Articles and Resources


ABSTRACTS DISCUSSING TREATMENT AND RESULTS OF VARIOUS CASE STUDIES

  1. Taxol inhibits growth of mesothelioma xenografts.
  2. Combined chemotherapy in pleurectomized malignant pleural mesothelioma patients.
  3. A phase II trial investigating primary immunochemotherapy for malignant pleural mesothelioma and the feasibility of adjuvant immunochemotherapy after maximal cytoreduction.
  4. Intrapleural chemotherapy for patients with incompletely resected malignant mesothelioma: the UCLA experience.
  5. Treatment of malignant mesothelioma with methotrexate and vinblastine, with or without platinum chemotherapy.
  6. Malignant mesothelioma and duration of asbestos exposure: correlation with tissue mineral fibre content.
  7. Mesothelioma as a risk indicator of asbestos exposure: the role of the pathologist.
  8. Clinical course of human epithelial-type malignant pleural mesothelioma replicated in an orthotopic-transplant nude mouse model.
  9. Malignant mesothelioma and duration of asbestos exposure: correlation with tissue mineral fibre content.
  10. Malignant pleural mesothelioma presenting as spontaneous pneumothorax: a case series and review.
  11. Trimetrexate in malignant mesothelioma: A Cancer and Leukemia Group B Phase II study
  12. Phase II Study of Vinorelbine in Patients With Malignant Pleural Mesothelioma
  13. A phase II trial of pleurectomy/decortication followed by intrapleural and systemic chemotherapy for malignant pleural mesothelioma
  14. Epirubicin in malignant mesothelioma: a phase II study of the European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group
  15. Combined Resection, Intraperitoneal Chemotherapy and Whole Abdominal Radiation for the Treatment of Peritoneal Mesothelioma
  16. Chemotherapy in malignant pleural mesothelioma. A review
  17. Impressive remission in a patient with locally advanced malignant pleural mesothelioma treated with gemcitabine.
  18. Malignant mesothelioma in women.
  19. Phase I and pharmacologic study of sequences of gemcitabine and the multitargeted antifolate agent in patients with advanced solid tumors.
  20. Gene-modified PA1-STK cells home to tumor sites in patients with malignant pleural mesothelioma.
  21. Operation and photodynamic therapy for pleural mesothelioma: 6-year follow-up.
  22. Talc induces apoptosis in human malignant mesothelioma cells in vitro.
  23. Peritoneal cancer and occupational exposure to asbestos: results from the application of a job-exposure matrix.
  24. Malignant pleural mesothelioma presenting as spontaneous pneumothorax: a case series and review.
  25. Epithelial mesothelioma with deciduoid features
  26. Malignant mesothelioma presenting as pulmonary metastasis ahead of growth of primary tumor.
  27. Video-assisted thoracoscopic excision of a benign cystic mesothelioma of pleura
  28. Malignant mesothelioma of the tunica vaginalis testis: a report of two cases and review of literature.
  29. Malignant mesothelioma of the pleura with a large tumor embolus in the left atrium: an autopsy case
  30. A Review of Dr. Sugarbaker's Results Using Tri-Modal Therapy on 183 Patients from 1980 to 1997
  31. Current Therapy for Mesothelioma, Sugarbaker, et al, 1997
  32. Successful Immunochemotherapy for Patients with Malignant Mesothelioma: Report of Two Cases
  33. Multimodality Management of Malignant Pleural Mesothelioma
  34. Familial Pleural Malignant Mesothelioma: Clustering in Three Sisters and One Cousin
  35. Pathology of Diffuse Malignant Pleural Mesothelioma
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Taxol inhibits growth of mesothelioma xenografts.
Abstract:
BACKGROUND: In vitro tests measuring inhibition of adenosine triphosphate activity predicted three mesothelioma xenografts would be sensitive to taxol. PURPOSE: The in vivo therapeutic efficacy of taxol was tested in nude mice carrying the subcutaneous tumors. METHODS: Once tumor growth reached 100mm3 in size, intraperitoneal taxol, 30 mg/kg, on a day 1, 4, and 8 schedule, was administered to mice bearing subcutaneous mesothelioma xenografts.
RESULTS: Taxol inhibits the growth of all three cell lines. It produces actual tumor regression including some complete responses. CONCLUSIONS: Taxol is an active drug against mesothelioma. The in vitro cell lines and the in vivo system are useful tools for screening and developing new treatments for mesothelioma.
Author: Lee JM, Bruckner HW, Szrajer L, Brenne U, Schindelheim G, Andreotti PE
Address: Derald H. Ruttenberg Cancer Center, Mount Sinai Medical Center, New York, NY 10029, USA.
Abbreviated Journal Title: Anticancer Res Date Of Publication: 1995 May-Jun

Combined chemotherapy in pleurectomized malignant pleural mesothelioma patients.
Abstract:
A phase II clinical trial of 20 cancer patients who presented with malignant pleural mesothelioma (MPM) between November 1991 and April 1993 was conducted. Of the histologically proven cases, 16 (80%) were epitheloid and 4 (20%) were mixed type MPM. Patients were treated with mitomycin C, cisplatin, and alpha interferon after pleurectomy. Our schedule consisted of 10 mg/m2 mitomycin C i.v. infusion, 50 mg/m2 cisplatin i.v. infusion, 10 mil Ur-alpha interferon i.m. and 10 mil Ur-alpha interferon i.v. infusion on the first day of treatment. Patients were given a mean of 4.5 chemotherapy cycles (range: 2-6). None of the patients showed complete or partial response. Stable disease was observed in 15 patients, while 5 patients had progressive courses. The overall median survival time after chemotherapy was 12 months (range: 3-31 months). Median survival after chemotherapy was 15 months (range: 4-31 months) in the stable disease group (n:15, 75%), and 5 months (range: 3-13 months) in progressive cases (n:5, 25%). The overall survival rates were 55% [95% Confidence Interval (CI):43%-88.8%] at one year and 15% (95% CI:5%-39.1%) at 2 years. Five patients had grade 3 alopecia, three had grade 2 vomiting and nausea, two had grade 2 leukopenia, one had grade 2 cardiotoxicity and another had discoloration on his fingernails. In our multimodal therapy protocol, we found no difference in survival and relapse rates between our combined modal therapy and other single modal therapies in the literature.
Author: Hasturk S, Tastepe I, Unlu M, Cetin G, Baris YI
Address: Department of Chest Diseases, Cukurova University, Adana, Turkey.
Abbreviated Journal Title: J Chemother Date Of Publication: 1996 Apr

A phase II trial investigating primary immunochemotherapy for malignant pleural mesothelioma and the feasibility of adjuvant immunochemotherapy after maximal cytoreduction.
Abstract:
BACKGROUND: The treatment of malignant pleural mesothelioma (MPM) continues to be inadequate with the use of standard techniques, including surgery, radiotherapy and chemotherapy. We initiated a phase II trial of immunochemotherapy with cisplatinum (25 mg/m2 four times weekly), interferon-alpha (5 mU/m2 s.c. three times weekly, and tamoxifen (20 mg orally twice a day for 35 days) (CIT) based on in vitro and in vivo data suggesting interrelating efficacy of this combination. METHODS: Since July 1991, 36 patients have been evaluable for response after receiving one to five cycles of CIT. Ten additional patients had debulking surgery followed by two cycles of postoperative adjuvant CIT commencing a mean of 6 weeks after surgery.
RESULTS: Toxicity was acceptable (4% grade III/IV). One treatment-related death (2%) occurred, from myocardial infarction. A 19% partial response rate, objectively quantified using three-dimensional computerized tomographic (CT) measurement of solid disease volume, was recorded. The median survival for the seven responders was 14.7 months, whereas that of the nonresponders was 8 months (p2 = 0.2). Median survival for the entire group was 8.7 months. Preoperative size, platelet count > 360,000/ml, and nonepithelial histology were associated with shortened survival. CONCLUSIONS: The CIT regimen has some activity in MPM and can be delivered after debulking resection. In good-risk patients, as defined by favorable prognostic factors, a randomized trial using this combination may be warranted.
Author: Pass HW, Temeck BK, Kranda K, Steinberg SM, Pass HI
Address: Thoracic Oncology Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Abbreviated Journal Title: Ann Surg Oncol Date Of Publication: 1995 May

Intrapleural chemotherapy for patients with incompletely resected malignant mesothelioma: the UCLA experience.
Abstract:
From 1986 to 1993, 15 patients with malignant pleural mesothelioma were treated by pleurectomy/decortication and intrapleural cisplatin (100 mg/m2) and cytosine arabinoside (1,200 mg). All patients were without known extrathoracic disease and had a mean age of 63 +/- 7.9 years (range 51-78); 13 were male. Histologic subtype of disease were epithelial (47%), sarcomatoid (27%), and mixed-biphasic (27%). The major morbidity and mortality rates were 13% and 0%, respectively. The mean length of hospital stay was 6.5 +/- 2.1 days. Postoperatively, adjuvant chemotherapy and radiation therapy were given to 46% and 73% of the patients respectively. Median survival from date of treatment was 11.5 months. Those patients with an epithelial histologic subtype experienced significantly improved survival compared to those of sarcomatoid subtype (P = 0.024). Whether adjuvant chemotherapy or radiation therapy were given had no significant effect on survival. These data suggest that although this treatment regimen can be administered with very limited morbidity and no mortality, the role of this approach in the treatment of malignant pleural mesothelioma appears limited and cannot currently be recommended.
Author: Lee JD, Perez S, Wang HJ, Figlin RA, Holmes EC
Address: Department of Surgery, University of California, School of Medicine, Los Angeles 90024, USA.
Abbreviated Journal Title: J Surg Oncol Date Of Publication: 1995 Dec

Treatment of malignant mesothelioma with methotrexate and vinblastine, with or without platinum chemotherapy.
Abstract:
STUDY OBJECTIVE: To determine the efficacy of methotrexate, vinblastine, and platinum chemotherapy in patients with diffuse unresectable malignant mesothelioma. DESIGN: Patients with histologically confirmed malignant mesothelioma were evaluated for treatment with methotrexate, vinblastine, and cisplatin chemotherapy. If the patient had preexisting hearing loss or neuropathy, or was significantly disabled (eg, spending greater than half of the day in bed or a chair), cisplatin therapy was withheld. SETTING: All patients were initially evaluated at the University of Washington Medical Center and received chemotherapy at the University of Washington or in the community. INTERVENTIONS: Between 1990 and 1994, 17 patients received this chemotherapy. Ten patients received cisplatin, 100 mg/m2 IV on day 1, methotrexate, 30 mg/m2 IV on days 8, 15, and 22, and vinblastine, 3 mg/m2 IV on days 8, 15, and 22, in 28-day cycles. One patient had carboplatin substituted for cisplatin due to preexisting hearing loss. Six patients received weekly methotrexate and vinblastine at the same doses without platinum.
MEASUREMENTS AND
RESULTS: Nine of the 17 (53%; 95% confidence interval [CI], 28 to 77%) patients responded, including two complete remissions, two partial remissions, and five regressions. Median time to progression is 8 months. The median survival time for all patients is 14 months. Projected 2-year survival is 35% (95% CI, 12 to 60%). CONCLUSIONS: Although the number of the patients in this study is small, the response rate and projected 2-year survival of 35% are better than those typically reported for unresectable malignant mesothelioma. Further investigation is warranted in confirmatory trials.
Author: Hunt KJ, Longton G, Williams MA, Livingston RB
Address: Department of Medicine, University of Washington Medical Center, Seattle, USA.
Abbreviated Journal Title: Chest Date Of Publication: 1996 May

Malignant mesothelioma and duration of asbestos exposure: correlation with tissue mineral fibre content.
Abstract:
Among 441 cases of malignant mesothelioma in the
Author's files, there were 324 for whom reliable information was available regarding the duration of exposure to asbestos. Included were 298 pleural and 26 peritoneal mesotheliomas. The mean duration of exposure to asbestos was 23 +/- 14 years for all cases, and was not different for the pleural and peritoneal groups. Lung tissue was available for analysis of mineral fibre content in 94 cases. Linear regression analysis showed a significant correlation between duration of exposure and asbestos bodies per gramme of wet lung as determined by light microscopy, and between duration of exposure and total uncoated fibres (5 microns or greater in length) as well as commercial amphibole fibres per gramme as determined by scanning electron microscopy.
Author: Roggli VL
Address: Department of Pathology, Durham Veterans Administration, NC 27710, USA.
Abbreviated Journal Title: Ann Occup Hyg Date Of Publication: 1995 Jun

Mesothelioma as a risk indicator of asbestos exposure: the role of the pathologist.
Abstract:
Malignant mesothelioma is an uncommon tumor, which has become an important epidemiological marker for exposure to asbestos. This tumour is characterised by a wide range of microscopic features which may be classified in three histologic patterns: epithelial, mesenchimal and mixed or biphasic. Histochemical staining is often necessary to distinguish mesothelioma from carcinoma. As regards immunohistochemistry, only the use of a combination of antibodies significantly decreases the risk of false-negative
RESULTS. Analytic electron microscopy techniques may also be useful, permitting the evaluation of the cumulative fiber burden in the target organ.
Author: Zampi G, Comin CE, Dini S
Address: Institute of Pathological Anatomy and Histology, University of Florence, Italy.
Abbreviated Journal Title: Med Lav Date Of Publication: 1995 Sep-Oct

Clinical course of human epithelial-type malignant pleural mesothelioma replicated in an orthotopic-transplant nude mouse model.
Abstract:
Malignant pleural mesothelioma is an aggressive tumor that is essentially unresponsive to standard medical and surgical therapies. Little is actually known about its biologic response to therapeutic interventions, in part because of a lack of a "patient-like" animal tumor model. Most experimental models thus far have been derived from inhalation or inoculation of asbestos fibers into animal subjects or by subcutaneous transplantation of human mesothelial cell lines into nude mice. These models are not representative of clinical malignant pleural mesothelioma. In this report, an animal model of human pleural malignant mesothelioma obtained by orthotopic transplantation of intact pleural tumor tissue into athymic nude mice is described. Pleural tumor obtained by thoracolscopy from a patient with epithelial-type malignant pleural mesothelioma was implanted as intact tissue by surgical orthotopic implantation (SOI) into the right pleural cavity of nude mice. Animals were sacrificed when moribund or 6 months after implantation. Tumor growth and regional spread in the mice evaluated at post-mortem examination mimicked the clinical pattern of progression of human disease. Histologic findings and the immunohistochemical profile were similar to those demonstrated on examination of thoracoscopic parietal pleural biopsy specimens and post-mortem examination of the original patient's tumor. This "patient-like" nude mouse model of epithelial-type malignant pleural mesothelioma, phenotypically similar to the original human tumor, should facilitate future investigation of tumorigenesis and metastatic potential of this neoplasm. The model should serve as a basis for assessing the impact of experimental and existing therapy on malignant mesothelioma.
Author: Colt HG, Astoul P, Wang X, Yi ES, Boutin C, Hoffman RM
Address: Division of Pulmonary and Critical Care Medicine, University of California San Diego Medical Center, 92103, USA.
Abbreviated Journal Title: Anticancer Res Date Of Publication: 1996 Mar-Apr

Malignant mesothelioma associated with low pulmonary tissue asbestos burdens: a light and scanning electron microscopic analysis of 18 cases.
Abstract:
Most malignant mesothelioma cases are associated with pulmonary asbestos body (AB) counts significantly greater than those of the general population. However, the question remains whether malignant mesothelioma cases associated with "normal" AB counts (i.e., indistinguishable from the general population) represent background incidence levels or are, actually, asbestos related. We performed AB counts (by light microscopy) and mineral fiber analysis (by scanning electron microscopy) in 18 mesothelioma cases with AB counts within our normal range (0 to 20 AB/G wet lung) and in 19 "control" cases. Our study demonstrated that approximately one-third (6 of 18) of the mesothelioma cases have asbestos fiber burdens greater than 95% of the control levels. These
RESULTS suggest that these six mesothelioma cases may be asbestos related despite AB counts similar to those of the general population. An asbestos etiology was suggested in three additional cases, but too few amphibole fibers were identified in these cases to be certain of a value above background. The remaining nine cases showed no evidence of an asbestos etiology. Electron microscopic analysis of pulmonary mineral fibers may be required to differentiate asbestos-related mesotheliomas from non-asbestos-related cases when AB counts are within the range of background values.
Author: Srebro SH, Roggli Vlk, Samsa GP
Address: Department of Pathology, Durham Veterans' Administration, North Carolina, USA.
Abbreviated Journal Title: Mod Pathol Date Of Publication: 1995 Aug

Malignant pleural mesothelioma presenting as spontaneous pneumothorax: a case series and review.
Abstract:
BACKGROUND: Malignant pleural mesothelioma (MPM) is thought to arise from the mesothelial cells that line the pleural cavities. Most patients initially experience the insidious onset of chest pain or shortness of breath, and it rarely presents as spontaneous pneumothorax. CASE REPORTS: We report four patients who presented in this manner. Three of the patients were exposed to asbestos directly or indirectly at shipyards during World War II; the fourth was exposed as an insulator's wife. Two of our cases were not recognized to have MPM on histologic examination at first thoracotomy and remained asymptomatic for 12 and 22 months, respectively. In none of the patients described herein, was spontaneous pneumothorax the cause of death. CONCLUSIONS: Since many people were exposed to asbestos during and after World War II, spontaneous pneumothorax in a patient with the possibility of such exposure should raise the suspicion of malignant pleural mesothelioma. Copyright 2000 Wiley-Liss, Inc.
Author: Alkhuja S, Miller A, Mastellone AJ, Markowitz S.
Address: Division of Pulmonary Medicine, Department of Medicine, Catholic Medical Center of Brooklyn and Queens, Jamaica, NY, USA. salkuja@aol.com Journal: Am J Ind Med 2000 Aug;38(2):219-23

Trimetrexate in malignant mesothelioma: A Cancer and Leukemia Group B Phase II study
Abstract:
PURPOSE: Folic acid antagonists are reported to have activity against mesothelioma. The Cancer and Leukemia Group B (CALGB) undertook this phase II study of the new antifolate, trimetrexate (TMTX), to evaluate its response rate and toxicity in chemotherapy-naive patients with malignant mesothelioma.
PATIENTS AND METHODS: Fifty-two patients were accrued to this protocol. Because of concerns about TMTX toxicity in patients with malignant effusions and/or hypoalbuminemia, the first 17 patients were treated at a dose of 6 mg/m2 daily for 5 days every 21 days. Because minimal toxicity was observed, the subsequent 35 patients were treated at a dose of 10 mg/m2.
RESULTS: Two of 17 patients (12%) in the 6-mg/m2 treatment group had a partial response (PR) and four of 34 eligible patients (12%) in the 10-mg/m2 treatment group had a PR or regression (R) of assessable disease. No patient achieved a complete response (CR). Median survival durations were 5.0 and 8.9 months in the 6- and 10-mg/m2 treatment groups, respectively, while the 2-year survival rates were identical at 18%. At the 10-mg/m2 dose, toxicity was tolerable, with one toxic death from sepsis and a 12% rate of grade 4 thrombocytopenia and granulocytopenia.
CONCLUSION: In this large trial, TMTX showed minor activity in the treatment of malignant mesothelioma. Myelosuppression was mild and dose-related. Future studies of higher doses of TMTX should be considered.
Author: NJ Vogelzang, LB Weissman, JE Herndon 2nd, KH Antman, MR Cooper, JM Corson and MR Green
Address: Department of Medicine, University of Chicago, IL 60637-1470. Journal: JCO

Phase II Study of Vinorelbine in Patients With Malignant Pleural Mesothelioma
Abstract:
PURPOSE: To evaluate the response rate and impact on quality of life of vinorelbine given as cycles of 30 mg/m2 weekly for 6 weeks to patients with malignant pleural mesothelioma.
PATIENTS AND METHODS: Twenty-nine patients with histologically proven malignant pleural mesothelioma were enrolled (26 male patients and three female patients; median age, 58 years [range, 29 to 77 years]). Seventeen patients had epithelioid tumors, two had sarcomatoid tumors, and 10 had biphasic tumors. The International Mesothelioma Interest Group staging system was used: one patient had stage Ib disease, 10 had stage II disease, eight had stage III disease, and 10 had stage IV disease. Patients were treated with weekly injections of vinorelbine 30 mg/m2. A cycle consisted of six weekly injections. The new guidelines to evaluate the response to treatment in solid tumors were used. Responses were measured by spiral computed tomography scan.
RESULTS: All twenty-nine patients had measurable disease and were assessed for response. There were seven partial responses (24% [95% confidence interval, 10% to 44%]), 16 patients had stable disease (55%), and six patients had disease progression on therapy (21%). The median number of vinorelbine injections was 12 (range, 2 to 30). Quality-of-life analyses showed a benefit for vinorelbine therapy.
CONCLUSION: Vinorelbine shows promise in the palliation of patients with malignant pleural mesothelioma. The relatively low toxicity of the drug suggests that trials of vinorelbine in combination with other agents should be feasible. The
Authors acknowledge the support of Pierre-Fabre Oncology for subsidized drug costs. By Jeremy P. C. Steele, Jonathan Shamash, Marie T. Evans, Nicole H. Gower, Marc D. Tischkowitz, Robin M. Rudd From the Department of Medical Oncology, St Bartholomew's Hospital, and the London Lung Cancer Group, London, United Kingdom.
Address reprint requests to Jeremy P.C. Steele, MD, MRCP, Department of Medical Oncology, St Bartholomew's Hospital, West Smithfield, London EC1A 7BE, United Kingdom; email j.p.steele@ mds.qmw.ac.uk. Journal:JCO

A phase II trial of pleurectomy/decortication followed by intrapleural and systemic chemotherapy for malignant pleural mesothelioma
Abstract:
PURPOSE: This study investigated the feasibility of a novel approach to the treatment of malignant pleural mesothelioma by combining surgical resection with immediate postoperative intrapleural chemotherapy and subsequent systemic chemotherapy.
PATIENTS AND METHODS: Patients with biopsy-proven, resectable malignant pleural mesothelioma underwent pleurectomy/decortication immediately followed by intrapleural chemotherapy with cisplatin 100 mg/m2 and mitomycin 8 mg/m2. Systemic chemotherapy was started 3 to 5 weeks postoperatively and included cisplatin 50 mg/m2 on days 1, 8, 15, 22, 36, 43, 50, and 57, and mitomycin 8 mg/m2 on days 1 and 36. Patients were then monitored by serial chest and abdominal computed tomographic (CT) scans every 3 months until death or for a minimum of 18 months, whichever occurred first.
RESULTS: Of 36 patients entered onto the study, 28 had pleurectomy/decortication and intrapleural chemotherapy. There was one postoperative death, and two episodes of grade 4 renal toxicity after intrapleural chemotherapy. The 23 patients who also had systemic chemotherapy received a median of 80% and 87% of the planned total cisplatin and mitomycin doses, respectively. No grade 3 or 4 toxicities were observed. The overall survival rate of the 27 patients who were originally candidates for systemic chemotherapy was 68% at 1 year and 40% at 2 years, with a median survival duration of 17 months. Locoregional disease was the most common form of relapse (16 of 20 patients).
CONCLUSION: This short but aggressive combined modality regimen was generally well tolerated, but should not be used outside of a protocol setting because of the potential for serious toxicity. Overall survival was as good or better than with previously reported multimodality approaches, but other strategies are needed to improve local control.
Author: V Rusch, L Saltz, E Venkatraman, R Ginsberg, P McCormack, M Burt, M Markman and D Kelsen
Address: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.

Epirubicin in malignant mesothelioma: a phase II study of the European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group
Abstract:
PURPOSE: The doxorubicin analog, epirubicin (EPI), was tested in patients with malignant mesothelioma.
PATIENTS AND METHODS: Sixty-three patients with malignant mesothelioma were given EPI 110 mg/m2 every 3 weeks. Histology was reviewed and confirmed by a pathology panel. On the basis of unconvincing or wrong histology, insufficient material or cytology only, nine cases were considered ineligible for the study. None of the patients had received prior chemotherapy.
RESULTS: The main side effects were myelosuppression, alopecia, and gastrointestinal toxicity. Tumor response, assessed by computed tomographic (CT) scans, was assessable in 48 patients. Seven patients (15%) achieved a partial response that lasted a median of 37 weeks; 19 patients had stable disease, and 22 patients progressed on treatment. Median survival time was 40 weeks from the start of chemotherapy, and the median survival of responding patients was 87 weeks. One responding patient is still alive and free of relapse 4 years from the start of chemotherapy.
CONCLUSION: We conclude that further testing of EPI in malignant mesothelioma is warranted.
Author: K Mattson, G Giaccone, A Kirkpatrick, D Evrard, L Tammilehto, FJ van Breukelen, HT Planteydt and N van Zandwijk
Address: University Central Hospital, Helsinki, Finland. JCO

Combined Resection, Intraperitoneal Chemotherapy and Whole Abdominal Radiation for the Treatment of Peritoneal Mesothelioma
Abstract:
Previous studies have suggested that multimodality therapy prolongs survival in patients with peritoneal mesothelioma. The feasibility of combined resection, intraperitoneal (IP) chemotherapy, and whole abdominal radiation (RT) were evaluated in this pilot study. Patients were scheduled to undergo debulking with intraperitoneal catheter placement followed 2-3 weeks postoperatively with five courses each of IP cisplatin 100 mg/m2 alternating with doxorubicin 25 mg given weekly for a total of ten courses. After re-exploration, to document disease status and to resect residual disease, patients were to receive 3080 cGy to the abdomen and pelvis. Ten symptomatic patients (5M/5F), median age 48 (45 - 71) were enrolled. Six patients had prior asbestos exposure. Two patients are currently awaiting second laparotomy: thus eight patients are evaluable. Of these, four patients underwent surgical debulking and IP chemotherapy but did not receive planned RT. Four completed all three modalities of treatment. There have been no toxic deaths or renal complications. Three patients had grade 3 nausea during IP chemotherapy. One blocked catheter required discontinuation of chemotherapy; no other intraperitoneal complications occurred. Two of the four patients receiving RT developed transient grade 3/4 colitis. Two patients died of progressive disease. Six of the eight evaluable patients are alive; 3 have no evidence of progressive disease; 2 have intra-abdominal disease; and 1 has a solitary metastasis to a left inguinal node. Surviving patients report decreased symptoms and improved quality of life after therapy. These
RESULTS confirm the tolerability and efficacy of combined multimodality treatment and has led to our current phase I/II study of intraperitoneal chemotherapy/interferon, surgery and radiotherapy.
Author: Keohan ML, Chabot J, Fountain K, Antman KH, Taub RN.
Address: Columbia University Divisions of Medical Oncology (MLK, KHA, RNT), Surgery (JC), Radiation Oncology (KF), Columbia-Presbyterian Medical Center, New York, NY 10032

Chemotherapy in malignant pleural mesothelioma. A review
Abstract:
PURPOSE AND DESIGN: We reviewed the published literature of clinical studies in malignant pleural mesothelioma, including phase II trials of the newer antifolates and plant derivatives, as well as older single- agent and combination chemotherapy trials. We excluded trials with less than 15 patients, although we have mentioned smaller trials in the text to make a specific point, as well as ones that show promise. We have also included confidence intervals when cited in the original reports, or calculated them when absent.
RESULTS: No drugs have consistently induced a response greater than 20%. Higher response rates have been reported with detorubicin, high-dose methotrexate, and edatrexate at 26%, 37%, and 25%, respectively, but these have yet to be confirmed. Agents that produce response rates in 10% to 20% of patients include doxorubicin, epirubicin, mitomycin, cyclophosphamide, ifosfamide, cisplatin, and carboplatin. Combination chemotherapy trials do not demonstrate a consistently greater response rate than single-agent trials. However, the combination of doxorubicin, cisplatin, bleomycin, and mitomycin demonstrated a response rate of 44% (95% confidence interval, 27% to 63%), but this remains unconfirmed. Intrapleural therapy using interferon gamma, particularly for small-volume disease, shows promise.
CONCLUSION: The successful treatment of unresectable pleural mesothelioma awaits the discovery of active drugs. Recent trials of high-dose methotrexate and other antifolates are encouraging. Newer agents, including suramin, should be evaluated in phase II trials. Off-protocol combination therapy cannot be recommended over single-agent therapy, but studies that use combinations of the newer agents should be conducted.
Author: ST Ong and NJ Vogelzang
Address: Department of Medicine, University of Chicago, IL, USA.

Impressive remission in a patient with locally advanced malignant pleural mesothelioma treated with gemcitabine.
Abstract:
The
RESULTS of treatment of malignant pleural mesothelioma are quite unsatisfactory regardless of the substance or schedule employed. Although some activity is proved for anthracyclines, platinum compounds and alkylating substances, no chemotherapeutic regimen has emerged as a standard of care. Response rates documented in literature are between 10 and 20% for all these regimens. We report about a patient with locally advanced, unresectable pleural mesothelioma treated with the nucleoside analog gemcitabine (2,2-difluorodeoxycytidine). A 54-year-old male patient with unresectable pleural mesothelioma confirmed by thoracoscopic biopsy was treated with seven cycles of gemcitabine (1000 mg/m2 on day 1, 8 and 15) over a period of 36 weeks. Restaging by thoracic computed tomography (CT) scan was performed after 8, 20 and 36 weeks. At week 36 after beginning of treatment, the CT scan exhibited a substantial partial remission with a reduction of tumor volume of over 50%. The adverse effects of the therapy were very moderate with a hematotoxicity not exceeding WHO grade I and a mild 'flu-like syndrome' during the first three cycles which responded quite well to steroids. The compliance of the patient was excellent and his general condition improved significantly under therapy. Gemcitabine seems to be an active drug for the treatment of pleural mesothelioma. Compared to other active regimens it is normally very well tolerated by the patients. Because of these characteristics gemcitabine seems a suitable antineoplastic substance, especially in palliative settings. It would be worthwhile to test its activity in pleural mesotheliomas in controlled trials.
Author: Weinmann M, Brandes A, Classen J, Schott U, Bamberg M.
Address: Department of Radiation Oncology, University of Tubingen, Germany. martin.weinmann@uni.tuebingen.de Journal: Anticancer Drugs 1999 Jan

Malignant mesothelioma in women.
Abstract:
About 8% of our cases of mesothelioma occur in women, with a median age of 59 years. Our percentage is lower than other series reported in the literature because of the large number of occupationally exposed men referred to our laboratory. Tumor arose in the pleura in 86% of the women in our study, and the majority were epithelial. Pleural plaques were found in half of the women for which this information was available, and asbestosis was found in only 16%. A history of exposure to asbestos was identified in three quarters of the women, more than half of whom were household contacts of asbestos workers. Occupational exposure to asbestos was identified in only 19% of patients. An elevated tissue asbestos burden was noted in 70% of women from whom lung tissue was available for analysis. The main fiber type identified was amosite, followed by tremolite and chrysotile. These findings and those from other countries suggest a need for reassessment of the background rate of mesothelioma in industrialized nations.
Author: Roggli VL, Oury TD, Moffatt EJ.
Address: Durham VA and Duke University Medical Centers, North Carolina, USA. Journal: Anat Pathol 1997

Phase I and pharmacologic study of sequences of gemcitabine and the multitargeted antifolate agent in patients with advanced solid tumors.
Abstract:
PURPOSE: Multitargeted antifolate (MTA) is an investigational agent that, like gemcitabine, exhibits broad activity in solid tumors. A phase I trial of MTA and gemcitabine was undertaken, based on the demonstration of preclinical cytotoxic synergy.
PATIENTS AND METHODS: Thirty-five patients (group I) received 164 courses (median, four; range, one to 14 courses) of treatment of gemcitabine at doses of 1,000 and 1,250 mg/m(2) on days 1 and 8 and MTA at doses of 200, 300, 400, 500, and 600 mg/m(2), given 90 minutes after gemcitabine on day 1. Courses were repeated every 3 weeks. Because the day 8 dose of gemcitabine was reduced or omitted in 57% of courses due to neutropenia, 21 patients (group II) were treated on an alternate schedule, with MTA administered on day 8 rather than day 1. This group received 85 treatment courses (median, four; range, one to 10 courses).
RESULTS: The most common and dose-limiting toxicity was neutropenia. Other toxicities included nausea, fatigue, rash, and elevated hepatic transaminases. The maximum-tolerated dose was gemcitabine/MTA 1,000/500 mg/m(2) for group I and 1,250/500 mg/m(2) for group II. Thirteen objective responses were documented (colorectal cancer, n = 3; non-small-cell lung cancer, n = 3; cholangiocarcinoma, n = 2; ovarian carcinoma, n = 2; mesothelioma, n = 1; breast cancer, n = 1; and adenocarcinoma of unknown primary site, n = 1). Gemcitabine had no effect on the disposition of MTA.
CONCLUSION: The gemcitabine/MTA combination is broadly active and warrants further evaluation. The sequence of gemcitabine administered on days 1 and 8 with MTA administered on day 8 is better tolerated and is recommended for further study at doses of gemcitabine/MTA 1,250/500 mg/m(2).
Authors: Adjei AA, Erlichman C, Sloan JA, Reid JM, Pitot HC, Goldberg RM, Peethambaram P, Atherton P, Hanson LJ, Alberts SR, Jett J.
Address: Department of Oncology, Mayo Clinic and Foundation, Rochester, MN 55905, USA. adjei.alex@mayo.edu

Gene-modified PA1-STK cells home to tumor sites in patients with malignant pleural mesothelioma.
Abstract:
BACKGROUND: Malignant mesothelioma is an uncommon but lethal cancer of increasing incidence, particularly among patients with a history of exposure to asbestos. Although numerous treatments have been employed, including chemotherapy, radiation therapy, surgical resection, and combinations of the above, no satisfactory treatment yet exists, and affected patients will die of this disease, usually within 12 months. Gene-based therapies constitute a new approach that offers hope of improved control of these tumors while being associated with less morbidity than conventional chemotherapeutic or surgical regimens. We demonstrated that PA1-STK cells home in vivo to mesothelioma deposits, a phenomenon that is required for optimal exertion of this therapeutic concept. METHODS: Gene-modified ovarian cancer cells expressing the thymidine-kinase gene (PA1-STK) were radiolabeled with 99Tc and infused into the pleural space of 4 patients with malignant pleural mesothelioma, then scanned to determine distribution of the cells.
RESULTS: PA1-STK cells recognized and adhered preferentially to mesothelioma lining the chest wall. CONCLUSIONS: Cell-based "suicide gene" therapy utilizing the "bystander effect" with the gene-modified ovarian cancer cell line PA1-STK is feasible in human pleural mesothelioma. We have shown that this trafficking and homing of the therapeutic cells to the intrapleural tumor sites, a requirement for success with this novel therapeutic concept, is also valid in humans.
Authors: Harrison LH Jr, Schwarzenberger PO, Byrne PS, Marrogi AJ, Kolls JK, McCarthy KE
Address: Department of Surgery, Louisiana State University Health Sciences Center, New Orleans 70112-2822, USA. lharri@lsumc.edu Journal: Ann Thorac Surg 2000 Aug;70(2):407-11

Operation and photodynamic therapy for pleural mesothelioma: 6-year follow-up.
Abstract:
BACKGROUND: Conventional therapy for pleural mesothelioma has met with disappointing
RESULTS. METHODS: From 1991 to 1996, 40 patients with malignant pleural mesothelioma were treated with surgical resection followed by immediate intracavitary photodynamic therapy.
RESULTS: The series included 9 women and 31 men with a mean age of 60 years. Morbidity and treatment-related mortality rates for the entire series, pleurectomy, and extrapleural pneumonectomy were 45% and 7.5%, 39% and 3.6%, and 71% and 28.6%, respectively. Median survival and the estimated 2-year survival rate for the entire series, stages I and II patients (n = 13), and stages III and IV patients (n = 24) were 15 months and 23%, 36 months and 61%, and 10 months and 0%, respectively. Multivariate analysis identified stage, length of hospital stay, photodynamic therapy dose, and nodal status as independent prognostic indicators for survival. CONCLUSIONS: Surgical intervention and photodynamic therapy offer good survival
RESULTS in patients with stage I or II pleural mesothelioma. For patients in stage III or IV, better treatment modalities need to be developed. Improvements in early detection and preoperative staging are necessary for proper patient selection for treatment.
Author: Moskal TL, Dougherty TJ, Urschel JD, Antkowiak JG, Regal AM, Driscoll DL, Takita H.
Address: Department of Radiation Biology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA. Journal: Ann Thorac Surg 1998 Oct

Talc induces apoptosis in human malignant mesothelioma cells in vitro.
Abstract:
Pleurodesis with talc is an accepted method for the treatment of symptomatic pleural effusions secondary to mesotheliomas. Patients with mesothelioma who have talc-induced pleurodesis have a lower morbidity than do those who do not have pleurodesis. The mechanisms whereby talc mediated these effects were considered to be secondary to a decrease or absence of a pleural effusion. The possibility that talc may directly affect malignant cells was not considered. The present study was designed to evaluate if talc directly effects cell death of malignant mesothelioma cells (MMC) or normal pleural mesothelial cells (PMC). Three confluent MMC and PMC were exposed to talc for 24, 48, and 72 h. In parallel experiments, glass beads similar in size to talc were included as control. Apoptosis was determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) and DNA electrophoresis. Our
RESULTS demonstrated that talc at a therapeutically achievable concentration (6 microg/cm(2)) induces significant apoptosis in MMC. Talc-induced maximum apoptosis in MMC (39.50 +/- 2.55%, 31.87 +/- 4.69%, and 15.10 +/- 3.93% in CRL-2081, CRL-5820, and CRL-5915, respectively) at 48 h, which was significantly (p < 0.05) greater than that in control cells. Electrophoresis of DNA isolated from talc-exposed MMC demonstrated the typical ladder pattern of internucleosomal DNA cleavage. Talc did not induce apoptosis in PMC, and glass beads did not cause significant apoptosis in either MMC or PMC. The present study has demonstrated that talc induces apoptosis in MMC without affecting normal mesothelial cells of the pleura.
Author: Nasreen N, Mohammed KA, Dowling PA, Ward MJ, Galffy G, Antony VB.
Address: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Veterans' Affairs Medical Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.

Peritoneal cancer and occupational exposure to asbestos:
RESULTS from the application of a job-exposure matrix.

Abstract:
BACKGROUND: Because of the rarity of peritoneal mesothelioma, occupational risks associated with it have seldom been studied, particularly among women. In this respect, death certificates databases may provide numbers large enough for analysis, although the International Classification of Diseases, 9th revision (ICD-9) does not single out mesothelioma from the rest of peritoneal cancers. The aim of this paper is twofold: to explore occupational risks of peritoneal cancer among men and women, and to test the performance of a job-exposure matrix in detecting its association with asbestos exposure using the occupation and industry reported in the death certificate. METHODS: From a large database containing information on the 1984-1992 death certificates of 24 U.S. states, we identified 657 deaths from peritoneal cancer and 6,570 controls who died from non-malignant diseases, 1:10 matched by region, gender, race, and 5-year age group.
RESULTS: Occupations at risk included insulators among men, and machine operators among women. Among men, we found a significant increase in risk associated with employment in manufacturing industries, such as industrial and miscellaneous chemicals; miscellaneous non-metallic mineral and stone products; construction and material handling machines; and electrical machinery, equipment, and supplies; as well as in services to dwellings and other buildings. Industries at increased risk among women included elementary and secondary schools; miscellaneous retail stores; and publishing and printing. Our job-exposure matrix classified 17 male cases and 3 controls in the high probability category of exposure to asbestos (OR = 61.6). Among men, risk of peritoneal cancer increased significantly by probability and intensity of exposure to asbestos. No such pattern was observed among women. The job-exposure matrix did not classify any female subjects in the high probability or intensity of asbestos exposure. DISCUSSION: This study provides evidence that death certificate data and job-exposure matrices are useful tools to observe well-established associations, such as the one existing between peritoneal cancer and asbestos exposure among men, in spite of crude information, disease misclassification, and occupational misclassification. These factors are more likely to preclude meaningful
RESULTS among women.
Authors: Cocco P, Dosemeci M.
Address: Occupational Studies Section, National Cancer Institute, Bethesda, MD 20892, US Journal: Am J Ind Med 1999 Jan;35(1):9-14

Malignant pleural mesothelioma presenting as spontaneous pneumothorax: a case series and review.
Abstract:
BACKGROUND: Malignant pleural mesothelioma (MPM) is thought to arise from the mesothelial cells that line the pleural cavities. Most patients initially experience the insidious onset of chest pain or shortness of breath, and it rarely presents as spontaneous pneumothorax. CASE REPORTS: We report four patients who presented in this manner. Three of the patients were exposed to asbestos directly or indirectly at shipyards during World War II; the fourth was exposed as an insulator's wife. Two of our cases were not recognized to have MPM on histologic examination at first thoracotomy and remained asymptomatic for 12 and 22 months, respectively. In none of the patients described herein, was spontaneous pneumothorax the cause of death. CONCLUSIONS: Since many people were exposed to asbestos during and after World War II, spontaneous pneumothorax in a patient with the possibility of such exposure should raise the suspicion of malignant pleural mesothelioma. Copyright 2000 Wiley-Liss, Inc.
Authors: Alkhuja S, Miller A, Mastellone AJ, Markowitz S.
Address: Division of Pulmonary Medicine, Department of Medicine, Catholic Medical Center of Brooklyn and Queens, Jamaica, NY, USA. salkuja@aol.com Journal: Am J Ind Med 2000 Aug;38(2):219-23

Epithelial mesothelioma with deciduoid features.
Abstract:
A rare case of malignant mesothelioma in a 15-year-old girl is described. The patient presented with secondary amenorrhoea and clinical symptoms resembling those of an ovarian cyst. One large and multiple small peritoneal nodules were found at laparoscopy. Histologically the tumour was characterised by an unusual pattern with a superficial resemblance to decidual reaction, but because of significant mitotic activity the diagnosis of a malignant tumour, epithelial mesothelioma with deciduoid features, was made. The patient died 11 months after diagnosis. Post-mortem examination revealed extensive extraperitoneal spread.
Authors: Orosz Z, Nagy P, Szentirmay Z, Zalatnai A, Hauser P.
Address: Center of Diagnostic and Experimental Tumour Pathology, National Institute of Oncology, Budapest, Hungary. zso@oncol.hu Journal: Virchows Arch 1999 Mar;434(3):263-6

Malignant mesothelioma presenting as pulmonary metastasis ahead of growth of primary tumour.
Abstract:
A 59-year-old woman was admitted to Houju Memorial Hospital, Ishikawa, Japan, because of cough and fever on 30 March 1997. A diagnosis of pneumonia was made and she was given antibiotics. Her symptoms improved but failed to resolve completely on antibiotic therapy. On 9 September 1997, she revisited the hospital because of bodyweight loss and malaise. There was no history of exposure to asbestos. The chest roentgenogram revealed infiltrative shadows with vague and indistinct margins suggesting inflammatory processes, which were more extensive than those investigated on her last visit. One month later, a giant tumour was detected rapidly growing from the mediastinum and open biopsy was performed. The histological examination confirmed that the tumour was a malignant mesothelioma and the intrapulmonary nodules were its metastases. This is a rare case of pulmonary metastasis being present for several months before an appearance of primary mesothelioma.
Authors: Heki U, Fujimura M, Kasahara K, Matsubara F, Matsuda T.
Address: Third Department of Internal Medicine, Kanazawa University School of Medicine, Japan. Journal: Respirology 1999 Sep;4(3):279-81

Video-assisted thoracoscopic excision of a benign cystic mesothelioma of pleura.
Abstract:
We are reporting on the case of a 44-year-old woman upon which video-assisted thoracoscopic excision of a benign cystic mesothelioma of the pleura was performed. To our knowledge, this is the second report on a case of a benign cystic mesothelioma of the pleura. The cyst in our case was solitary and was easily excised. Microscopic examination revealed that the cyst was lined by a single layer of flattened and cuboidal cells. Immunohistochemical analysis revealed that the cells lining the cyst stained positively for keratin and negatively for factor VIII-related antigen. Benign cystic mesothelioma of the pleura was diagnosed based on histological findings. For seven months her condition has been monitored at our out-patient clinic with no signs of recurrence. However, continued careful observation is required because benign cystic mesothelioma often recurs locally. Local recurrence is thought to be related to incomplete resection of the tumor. Therefore, careful observations and techniques to ensure complete resection of the cyst, are important during video-assisted thoracoscopic surgery.
Authors: Haraguchi S, Koizumi K, Kawamoto M, Tanaka S, Tanaka S.
Address: Department of Surgery II, National Defense Medical College, Saitama, Japan. Journal: Jpn J Thorac Cardiovasc Surg 1998 Aug;46(8):664-6

Malignant mesothelioma of the tunica vaginalis testis: a report of two cases and review of literature.
Abstract:
Two cases of rare malignant mesothelioma of tunica vaginalis testis are presented. Both cases were advanced on clinical and radiological studies. One patient was treated with surgical excision followed by chemotherapy and radiotherapy and the other patient was treated with surgery and chemotherapy. Despite aggressive therapy both the patients died within 18 months of treatment. Review of the literature with suggested treatment protocol is presented. The response of malignant mesothelioma to chemotherapy and radiotherapy is poor as indicated by both of our cases. Initial aggressive surgery and adjuvant procedures are necessary soon after diagnosis to achieve long-term survival.
Authors: Gupta NP, Agrawal AK, Sood S, Hemal AK, Nair M.
Address: Department of Urology, All India Institute of Medical Sciences, New Delhi. narmadagupta@hotmail.com Journal: J Surg Oncol 1999 Apr;70(4):251-4

Malignant mesothelioma of the pleura with a large tumor embolus in the left atrium: an autopsy case.
Abstract:
Malignant mesothelioma of the pleura often involves the heart but seldom invades the intracardiac cavity. We report a 78-year-old woman with right pleural mesothelioma who died of heart failure. An autopsy revealed that the tumor was present at the right pleura and invaded the right upper lobe of the lung and the mediastinum. The tumor also extended to the left atrium via the right pulmonary vein and filled the atrial cavity. Repeated transthoracic echocardiography failed to detect the tumor, but magnetic resonance imaging was useful for diagnosis.
Authors: Ishiyama Y, Hisanaga S, Asada Y, Sumiyoshi A, Eto T.
Address: First Department of Internal Medicine, Miyazaki Medical College, Kiyotake Journal: Intern Med 1998 Jul;37(7):614-7

A Review of Dr. Sugarbaker's
RESULTS Using Tri-Modal Therapy on 183 Patients from 1980 to 1997

Abstract:
We review our experience with extrapleural pneumonectomy (EPP) in the multimodality management of MPM. METHODS: From 1980 to 1997, 183 consecutive patients underwent trimodality therapy involving EPP followed by adjuvant chemotherapy and radiotherapy. Standardized systematic pathologic analysis was undertaken.
RESULTS: The cohort included 43 women and 140 men with a mean age of 57 years (range 31-76) and a median follow-up interval of 13 months. Overall survival was 36% at 2 yrs and 14% at 5 yrs (median 17 mo.). There were seven perioperative deaths (3.8% mortality). Factors affecting long-term survival were evaluated in 176 patients surviving surgery (among these, survival was 38% at 2 yrs and 15% at 5 yrs; median 19 mo.). As indicated in the table below, lack of N2 nodal involvement, negative resection margins and epithelial histology were associated with improved survival. Factorial grouping by N2 status and resection margins significantly stratified survival among all patients surviving surgery (p<0.02), and among those with epithelial histology (p<.02). Thirty-one patients with epithelial tumors, negative resection margins and without N2 involvement had a 51 mo. median survival (68% 2-yr, 46% 5-yr). A clinico-pathologic staging system previously published stratified survival (p<0.05; see table). Variable N 2-Year 5-Year Median(months) P Value Epithelial 103 52% 21% 26 0.0001 Mixed/Sarcom 73 16% 0% 13 Margins(+) 110 33% 9% 15 0.02 Margins(-) 66 44% 25% 23 N2(+) 40 23% 0% 14 0.004 N2(-) 136 42% 17% 21 Epithel.N2(+) 21 38% 0% 20 0.052 Epithel.N2(-) 82 56% 24% 34 Epithel.N2(+) Marg(+) 12 29% 0% 14 0.013 Epithel.N2(+) Marg(-) 9 43% 0% 22 Epithel.N2(-) Marg(+) 51 49% 14% 22 Epithel.N2(-) Marg(-) 31 68% 46% 51 StageI 66 53% 20% 25 0.048 StageII 41 44% 14% 20 StageIII 69 17% 14% 16 These data support the following CONCLUSIONs: Multimodality therapy including EPP is feasible in selected patients with MPM, Microscopic resection margins affect long-term survival, pointing to the need for further investigation of local-regional control strategies, Mediastinoscopy to evaluate N2 nodes is recommended, and Patients with epithelial, margin-negative, N2-negative resection enjoy long-term survival.
Author: Dr. David Sugarbaker Adress: Brigham and Womens Hospital in Boston

Current Therapy for Mesothelioma, Sugarbaker et al, 1997
Abstract:
Background: Diffuse malignant pleural mesotheliomas (DMPMs) are highly lethal tumors that are becoming more common. Standard management approaches have provided limited effectiveness. METHODS: The literature on management has been revised, and the
Authors present their data on outcomes for 120 patients treated with an aggressive trimodality approach.
RESULTS: An aggressive trimodality approach including extrapleural pneumonectomy followed by chemoradiation produces low mortality and acceptable morbidity. The five-year survival rate in patients with epithelial histology and negative nodes approaches 40%. CONCLUSIONS: Nodal status and histologic subtype are major predictors for survival in patients with early DMPM. A uniformly accepted staging system would allow comparison of treatment approaches from various institutions. More effective management interventions are required.
Authors: David J. Sugarbaker, MD, Jose J. Norberto, MD, and Raphael Bueno, MD
Address: Division of Thoracic Surgery, Brigham and Women's Hospital, Boston Mass

Successful Immunochemotherapy for Patients with Malignant Mesothelioma: Report of Two Cases
Abstract:
Malignant mesothelioma is a clinically aggressive tumor and has a poor prognosis; therefore, the selection of therapeutic strategies is important to improve the prognosis. Two patients with intraperitoneal malignant mesothelioma received combination therapy as follows: (1) case-oriented chemotherapy according to the
RESULTS of a chemosensitivity test, and (2) adoptive immunotherapy using cytotoxic T lymphocytes (CTL). The chemosensitivity test was assessed by an MTT colorimetric assay. CTL was generated by a mixed culture with autologous tumor cells, and activated by immobilized anti-CD3 monoclonal antibody and interleukin-2. The MTT assay indicated that cisplatin and adriamycin were sensitive drugs in both patients, and they thus received the case-oriented chemotherapy according to the MTT assay. The activated CTL exhibited a high cytotoxicity against autologous malignant mesothelioma cells, and were transferred intraperitoneally. The patients were controllable for ascites, and the tumor masses gradually vanished (partial response). Chemoimmunotherapy is thus considered to be an effective treatment for intraperitoneal malignant mesothelioma, especially to improve the quality of life.
Address:SecondDepartmentofSurgery,WakayamaMedicalSchool,Japan.
Author: Tani M; Tanimura H; Yamaue H; Mizobata S; Yamamoto M; Iwahashi M; Ura K; Nagai Y; Tsunoda T; WakasakiH;NanjoK;FujinoK;YukawaS Journal: Surg Today, 28(6):647-51 1998

Multimodality Management of Malignant Pleural Mesothelioma
Abstract:
In this article, we explain the current trimodality approach used to treat malignant pleural mesothelioma. Our current approach employs extrapleural pneumonectomy as the cytoreductive procedure followed by combination chemoradiotherapy. Trimodality therapy was performed at the Dana-Farber Cancer Institute/Brigham and Women's Hospital Thoracic Oncology Program. From 1980 to 1995, we prospectively followed up a series of 120 patients with confirmed malignant pleural mesothelioma who underwent trimodality therapy. Two- and 5-year survival rates for the entire cohort were 45% and 22%, respectively. Survival rates were 65% and 27%, respectively, at 2 and 5 years for patients with epithelial histology. Patients with sarcomatous or mixed histology had the poorest prognosis, with 2- and 5-year survival rates of 20% and 0%, respectively. For patients with epithelial tumors and negative nodes, survival at 2 and 5 years was 74% and 39%, respectively. Extrapleural pneumonectomy in the context of trimodality therapy is a potential surgical option for a selected group of patients with malignant pleural mesothelioma.
Author: Sugarbaker DJ; Norberto JJ
Address: Division of Thoracic Surgery, Brigham and Women's Hospital, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, MA 02115, USA. Journal: Chest, 113(1 Suppl):61S-65S 1998 Jan

Familial Pleural Malignant Mesothelioma: Clustering in Three Sisters and One Cousin
Abstract:
Malignant mesothelioma is associated with asbestos, yet its occurrence in genetically-related individuals suggests a role of host predisposition. We have identified a cluster of pleural malignant mesothelioma in three sisters and one cousin (male). The women had worked in the same confectionery shop as pastry cooks and/or pastry shop assistants; the use of an asbestos-insulated oven was the putative source of exposure. The man had occupational exposure as a heating system installation worker. The family history reported malignant cancers in first-degree (larynx, brother; pleura and lung, mother), second-degree (lung, aunt and uncle) and third-degree (lung, cousin) relatives. The study reveals the potential existence of the mesothelioma risk among pastry cooks and highlights the fact that inherited factors may be involved in the development of this tumour.
Authors: Ascoli V; Scalzo CC; Bruno C; Facciolo F; Lopergolo M; Granone P; Nardi F
Address: Anatomia Patologica, Dipartimento di Medicina Sperimentale e Patologia, Ospedale Policlinico Umberto I, Universit`a La Sapienza, Rome, Italy. Journal : Cancer Lett, 130(1-2):203-7 1998 Aug 14

Pathology of Diffuse Malignant Pleural Mesothelioma
Abstract:
An accurate diagnosis is essential to a rational approach to the treatment of diffuse malignant pleural mesothelioma and generally requires pathological examination with the application of special techniques. In recent years, immunohistochemistry has greatly abetted the distinction of mesothelioma from its many morphological mimics, yet diagnostic difficulties still remain because reactive hyperplasias and diverse tumors closely mimic mesothelioma. Mesotheliomas are classified into epithelial, mixed, sarcomatoid and undifferentiated types, based on conventional histological examination. The classification provides important prognostic information. Furthermore, differential diagnosis is directly related to histological type. Although such special techniques as histochemistry and electron microscopy continue to play an important role in some cases, immunohistochemistry often has replaced these in distinguishing epithelial-type mesothelioma from metastatic adenocarcinoma. It is also helpful in distinguishing sarcomatoid mesothelioma from it numerous morphological mimics. The distinction of mesothelioma from reactive mesothelial proliferations is still based on morphological examination and may be quite problematic. Recent cytogenetic studies, which have identified characteristic clonal deletions in mesotheliomas, give promise of providing valuable assistance in this distinction in the future.
Author: Corson JM
Address: The Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA. Journal: Semin Thorac Cardiovasc Surg, 9(4):347-55 1997 Oct