Diffuse Malignant Mesothelioma Research Articles

Gemcitabine combined with oxaliplatin in pretreated patients with malignant pleural mesothelioma: an observational study

BackgroundThe aim of this study was to investigate the efficacy and safety of oxaliplatin ± gemcitabine in patients with diffuse malignant pleural mesothelioma (MPM) pretreated with pemetrexed.MethodsThe study enrolled consecutive patients with relapsed MPM, all of them pretreated with a platin-pemetrexed-based chemotherapy. Oxaliplatin 80 mg/m2 was administered as monotherapy or in combination with gemcitabine 1000 mg/m2 given on day 1 and 8. Cycles were repeated every 21 days. The primary endpoints were response rate and disease control rate. Secondary endpoints included overall survival (OS), time to tumour progression (TTP), progression-free survival (PFS), time to treatment failure (TTF), and toxicity.ResultsBetween February 2005 and September 2007 29 patients (median age: 65.0 years, World Health Organisation (WHO) performance status: 0–3) were enrolled. The follow-up period encompassed 5.4 to 97.4 weeks (median: 24.3 weeks). Out of these 29 patients, 15 were treated in second, 10 in third, 3 in fourth and 1 in fifth line, respectively. The majority of the patients received the combination oxaliplatin and gemcitabine (n = 25 vs. 4; 86.2 vs. 13.8%).The median overall survival (OS) was 71.7 weeks (30.6–243.3 weeks), whereas survival from the start of oxaliplatin/gemcitabine-treatment was 24.3 weeks (5.4–97.3 weeks). Median time to tumour progression (TTP) was 9.3 weeks (3.0–67.6 weeks).Partial response (PR) was observed in 2 patients (6.9%), stable disease (SD) for at least three courses of treatment in 11 patients (37.9%). Thus, disease control rate was 44.8%, whereas 16 of 29 patients exhibited progressive disease (55.2%).The toxicity profile was favourable, with no WHO grade 4-toxicities, only few dose-reductions were performed due to non-symptomatic haematotoxicities (neutropenia, thrombopenia). Mild WHO grade 2 neurotoxicity was seen in 6 patients.ConclusionPemetrexed-pretreated patients with progressive MPM may benefit from a consecutive chemotherapy with oxaliplatin and gemcitabine without significant toxicity.

Pulmonary epithelioid hemangioendothelioma mimicking mesothelioma

An intrathoracic mass was discovered on magnetic resonance imaging (MRI) of the spine in a 37-year-old Caucasian man with a 1 year history of progressively severe upper back pain. A subsequent chest CT scan indicated a 4 cm left hilar mass, extending to the apex and encasing a portion of the left bronchus and pulmonary artery. Initial bronchoscopic and transthoracic biopsies failed to obtain diagnostic material. The patient underwent thoracotomy and was found to have a locally advanced, surgically unresectable lung tumor, involving the pleura, pericardium and diaphragm. The patient failed to respond to radiochemotherapy, and died 11 months following the diagnosis with tamponade and metastasis to the skin of the thoracoabdominal wall. Histologically the tumor had an epithelioid and spindled appearance, without high-grade histological features, and was initially thought to represent biphasic diffuse malignant mesothelioma. Positive immunohistochemistry for vascular markers (CD31, CD34, and FLI-1) disclosed the vascular nature of the tumor. Mesothelioma markers were universally negative and cytokeratin was focally reactive only in some epithelioid cells. Epithelioid hemangioendothelioma is a rare tumor in the lung that can mimic other more common pathological entities, and should be included in the differential diagnosis of unusual pulmonary neoplasms with epithelioid or biphasic morphology.

Mésothéliome péritonéal : traitement par l’association chirurgie de cytoréduction et chimiothérapie hyperthermique intrapéritonéale

Diffuse malignant peritoneal mesothelioma is a rare and lethal disease. Locoregional treatments combining cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) seem to improve prognosis. Cytoreductive surgery and HIPEC was performed in 22 patients at the Centre Hospitalier-Lyon Sud between 1989 and 2006. A retrospective analysis of survival was carried out to assess clinical and histological prognostic factors. Nineteen patients with diffuse malignant peritoneal mesothelioma were included (16 epithelial, 3 biphasic and 3 multicystic forms). Sixteen patients presented stage 3 or 4 peritoneal mesothelioma according to the Gilly classification. Optimal cytoreductive surgery was performed for 11 patients (complete macroscopic resection or residual tumor nodules less than 2.5mm). No post-operative deaths occurred but 9 patients (47%) presented grade III or IV post-operative complications. The overall median survival was 36.9 months; completeness of cytoreduction was the only significant prognostic factor. Cytoreductive surgery combined with HIPEC may improve the length of survival for patients with diffuse malignant peritoneal mesothelioma; such patients should be treated in specialized centers.

Consensus statement on peritoneal mesothelioma

Diffuse malignant peritoneal mesothelioma (DMPM) has been traditionally regarded as a rapidly lethal disease. Recently, several independent prospective trials have reported improved survival with an intensive loco-regional treatment strategy including cytoreductive surgery (CRS) along with peri-operative intra-peritoneal chemotherapy (PIC). However, most of the surgical data comes from mono-institutional phase I or II studies and there is a broad range of variability regarding inclusion criteria, cytoreductive surgical procedures, drugs, temperatures and methods of delivering the heated chemotherapy (open vs. closed abdomen). This manuscript critically analyze and discuss the results of a group of health care providers trying to achieve a consensus statement in the management of this group of patients. The main conflicting points regarding preoperative evaluation, patient eligibility, combined treatment methodology, postoperative follow-up and future investigational perspectives were summarized as a list of multiple-choice questions. A questionnaire was placed on the website of the "5(th) International Workshop on Peritoneal Surface Malignancies" and the group members voted via internet. The results were presented for further debate during a dedicated session of the Workshop. The general treatment guidelines and future investigational perspectives were defined.

Primary Pleural Neoplasia: Entities Other Than Diffuse Malignant Mesothelioma

Overwhelmingly, the most common neoplasm involving the pleura is metastatic carcinoma. In contrast, diffuse malignant mesothelioma occurs relatively rarely; however, it is nonetheless the most common neoplasm primary to the pleura. Metastatic carcinoma and diffuse malignant mesothelioma each have their own prognostic and therapeutic characteristics. Other primary pleural neoplasms occur uncommonly or rarely, with their own prognostic and therapeutic characteristics. To review primary pleural neoplasms other than diffuse malignant mesothelioma, to better ensure correct diagnosis and optimal assessment of prognosis and treatment. Literature review and primary material from the authors' institutions. A nonexhaustive group of uncommon to rare benign and malignant primary pleural neoplasms--other than diffuse malignant mesothelioma--are presented, of which one must be aware in order to maintain an appropriate index of suspicion to include them in the differential diagnosis of a pleural tumor.

Multiple Mechanisms of Telomere Maintenance Exist and Differentially Affect Clinical Outcome in Diffuse Malignant Peritoneal Mesothelioma

This study aims to investigate the prevalence of the two known telomere maintenance mechanisms, telomerase activity (TA) and alternative lengthening of telomeres (ALT), and to assess their prognostic relevance in diffuse malignant peritoneal mesothelioma (DMPM). In 44 DMPM specimens obtained from 38 patients, TA was determined using the telomeric repeat amplification protocol and ALT was detected by assaying ALT-associated promyelocytic leukemia nuclear bodies. The prognostic significance of telomere maintenance mechanisms was analyzed by Cox regression in the overall series and in a subset of 29 patients who underwent a uniform treatment regimen consisting of cytoreductive surgery and hyperthermic i.p. chemotherapy. Telomere maintenance mechanisms were detectable in 86.4% of DMPM: ALT or TA alone was found in 18.2% or 63.6% of lesions, respectively, whereas two cases (4.6%) were ALT+/TA+. TA and ALT proved to be inversely associated (P = 0.002). In the overall series, TA was prognostic for 4-year relapse (TA+ versus TA-, hazard ratio, 3.30; 95% confidence interval, 1.23-8.86; P = 0.018) and cancer-related death (TA+ versus TA-, hazard ratio, 3.56; 95% confidence interval, 1.03-12.51; P = 0.045), whereas ALT failed to significantly affect clinical outcome. These results held true also in the subset of patients submitted to uniform treatment with cytoreductive surgery and hyperthermic i.p. chemotherapy. Our results indicate that both known telomere maintenance mechanisms, TA and ALT, are present in DMPM and differentially affect patient prognosis.

Primary pleural neoplasia: Entities other than diffuse malignant mesothelioma

Abstract Context.—Overwhelmingly, the most common neoplasm involving the pleura is metastatic carcinoma. In contrast, diffuse malignant mesothelioma occurs relatively rarely; however, it is nonethe...

Pulmonary sarcomatous tumors.

Abstract Context.—Sarcomatous pulmonary neoplasms are a rare and diagnostically challenging group of tumors. Primary pulmonary sarcomas must be distinguished from the more frequent occurrence of sarcoma metastatic to the lung, primary pulmonary sarcomatoid carcinoma, and diffuse malignant mesothelioma involving the lung. In current practice, the general availability of ancillary diagnostic techniques, such as immunohistochemistry and molecular analysis, can reliably classify many sarcomatoid lesions. Objective.—To review the literature and report on additional primary material about the application of immunohistochemistry and molecular analysis in the differential diagnosis pulmonary sarcomatous neoplasms. Data Sources.—Literature review of relevant articles indexed in PubMed (National Library of Medicine) between 1961 and 2007 and primary material from the author's institution. Conclusions.—This review discusses specific criteria for the diagnosis of primary lung sarcomas and offers a practical approach ...

Pulmonary Sarcomatous Tumors

Sarcomatous pulmonary neoplasms are a rare and diagnostically challenging group of tumors. Primary pulmonary sarcomas must be distinguished from the more frequent occurrence of sarcoma metastatic to the lung, primary pulmonary sarcomatoid carcinoma, and diffuse malignant mesothelioma involving the lung. In current practice, the general availability of ancillary diagnostic techniques, such as immunohistochemistry and molecular analysis, can reliably classify many sarcomatoid lesions. To review the literature and report on additional primary material about the application of immunohistochemistry and molecular analysis in the differential diagnosis pulmonary sarcomatous neoplasms. Literature review of relevant articles indexed in PubMed (National Library of Medicine) between 1961 and 2007 and primary material from the author's institution. This review discusses specific criteria for the diagnosis of primary lung sarcomas and offers a practical approach to excluding other sarcoma-like lesions involving the lung. The pathologist has an essential role in evaluating these tumors and will often be the first to suggest an unusual, alternative diagnosis, which may have significant implications for patient care, therapy, and prognosis.

Cytomorphologic features of well‐differentiated papillary mesothelioma in peritoneal effusion: A case report

Well-differentiated papillary mesothelioma (WDPM), a distinct subtype of diffuse malignant mesothelioma, usually occurs in the peritoneum and is seen most commonly in women of reproductive age. Histologic features of WDPM include papillary growth and stout fibrous cores surrounded by a single layer of tumor cells. We present the case of a 73-year-old woman without subjective symptoms who showed signs of peritoneal effusion during a routine examination and for whom cytologic examination of the ascitic fluid was performed. Many spherical clusters, with a smooth external surface composed of a single layer of uniform cuboidal cells, were observed. Within each cluster, a collagenous ball showed light green Papanicolaou staining. Immunohistochemistry of surgical specimens showed tumor cells positive for calretinin, D(2)-40, and HBME-1 staining. The histologic diagnosis was WDPM. The identification of a collagenous ball within these clusters is a useful cytologic finding for the diagnosis of WDPM. WDPM should be suspected when numerous collagenous balls are present by effusion cytology and isolated cells are not.

Primary peritoneal mesotheliomas in children: a clinicopathological and immunohistochemical study of eight cases

To present eight cases of primary diffuse peritoneal malignant mesothelioma in children <15 years old, with a discussion of the pitfalls of this diagnosis in the paediatric age group. The cases were selected based on the following criteria: (i) primary peritoneal neoplasms confined grossly or radiographically to the abdominal cavity; (ii) negative history of previous or another associated malignancy; (iii) histopathological confirmation. All patients (five female, three male) presented clinically with symptoms of abdominal pain, distention and ascites. Grossly, the tumours showed multiple, diffuse peritoneal nodules. Histologically, seven cases corresponded to epithelioid mesotheliomas and one case displayed biphasic (epithelioid and spindle) cellular proliferation. Immunohistochemical studies for cytokeratin (CK) 5/6, calretinin and low-molecular-weight CK (CAM5.2) showed strong cytoplasmic positivity in the neoplastic cells. Three patients were treated by chemotherapy. On clinical follow-up, four patients with epithelioid mesotheliomas were alive and well from 12 to 18 months after initial diagnosis; one patient with a mixed (biphasic epithelioid/sarcomatoid) mesothelioma died of tumour 24 months after diagnosis. Peritoneal malignant mesothelioma in children is a rare condition that can introduce difficulties in histopathological diagnosis.

Results of flexible 3D-conformal radiotherapy for patients with diffuse malignant pleural mesothelioma and comparative study of this technique with conventional radiotherapy

Objective To observe the effects of the new technique of flexible 3D-conformal radiotherapy with combination of photon and electron (3DCRT) in the treatment of the patients with diffuse malignant pleural mesothelioma (MPM), and carry out the comparative study between flexible 3DCRT and hemithoracic conventional radiotherapy (CRT).

Targeting tumor-associated macrophages in an orthotopic murine model of diffuse malignant mesothelioma

Tumors are a mixture of neoplastic and host stromal cells, which establish a microenvironment that contributes to tumor progression. In this study, the contribution of tumor-associated macrophages (TAMs) to tumor growth and metastasis was examined using an orthotopic, immunocompetent murine model of diffuse malignant peritoneal mesothelioma. The expression profile of cytokines and chemokines in solid tumors was consistent with a M2-polarized, TAM-mediated immunosuppressive microenvironment. TAMs were targeted using liposome-encapsulated clodronate (CLIP). Exposure of tumor spheroids to CM-DiI-labeled CLIP in situ confirms targeting of macrophages and not mesothelioma cells. Intraperitoneal (i.p.) delivery of CLIP produced apoptosis in tumor spheroids and solid tumors in contrast to delivery of liposome-encapsulated PBS or PBS. Mice received an i.p. injection of mesothelioma cells with CLIP delivered i.p. every 5 days. This treatment protocol produces a 4-fold reduction in the number of tumors, a 17-fold reduction in the relative tumor burden, and a 5-fold reduction in invasion and metastasis when compared with mice exposed to liposome-encapsulated PBS or PBS. Following transplantation of tumor spheroids and treatment with CLIP, mice showed a 4-fold reduction in the number of tumors and a 15-fold reduction in relative tumor burden. Mice bearing established tumors showed a 2-fold reduction in the number of tumors and relative tumor burden when exposed to half the previous dose of CLIP delivered by repeated i.p. injection. These reductions in tumor burden are statistically significant and identify TAMs as an important host-derived cell that contributes to growth, invasion, and metastasis in diffuse malignant peritoneal mesothelioma.

Carcinoembryonales Antigen in Serum und Pleuraerguß zur Unterscheidung von Bronchialkarzinom und Pleuramesotheliom*

The concentrations of carcinoembryonic antigen (CEA) were measured, partly retrospectively and partly prospectively, in 94 patients with diffuse malignant mesothelioma and in 79 with bronchial carcinoma and pleural involvement. Serum concentrations were measured in all patients, pleural-fluid concentrations additionally in 53 patients of the former and 39 of the latter group. The concentrations were significantly higher in those with bronchial carcinoma (P less than 0.001). The two groups could be distinguished by serum concentrations, using 5.2 ng/ml as the limit, with a sensitivity of 68%, specificity of 98% and a predictive value of 96%. Measurement of CEA in pleural fluid (at a limit of 4.5 ng/ml) had a specificity of 94% and a positive predictive value of 90%, sensitivity being similar to that for serum. The negative predictive value for serum CEA concentration was 79%, for pleural fluid it was 81%. Thus in most cases measurement of CEA in serum and, to a lesser extent in pleural fluid, is a very simple method to exclude mesothelioma with a high degree of certainty. If the CEA concentration is below the stated level, either may be present.

Acne inversa complicated by squamous cell carcinoma in association with diffuse malignant peritoneal mesothelioma arising in the absence of predisposing factors: a case report

Diffuse malignant peritoneal mesothelioma (DMPM) is a relatively rare neoplasm. Risk factors associated with its development include asbestos exposure, chronic irritation or inflammation of the peritoneum, abdominal radiotherapy, familial Mediterranean fever and simian virus 40. A familial segregation of this neoplasia has been reported in small villages of the Cappadocian region of Turkey, and it has been postulated that hereditary factors may predispose to mesothelioma, even with exposure to small amounts of asbestos. We report a case of DMPM, which apparently occurred in the absence of predisposing factors in a patient with a clinical history characterized by recurrent pre-sacral acne inversa of long duration. The association of this chronic inflammatory disease with DMPM has never been reported. The genetic locus for acne inversa has recently been identified within the 1p21.1-1q25.3 chromosomal region. Interestingly, frequent losses in chromosomal region 1p.21-22 have been found in mesothelioma as well. It is thus tempting to speculate that genetic mutations involving chromosome 1p.21-22 may account for the development of both diseases.

MUC4 is upregulated in ovarian carcinoma effusions and differentiates carcinoma cells from mesothelial cells

Using gene expression arrays, we recently showed that MUC4 expression is significantly higher in ovarian/primary peritoneal serous carcinoma (OC/PPC) compared to diffuse peritoneal malignant mesothelioma (DMPM). In the present study, we analyzed the anatomic site-related expression of MUC4 in OC/PPC and studied its prognostic role. We additionally studied the ability of MUC4 to differentiate between OC/PPC and reactive mesothelial cells (RMC). OC/PPC effusions (n = 142) and benign reactive effusions (n = 10) were immunostained for MUC4 expression. Immunoreactivity was scored in carcinoma cells and RMC and was compared with tumor cell expression in 60 previously studied primary carcinomas and solid metastases and analyzed for association with clinicopathologic parameters, including survival. MUC4 was detected in carcinoma cells in 141/142 (99%) effusions, with comparable expression in peritoneal and pleural effusions. RMC were present in 72 malignant effusions and were MUC4-negative in all specimens, as well as in the 10 reactive effusions. MUC4 expression in carcinoma cells in effusions was significantly higher than in primary carcinomas and solid metastases (P < 0.001). Higher MUC4 expression was seen in tumors from older (>60 year) patients (P = 0.049). No association was found between MUC4 expression and other clinicopathologic parameters, including survival. MUC4 is universally expressed in OC/PPC effusions and is upregulated at this anatomic site compared to primary carcinomas and solid metastases. The data in the present study, together with our earlier report, show that MUC4 is an excellent marker for differentiating OC/PPC from both benign and malignant mesothelial cells.

Malignant peritoneal mesothelioma: treatment with maximal cytoreductive surgery plus intraperitoneal chemotherapy

To report survival results in patients with diffuse malignant peritoneal mesothelioma (MPM) treated with maximal cytoreductive surgery followed by immediate intraperitoneal chemotherapy, and to compare them with the median survival of 12-24 months obtained with the standard treatment based on systemic chemotherapy. Twenty-six patients underwent this new regional approach and a median follow-up of 55 months was achieved after this treatment. Complete cytoreductive surgery (residual disease < 2 mm) was performed in all but one patient. Intraperitoneal chemotherapy was performed with hyperthermia (4245 degrees C) and oxaliplatin in 22 patients. The last 12 patients additionally received irinotecan. Data were prospectively verified and retrospectively analyzed. One patient died postoperatively (4%), and morbidity attained 54%. The median survival exceeded 100 months and the overall 5-year survival rate was 63%. This small series lacks the statistical power required to conduct a well-grounded study on prognostic factors, particularly as the completeness of the surgery is not analyzable here. However, the low-grade histological types had a better disease-free survival rate that was of borderline significance compared to their high-grade counterparts. This new approach combining complete cytoreductive surgery considerably increases the survival of patients with MPM compared with the standard treatment based on systemic chemotherapy.

Unusual tumours of the lung and pleura

Abstract: There are about a hundred histological types of tumour which involve the lung and pleura ranging from inflammatory pseudotumours to highly aggressive malignancies such as small cell carcinoma (Brambilla et al. 2001). The commonly used term lung cancer encompasses only a few histological types – squamous cell carcinoma, adenocarcinoma, small cell carcinoma and large cell carcinoma – but these account for about 95% of lung tumours. The clinical presentation of these tumours reflects their location and aggressiveness and are not specific to any one tumour. Tumours affecting large airways tend to present with obstructive symptoms namely cough, shortness of breath, haemoptysis, and wheeze whereas peripheral tumours are associated with pleural effusion and chest pain. Tumours such as small cell carcinoma mat present with metastases.In this presentation it is not possible to describe every unusual tumour of the lung and pleura so a select few will be presented. Carcinomas with pleomorphic, sarcomatoid or sarcomatous elements These are rare tumours which are poorly differentiated non‐small cell carcinomas that contain a component of sarcoma or sarcoma‐like elements. They contain spindle, giant cells or a mixture of these cell types. Although rare they represent the most common spindle cell malignancies of the airways. They are most frequently seen in middle aged to elderly men with a history of heavy smoking. They can be centrally or peripherally located. Although frequently surgically respectable overall 5‐year survival is about 20% (Nappi et al. 1994). Pleomorphic carcinomas are tumours which contain spindle and/or giant cells with or without a component of squamous cell carcinoma, adenocarcinoma or large cell carcinoma. Immunohistochemical markers for keratin or EMA are frequently positive but not always so. Spindle cell carcinomas consist solely of spindle cells and usually show immunopositivity for epithelial markers. If a tumour shows heterologous elements such as malignant cartilage, bone or skeletal muscle it is designated as a carcinosarcoma. Pulmonary blastoma is a biphasic malignant neoplasm, that despite its name, occurs overwhelmingly in adults. The epithelial component resembles primitive fetal pulmonary glandular structures and the malignant stromal component consists of blunt fusiform cells. Mortality is of the order of 30 to 70% with death usually related to distant metastases. Epithelioid haemangioendothelioma is a low grade angiosarcoma which may occur in lung, pleura, liver, soft tissue and bone. It is composed of short cords and nests of epithelioid endothelial cells, often with intacytoplasmic vacuoles, embedded in a hypocellular, myxoid, hyaline matrix. Immunostains for CD31, CD34 and factor 8 are helpful in confirming the diagnosis. In the lung it usually presents as multiple nodules typically in females (80%) often less than 40 years of age. It is often asymptomatic when first discovered and it is associated with a protracted clinical course (Kitaichi et al 1998). However, death from respiratory failure usually occurs several years after diagnosis. When it involves the pleura it can be diffuse and can mimic malignant mesothelioma both clinically, histopathologically and prognostically (Lin et al. 1996; Galateau‐Salle F 2006). Solitary fibrous tumour These are soft tissue tumours, which can be benign or malignant, with a propensity to occur in the pleura and less frequently in the lung. They are spindle celled tumours with a variety of patterns : ‘‘patternless’’, haemangiopericytoma‐like, diffuse sclerosing and myxoid. Immunostains are negative for cytokeratin and usually positive for CD34, bcl2 and CD99. The less common malignant forms usually show a high mitotic rate (&gt;4 mitoses per 10 hpf), abnormal mitotic figures, cellular pleomorphism and high cellularity, size greater than 10 cm, and areas of necrosis (England et al. 1989; Galateau‐Salle 2006). Well differentiated papillary mesothelioma This tumour should be carefully separated from diffuse malignant mesothelioma because it shows a much better prognosis, there is not a close association with asbestos exposure, and there are different therapeutic implications. It is a rare tumour, more frequently occurring in the peritoneum of young women, than in the pleura (Daya &amp; McCaughey 1990; Galateau‐Salle et al. 2004). Grossly it consists of small nodules usually less than a centimetre, in contrast to the diffuse thickening seen with diffuse malignant mesothelioma. It is characterised by stout papillary structures with myxoid cores lined by bland, cuboidal mesothelial cells without mitoses. There is little or no invasion. The tumour usually follows a benign or indolent course but occasionally progresses.

Cytoreductive Surgery and Perioperative Intraperitoneal Chemotherapy for Colorectal Carcinomatosis: If at First You Don't Succeed...

The management and outcomes of stage IV colorectal cancer have changed significantly over the past 5–10 years. The advent of relatively effective, multimodality regimens of 5-fluorouracil and leucovorin combined with cytotoxic agents (e.g., oxaliplatin or irinotecan) and targeted therapies (e.g., bevacizumab or cetuximab) has resulted in unprecedented rates of both tumor response and patient survival. Simultaneously the indications for surgery in the management of hepatic and pulmonary metastases from colorectal cancer continue to expand. However, for patients with carcinomatosis from colorectal cancer, the view remains generally nihilistic for a number of reasons. First, the historical life expectancy of patients with colorectal carcinomatosis was a dismal 6–7 months. Second, surgery has traditionally not been shown to play any significant role other than selective palliation. Third, despite the overall results of the more efficacious chemotherapy regimens, the actual benefit to patients with carcinomatosis has yet to be determined. Consequently, while evidence-based guidelines recommending neoadjuvant chemotherapy followed by surgery for the management of patients with hepatic and pulmonary metastases are readily available, there are no management guidelines for patients with carcinomatosis. Despite this daunting backdrop, significant efforts are being made to improve the outcome of patients with carcinomatosis. One such effort is the use of a combined treatment approach involving cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC). Currently, this approach is gaining recognition as a treatment option for a variety of peritoneal surface-based malignancies. Significant improvements in disease-free and overall survival from CRS and PIC have been demonstrated in patients with peritoneal dissemination of appendiceal and ovarian cancers and diffuse malignant peritoneal mesothelioma. In fact, CRS and PIC are considered by many to be the standard of care for select patients with peritoneal-based disease from these malignancies. CRS and PIC have also been used in the treatment of carcinomatosis from colorectal cancer with some centers publishing 5-year survival rates of 30% or higher. For such a historically hopeless clinical situation, these results seem almost miraculous. Consequently, and despite a paucity of high-level evidence, a consensus statement has been published advocating the use of CRS and PIC in select colorectal patients with carcinomatosis. In ‘‘Failure Analysis of Recurrent Disease Following Complete Cytoreduction and Perioperative Intraperitoneal Chemotherapy in Patients with Peritoneal Carcinomatosis from Colorectal Cancer,’’ Bijelic et al. 15 are the first to analyze the anatomic distribution, timing, and outcomes of recurrent peritoneal disease after complete cytoreduction and PIC for peritoneal carcinomatosis from colorectal cancer. The data are derived from a single-institution experience, spanning Received July 10, 2007; accepted July 11, 2007; published online: August 29, 2007. Address correspondence and reprint requests to: Paul F. Mansfield, MD; E-mail: ansmith@mdanderson.org

The risk of mesothelioma from exposure to chrysotile asbestos

This review assesses the risk of developing diffuse malignant mesothelioma of the pleura from exposures to chrysotile fibers and contrasts it with the known risk of amphibole asbestos. Although a rare cancer, the mortality rates of pleural mesothelioma continue to be significantly elevated because of past occupational exposures to airborne asbestos fibers. New analyses of occupational epidemiologic studies for highly exposed workers show a substantially lower potency and suggest an empiric threshold for chrysotile compared with amphibole asbestos. Important kinetic and pathological differences between chrysotile and amphiboles have been substantiated that support chrysotile's impotency in causing pleural mesothelioma. Excess risk of pleural mesothelioma from past exposures to asbestos, as evidenced by a trend of high incidence rates during the last half century, appears to be the result of nonchrysotile asbestiform fibers. Although scientific efforts and legal arguments continue, the risk of pleural mesothelioma in human populations is probably negligible for exposures to airborne chrysotile asbestos that is not known to be contaminated by amphibole. This distinction for asbestos fiber types is pivotal for understanding hazards and characterizing risks of continued use of natural chrysotile asbestos today and also new nanofibers.