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The Chicago Consensus Working Group provides multidisciplinary recommendations for the management of peritoneal mesothelioma. These guidelines are developed with input from leading experts, including surgical oncologists, medical oncologists, pathologists, radiologists, palliative care physicians, and pharmacists. These guidelines recognize and address the emerging need for increased awareness of the appropriate management of peritoneal surface disease. They are not intended to replace the quest for higher levels of evidence., (© 2020 by the American Cancer Society and Society of Surgical Oncology.)

Background: In the current study, the authors report the clinicopathologic features of patients with peritoneal diffuse malignant mesothelioma (DMM) who were treated in a uniform fashion at a single institution to assess prognostic factors., Methods: Thirty-five patients were treated with cytoreductive surgery (CRS) and intraperitoneal hyperthermic perfusion (IPHP). The tumors were classified into epithelial, sarcomatoid, and biphasic types. Immunohistochemistry stains were performed for calretinin, WT-1, pCEA, Ber-EP4, epidermal growth factor receptor (EGFR), p16, matrix metalloprotease-2 (MMP-2), and MMP-9. Statistical correlation was evaluated for age, gender, completeness of cytoreduction (CC), tumor histotype, mitotic count (MC), necrosis, nuclear grade (NG), and biologic markers with regard to overall survival (OS) and progression-free survival (PFS)., Results: The patient group was comprised of 15 men and 20 women with a median age of 52 years (range, 24-73 yrs). Twenty-five patients underwent optimal cytoreduction. There were 32 epithelial tumors and 3 biphasic tumors, and 3 patients had an NG of 1, 19 had an NG of 2, and 13 had an NG of 3. The mean MC was 14.1 (range, 0-160 per 50 high-power fields). Necrosis was present in 11 cases. All the tumors were found to be positive for calretinin and WT-1 and were negative for pCEA and Ber-EP4. The NG and MC were found to be significantly associated with OS (P = 0.02 and P = 0.01, respectively) whereas CC was found to be associated with both OS (P = 0.05) and PFS (P = 0.03). No biologic markers were found to be of prognostic significance., Conclusions: The results of the current study indicate that NG, MC, and CC may be useful prognostic factors in patients treated with CRS and IPHP. The expression of EGFR, MMP-2, and MMP-9 and absent and/or reduced expression of p16 in DMMs confirms the results of previous studies suggesting their role in tumor pathogenesis and kinetics., (Copyright 2005 American Cancer Society)

Background: Malignant peritoneal mesothelioma is a rare and fatal disease. Until recently, the treatment options were very limited and ineffective. The new comprehensive approach of cytoreductive surgery with perioperative intraperitoneal chemotherapy offers improved survival rates at a cost of considerable morbidity and mortality as in other peritoneal surface malignancies. The outcome after these treatments is predominantly dependent on adequate cytoreduction. The aim of the current study was to identify computed tomography (CT) scan images that are useful in patient selection for this comprehensive approach., Methods: An analysis of the preoperative CT scans of 30 patients with peritoneal mesothelioma treated with cytoreductive surgery and perioperative intraperitoneal chemotherapy at a single institution was performed. Based on the size of residual tumor nodules after cytoreductive surgery, patients were divided into 2 groups: those with residual lesions2.5 cm (suboptimal cytoreduction). The CT scans for each patient were evaluated by a standardized scoring system with the reader blinded to the operative findings. Thirty-nine CT scan parameters were obtained and statistically analyzed to determine their association with the study outcome variables, namely, adequacy of cytoreduction., Results: Seven patients (64%) in the suboptimal cytoreduction group and 2 patients (11%) in the adequate cytoreduction group had a >5-cm tumor mass in the epigastric region (P=0.004). Nine patients (82%) in the suboptimal group and 2 patients (11%) in the adequate cytoreduction group had CT scans that showed loss of normal architecture of the small bowel and its mesentery (P<0.001). In a composite analysis of these 2 radiologic features, none of the patients with a >5-cm tumor mass in the epigastric region and loss of normal architecture of the small bowel and its mesentery had an adequate cytoreduction. Patients who lacked these two preoperative CT scan findings had a 94% probability of an adequate cytoreduction., Conclusions: CT scans effectively identified large peritoneal mesothelioma tumors at crucial anatomic sites. Because adequate cytoreduction is necessary to achieve prolonged survival, CT scans became an accurate prognostic radiologic test for patient selection for comprehensive treatment., (Copyright (c) 2005 American Cancer Society.)

Background: The behavior of diffuse peritoneal mesotheliomas in women and the possible relation between tumor morphology and outcome are uncertain. Reported survival has ranged from < 1 month to > 14 years, and a previous study found that tumor morphology could not be used reliably for predicting outcome. The authors examined the behavior of diffuse epithelial peritoneal mesotheliomas in women and the possible relation between pathologic features and outcome., Methods: Twenty-five female patients with diffuse peritoneal epithelial malignant mesotheliomas were divided into two groups: those who survived for < 4 years (60%) and those who survived for > 4 years (40%). Both groups were compared in terms of age, presentation, treatment, survival, tumor architecture, mitotic rate, necrosis, nuclear grade, and immunohistochemical profile., Results: Patients in the two groups were similar in terms of age at diagnosis (median ages, 50.7 years and 49.9 years), presentation, initial tumor burden, and treatment. In both groups, the most common initial clinical presenting features were ascites and abdominal pain. The tumors typically took the form of multiple nodules measuring < 1.5 cm in greatest dimension. Slightly less than 50% of patients in both groups received some form of chemotherapy or radiation therapy after undergoing tumor-reductive surgery or biopsy. Overall survival ranged from 1 month to 15 years. The median survival was 12 months in the group of women who survived for < 4 years and 7 years in the group of women who survived for > 4 years. Overall, 10 of 25 patients survived for > or = 5 years. One patient was alive with disease 15 years after diagnosis. Although there was a suggestion that the tumors in patients with short survival more often had solid architecture and high-grade nuclei, these findings were not significant statistically. The frequency of necrosis and the mitotic activity were the same in both groups., Conclusions: The spectrum of diffuse epithelial peritoneal mesotheliomas in women includes tumors that are highly aggressive and behave much like pleural mesotheliomas, although a sizeable number of tumors, unlike the pleural tumors, are relatively indolent. However, because there do not appear to be morphologic features that reliably identify favorable tumors versus unfavorable tumors, aggressive therapy for all women with diffuse peritoneal mesotheliomas may be warranted.

Background: Peritoneal mesothelioma is regarded as a fatal disease that presents with progressive ascites in a relatively late stage of its natural history. To the authors' knowledge, prior published articles have not described the early manifestations of this cancer., Methods: A 30-year-old asymptomatic woman underwent laparoscopy for an infertility workup. Nodules noted in the pelvis were biopsied and determined to be mesothelioma. Standard immunohistochemical studies were performed. Cytoreductive surgery and heated intraoperative intraperitoneal chemotherapy were used for treatment., Results: Multiple (approximately 30) tumor nodules up to 2 mm in dimension and limited to the pelvis were observed and resected. No primary tumor focus was evident. These tumor nodules stained positive for Calretinin and negative for carcinoembryonic antigen immunohistochemically., Conclusions: In this patient, no incidence for transcoelomic dissemination of mesothelioma from a single primary site was observed. Rather, this patient's clinical presentation suggested that mesothelioma may be multifocal in origin within a limited region of the peritoneal cavity. This hypothesis may support a rationale for aggressive local-regional management of selected patients in whom peritoneal mesothelioma is of limited distribution and mass., (Copyright 2000 American Cancer Society.)

Background: Only 73 cases of malignant mesothelioma of the tunica vaginalis testis have been reported in the last 30 years. Although these tumors were most often seen in patients between ages 55 and 75 years, 10% of the patients were younger than 25 years. Because prognostic parameters have not yet been reported, the authors present another case of a male age 14 years and a review of the available literature, which they conducted to determine prognostic parameters., Methods: The medical literature about malignant mesothelioma of the tunica vaginalis testis was reviewed. For the determination of prognostic parameters, a univariate and multivariate Cox regression model was used to assess the relevance of the patient's age, history of asbestos exposure, tumor histology, primary therapeutic approach, and presence of metastatic disease to survival., Results: Previous exposure to asbestos or asbestos-containing materials must be considered a risk factor for the development of malignant mesothelioma. The major difficulty in managing patients with malignant mesothelioma of the tunica vaginalis testis was determining an accurate preoperative diagnosis, which was reported in only two cases. Due to the lack of characteristic symptoms, 97.3% of the cases were diagnosed intraoperatively. Of patients who underwent local resection of the hydrocele wall, 35.7% experienced local tumor recurrence, as compared with 10.5% after scrotal orchiectomy and 11.5% after inguinal orchiectomy. Therefore, radical orchiectomy should be the first-line therapy. The median survival of the patients was 23 months, which decreased to 14 months in cases of recurrence. The overall recurrence rate (local and disseminated) was 52.5%. More than 60% of recurrences developed within the first 2 years of the follow-up. In some cases of disseminated mesothelioma, adjuvant chemotherapy or radiotherapy was given. Although reports on adjuvant treatments were limited, radiotherapy appeared to be more effective than chemotherapy. However, 37.9% died of disease progression. Assessment of prognostic parameters revealed a significant correlation of patient's age with survival (P < 0.01), with a better outcome for younger patients and a worse disease course for patients with primary disseminated disease (P < 0.05) in univariate analysis. A multivariate Cox regression model of prognostic parameters concerning survival did not yield statistically significant results., Conclusions: Malignant mesotheliomas of the tunica vaginalis testis rarely occur, but the possibility should be considered for all age groups. Univariate analysis determined that a patient's age and the presence of primary disseminated disease were prognostic parameters related to survival. Due to the invasive potential of this disease and the risk of tumor recurrence, radical orchiectomy and close follow-up are strongly recommended.

Background: This report presents the results of a prospective multi-institutional study of intrapleural treatment with gamma-interferon in patients with Butchart's Stages I and II epithelial or mixed malignant pleural mesothelioma., Methods: Interferon was administered at a dose of 40 million units twice a week for 8 weeks intrapleurally via a catheter or an implantable port. Thoracoscopic or surgical biopsy was performed if computed tomography scan 2 weeks after the end of treatment demonstrated a reduction in tumor size. Survival was calculated after a follow-up of at least 18 months. Prognostic factors were identified by univariate and multivariate analyses (Cox model)., Results: Eighty-nine patients were included over 46 months. Eight histologically confirmed complete responses and nine partial responses with at least a 50% reduction in tumor size were obtained. The overall response rate was 20%. Most responses were achieved in patients with early stage disease. The response rate for patients with Stage I disease was 45%. Tolerance of interferon was good. Treatment was performed on an outpatient basis. The main side effects were hyperthermia, liver toxicity, neutropenia, and catheter-related infection., Conclusions: Gamma-interferon is effective mainly in Stage I mesothelioma, especially if the tumor is confined to the parietal or diaphragmatic pleura (Stage IA).

Background: Medical records of 50 patients with malignant mesothelioma were reviewed to determine the clinical features and factors influencing survival., Methods: Charts of all patients whose conditions were diagnosed as malignant mesothelioma were abstracted and analyzed by statistical software., Results: The male-to-female ratio was 4:1. The age distribution was younger than 45 years of age, 10%; 45-54 years of age, 12%; 55-64 years of age, 37%; 65-74 years of age, 33%; and 75 years of age or older, 8%. Both mean and median ages were 58 years. Among the 32 patients in whom asbestos exposure was recorded, 24 had documented exposure. The sites were pleura, 73%; peritoneum, 20%; and both, 6%. The histologic types were epithelial, 51%; sarcomatous, 10%; mixed, 15%; and not specified, 24%. The stage at presentation was Stage I, 37%; II, 39%; III, 12%; IV, 6%; and unknown, 6%. The common symptoms in pleural disease were dyspnea and pain; in peritoneal disease, abdominal distension and pain were common. The median time from first symptom to diagnosis was 3 months (range, 0-23 months). The median survival after the appearance of symptoms, the diagnosis, and the treatment were 13, 10, and 8 months, respectively., Conclusions: The survival was independent of age, sex, and smoking behavior. It was longer in patients with earlier-stage disease, a good performance status, a longer duration of symptoms, an absence of pain, and who were treated with combined surgery and chemotherapy. Chemotherapy using anthracyclines yielded more remissions (9 of 21) than that using nonanthracyclines (0 of 13). The remission rate after primary chemotherapy with anthracyclines (7 of 16) may be higher than in recurrent tumor (2 of 14). In future trials, stratification into primary chemotherapy and chemotherapy of recurrent cancer is suggested. There is a need for multitechnique trials incorporating primary chemotherapy.

There is no effective therapy for human malignant mesothelioma, and its susceptibility to recombinant cytokines has not been studied extensively. Recombinant human tumor necrosis factor alpha (rHuTNF alpha) was evaluated for its in vitro and in vivo antitumor activity using a human malignant mesothelioma cell line [DeH128(m)], both in culture and heterotransplanted in nude mice. In vitro, rHuTNF alone had no direct antimesothelioma activity assessed using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide assay, but in combination with the transcription inhibitor, dactinomycin (AD), mesothelioma cell metabolic activity was inhibited (80% of control). The effects of this combination of agents were studied on DeH128(m) cells heterotransplanted as subcutaneous tumors in nude mice. In vivo there was no significant inhibition of tumor growth by combined rHuTNF alpha and AD therapy, but the combination produced marked cachexia in doses at which each component (rHuTNF alone or AD alone) was well tolerated. The authors conclude that the well-described in vitro interaction between AD and rHuTNF also operates in vivo to produce cachexia and that the combination of these two agents is likely to have a low therapeutic index in malignant mesothelioma.

Twenty-two consecutive patients with malignant diffuse pleural mesothelioma were treated with recombinant gamma-interferon by the intrapleural route. Diagnosis was made by thoracoscopic examination and all cases were confirmed by the French Mesothelioma Panel of Pathologist. Patients were staged based on thoracoscopic examination and computed tomography (CT) scan: 12 patients were classified as Stage I and 10 were Stage II. A solution of gamma-interferon (40 X 106 U) was infused twice a week over 2 months. Every patient experienced fever. One patient had a Grade 2 leukopenia and one patient suffered from pleural empyema. Response evaluation was based on the following: (1) CT scan performed 2 weeks after treatment ended, and (2) repeat thoracoscopic examination with histopathologic verification in nine patients who had demonstrated a stabilization or a regression of the disease on CT scan. From the original group, 19 patients could be evaluated. Four complete thoracoscopic histopathologic responses and one partial response were observed in Stage I patients (56%). One partial response was observed in Stage II patients.

Twenty-two cases of well-differentiated papillary mesothelioma of the peritoneum (WDPMP) are described. Eighteen of the 22 patients were women. The peritoneal tumor was usually multifocal. Many of the tumors appear to be indolent or inactive and for practical purposes are benign. However, a few patients receiving adjuvant therapy have died under circumstances that make it difficult to determine whether the tumor was responsible for the death. It is suggested that adjuvant therapy be withheld from patients with WDPMP, unless there is clear evidence of progression. The cause of these rare tumors is not apparent, although three patients had had possible exposure to asbestos and two were sisters.

Clinical, radiographic, surgical, and pathologic findings and survival in 92 patients with diffuse malignant mesothelioma (DMM) of the pleura who were examined at the Mayo Clinic between 1950 and 1980, were studied retrospectively. With the use of defined criteria and ordinary tissue stains, the 92 cases were classified into the following histologic subtypes: purely epithelial, 42 cases; mixed, 29 cases; and sarcomatous, 21 cases. Eight of the sarcomatous cases were desmoplastic. Median survivals were 12, 5, and 3 months for the patients in the epithelial, mixed, and sarcomatous groups, respectively. Survival was significantly longer for patients with epithelial DMM. Women survived longer than men but more often had epithelial DMM. Early disease manifested as multiple discrete pleural nodules, predominantly on the parietal pleura. However, nine patients had a dominant mass. Radiographic signs especially suggestive of DMM were nodular pleural thickening, irregular thickening of interlobar fissures, a dominant mass, or decreased volume of the affected hemithorax.

Thirty-six patients with diffuse malignant pleural mesothelioma were seen over a period of 15 years. The median age was 60 years (range, 21 to 75 years), and the male to female ratio was 2.3 to 1. The most common symptoms were chest pain and shortness of breath and all patients presented with pleural effusion on chest x-ray. The diagnosis was established by tissue biopsy in all cases. The median survival time for all patients was 12.5 months. Twenty-one patients were treated with an adriamycin-containing regimen and in this group, the median survival time from histological diagnosis was 14 months. In contrast, the median survival time for the 15 patients, who did not receive adriamycin, was 6 months (p = 0.009). The median survival time from the initiation of chemotherapy was 9 months for the adriamycin group and 2 months for patients treated with other type of chemotherapy (p = 0.001). Adriamycin appears to be of benefit in the treatment of diffuse malignant pleural mesothelioma.

The serum hyaluronan levels of 37 patients with malignant mesothelioma were followed during the course of treatment (high doses of methotrexate were given to 32 of these patients). The patients could be divided into the following two groups: (1) those with progressive disease (n = 17) or (2) those showing improvement during therapy (complete remission [n = 2], partial remission, or no change [n = 18]). On admission to the hospital, the patients with progressive disease showed significantly higher initial serum hyaluronan levels (median value, 250 micrograms/l) than those in the second group (median value, 97 micrograms/l) (P less than 0.005, Wilcoxon). Serum hyaluronan as a predictor of progressive disease has a sensitivity of 65% and a specificity of 85%. There was a significant increase in serum hyaluronan levels during treatment in patients with progression (P less than 0.01). In three patients with initially high levels there was a clear decrease in parallel with the reduction in tumor burden. In the remaining patients of the responder group, the values were constantly low. There was no significant correlation between the hyaluronan level and any other laboratory test performed on blood samples. Pleural fluid was removed for medical reasons from 13 patients. Neither the presence of pleural fluid nor its hyaluronan level were correlated to the progression of the disease. However, there was an interesting negative correlation between serum and pleural hyaluronan levels, indicating that an elevated serum hyaluronan level does not reflect high production in the pleural cavity.

Between 1950 and 1981, 31 patients with mesothelioma were treated at the University of Minnesota. An average of 0.2 to 0.6 patients were seen per year between 1950 and 1970, and since 1970 there has been an average of 1.4 to 2.4 patients per year. Twenty-seven of the 28 patients with malignant mesothelioma are known or presumed dead. Mesotheliomas occurred in all areas of Minnesota, and 28.6% of the patients had a definite history of asbestos exposure. This was also a probable cause of the disease in an additional 25% of patients. The clinical findings and course of the disease were similar to other series. The median survival of all patients was eight months. Doxorubicin-treated patients survived a median of 16 months (range, 2-36 months). Malignant mesothelioma is being increasingly recognized in Minnesota and has a grim prognosis in spite of doxorubicin therapy.

Twelve patients with pulmonary neoplasms treated at the Fox Chase Cancer Center were found to have a syndrome of axillary-subclavian vein occlusion. Ten patients had non-small-cell lung carcinoma, one had small cell carcinoma, and one had mesothelioma. In eight patients, this vascular syndrome developed as a consequence of progressive or metastatic recurrent disease, while in four patients it presaged the appearance of the initial malignant disease. Axillary-subclavian vein occlusion should be easily differentiated from the superior vena cava syndrome. Treatment with anticoagulation therapy in addition to specific antitumor therapy may relieve symptoms and signs without altering the occlusion itself.

Seventy-six patients with pleural mesothelioma were seen at Memorial Hospital from 1939 to 1972. There were 10 with benign and 66 with malignant mesotheliomas. The latter were histologically divided into 39 epithelial and 27 fibrosarcomatous types. Main symptoms were chest pain, dyspnea, and cough. Most of the patients with malignant disease had clinical and radiologic evidence of effusion with or without an intrathoracic mass. Thirty-seven patients had primary untreated mesothelioma and 29 patients had disease that had previously been treated elsewhere. Treatment at Memorial Hospital consisted of surgery, with or without radiation therapy, and supplemental chemotherapy. Survival was related to extent of disease and to treatment. In patients with epithelial mesothelioma confined to the hemithorax, resection was associated with a median survival of 21 months. When irradiation was the primary treatment, the median survival was 8 months. In fibrosarcomatous mesotherlioma, the median survival with resection was 11 months and with radiation, 9 months. Median survival in patients with advanced or recurrent disease was 3 to 6 months. It is concluded that epithelial mesotherlioma with diffused pleural involvement continues to carry a grave prognosis. Better survival is obtained where pleurectomy with resection of the bulk of the tumor is combined with external irradiation and systemic chemotherapy. In fibrosarcomatous mesothelioma, complete resection offers a significant chance of long-term survival. In patients with benign mesothelioma, none had recurrence nor died of disease after adequate resection.

In this series of nine patients with primary pleural mesothelioma, three patients, all women, had "localized benign" tumors located in the left chest, although one had a recurrence on the right. Five patients all male, had the "diffuse malignant" type, and one woman had "multiple discrete" pleural tumors. Classification on the basis of gross appearance is useful clinically and prognostically, as reflected by the relatively benign behavior of localized pleural mesothelioma in contrast to the relentless lethal nature of the diffuse type. Although seven patients had pleural effusion, cytologic studies were of little help in establishing the diagnosis and all underwent thoracotomy. None of these patients had hypoglycemia or evidence of asbestosis, although three patients had a history of previous asbestos exposure.