Results and follow-up of locally advanced cancer of the exocrine pancreas treated with radiochemotherapy.
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In locally advanced carcinoma of the exocrine pancreas combined radiochemotherapy has been established as a standard treatment. MATERIALS AND METHODS: Two different treatment schemes have been consecutively used. Between 1/1994 and 12/2001, a total of 110 patients with locally advanced adenocarcinoma of the pancreas were treated with hyperfractionated accelerated radiotherapy to a total dose of 44.8 Gy combined with 5-fluorouracil (5-FU) (600 mg/m2) and folinic acid (FA) (300 mg/m2) injection. Chemotherapy was repeated monthly in non-progressive disease. From 1/2002 to 11/2003, in another 15 consecutive patients, chemotherapy was changed to gemcitabine (Gem) (300 mg/m2) and cisplatinum (Cis) (30 mg/m2), followed by gemcitabine (1000 mg/m2) every 2 weeks in non-progressive patients. RESULTS: Median survival in the 5-FU/FA group was 10.3 months with a 1-year survival of 46.6% and a 2-year survival of 20.1%. Median time to progression was 8.6 months. Treatment was well tolerated with nausea/vomiting grade I/II in 58.2%, grade III/IV in 14.5%, diarrhea grade I/II in 27.3%, leucopenia/thrombopenia grade I/II in 21.8%, grade III/IV in 7.2%, and mucositis grade III/IV in 7.2%. In the Gem/Cis group, median survival was 13.8 months with a 1-year survival of 54.9% and a 2-year survival of 24.4%. The toxicity data also revealed comparable feasibility: nausea/vomiting grade I/II in 46.7%, grade III/IV in 20%, diarrhea grade I/II in 20%, leucopenia/thrombopenia grade I/II in 26. 7%, and grade III/IV in 13.3%. CONCLUSION: Radiochemotherapy in locally advanced pancreatic cancer is an effective and well-tolerated treatment. The long-term efficacy concerning survival is limited. The integration of predictive factors and new chemotherapeutic agents like gemcitabine in the multimodality treatment may give a more promising perspective. Because of the narrow therapeutic index of gemcitabine-based radiochemotherapy schemes, a feasible combination of radiotherapy treatment volume and gemcitabine dose must be found. (+info)
Further evidence for prolongation of survival of pancreatic cancer patients by efficacy orientated sequential polychemotherapy (EOSPC) based on serial tumor marker determinations (CA 19-9/CEA).
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The results of palliative chemotherapy in 55 patients suffering from exocrine pancreatic cancer are reported, following our concept of efficacy orientated sequential polychemotherapy (EOSPC). Tumor answer/regression was mainly analyzed on the basis of the serum courses of the tumor markers CA 19-9 and CEA. Up to four different treatment trials were tried in the individual patients. The results confirm previously published data: a prolongation of survival in relation to the number of effective treatments (CR/PR/MR/SD vs. PD). The median survival of the whole group of patients (n=55, including n=39 patients with distant metastasis) was 12 months. The results support our concept of EOSPC in pancreatic cancer patients in order to improve survival. Furthermore, the data should stimulate attention not only on new and potentially more effective 1st- line regimens, but also to effective 2nd- and/or 3rd-line treatments. Moreover, the results should encourage clinicians to rediscuss the actual concepts of prospective therapeutical trails mainly based on analyzing the effects of single agents or drug combinations on survival. Furthermore, a comparison of 1st-line treatments with gemcitabine as monotherapy, and in combination with mitomycin-C, confirms that the combination of gemcitabine + mitomycin-C seems to be more active than gemcitabine monotherapy and that this combination might also be of value as 2nd-line therapy after gemcitabine monotherapy. (+info)
Expression of inhibin/activin subunits, sialyl-lewis A (CA 19-9, sLea) and sialyl-Lewis X (sLex) carbohydrate antigens in a hydatidiform mole with persistent polymorphic trophoblastic hyperplasia.
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The persistence of polymorphic trophoblastic hyperplasia in a hydatidiform mole is an extremely rare condition. Its early diagnosis is essential since such cases can transform into invasive tumours. MATERIALS AND METHODS: The paraffin-embedded biopsies were routinely stained with HE. Immunohistochemical staining reactions were performed with monoclonal antibodies against inhibin-alpha, inhibin-betaA and inhibin-betaB subunits. Additional immunohistochemical reaction was performed with, Sialyl-Lewis A and Sialyl-Lewis X and glycodelin. RESULTS: Large villi and hydatidiform villi with ranging syncyctio- and cytotrophoblasts were seen. Intervillous proliferating trophoblasts showed cell- and nuclear polymorphy with invasion of the myometrium wall. The immunohistochemistry exhibited strong positivity for inhibin-alpha, inhibin-betaA and inhibin-betaB subunits in trophoblastic tissue, while the decidua was negative. Sialyl-Lewis A and Sialyl-Lewis X showed no or minimal focal immunohistochemical reaction. CONCLUSION: A complete hydatidiform mole with hyperplasia and proliferation presents a high risk of developing a persistent (eventually metastatic) trophoblastic disorder and, in up to 15% of the cases, an invasive mole. In 2.5% of the cases it can transform into a choriocarcinoma. Since the inhibin/activin subunits reacted positively with trophoblastic tissue, they might be a useful diagnostic marker for hydatidiform mole with persistence of polymorphic trophoblastic hyperplasia. (+info)
Adjuvant radiochemotherapy of stage II and III rectal adenocarcinoma: role of CEA and CA 19-9.
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BACKGROUND: This analysis was undertaken to evaluate the impact of pre-radiotherapy CEA and CA 19-9 values on clinical outcome of locally advanced rectal cancer. PATIENTS AND METHODS: Retrospective data were collected from patients (n=203) with UICC stage II and III rectal adenocarcinomas, who underwent low anterior or abdominoperineal resection and received post-operative or pre-operative radiochemotherapy from January 1989 until July 2002. The rates of survival and distant and local recurrences were evaluated using Kaplan-Meier survival analysis, Log-rank test and Cox's proportional hazards (median follow-up 8 years). Multivariate analysis was used to assess the prognostic value of CEA and CA 19-9. RESULTS: The 5-year actuarial rates for patients with normal (n =118) and elevated (n=88) CEA values were as follows: overall survival 62.4% and 32.0% (p<0.001), local control 73.5% and 55.0% (p=0.007), and absence of distant metastasis 83.3% and 88.0% (n.s.), respectively. Similar results were obtained for patients with normal (n=82) and elevated (n = 10) CA 19-9 values: overall survival 60.7% and 14.0% (p=0.007), local control 83.7% and 80.0% (n.s.), and absence of distant metastasis 64.9% and 75.0% (n.s.), respectively. After adjustment for TNM stage, sex, age, LDH, tumor site and grading, the elevation of CEA proved to be an independent prognostic factor for overall survival (relative risk of 1.01 per ng/ml, CI 1.002 - 1.01; p=0.005). CONCLUSION: This study confirmed the prognostic value of pre-radiotherapy CEA and CA 19-9 in patients with stage II or III rectal carcinoma. (+info)
The diagnostic utility of immunohistochemistry and electron microscopy in distinguishing between peritoneal mesotheliomas and serous carcinomas: a comparative study.
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The histologic distinction between peritoneal epithelioid mesotheliomas and serous carcinomas diffusely involving the peritoneum may be difficult, but it can be facilitated by the use of immunohistochemistry and electron microscopy. D2-40 and podoplanin are two recently recognized lymphatic endothelial markers that can be expressed in normal mesothelial cells and mesotheliomas. The purpose of this study is to compare the value of these new mesothelial markers with those that are commonly used for discriminating between mesotheliomas and serous carcinomas, and also to determine the current role of electron microscopy in distinguishing between these malignancies. A total of 40 peritoneal epithelioid mesotheliomas and 45 serous carcinomas of the ovary (15 primary, 30 metastatic to the peritoneum) were investigated for the expression of the following markers: D2-40, podoplanin, calretinin, keratin 5/6, thrombomodulin, MOC-31, Ber-EP4, B72.3 (TAG-72), BG-8 (Lewis(Y)), CA19-9, and leu-M1 (CD15). All 40 (100%) of the mesotheliomas reacted for calretinin, 93% for D2-40, 93% for podoplanin, 93% for keratin 5/6, 73% for thrombomodulin, 13% for Ber-EP4, 5% for MOC-31, 3% for BG-8, and none for B72.3, CA19-9, or leu-M1. All 45 (100%) serous carcinomas were positive for Ber-EP4, 98% for MOC-31, 73% for B72.3, 73% for BG-8, 67% for CA19-9, 58% for leu-M1, 31% for keratin 5/6, 31% for calretinin, 13% for D2-40, 13% for podoplanin, and 4% for thrombomodulin. After analyzing the results, it is concluded that Ber-EP4 and MOC-31 are the best negative mesothelioma markers for differentiating between epithelioid mesotheliomas and serous carcinomas. The best discriminators among the positive markers for mesotheliomas are D2-40, podoplanin, and calretinin. From a practical point of view, Ber-EP4 and MOC-31, in combination with calretinin, and/or D2-40 or podoplanin allow the differential diagnosis to be established between mesothelioma and serous carcinoma in nearly all instances. As a clear distinction could be made between these two malignancies in all of the cases in which electron microscopy was performed, this technique can be very useful in establishing the correct diagnosis when the immunohistochemical results are equivocal or further support of a diagnosis of either mesothelioma or serous carcinoma is needed. (+info)
Fixed dose-rate gemcitabine infusion as first-line treatment for advanced-stage carcinoma of the pancreas and biliary tree.
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BACKGROUND: Gemcitabine infusion at the fixed dose rate of 10 mg/m(2) per minute (FDR-gemcitabine) has pharmacokinetic advantages and may result in improved therapeutic efficacy. METHODS: Between April 2002 and September 2003, 40 patients with advanced-stage pancreatic adenocarcinoma (PDAC; n = 27) or biliary tree carcinoma (BTC; n = 13) were treated with weekly FDR-gemcitabine (1000 mg/m(2)). The primary end point was the response rate. The secondary end points were progression-free and overall survival (PFS and OS), tumor marker response, and clinical benefit response (CBR). RESULTS: The overall response rate (ORR) on an intent-to-treat basis was 15% (95% confidence interval [95% CI], 4-26%). A positive CBR was obtained in 14 of 29 (48%) patients. Seventeen of 25 (68%) patients had a reduction in carbohydrate antigen 19-9 (CA 19-9) of > 25%. The median time to treatment failure and the median PFS were 17 weeks (95% CI, 13-22 weeks) and 19 weeks (95% CI, 15-23 weeks), respectively. The median OS was 40 weeks (95% CI, 36-45 weeks) and the 1-year actuarial survival rate was 25.8%. Multivariate analysis showed that a performance status score of 0-1 at study entry and locally advanced disease were the only independent predictors of longer PFS and OS, whereas a reduction in CA 19-9 serum levels > 75% was an independent predictor of longer PFS, but had no impact on OS. Toxicity was mild with Grade 3-4 neutropenia (according to the National Cancer Institute-Common Toxicity Criteria [version 2.0]) in 18 of 427 treatment weeks (4.2%), and Grade 3 anemia and thrombocytopenia in 6 of 427 treatment weeks (1.4%) and 9 of 427 treatment weeks (2.1%), respectively, and asymptomatic Grade 3-4 transaminase elevation in 21 of 427 treatment weeks (4.9%). CONCLUSIONS: FDR-gemcitabine at the weekly dose of 1000 mg/m(2) demonstrated promising activity, despite negligible toxicity, in patients with advanced-stage PDAC and BTC. (+info)
Diagnostic value of CYFRA 21-1, CEA, CA 19-9, CA 15-3, and CA 125 assays in pleural effusions: analysis of 116 cases and review of the literature.
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Levels of tumor markers in pleural effusions may help to establish the diagnosis of pleural malignancy, but the precise diagnostic value of each marker remains unclear. The aim of this study was to assess the diagnostic value of five common pleural fluid tumor markers, carcinoembryonic antigen (CEA), cytokeratin fragment (CYFRA) 21-1, cancer antigen (CA) 15-3, CA 19-9, and CA 125, and to review the literature from the past 15 years. Pleural fluid samples were collected prospectively from 116 patients and assayed for CEA, CYFRA 21-1, CA 15-3, CA 19-9, and CA 125 levels. A MEDLINE search of the English-language literature from the past 15 years was also done. Effusions were classified as benign or malignant on the basis of their definitive pathologic or cytologic diagnoses. The levels of all pleural tumor markers were statistically significantly higher in the malignant group than in the benign group. The marker with the highest accuracy was CEA (85.3%); CA 15-3, CYFRA 21-1, and CA 19-9 had similar accuracies (75.2%, 72.4%, and 71.5%, respectively), and CA 125 had the lowest accuracy (40.5%). On univariate analysis, tumor-marker combinations did not result in a greater accuracy than that of CEA alone. On multivariate logistic regression, CA 15-3 and CYFRA 21-1 were significant predictors of malignancy. Among the nine reports in the literature comparing 11 different tumor markers, CEA, CA 15-3, and CYFRA 21-1 yielded the best results. We conclude that pleural fluid analysis should include CEA for the diagnosis of malignancy. CA 15-3 and CYFRA 21-1 may serve as alternative options. (+info)
Adjusted carbohydrate antigen 19-9. Correlation with histological grade in pancreatic adenocarcinoma.
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BACKGROUND: The serum level of carbohydrate antigen 19-9 (CA 19-9) depends on the tumor size and differentiation grade. Jaundice can cause an elevation of serum CA 19-9, although the nature of this interaction is not fully understood. PATIENTS AND METHODS: This was a retrospective study of 26 patients with potentially resectable pancreatic adenocarcinoma. Serum CA 19-9 was correlated with the histological differentiation. CA 19-9 adjusted for serum bilirubin was determined and analyzed. RESULTS: No correlation between CA 19-9 and histological differentiation was determined (p>0.05). The median adjusted CA 19-9 level was significantly lower (p=0.01) in patients with normal biliary excretion than those with bilirubin levels >2 mg/dL. CONCLUSION: These data are consonant with the theory of a dual contribution to the serum CA 19-9 level from biliary obstruction and tumor cell synthesis. (+info)