cleary KR, Norton GS, and Mun SK
- Subjects
- Computer Communication Networks, Computer Systems, Data Display, Humans, Lasers, Military Medicine, Printing, Radiography, Radiology Information Systems, Software, Systems Integration, Teleradiology instrumentation, Tomography, X-Ray Computed, Ultrasonography, United States, Teleradiology methods
- Abstract
Objective: The ISIS Center at Georgetown University received a grant from the U.S. Army to act as systems integrator for a project to design, develop, and implement a commercial off-the-shelf teleradiology system to support the U.S. troops in Bosnia-Herzegovina. The goal of the project was to minimize troop movement while providing primary diagnosis to military personnel. This paper focuses on Digital Imaging Communications in Medicine (DICOM) 3.0 related issues that arose from this type of teleradiology implementation. The objective is to show that using the DICOM standard provides a good starting point for systems integration but is not a plug-and-play operation., Methods: Systems were purchased that were based on the DICOM 3.0 standard. The modalities implemented in this effort were computed radiography (CR), computed tomography (CT), film digitization (FD), and ultrasonography (US). Dry laser printing and multiple-display workstations were critical components of this network. The modalities and output devices were integrated using the DICOM 3.0 standard. All image acquisition from the modalities is directly to a workstation. The workstation distributes the images to other local and remote workstations, to the dry laser printer, and to other vendors' workstations using the DICOM 3.0 standard. All systems were integrated and tested prior to deployment or purchase. Local and wide area networking were also tested prior to implementation of the deployable radiology network., Results: The results of the integration of the multivendor network were positive. Eventually, all vendors' systems did communicate. Software configuration and operational changes were made to many systems in order to facilitate this communication. Often, software fixes or patches were provided by a vendor to modify their DICOM 3.0 implementation to allow better communications with another vendor's system. All systems were commercially available, and any modifications or changes provided became part of the vendor's commercially available package., Conclusion: Seven DICOM interfaces were implemented for this project, and none was achieved without modification of configuration files, changes or patches in vendor software, or operational changes. Some of the problems encountered included missing or ignored required data elements, padding of data values, unique study identifiers (UID), and the use of application entity titles. The difficulties with multivendor connectivity lie in the understanding and interpretation of standards such as DICOM 3.0. The success of this network proves that these problems can be overcome and a clinically successful network implemented utilizing multiple vendors' systems.
- Published
- 1998
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38. p53, vessel count, and vascular endothelial growth factor expression in human colon cancer.
- Author
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Takahashi Y, Bucana CD, Cleary KR, and Ellis LM
- Subjects
- Adenoma blood supply, Adenoma metabolism, Colonic Neoplasms blood supply, Humans, Neoplasm Metastasis, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factors, Colonic Neoplasms metabolism, Endothelial Growth Factors metabolism, Lymphokines metabolism, Tumor Suppressor Protein p53 metabolism
- Abstract
We previously demonstrated an association between vascular endothelial growth factor (VEGF), vessel counts and metastasis in human colon cancer specimens. Mutant p53 has been implicated in the regulation of angiogenesis. Immuno-histochemical detection of p53 protein has been associated with p53 gene mutations. We sought to determine a correlation between p53 protein detection (i.e., mutant p53), VEGF expression and vessel counts in human colon cancer. Surgical specimens from 93 patients with colon cancer were stained immuno-histochemically for p53, VEGF and factor VIII. Vessel counts were greater in metastatic tumors than in nonmetastatic tumors and adenomas, and greater in nonmetastatic tumors than in adenomas. Vessel counts were highest in tumors with the highest VEGF expression. Vessel counts and VEGF expression were greater in p53-positive tumors than in p53-negative tumors. p53 expression correlated with both VEGF expression and vessel count. The association of p53 expression with VEGF and vessel count suggests that the poor prognosis associated with p53 mutations may be due, in part, to the role of mutant p53 in promoting angiogenesis.
- Published
- 1998
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39. Significance of platelet-derived endothelial cell growth factor in the angiogenesis of human gastric cancer.
- Author
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Takahashi Y, Bucana CD, Akagi Y, Liu W, Cleary KR, Mai M, and Ellis LM
- Subjects
- Adult, Aged, Endothelial Growth Factors biosynthesis, Female, Humans, Immunohistochemistry, Lymphokines biosynthesis, Male, Middle Aged, Neoplasm Staging, Stomach Neoplasms pathology, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factors, Neovascularization, Pathologic metabolism, Stomach Neoplasms blood supply, Thymidine Phosphorylase biosynthesis
- Abstract
We have previously shown that platelet-derived endothelial cell growth factor (PD-ECGF) is associated with angiogenesis of human colon cancer; this factor is expressed at high levels in vascular tumors that express low levels of vascular endothelial growth factor (VEGF). In these colon cancers, the major source of PD-ECGF is the infiltrating cells. In this study, we examined the role of PD-ECGF in the angiogenesis of human gastric cancer. Immunostaining for PD-ECGF was done on 93 gastric cancers previously stained for VEGF, basic fibroblast growth factor, and factor VIII-related antigen (specific for endothelial cells). To determine the cell type expressing PD-ECGF, double staining was done using antibodies to both PD-ECGF and CD68 (specific for macrophages). PD-ECGF was expressed more frequently in infiltrating cells (positive CD68 staining; 53.8%) than in tumor epithelium (9.7%; P < 0.0001). Infiltrating cells simultaneously stained positive for both PD-ECGF and CD68. An association between PD-ECGF expression in infiltrating cells, VEGF expression in tumor epithelium, and vessel count was observed in intestinal-type gastric cancer but not in diffuse-type gastric cancer. Vessel count was greater in tumors with high expression of both PD-ECGF and VEGF than in those with high expression of either factor alone (P = 0.002). Multiple angiogenic factors expressed by both tumor cells and infiltrating cells may play a role in the regulation of angiogenesis in intestinal-type gastric cancer.
- Published
- 1998
40. p53 immunohistochemical staining predicts residual disease after chemoradiation in patients with high-risk rectal cancer.
- Author
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Spitz FR, Giacco GG, Hess K, Larry L, Rich TA, Janjan N, Cleary KR, and Skibber JM
- Subjects
- Adult, Aged, Aged, 80 and over, Biopsy, Cell Differentiation, Combined Modality Therapy, Female, Humans, Immunoenzyme Techniques, Lymphatic Metastasis, Male, Middle Aged, Neoplasm, Residual, Predictive Value of Tests, Preoperative Care, Rectal Neoplasms drug therapy, Rectal Neoplasms pathology, Rectal Neoplasms radiotherapy, Rectal Neoplasms surgery, Remission Induction, Retrospective Studies, Risk, Antimetabolites, Antineoplastic therapeutic use, Biomarkers, Tumor analysis, Chemotherapy, Adjuvant, Fluorouracil therapeutic use, Neoplasm Proteins analysis, Radiotherapy, Adjuvant, Rectal Neoplasms chemistry, Tumor Suppressor Protein p53 analysis
- Abstract
This study was conducted to investigate the value of p53 immunohistochemical staining of pretreatment biopsy specimens in predicting the response of rectal cancer to chemoradiation. The study group comprised 42 patients with high-risk rectal cancer treated between July 1990 and July 1995 with a preoperative chemoradiation regimen of 45 Gy of external-beam irradiation and continuous-infusion 5-fluorouracil followed by surgical resection. p53 immunohistochemical staining was performed on pretreatment biopsy specimens. p53 immunohistochemical staining pattern and standard clinical and pathological parameters were correlated with extent of residual cancer in the surgical specimen. Twenty tumors were positive for p53 on immunohistochemical staining, 19 were negative, and 3 were focally positive. Thirteen patients experienced a complete response to chemoradiation. Aberrant p53 protein accumulation, as measured by immunohistochemical staining, correlated inversely with a complete pathological response to chemoradiation (P = 0.005; correlation coefficient = -0.43) and directly with an increased likelihood of residual cancer in the lymph nodes of surgical specimens (P = 0.02; correlation coefficient = 0.39). p53 immunohistochemical staining of pretreatment biopsy specimens correlates with the extent of residual disease after chemoradiation in patients with high-risk rectal cancer.
- Published
- 1997
41. Solid and papillary tumor of the pancreas: ultrastructural observations on two contrasting cases.
- Author
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de la Roza G, Cleary KR, Ordóñez NG, el-Naggar A, Mackay B, and Romsdahl MM
- Subjects
- Adult, Biomarkers analysis, Biopsy, Fatal Outcome, Female, Humans, Microscopy, Electron, Middle Aged, Pancreatic Neoplasms chemistry, Ploidies, Retroperitoneal Neoplasms chemistry, Pancreatic Neoplasms pathology, Retroperitoneal Neoplasms pathology
- Abstract
Two papillary and solid tumors of the pancreas are reported which differed in their clinical features, ultrastructure, and biologic behavior. Both tumors contained papillary and solid areas by light microscopy. One tumor followed the more usual indolent course. The second patient presented with a liver metastasis and died of progressive disease in a relatively short period of time. Neither neoplasm showed convincing immunohistochemical or ultrastructural evidence of endocrine differentiation, but the electron microscopic findings hinted that this tumor possesses at least latent endocrine properties.
- Published
- 1997
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42. Small cell undifferentiated carcinoma of the pancreas.
- Author
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Ordóñez NG, Cleary KR, and Mackay B
- Subjects
- Adult, Biomarkers analysis, Biopsy, Carcinoma, Small Cell chemistry, Carcinoma, Small Cell therapy, Carcinoma, Small Cell ultrastructure, Chromogranin A, Chromogranins analysis, Fatal Outcome, Female, Humans, Immunohistochemistry, Keratins analysis, Microscopy, Electron, Pancreatic Neoplasms chemistry, Pancreatic Neoplasms therapy, Pancreatic Neoplasms ultrastructure, Phosphopyruvate Hydratase analysis, Carcinoma, Small Cell pathology, Pancreatic Neoplasms pathology
- Abstract
Small cell undifferentiated carcinoma of the pancreas is a rare neoplasm: Only 12 cases have previously been documented. This paper describes the clinical evolution, immunohistochemical profile, and ultrastructural features of a case occurring in a 37-year-old woman.
- Published
- 1997
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43. Sclerosing mucoepidermoid carcinoma with eosinophilia of the thyroid: report of two patients, one with distant metastasis, and review of the literature.
- Author
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Sim SJ, Ro JY, Ordonez NG, Cleary KR, and Ayala AG
- Subjects
- Aged, Carcinoma, Mucoepidermoid chemistry, Carcinoma, Mucoepidermoid secondary, Carcinoma, Squamous Cell pathology, Diagnosis, Differential, Female, Humans, Immunohistochemistry, Keratins analysis, Lung Neoplasms secondary, Thyroid Neoplasms chemistry, Thyroiditis, Autoimmune pathology, Carcinoma, Mucoepidermoid pathology, Eosinophilia pathology, Sclerosis pathology, Thyroid Neoplasms pathology
- Abstract
Sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE) is a recently recognized malignant neoplasm of the thyroid gland. Two additional cases of this condition which occurred in a 70-year-old woman and a 69-year-old woman are presented. The case of the 70-year-old woman (patient 1) is the first report of distant metastasis, besides lymph node metastasis, for this type of tumor. The patient initially presented with a thyroid mass, and the thyroid gland with surrounding cervical lymph nodes was removed. Because of focal keratin "pearl" formation, the tumor was misinterpreted as a metastatic squamous cell carcinoma to the thyroid. Approximately 4 years later, the patient developed a left supraclavicular mass and lung densities. A pathological fracture of the right humeral head followed, and the left supraclavicular mass recurred along with newly developed subcutaneous nodules on the chest wall and arm. Open lung and bone biopsies revealed metastatic SMECE, which was morphologically identical to that of the thyroid mass. The 69-year-old woman (patient 2) had, in 1983, undergone thyroidectomy with left radical neck dissection; this had been diagnosed as follicular carcinoma of the thyroid with lymph node involvement. After multiple isolated lymph nodes metastases, the patient developed locally extensive, recurrent tumor that showed microscopic features of SMECE. Review of the previous thyroid tumor and lymph nodes revealed the same type of histology. To our knowledge, only a single report containing eight cases of this distinctive carcinoma of the thyroid has been published. Herein we describe characteristic morphological features of two additional cases of this rare malignancy, one with distant metastasis, and we review the related literature.
- Published
- 1997
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44. Vessel counts and expression of vascular endothelial growth factor as prognostic factors in node-negative colon cancer.
- Author
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Takahashi Y, Tucker SL, Kitadai Y, Koura AN, Bucana CD, Cleary KR, and Ellis LM
- Subjects
- Adult, Aged, Blood Vessels, Colonic Neoplasms epidemiology, Colonic Neoplasms pathology, Female, Follow-Up Studies, Humans, Lymphatic Metastasis, Male, Middle Aged, Multivariate Analysis, Neoplasm Recurrence, Local epidemiology, Predictive Value of Tests, Prognosis, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factors, Colonic Neoplasms blood supply, Colonic Neoplasms chemistry, Endothelial Growth Factors analysis, Lymphokines analysis, Neoplasm Recurrence, Local diagnosis
- Abstract
Background: The value of these prognostic factors was compared with that of other clinicopathologic factors such as tumor grade, tumor stage, mucin production, vascular invasion, perineural invasion, and lymphatic invasion., Objective: To determine whether the development of distant recurrence in patients with node-negative colon cancer could be predicted using vessel count and vascular endothelial growth factor (VEGF) expression., Design: Paraffin-embedded colon cancers were immunostained for factor VIII, VEGF, basic fibroblast growth factor, and proliferating cell nuclear antigen; slides were reviewed for differentiation, mucin production, and the presence of vascular, lymphatic, and/or perineural invasion., Setting: A large academic cancer referral center where 27 patients with node-negative colon cancer were operated on during 1988 and 1989., Main Outcome Measure: The development of and interval to recurrence., Results: Eight patients developed liver, lung, or lymph node metastases at a median of 24 months. The median follow-up for patients without cancer recurrence was 60 months. The mean tumor vessel count for those patients who remained disease-free was significantly fewer than for those patients who suffered a recurrence (20 vs 33, respectively). By univariate analysis, 3 factors- perineural invasion, vessel count, and VEGF expression- were correlated with time to recurrence. By multivariate analysis, only vessel count was significantly related to differences in time to recurrence. Expression of VEGF correlated with vessel count., Conclusion: Vessel count and expression of VEGF may be useful for predicting distant recurrence in patients with node-negative colon cancer.
- Published
- 1997
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45. bcl-2 and p53 expression in resectable pancreatic adenocarcinomas: association with clinical outcome.
- Author
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Sinicrope FA, Evans DB, Leach SD, Cleary KR, Fenoglio CJ, Lee JJ, and Abbruzzese JL
- Subjects
- Adenocarcinoma genetics, Adenocarcinoma mortality, Adenocarcinoma pathology, Adult, Aged, Aged, 80 and over, Female, Humans, Immunohistochemistry, Male, Middle Aged, Outcome Assessment, Health Care, Pancreatic Neoplasms genetics, Pancreatic Neoplasms mortality, Pancreatic Neoplasms pathology, Prognosis, Proto-Oncogene Mas, Proto-Oncogene Proteins c-bcl-2 genetics, Survival Analysis, Tumor Suppressor Protein p53 genetics, Adenocarcinoma metabolism, Pancreatic Neoplasms metabolism, Proto-Oncogene Proteins c-bcl-2 biosynthesis, Tumor Suppressor Protein p53 biosynthesis
- Abstract
The bcl-2 proto-oncogene and the p53 tumor suppressor gene are important determinants of tumor cell susceptibility to apoptosis. bcl-2 and mutant p53 proteins inhibit apoptosis in vitro and can provide prognostic information in certain tumor types. We analyzed bcl-2 and p53 expression in archival pancreatic (n = 35) and ampullary (n = 6) adenocarcinomas, resected for cure, and their relationship to overall survival. Patients were treated with 5-fluorouracil and irradiation either pre- (n = 21) or postoperatively (n = 15); 5 patients received surgery alone. Using specific monoclonal antibodies, cytoplasmic bcl-2 and nuclear p53 proteins were detected in 22 of 40 (55%) and 20 of 37 (54%) tumors, respectively. No relationship was found between bcl-2 and p53 expression. Neither bcl-2 nor p53 correlated with histological response to preoperative chemoradiation. Lymph node involvement predicted poor overall survival (P = 0.02). A trend toward improved survival was seen in well-differentiated (P = 0.08) tumors and in those with increased bcl-2 expression (P = 0.06). p53 expression was not related to clinical outcome. In a multivariate analysis, nodal status was the single most important predictor of overall survival. Of note, the combined variable of bcl-2 expression and histological grade was a stronger prognostic variable than nodal status alone. Unlike nodal status, these features can potentially be evaluated in preoperative biopsy specimens.
- Published
- 1996
46. Increased apoptosis accompanies neoplastic development in the human colorectum.
- Author
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Sinicrope FA, Roddey G, McDonnell TJ, Shen Y, Cleary KR, and Stephens LC
- Subjects
- Cell Division, Colorectal Neoplasms metabolism, Humans, In Situ Nick-End Labeling, Intestinal Mucosa metabolism, Intestinal Mucosa pathology, Neoplasm Staging, Proliferating Cell Nuclear Antigen analysis, Proliferating Cell Nuclear Antigen metabolism, Proto-Oncogene Proteins c-bcl-2 analysis, Proto-Oncogene Proteins c-bcl-2 metabolism, Tumor Suppressor Protein p53 analysis, Tumor Suppressor Protein p53 metabolism, Apoptosis, Colorectal Neoplasms pathology
- Abstract
A disturbance in the balance between cell proliferation and cell loss, or apoptosis, may underlie neoplastic development. Therefore, we determined spontaneous apoptotic and proliferative rates in normal, hyperplastic, adenomatous, and malignant colorectal epithelia. In paired sections, DNA strand breaks were detected using the terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling assay, and apoptotic cells were also identified in H&E-stained slides by morphological criteria. Cell proliferation, bcl-2, and p53 expression were analyzed using specific monoclonal antibodies. In normal mucosa, luminal epithelial cells demonstrated higher rates of apoptosis compared to cells in the proliferative zone. Neoplastic transformation was associated with a significant increase in rates of apoptosis and proliferation. However, apoptosis, but not proliferation, decreased at the adenoma-to-carcinoma transition coincident with expression of mutant p53. In carcinomas, both mutant p53 and bcl-2 protein levels were associated with attenuated apoptotic rates. In conclusion, apoptosis is an important regulator of growth in normal and neoplastic colorectal epithelia. Increased apoptosis and proliferation accompany neoplastic transformation, suggesting that an alteration in apoptotic rates is an important event in colorectal carcinogenesis. Furthermore, the imbalance in these processes found in carcinomas may facilitate tumor growth and progression.
- Published
- 1996
47. Multiparametric in situ mRNA hybridization analysis to predict disease recurrence in patients with colon carcinoma.
- Author
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Kitadai Y, Ellis LM, Tucker SL, Greene GF, Bucana CD, Cleary KR, Takahashi Y, Tahara E, and Fidler IJ
- Subjects
- Humans, Predictive Value of Tests, Recurrence, Carcinoma genetics, Carcinoma metabolism, Colonic Neoplasms genetics, Colonic Neoplasms metabolism, In Situ Hybridization, RNA, Messenger analysis, RNA, Neoplasm analysis
- Abstract
We examined the expression level of several genes that regulate different steps of metastasis in formalin-fixed, paraffin-embedded archival specimens of primary human colon carcinomas from patients with at least 5 years of follow-up. The expression of epidermal growth factor receptor, basic fibroblast growth factor, type IV collagenase, E-cadherin, and multidrug resistance (mdr-1) was examined by a colorimetric in situ mRNA hybridization technique concentrating on reactivity at the periphery of the neoplasms. The in situ hybridization technique revealed inter- and intratumor heterogeneity for expression of the metastasis-related genes. The expression of basic fibroblast growth factor, collagenase type IV, epidermal growth factor receptor, and mdr-1 mRNA was higher in Dukes's stage D than in Dukes' stage B tumors. Among the 22 Dukes' stage B neoplasms, 5 specimens exhibited a high expression level of epidermal growth factor receptor, basic fibroblast growth factor, and collagenase type IV. Clinical outcome data (5-year follow-up) revealed that all 5 patients with Dukes' stage B tumors developed distant metastasis (recurrent disease), whereas the other 17 patients with Dukes' stage B tumors expressing low levels of the metastasis-related genes were disease-free. Multivariate analysis identified high levels of expression of collagenase type IV and low levels of expression of E-cadherin as independent factors significantly associated with metastasis or recurrent disease. More specifically, metastatic or recurrent disease was associated with a high ratio (> 1.35) of expression of collagenase type IV to E-cadherin (specificity of 95%). Collectively, the data show that multiparametric in situ hybridization analysis for several metastasis-related genes may predict the metastatic potential, and hence the clinical outcome, of individual lymph-node-negative human colon cancers.
- Published
- 1996
48. Significance of vessel count and vascular endothelial growth factor and its receptor (KDR) in intestinal-type gastric cancer.
- Author
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Takahashi Y, Cleary KR, Mai M, Kitadai Y, Bucana CD, and Ellis LM
- Subjects
- Adult, Aged, Female, Fibroblast Growth Factor 2 biosynthesis, Filaggrin Proteins, Humans, Immunohistochemistry, Male, Middle Aged, Proto-Oncogene Proteins analysis, Receptor Protein-Tyrosine Kinases analysis, Receptor, Fibroblast Growth Factor, Type 2, Receptors, Fibroblast Growth Factor analysis, Receptors, Vascular Endothelial Growth Factor, Severity of Illness Index, Statistics as Topic, Stomach Neoplasms pathology, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factor Receptor-1, Vascular Endothelial Growth Factors, Endothelial Growth Factors biosynthesis, Lymphokines biosynthesis, Neovascularization, Pathologic metabolism, Receptor Protein-Tyrosine Kinases biosynthesis, Receptors, Growth Factor biosynthesis, Stomach Neoplasms metabolism
- Abstract
Angiogenesis is essential for tumor growth and metastasis and depends on the production of angiogenic factors by host and/or tumor cells. The role of angiogenesis and angiogenic factor expression in intestinal- and diffuse-type gastric cancer are undefined. Archival specimens of 51 intestinal-type and 38 diffuse-type human gastric carcinomas were examined for tumor vessel counts, angiogenic factor expression, and the presence or absence of angiogenic factor receptors on tumor endothelium using antibodies against vascular endothelial growth factor (VEGF) and its receptors (KDR and flt-1), basic fibroblast growth factor (bFGF) and its receptors (bek and flg), and factor VIII (endothelial cells). Vessel count and VEGF and bFGF expression were higher in intestinal-type than in diffuse-type gastric cancers (P = 0.01, P < 0.001, and P < 0.001, respectively). Similarly, vessel count and VEGF expression were higher in patients with liver metastasis than in patients with peritoneal dissemination (P = 0.003 and P = 0.01, respectively). Vessel count correlated with VEGF expression and the presence of endothelial KDR in intestinal-type gastric cancer (P = 0.003 and P = 0.02, respectively) but not diffuse-type gastric cancer. Vessel count, VEGF expression, and presence of endothelial KDR increased with increasing stage of disease in intestinal-type gastric cancer but not diffuse-type gastric cancer. The expression of bFGF and its receptors did not correlate with vessel count in either cancer type. These findings suggest that the pattern of metastasis in intestinal-type gastric cancer is angiogenesis dependent. The correlation of VEGF expression and its endothelial receptor with vessel count and stage of disease suggests that VEGF is at least one of the factors responsible for the induction of angiogenesis in intestinal-type gastric cancer.
- Published
- 1996
49. The need for standardized pathologic staging of pancreaticoduodenectomy specimens.
- Author
-
Staley CA, Cleary KR, Abbruzzese JL, Lee JE, Ames FC, Fenoglio CJ, and Evans DB
- Subjects
- Adenocarcinoma surgery, Cell Differentiation, Humans, Lymph Nodes drug effects, Lymph Nodes radiation effects, Lymphatic Metastasis, Neoplasm Invasiveness, Pancreatic Neoplasms surgery, Pancreaticoduodenectomy, Prospective Studies, Adenocarcinoma pathology, Lymph Nodes pathology, Neoplasm Staging standards, Pancreatic Neoplasms pathology
- Abstract
A standardized method for pathologic evaluation and staging of pancreaticoduodenectomy (PD) specimens is critical for accurate reporting of the number and location of lymph nodes and margins of resection. We examined the impact of standardized pathologic evaluation (SPE) of PD specimens on the identification of regional lymph nodes and describe our detailed system for the pathologic analysis of the PD specimen. Forty consecutive patients underwent PD for histologically confirmed adenocarcinoma of the pancreatic head between April 1990 and August 1993. Fifteen consecutive specimens were examined before the introduction of the SPE, and 25 consecutive specimens underwent SPE. Resection margins were evaluated by frozen-section analysis, and then the specimen was divided into six regions on an anatomic dissection board for lymph node identification. The 25 specimens examined according to the SPE had a significantly increased number of lymph nodes identified (P = 0.0001) compared with the 15 specimens examined without the SPE. Twelve of the 25 specimens contained positive lymph nodes, 6 of which were confined to the pancreaticoduodenal region. No positive nodes were found in the periaortic region. There were no differences in pathologic variables between patients found to have negative and those with positive regional lymph nodes. SPE of PD specimens provides a method for improved lymph node identification, ensures accurate prospective evaluation of margins of resection, and provides a complete analysis of potentially important pathologic variables. We offer this system as a standardized model for groups engaged in protocol-based clinical research examining innovative multimodality treatment strategies for patients with resectable pancreatic cancer.
- Published
- 1996
- Full Text
- View/download PDF
50. Extramedullary plasmacytoma mimicking primary colonic carcinoma in a patient with Crohn's disease. Case report and literature review.
- Author
-
Ligato S, El-Naggar A, Cleary KR, and Manning J
- Subjects
- Carcinoma complications, Colonic Neoplasms complications, Crohn Disease pathology, Diagnosis, Differential, Follow-Up Studies, Humans, Male, Middle Aged, Plasmacytoma complications, Carcinoma pathology, Colonic Neoplasms pathology, Crohn Disease complications, Plasmacytoma pathology
- Abstract
We present the case of a 45-year-old man who underwent segmental resection for what was considered clinically to be a primary colonic carcinoma. Histopathologic evaluation revealed the tumor to be a malignant plasmacytoma of the colon. Additionally, the entire segment of distal ileum and colon was involved by an inflammatory process with the features of Crohn's disease, accompanied by focal glandular dyplasia of the colonic mucosa. This case reemphasizes that plasmacytoma of the colon can closely mimic carcinoma of the colon in its presentation. The association between plasmacytoma of the colon and Crohn's disease has not, to our knowledge, been described previously.
- Published
- 1996
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