Treatment of Malignant Peritoneal Mesothelioma.

Malignant mesothelioma is a highly malignant disease that most often occurs in the pleura of the thoracic cavity, followed by the peritoneum, pericardium, or tinea vaginalis testis. Malignant peritoneal mesothelioma (MPM) accounts for 10-15% of all mesotheliomas. The most significant risk factor for MPM is exposure to asbestos. There is no specific symptomatology, and imaging (computed tomography) and histopathology are crucial for diagnosis. There are no generally accepted guidelines for radical treatment of MPM. Previously, the prognosis of MPM patients was poor, with survival of up to 1 year. However, median survival of patients who are suitable candidates for radical therapy is currently 3-5 years. A combination of cytoreductive surgery (CRS) and hyperthermic perioperative chemotherapy (HIPEC) is recommended in selected patients, while chemotherapy alone has insufficient efficacy. Systemic chemotherapy remains the only treatment option for patients who are unsuitable for CRS and HIPEC. In selected patients scheduled for or currently undergoing CRS and HIPEC, surgery may be performed in combination with systemic chemotherapy in the neoadjuvant or adjuvant setting; however, the benefit is unclear. There are no recommendations for follow-up of MPM patients after radical surgery. Existing guidelines for the pleural form (e.g., those issued by the European Society for Medical Oncology) do not specify the frequency or method of investigation. In the absence of specific serum markers, only CA 125 and mesothelin are generally available. Imaging methods include ultrasonography, computed tomography, and magnetic resonance imaging.

Prognostic Factors of Malignant Peritoneal Mesothelioma Experienced in Japanese Peritoneal Metastasis Center.

BACKGROUND AND OBJECTIVES: The current standard of treatment for malignant peritoneal mesothelioma(MPM)is cytoreductive surgery(CRS)plus perioperative intraperitoneal or systemic chemotherapy(comprehensive treatment), The present study was performed to clarify the prognostic factors of PMP after comprehensive treatment. METHODS: Among 63 patients with MPM, male and female patients were 34 and 29. CRSwas performed in 47 patients and complete cytoreduction(CC-0) was performed in 14(22%)patients. Mean numbers of resected peritoneal sectors and organs were 5.2(1-13), and 2.9(0- 9), respectively. Hyperthermic intraperitoneal chemoperfusion(HIPEC)was performed in 27 patients. Grade 1/2, Grade 3, and Grade 4 complications were experienced in 5, 6, and 3 patients, respectively. One patient died of sepsis, and the mortality rate was 2.3%. Independent prognostic factors for favorable prognosis were performance of HIPEC, peritoneal cancer index (PCI)score C12, no distant metastasis and histologic epithelial type. Relative risk of no HIPEC, PCI score B13, presence of distant metastasis and non epithelial type were 7.69, 22.1, 3.6 and 3.9, respectively. CONCLUSIONS: Risk factors for death after comprehensive treatment were no HIPEC, PCI score B13, and non epithelial type. However, only 11(17%)patients showed PCI score C12. Accordingly, PCI score should be reducedC12 before CRSby neoadjuvant chemotherapy.

Well differentiated papillary peritoneal mesothelioma treated by cytoreduction and hyperthermic intraperitoneal chemotherapy-the experience of the PSOGI registry.

BACKGROUND: Well differentiated papillary peritoneal mesothelioma (WDPPM) is a rare variant of mesothelioma which affects mainly women in the reproductive age. The disease may present multifocally and recur after primary resection. Our aim was to describe the outcomes of cytoreduction (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in this disease. METHODS: Patients with histological diagnosis of WDPPM were retrieved from the PSOGI registry. Demographical and clinical data were extracted as well as outcomes data (overall survival (OS) and recurrence free survival (RFS)). RESULTS: We analyzed 45 patients for whom complete data was available. The majority of patients were women (n = 33, 73%) with a median age of 44 years. Preoperative chemotherapy (CT) was administered in 8 patients (18%). Median peritoneal carcinomatosis index was 9 (1-30), and complete cytoreduction was achieved in 69% of patients. There was one case (2%) of postoperative mortality, and 24% rate of severe morbidity. Overall, there were 4 deaths and 5 years OS was 80%. 8 patients (18%) had disease recurrence, all within 5 years from operation. On univariate analysis preoperative CT, high PCI and severe morbidity were associated with reduced RFS. On multivariate analysis, only preoperative CT (HR = 32.6, 95% CI: 2.39-446.2, p = 0.009) and high PCI (HR = 21.7, 95% CI: 1.11-425.7, p = 0.04) remained significant risk factors. CONCLUSIONS: WDPPM can be a lethal disease with substantial recurrence even after aggressive treatment. Patients presenting with extensive disease or disease recurrence after surgical excision are at increased risk for relapse. CRS + HIPEC can be safely applied to WDPPM in specialized centers.

Incidence of cutaneous reactions with pemetrexed: Comparison of patients who received three days of oral dexamethasone twice daily to patients who did not.

Pemetrexed is a multitargeted antifolate indicated for locally advanced or metastatic non-squamous non-small-cell lung cancer and malignant pleural mesothelioma. Cutaneous reactions are associated with pemetrexed use. Pemetrexed prescribing information recommends oral dexamethasone 4 mg twice daily for three days starting the day before pemetrexed infusion to prevent cutaneous reactions. Patients receive intravenous dexamethasone before pemetrexed infusion at the University of New Mexico Comprehensive Cancer Center, but the oral dexamethasone recommendation is not always followed. The objective of this study was to determine if there is a difference between patients who received three days of oral dexamethasone starting the day before pemetrexed infusion and patients who did not by determining incidence of cutaneous reactions, delay in therapy, and therapy change due to adverse reactions. Eighty-five patients received at least one dose of pemetrexed between August 1, 2012 and August 31, 2017. Twenty-nine patients did not receive three days of oral dexamethasone 4 mg twice daily and 56 patients did (34.1% vs. 65.9%). There was no statistically significant difference in the incidence of cutaneous reactions between the intervention group and the control group (13.8% vs. 25.0%; p = 0.384), delay in pemetrexed therapy between groups (44.8% vs. 32.1%; p = 0.2), or therapy change due to adverse events (34.5% vs. 23.2%; p = 0.654). Results suggest three days of oral dexamethasone 4 mg twice daily did not significantly affect incidence rates of cutaneous reactions, delay in therapy, or therapy change in patients who received intravenous dexamethasone before pemetrexed infusion at University of New Mexico Comprehensive Cancer Center.

Mesothelin and osteopontin as circulating markers of diffuse malignant peritoneal mesothelioma: A preliminary study.

BACKGROUND: The differential diagnosis between diffuse malignant peritoneal mesothelioma (DMPM) and other peritoneal surface malignancies (PSM) is still challenging. Serum mesothelin and osteopontin are increasingly used as markers of pleural mesothelioma, but their role in DMPM is unclear. We assessed the diagnostic and prognostic values of mesothelin, osteopontin, CEA, CA19.9, CA125, and CA15.3 in DMPM patients. METHODS: Markers were dosed before cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) by enzyme-linked immunosorbent assay (ELISA) in 30 DMPM patients and 14 controls with other PSMs. Receiver-operating characteristics (ROC) curve were plotted. The performance of each marker was assessed by the area under the ROC curve (AUC-ROC). RESULTS: Mean mesothelin levels were 7.84 ng/dl (SD = 5.14) in DMPM group and 3.00 ng/dl (SD = 1.25) in controls (P = 0.001). Mean CEA levels were 5.3 ng/dl (SD = 4.7), and 61.96 ng/dl (SD = 112.5) in the two groups (P = 0.008). No statistical difference was seen for osteopontin (P = 0.738), CA19.9 (P = 0.081), CA125 (P = 0.600), and CA15.3 (P = 0.365). AUC-ROC was 0.836 for CA19.9, 0.812 for mesothelin, 0.793 for CEA, and lower for CA125 (0.652), osteopontin (0.531), and CA15.3 (0.481). Using diagnostic cut-offs selected by ROC methodology, sensitivity, specificity, positive and negative predictive values were 70.0%, 100.0%, 100.0%, and 60.9% for mesothelin >5.21 ng/dl, and 90.0%, 85.7%, 93.1%, and 80.0% for CA19.9 < 8.8 U/dl. At multivariate analysis, osteopontin correlated with survival (hazard rate 6.46; 95%CI 1.81-23.05; P = 0.004). CONCLUSION: When assessing PSMs of unknown origin, elevated mesothelin with low CA19.9 may increase the suspicion index for DMPM. Ospeopontin warrants further investigations as a prognostic marker for DMPM.

Compound Functional Prediction Using Multiple Unrelated Morphological Profiling Assays.

Phenotypic cell-based assays have proven to be efficient at discovering first-in-class therapeutic drugs mainly because they allow for scanning a wide spectrum of possible targets at once. However, despite compelling methodological advances, posterior identification of a compound's mechanism of action (MOA) has remained difficult and highly refractory to automated analyses. Methods such as the cell painting assay and multiplexing fluorescent dyes to reveal broadly relevant cellular components were recently suggested for MOA prediction. We demonstrated that adding fluorescent dyes to a single assay has limited impact on MOA prediction accuracy, as monitoring only the nuclei stain could reach compelling levels of accuracy. This observation suggested that multiplexed measurements are highly correlated and nuclei stain could possibly reflect the general state of the cell. We then hypothesized that combining unrelated and possibly simple cell-based assays could bring a solution that would be biologically and technically more relevant to predict a drug target than using a single assay multiplexing dyes. We show that such a combination of past screen data could rationally be reused in screening facilities to train an ensemble classifier to predict drug targets and prioritize a possibly large list of unknown compound hits at once.

Open access phone triage for veterans with suspected malignant pleural mesothelioma.

BACKGROUND: Phone triaging patients with suspected malignant pleural mesothelioma (MPM) within the Veterans Healthcare Administration (VHA) system offers a model for rapid, expert guided evaluation for patients with rare and treatable diseases within a national integrated healthcare system. To assess feasibility of national open access telephone triage using evidence-based treatment recommendations for patients with MPM, measure timelines of the triage and referral process and record the impact on "intent to treat" for patients using our service. METHODS: A retrospective study. The main outcome measures were: (1) ability to perform long distance phone triage, (2) to assess the speed of access to a mesothelioma surgical specialist for patients throughout the entire VHA, and (3) to determine if access to a specialist would alter the plan of care. RESULTS: Sixty veterans were screened by our phone triage program, 38 traveled an average of 997 miles to VA Boston Healthcare system. On average, 14 d elapsed from initial phone contact until the patient was physically evaluated in our general thoracic clinic in Boston. The treatment plan was altered for 71% of patients evaluated at VA Boston Healthcare system based on 2012 International Mesothelioma Interest Group guidelines. CONCLUSIONS: Our initial experience demonstrates that in-network centralized care for Veterans with MPM is feasible within the VHA. National open access phone triage improves access to expert surgical advice and can be delivered in a timely manner for Veterans using our service. Guideline-based treatment recommendations ("intent to treat") changed the therapeutic course for the majority of patients who used our service.

Review: New diagnostic and therapeutic avenues for mesothelioma.

Mesothelioma is a rare form of cancer affecting the mesothelium lining. It is usually caused by asbestos exposure or exposure to nanofibers. Median survival is less than one year in the mesothelioma patients. Due to its severity, there is a dire necessity to find out new diagnostic and therapeutic strategies. Some recent strategies could help us in fighting against mesothelioma. Diagnostic tools include a range of biomarkers or biotechnological procedure. Therapeutic tools include chemotherapeutic strategies along with immunotherapy, gene therapy and alternative therapy.

Flex-rigid pleuroscopy under local anesthesia in patients with dry pleural dissemination on radiography.

OBJECTIVE: Medical thoracoscopy using a flex-rigid pleuroscope under local anesthesia is a recent diagnostic procedure for malignant pleural disease. Although most previous studies have reported its usefulness, especially in wet pleural dissemination, the feasibility of flex-rigid pleuroscopy in patients with dry pleural dissemination is not well established.We assessed the diagnostic performance of flex-rigid pleuroscopy under local anesthesia in patients suspected of dry pleural dissemination on radiography. METHODS: The pleuroscopic parameters of all patients (n = 56) who underwent flex-rigid pleuroscopy at the National Cancer Center Hospital from October 2011 to September 2013 were retrospectively reviewed. Those with computed tomography findings of asymmetric pleural thickening or pleural nodules without pleural effusion (dry group, n = 16) were compared with the remaining patients with pleural effusion (wet group). RESULTS: The dry group consisted of eight men and eight women, with a median age of 61 years (range, 48-79 years). The definitive diagnoses were adenocarcinoma (n = 10), mesothelioma (n = 2) and chronic inflammation (n = 3). The diagnostic accuracy was 93.8% (15/16). Only two minor complications were observed: mild chest pain (n = 1) and transient hypoxia (n = 1). No major complications such as pneumothorax were observed. The mean duration of post-operative chest tube drainage in the dry group was 2.31 ± 2.26 days. Complications, operation duration and diagnostic accuracy did not statistically differ between the two groups. CONCLUSIONS: Flex-rigid pleuroscopy under local anesthesia can be a well-tolerated diagnostic procedure for radiographic dry pleural dissemination with respect to diagnostic yield and complications.

Treatment of diffuse malignant peritoneal mesothelioma (DMPM) by cytoreductive surgery and HIPEC.

AIM: Diffuse malignant peritoneal mesothelioma (DMPM) is a rare and locally aggressive tumor with poor prognosis, related in most cases to asbestos exposure. It is increasing in frequency, but currently no standard therapy is available. The biology of this disease is still poorly understood. Several highly specialized centers have recently reported improved survival by means of an innovative local-regional approach. The purpose of this article is to evaluate the survival benefit and the morbidity rate of patients affected by DMPM treated at our institution by cytoreductive surgery (CRS) associated with hyperthermic intraperitoneal perioperative chemotherapy (HIPEC). METHODS: This study includes 42 patients affected by DMPM treated by an uniform approach consisting of cytoreductive surgery associated with HIPEC using cisplatin and doxorubicin. The primary end point was overall survival and morbidity rate. The secondary end point was evaluation of prognostic variables for overall survival. RESULTS: The median follow-up period was 72 months (range 1-235 months). Thirty-five patients (83.3%) presented epithelial tumors and 7 were affected by multicystic mesothelioma. The mean peritoneal cancer index (PCI) was 13. Thirty-eight patients (90.4%) had complete cytoreduction (CC-0/1). The overall morbidity rate was 35.7% associated to a perioperative mortality of 7.1%. Median overall survival rate was 65 months with a 1- and 5-year survival rates of 63% and 44%, respectively. CONCLUSION: The treatment of DMPM by CRS+HIPEC in selected patients is a feasible technique that allows to achieve encouraging results in terms of overall survival rate, with an acceptable morbidity rate. Further investigations are needed to clarify the role and the timing of this promising technique.

Therapeutic strategies for well-differentiated papillary mesothelioma of the peritoneum.

OBJECTIVE: Well-differentiated papillary mesothelioma is an uncommon subtype of mesothelioma with a frequently indolent course, although it occasionally manifests in a more aggressive form. To establish a treatment strategy for this rare disease, we report the clinical characteristics and outcomes of 15 patients with well-differentiated papillary mesothelioma. METHODS: All pathologically diagnosed well-differentiated papillary mesothelioma cases were reviewed between 1998 and 2012. RESULTS: Of the 15 cases, 8 and 7 presented with single and multiple lesions, respectively. All cases with single lesions were asymptomatic, while 4 out of the 7 cases with multiple lesions were symptomatic. After tumor excision, none of the eight single-lesion cases experienced tumor recurrence. Among the other seven cases with multiple lesions, only one patient with disseminated lesions died due to disease burden. Five patients with multiple lesions received cisplatin-based intravenous or intraperitoneal chemotherapy, with a mix of complete (n= 2) and partial (n= 2) responses observed. Of particular note, one patient receiving cisplatin and pemetrexed combination chemotherapy experienced complete tumor resolution without any serious toxicity. CONCLUSIONS: We recommend different treatment strategies based on the disease status. If the tumor is completely resectable, an excisional biopsy seems to be sufficient. If complete resection is unavailable for the asymptomatic patient with a localized tumor extent, close follow-up is an appropriate option. When the tumor is extensive or accompanied by symptoms, chemotherapy should be strongly considered.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal mesothelioma.

INTRODUCTION: Peritoneal mesothelioma is a rare neoplasm. Due to the limited understanding of its biology and behaviour, peritoneal mesothelioma poses a diagnostic and management challenge. The management of peritoneal mesothelioma has been controversial; systemic chemotherapy, palliative surgery and cytoreductive surgery (CRS) with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) have been described. MATERIALS AND METHODS: This study shares our experience with cytoreductive surgery and HIPEC for 5 out of the 6 cases of peritoneal mesotheliomas treated surgically, at a single institution in Singapore over the past 2 years. Computed tomography (CT) scans, positron emission tomography (PET)-CT scans and tumour markers were performed preoperatively but were not conclusive for the disease. All 6 cases presented to the Department of Surgical Oncology at National Cancer Centre Singapore, were diagnosed by histology of intraoperative biopsies. The combination of aggressive cytoreductive surgery and HIPEC was performed in 5 patients, with abandonment of procedure in 1 with extensive disease, who was treated with systemic chemotherapy instead. RESULTS: Median duration of surgery, median length of hospital stay, and median follow-up duration were 7.04 hours, 11 days, and 15 months respectively. One postoperative morbidity relating to chemical peritonitis required exploratory laparotomy with good outcome. There were no mortality. All patients are alive at the last follow-up with no evidence of recurrences at 4 to 31 months from the time of their surgery. CONCLUSION: Peritoneal mesothelioma is a rare disease that requires early diagnosis and can be effectively treated by CRS and HIPEC in selected group of patients.

Peritoneal mesothelioma: the site of origin matters.

The etiology, gender distribution, pathology, natural history, and treatment options for mesothelioma (MM) differ substantially depending on the site of origin. Peritoneal mesothelioma (MPeM) is a rare disease, comprising only approximately 10% to 15% of the 2,500 cases of MM diagnosed in the United States each year. Patients with MPeM are younger than patients with pleural MM, and a higher proportion, mostly women, are long-term survivors. Most MPeM is caused by asbestos exposure. Germ-line mutations of BAP1 (BRCA associated protein 1) can predispose to MM, uveal melanoma, and potentially other cancers. MPeM can be challenging to diagnose, and cytology is rarely helpful. Review by an experienced pathologist using a panel of at least two positive and two negative immunohistochemical stains is essential. The three major pathologic subtypes are epithelial, sarcomatoid, and biphasic. Most cases are epithelial; the others have a dismal prognosis. Two indolent subtypes of borderline malignant potential-well-differentiated papillary mesothelioma and benign multicystic mesothelioma-are more common in the peritoneum and are treated surgically. In highly selected patients receiving treatment at experienced referral centers, an aggressive locoregional strategy that combines cytoreductive surgery to remove all gross disease and hyperthermic intraperitoneal chemotherapy to treat residual microscopic tumors yields a 3-year survival of 60% and a median survival approaching 5 years, far better than expected from historic controls. This approach also provides durable palliation of malignant ascites in nearly all patients. Pemetrexed is the only U.S. Food and Drug Administration (FDA)-approved systemic chemotherapy for pleural MM. Largely on the basis of data from pharmaceutical registry studies, the activity of pemetrexed-based chemotherapy appears to be similar in pleural MM and MPeM.

A novel nomogram for peritoneal mesothelioma predicts survival.

BACKGROUND: Malignant peritoneal mesothelioma (MPM) is a rare disease treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Estimation of personalized survival times can potentially guide treatment and surveillance. METHODS: We analyzed 104 patients who underwent CRS and cisplatin-based HIPEC for MPM. By means of 25 demographic, laboratory, operative, and histopathological variables, we developed a novel nomogram using machine-learned Bayesian belief networks with stepwise training, testing, and cross-validation. RESULTS: The mean peritoneal carcinomatosis index (PCI) was 15, and 66 % of patients had a completeness of cytoreduction (CC) score of 0 or 1. Eighty-seven percent of patients had epithelioid histology. The median follow-up time was 49 (1-195) months. The 3- and 5-year overall survivals (OS) were 58 and 46 %, respectively. The histological subtype, pre-CRS PCI, and preoperative serum CA-125 had the greatest impact on OS and were included in the nomogram. The mean areas under the receiver operating characteristic curve for the 10-fold cross-validation of the 3- and 5-year models were 0.77 and 0.74, respectively. The graphical calculator or nomogram uses color coding to assist the clinician in quickly estimating individualized patient-specific survival before surgery. CONCLUSIONS: Machine-learned Bayesian belief network analysis generated a novel nomogram predicting 3- and 5-year OS in patients treated with CRS and HIPEC for MPM. Pre-CRS estimation of survival times may potentially individualize patient care by influencing the use of systemic therapy and frequency of diagnostic imaging, and might prevent CRS in patients unlikely to achieve favorable outcomes despite surgical intervention.

What is the optimum strategy for thromboembolic prophylaxis following extrapleural pneumonectomy in patients with malignant pleural mesothelioma?

Malignant pleural mesothelioma (MPM) increases the risk of venous thromboembolic (VTE) events. This risk is higher following extrapleural pneumonectomy (EPP) as part of trimodality therapy, where VTE can be catastrophic. In our series, the impact of warfarin in preventing a pulmonary embolus (PE) after neoadjuvant chemotherapy and EPP for MPM was analysed. A retrospective analysis of 21 consecutive patients undergoing EPP for MPM was conducted. The first 10 patients (Group A) had VTE prophylaxis by subcutaneous enoxaparin and compression stockings commenced a day prior to surgery, intraoperative pneumatic calf compression and early post-operative mobilization. Enoxaparin was continued for 30 days postoperatively. The following 11 patients (Group B) had the same VTE prophylaxis, together with warfarin, started prior to hospital discharge and continued for 6 months postoperatively. All patients had a computed tomography pulmonary angiogram within 8 weeks after surgery and a full examination at 1, 3, 6 and 12 months. Both groups were comparable for characteristics. Three patients in Group A suffered a PE at 4, 6 and 16 weeks postoperatively. One PE was fatal. No patient in Group B suffered VTE (P = 0.05, χ(2) test) or haemorrhagic complications. Warfarin anticoagulation following EPP is feasible and safe, and is associated with a significant reduction in VTE complications.

['Malignant peritoneal mesothelioma': a condition difficult to diagnose]. / 'Maligne peritoneaal mesothelioom': een moeilijk te stellen diagnose.

BACKGROUND: Malignant mesothelioma is an aggressive neoplasm, which arises from serous membranes, such as the pleura and the peritoneum. Malignant peritoneal mesothelioma is relatively rare, but the incidence is increasing worldwide because of intensive asbestos use during the 20th century. CASE DESCRIPTION: A 60-year-old man complained of malaise, night sweating and weight loss and was seen by a specialist in internal medicine. Additional investigation included a CT scan, 2 PET-CT scans, 2 diagnostic laparoscopies and histological examination of peritoneum biopsies. After 7 months the diagnosis of malignant peritoneal mesothelioma was made. CONCLUSION: Histological investigation is of great importance when there is indication of malignant peritoneal mesothelioma. There is not yet a consensus concerning the optimal treatment, but a small increase in survival can be achieved by systemic chemotherapy or intraperitoneal therapy consisting of hyperthermic intraperitoneal chemotherapy after cytoreductive surgery.

Volumetry: an alternative to assess therapy response for malignant pleural mesothelioma?

The purpose of our study was to assess robustness of volumetric measurement of malignant pleural mesothelioma (MPM) before and after chemotherapy to modified RECIST (response evaluation criteria in solid tumours) criteria. 30 patients with digitally available chest computed tomography (CT) scans before and after three cycles of chemotherapy were included. Three readers independently assessed tumour response using two different methods: 1) the modified RECIST criteria; and 2) the tumour volumetric approach using dedicated software (Myrian; Intrasense, Paris, France). Inter-rater reliability of unidimensional and volumetric measurements was assessed using intraclass correlation. Tumour response classification for modified RECIST was compared to the volumetric approach applying unidimensional RECIST volumetric equivalent criteria. The determination of unidimensional tumour measurement (RECIST) revealed a low inter-rater reliability (0.55) and a low interobserver agreement for tumour response classification (general κ 0.33). Only 14 patients were classified equally. A high inter-rater reliability (0.99) and interobserver agreement (general κ 0.9) were found for absolute tumour volumes (volumetric measurements). 27 cases were classified equally. The number of cases classified as "stable disease" was higher for the volumetric approach using tumour-equivalent criteria compared to modified RECIST. Volumetric measurement of MPM on CT using Myrian software is a reliable, reproducible and sensitive method to measure tumour volume and, thus, therapy response after induction chemotherapy.

[Pulmonary concentration of asbestos fibers in steel workers with pleural mesothelioma]. / Concentrazione polmonare di fibre di amianto in lavoratori siderurgici affetti da mesotelioma pleurico.

The asbestos fibre burden of the lung has been used in the past as a biological indicator of cumulative exposure to the mineral so much so that in 1997 reference limits even for non-occupationally exposed people have been proposed. This kind of analysis was performed on groups of workers of different type of industries and allowed to achieve a qualitative-quantitative estimate of past exposure to asbestos, even in absence of exposure estimates by environmental monitoring. An important example is the steel industry where asbestos was widely used in the past, but for which there are not available exposure estimates of workers. Among the mesothelioma cases collected by the Mesothelioma Registry of the Province of Brescia from 1980 to present there are 55 workers who spent at least 5 years in steel industry, on a total of 289 cases classified as asbestos exposed (19%). For 8 subjects who worked in steel mills and production of electrical steel pipes, of which 4 in the same plant, lung tissue samples were available for the asbestos fibres burden analysis (7 samples coming from autopsies and 1 from extra-pleural pneumonectomy). In all cases the diagnosis was given with histological analyses supplemented with immunohistochemistry. In 7 cases autopsied the diagnosis was confirmed. The work histories have been reconstructed in detail through the interview process, inclusive of details of duties performed. The asbestos fibre burden analyses showed a range of concentrations between 260,000 and 11,000,000 ff per grams of dry tissue; the concentration of amphiboles was much higher than that of chrysotile. The highest body burden was detected in the maintenance workers of the same plant in witch a cluster of malignant mesothelioma was observed. In conclusion, this study illustrates the results of asbestos fibres burden analyses in subjects where exposure to asbestos is sure but not quantifiable. The results showed also that these concentrations can reach values that overlap with those found in asbestos-cement workers and in asbestos-textile workers. These data suggest to consider the cases of mesothelioma occurred in the steel workers at least as "possible" exposure, even in the absence of adequate information on the circumstances of contact with asbestos. This study, although based on a small number of cases, is the only one ever held in Italy on workers in this sector.

Role of explorative laparoscopy to evaluate optimal candidates for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal mesothelioma.

BACKGROUND: Prognosis of peritoneal mesothelioma (PM) treated by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is closely related to the completeness of the surgical cytoreduction. The reliability of explorative laparoscopy (EL) in selecting patients with PM amenable to optimal combined treatment has never been specifically assessed. PATIENTS AND METHODS: Thirty-three patients with PM underwent EL before CRS and closed-abdomen HIPEC with cisplatin and doxorubicin. EL effectiveness in predicting complete cytoreduction (residual tumour nodules < or = 2.5 mm) was analyzed. RESULTS: At EL, peritoneal involvement was considered amenable to complete CRS in 30 out of 33 patients (91%). In this group, cytoreduction was complete in 29 patients and incomplete in one. Three patients were judged not amenable to complete CRS and subsequently were not able to undergo complete cytoreduction. CONCLUSION: EL findings can integrate clinical and radiological information in the selection process of patients with PM for combined treatment.

Surgical biology for the clinician: peritoneal mesothelioma: current understanding and management.

Mesothelioma is an asbestos-related tumour. Mesothelioma in the thorax occurs on the pleura and is known as pleural mesothelioma. It is the more common form of mesothelioma, accounting for 70% of cases. The other form occurs in the abdomen. It accounts for much of the remaining 30% and is known as peritoneal mesothelioma. Early diagnosis of peritoneal mesothelioma is often difficult because the early symptoms are often overlooked as being a benign ailment of the gastrointestinal tract. Therefore, diagnosis often occurs at an advanced stage when disease is widespread throughout the peritoneal cavity. Treatment approaches have evolved in the last decade from systemic chemotherapy and palliative surgery to aggressive cytoreductive surgery and perioperative intraperitoneal chemotherapy. This has led to a marked increase in survival among patients who were once classified as "preterminal." We update on the current understanding of peritoneal mesothelioma from a clinical perspective in hope that greater clinician awareness will promote best practice management of this condition.