Hyperthermic intrathoracic extracorporeal chemotherapy for secondary malignant pleural disease.

OBJECTIVES: Pleural metastasis has extremely poor prognosis. Resection of pleural implants with infusion of intrathoracic hyperthermic chemotherapy may offer a survival advantage in selected patients. We evaluated the safety and efficacy of hyperthermic intrathoracic extracorporeal chemotherapy (HITEC) in patients who underwent pleurectomy/decortication (P/D) for secondary malignant pleural disease (SPD). METHODS: A total of 101 patients were evaluated over 72 months, with 35 patients electing to proceed with P/D and 60 minutes of HITEC with cisplatin at 42°C. Inclusion criteria were adults 18-79 years with unilateral pleural dissemination. Exclusion criteria were patients without control of primary site, extrathoracic metastatic disease, significant comorbidities, and a history of adverse reaction to cisplatin. RESULTS: Median age was 56 years (36-73); 60% were women. SPD was thymoma in 13, breast cancer in 9, lung cancer in 6, colon cancer in 2, renal cell in 2, and esophageal, anal, and thymic cancers in one each. There was no operative mortality. Postoperative complications occurred in 18 patients (51%). No patient developed renal failure. Median follow-up was 24 months (4-60). The overall survival rate was 61%; 17 patients (49%) developed recurrent disease at a median of 12 months (6-36). There were no recurrences after 36 months Eleven patients (31%) died of metastatic disease at a median of 17 months (7-25). CONCLUSIONS: Surgical cytoreduction of SPD followed by HITEC with cisplatin was well tolerated. No patient developed cisplatin-related toxicities. Long-term follow-up is warranted to determine survival advantage and refinement of inclusion criteria.

Comparison of Survival by Multimodal Treatment Regimen Among Malignant Pleural Mesothelioma Patients in an Integrated Health System.

BACKGROUND: Optimal therapy for malignant pleural mesothelioma (MPM) remains unclear. We compared overall survival in patients with MPM after various multimodal treatment regimens including combinations of immunotherapy, chemotherapy, and surgery. PATIENTS AND METHODS: We examined MPM patients treated within our integrated health system from January 1, 2009 to December 31, 2020. Patients were grouped based on treatment regimen: chemotherapy alone (CT), immunotherapy with or without chemotherapy (iCT), surgery with chemotherapy (sCT), and surgery with immunotherapy and chemotherapy (siCT). We analyzed baseline characteristics and overall patient survival among these groups and several subgroups. RESULTS: One hundred seventy-nine patients were included. Among the study groups, there was no difference in age, sex, race/ethnicity, Charlson Comorbidity Index, or Eastern Cooperative Oncology Group performance status. Patients treated with CT (N = 109), iCT (N = 35), sCT (N = 26), and siCT (N = 9) had median (95% confidence interval) survivals of 11.7 (9.9-16.3), 18.2 (14.5-29.8), 20.7 (11.6-37.2), and 22.6 (19.7-37.8) months, respectively (P < .001). Median survival among patients with and without immunotherapy was 19.7 (17.4-29.8) and 12.3 (10.6-17.3) months, respectively (P = .023). Median survival among patients with and without surgery was 21.7 (17.6-34.8) and 13.6 (11.5-17.3) months, respectively (P = .007). Patients with biphasic/sarcomatoid subtypes who received immunotherapy experienced 76.2% (55.8%-100.0%) 12 month survival vs. 13.6% (4.8%-39.0%) among those who did not (P < .001). CONCLUSION: MPM patients receiving surgery and immunotherapy as part of multimodal treatment regimens experienced the longest survival. Surgery and immunotherapy are each associated with survival. Further investigations are warranted to assess the benefit of immunotherapy within multimodal treatment regimens for MPM.

A comprehensive study of alternative splicing in malignant pleural mesothelioma identifies potential therapeutic targets in a new cluster with poor survival.

BACKGROUND: Malignant pleural mesothelioma (MPM) is one of the most aggressive tumors with few effective treatments worldwide. It has been suggested that alternative splicing at the transcriptome level plays an indispensable role in MPM. METHODS: We analyzed the splicing profile of 84 MPM patients from the TCGA cohort by using seven typical splicing types. We classified MPM patients based on their splicing status and conducted a comprehensive analysis of the correlation between the splicing classification and clinical characteristics, genetic variation, pathway changes, immune heterogeneity, and potential therapeutic targets. RESULTS: The expression of the alternative splicing regulator SRPK1 is significantly higher in MPM tissues than in normal tissues, and correlates with poor survival. SRPK1 deficiency promotes MPM cell apoptosis and inhibits cell migration in vitro. We divided the MPM patients into four clusters based on their splicing profile and identified two clusters associated with the shortest (cluster 3) and longest (cluster 4) survival time. We present the different gene signatures of each cluster that are related to survival and splicing. Comprehensive analysis of data from the GDSC and TCGA databases revealed that cluster 3 MPM patients could respond well to the small-molecule inhibitor CHIR-99021, a small-molecule inhibitor of GSK-3. CONCLUSION: We performed unsupervised clustering of alternative splicing data from 84 MPM patients from the TCGA database and identified a cluster associated with the worst prognosis that was sensitive to a GSK-3 inhibitor.

Near Infrared Photoimmunotherapy for Mouse Models of Pleural Dissemination.

The efficacy of photoimmunotherapy can be evaluated more accurately with an orthotopic mouse model than with a subcutaneous one. A pleural dissemination model can be used for the evaluation of treatment methods for intrathoracic diseases such as lung cancer or malignant pleural mesothelioma. Near-infrared photoimmunotherapy (NIR-PIT) is a recently developed cancer treatment strategy that combines the specificity of tumor-targeting antibodies with toxicity caused by a photoabsorber (IR700Dye) after exposure to NIR light. The efficacy of NIR-PIT has been reported using various antibodies; however, only a few reports have shown the therapeutic effect of this strategy in an orthotopic model. In the present study, we demonstrate an example of efficacy evaluation of the pleural disseminated lung cancer model, which was treated using NIR-PIT.

Curcumin as an Anticancer Agent in Malignant Mesothelioma: A Review.

Malignant mesothelioma is an infrequent tumor that initiates from the mesothelial cells lining of body cavities. The great majority of mesotheliomas originate in the pleural cavity, while the remaining cases initiate in the peritoneal cavity, in the pericardial cavity or on the tunica vaginalis. Usually, mesotheliomas grow in a diffuse pattern and tend to enclose and compress the organs in the various body cavities. Mesothelioma incidence is increasing worldwide and still today, the prognosis is very poor, with a reported median survival of approximately one year from presentation. Thus, the development of alternative and more effective therapies is currently an urgent requirement. The aim of this review article was to describe recent findings about the anti-cancer activity of curcumin and some of its derivatives on mesotheliomas. The potential clinical implications of these findings are discussed.

Surgical treatment of pleural recurrence of thymoma: is hyperthermic intrathoracic chemotherapy worthwhile?

OBJECTIVES: Recurrence of thymoma is described in 10-30% of cases after surgical resection. Iterative surgery for thymoma pleural relapses (TPRs) is often part of a multimodal treatment. Hyperthermic intrathoracic chemotherapy (HITHOC) following macroscopic radical surgery is an option that combines the effects of mild hyperthermia with those of chemotherapeutic agents. We evaluated the effectiveness of surgery + HITHOC, compared with surgery alone, in the treatment of TPR. METHODS: We retrospectively collected data of all patients who underwent surgery for TPR in our centre from 2005 to 2017. Relapses were treated by partial pleurectomy with radical intent, followed by HITHOC when not contraindicated. Patients were divided into 2 groups: surgery + HITHOC and surgery alone. We collected demographic and clinical data and analysed postoperative results together with oncological outcomes. RESULTS: Forty patients (27: surgery + HITHOC, 13: surgery alone), mean age 49.8 (±13.7) years, were included in this study. There were no perioperative deaths. We experienced 33.3% perioperative morbidity in the surgery + HITHOC group compared with 23.1% in the surgery alone group (P = 0.71). The overall survival rate was comparable between the 2 groups (P = 0.139), whereas the local disease-free interval was 88.0 ± 15 months in the surgery + HITHOC group and 57 ± 19.5 months in the surgery alone group (P = 0.046). The analysis of factors affecting the outcomes revealed that radical surgery is related with a better survival rate whereas the local disease-free interval was significantly influenced by HITHOC. CONCLUSIONS: The safety and feasibility of HITHOC in the treatment of TPR are already known, even if it should be reserved for selected patients. Surgery + HITHOC seems to be associated with a longer local disease-free time compared to surgery alone.

Adequate nephroprotection reduces renal complications after hyperthermic intrathoracic chemotherapy.

BACKGROUND AND OBJECTIVES: Hyperthermic intrathoracic chemotherapy (HITOC) is used for the treatment of malignant pleural tumors. Although HITOC proved to be safe, postoperative renal failure due to nephrotoxicity of intrapleural cisplatin remains a concern. METHODS: This single-center study was performed retrospectively in patients who underwent pleural tumor resection and HITOC between September 2008 and December 2018. RESULTS: A total of 84 patients (female n = 33; 39.3%) with malignant pleural tumors underwent surgical cytoreduction with subsequent HITOC (60 minutes; 42°C). During the study period, we gradually increased the dosage of cisplatin (100-150 mg/m2 BSA n = 36; 175 mg/m2 BSA n = 2) and finally added doxorubicin (cisplatin 175 mg/m2 BSA/doxorubicin 65 mg; n = 46). All patients had perioperative fluid balancing. The last 54 (64.3%) patients also received perioperative cytoprotection. Overall 29 patients (34.5%) experienced renal insufficiency. Despite higher cisplatin concentrations, patients with cytoprotection showed significantly lower postoperative serum creatinine levels after 1 week (P = .006) and at discharge (P = .020). Also, they showed less intermediate and severe renal insufficiencies (5.6% vs 13.3%). CONCLUSIONS: Adequate perioperative fluid management and cytoprotection seem to be effective in protecting renal function. This allows the administration of higher intracavitary cisplatin doses without raising the rate of renal insufficiencies.

Managing malignant pleural mesothelioma: experience and perceptions of health care professionals caring for people with mesothelioma.

BACKGROUND: Malignant pleural mesothelioma (MPM) has a poor prognosis and heavy symptom burden. Here, we investigate health professionals' attitudes to management and decision-making in people with MPM. METHODS: Survey questions were based on previous interviews with health professionals, MPM patients, and caregivers. Surveys were sent to specialist doctors and nurses who treat MPM. RESULTS: Surveys were completed by 107 doctors and 19 nurses from January-September 2014. Most doctors were respiratory physicians (50%) or medical oncologists (35%). Overall, 90% of doctors estimated > 10% of eligible MPM patients did not receive chemotherapy; 43% estimated the rate was > 20%. Doctors believed clinical barriers to chemotherapy were clinician nihilism (70%); non-referral to medical oncology (49%); and lack of specialists in rural/regional areas (44%). Nurses perceived barriers as follows: delayed diagnosis (74%); non-referral to medical oncology (63%); lack of clinician knowledge (58%). Patient-related barriers were negative perception of chemotherapy (83%) and belief survival benefit not worthwhile (63%). Doctors' preference in decision-making was for the patient to make the decision while strongly considering the doctor's opinion (33%); equally with the doctor (29%); and using knowledge gained (23%). Nurses described their roles as providing patient support (100%); information (95%); intermediary (74%); and link to palliative care (74%). Overall, 95% believed they enabled better resource allocation and provided patients with holistic care (95%); clearer communication (89%); more time (89%); additional information (89%); timely referrals (89%). CONCLUSIONS: Caring for patients with MPM is challenging and complex. Health care professionals believe under-utilisation of chemotherapy is occurring, primarily due to clinician nihilism and lack of medical oncology referral.

Pleuropulmonary Recurrence Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemoperfusion for Appendiceal Pseudomyxoma Peritonei.

BACKGROUND: The aim of this study was to identify factors associated with pleuropulmonary disease recurrence following cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (CRS/HIPEC) for appendiceal pseudomyxoma peritonei (PMP) and to evaluate the oncologic impact of pleuropulmonary disease recurrence compared with isolated peritoneal recurrence. METHODS: From a prospective database, we identified patients who developed pleuropulmonary recurrence, isolated peritoneal recurrence, or no recurrence following CRS/HIPEC for appendiceal PMP. Clinicopathologic, perioperative, and oncologic data associated with the index CRS/HIPEC procedure were reviewed. The Kaplan-Meier method was used to estimate survival. Multivariate analyses identified associations with recurrence and survival. RESULTS: Of 382 patients undergoing CRS/HIPEC, 61 (16%) developed pleuropulmonary recurrence. Patients who developed a pleuropulmonary recurrence were more likely to have high-grade (American Joint Committee on Cancer [AJCC] grade 2/3) tumors (74% vs. 56%, p = 0.02) and increased operative blood loss (1651 vs. 1201 ml, p = 0.05) and were more likely to have undergone diaphragm stripping/resection (79% vs. 48%, p < 0.01) compared with patients with an abdominal recurrence. In a multivariate analysis, pleuropulmonary recurrence after CRS/HIPEC was associated with diaphragm stripping/resection, incomplete cytoreduction, and higher AJCC tumor grade. There was a trend towards reduced survival in patients with pleuropulmonary recurrence compared with patients with isolated peritoneal recurrence (median overall survival 45 vs. 53 months, p = 0.87). CONCLUSION: Pleuropulmonary recurrence of appendiceal PMP following CRS/HIPEC is common and may negatively impact survival. Formal protocols for surveillance and therapeutic intervention need to be studied and implemented to improve oncologic outcomes.

Treatment of malignant pleural mesothelioma with chemotherapy preceding versus after surgical resection.

OBJECTIVES: There are 2 main treatment paradigms recognized by the National Comprehensive Cancer Network for resectable malignant pleural mesothelioma (MPM): induction chemotherapy followed by resection (IC/R), and up-front resection with postoperative chemotherapy (R/PC). These paradigms are being compared in an accruing randomized phase II trial. In the absence of such completed trials, in this study we evaluated overall survival (OS) and postoperative outcomes of IC/R and R/PC. METHODS: The National Cancer Database was queried for newly diagnosed epithelioid/biphasic MPM. Metastatic, node-positive, and/or cT4 disease was excluded, along with nondefinitive surgery and lack of chemotherapy. Multivariable logistic regression ascertained factors independently associated with induction chemotherapy delivery. Kaplan-Meier analysis was used to evaluate OS between cohorts; multivariable Cox proportional hazards modeling was used to assess factors associated with OS. Survival was also evaluated between propensity-matched populations. Last, postoperative outcomes were assessed between groups. RESULTS: Overall, 361 patients (182 IC/R, 179 R/PC) were analyzed. Temporal trends revealed that IC/R is decreasing over time. Survival of the IC/R cohort was similar to that of R/PC patients (20.9 vs 21.7 months; P = .500); this persisted after propensity matching (20.8 vs 22.0 months; P = .270). However, patients who underwent IC/R experienced longer postoperative hospitalization (median 7 days vs 6 days; P = .001) and higher 30-day mortality (3.3% vs 0%; P = .020). CONCLUSIONS: To our knowledge, this is the only comparative investigation of the 2 major management paradigms of operable MPM. IC/R regimens are decreasing over time in the United States. Although associated with survival similar to R/PC, IC/R might be associated with worse postoperative outcomes. Careful induction chemotherapy patient selection is thus highly recommended.

Abrupt hemodynamic changes accompanying intrapleural hyperthermic chemotherapy: Case series.

RATIONALE: Intrapleural hyperthermic chemotherapy (IPHC) is the preferred method to locally treat lung cancer with pleural seeding. Anesthetic management during IPHC is a very challenging task for the anesthesiologist because of the hemodynamic instability associated with the procedure; however, there is no report on anesthetic considerations during the IPHC procedure. PATIENT CONCERNS: Three patients who diagnosed lung cancer with pleural invasion scheduled for IPHC were reported in this case series. DIAGNOSIS: Case 1, a 48-year-old woman, suffered from lung cancer (adenocarcinoma, T2NxM1a) with diffuse pleural seeding. Case 2, a 58-year-old female, diagnosed with lung cancer (adenocarcinoma, T3N0M1a) with pleural dissemination. Case 3, a 47-year-old male, diagnosed as sarcoma on the left lung with right pericardial invasion and right hemidiaphragm invasion (stage, T3N0M1a). INTERVENTION: All three patients underwent IPHC with cisplatin diluted in normal saline (2000 ml) at a rate of 600 ml/min. Inflow temperature of 42°C was using a heart-lung machine over 90 minutes. Hemodynamic changes were monitored through the procedure. OUTCOMES: The patient did not require supplemental oxygenation anymore after he recovered from lung transplantation. LESSONS: There was sudden drop in the cardiac output and an increase in the pulmonary vascular resistance, which were caused by the volume and temperature of the hyperthermic chemotherapeutic drugs in the pleura during the early stage of IPHC; these changes can be a major problem during the procedure, and supportive hemodynamic management may be needed.

Establishment of a human intrapleural hyperthermic perfusion model and analysis of pleural malignancy treatment depth.

INTRODUCTION: Although human intrapleural hyperthermic perfusion (HIHP) has achieved excellent palliative effects in metastatic pleural malignancies, the optimum treatment conditions, including inlet temperature and treatment times based on tumor size, have yet to be determined. However, such information is recognized to be critical for treatment planning in clinics. Therefore, the current research aimed to solve these issues. METHODS: Using the finite-element method (FEM), a simplified three-dimensional HIHP model was established and verified according to the temperature data of specific measuring points based on a clinical therapeutic case. Ultimately, the treatment depth of pleural malignancies was obtained by employing an equivalent thermal dose of 80 min as the damage threshold. RESULTS: The treatment depth of parietal pleural malignancies (PPM) is much larger than that of visceral pleura malignancies (VPM), and can therefore be overlooked. In addition, the average treatment depth of the PPM increased by 1 mm as treatment time increased by 30 min during the 60-120 min time frame and as the inlet temperature increased by 1 °C, while there was no further increase when treatment time exceeded 120 min. CONCLUSIONS: HIHP can provide superior treatment for PPM and only provided faintly therapeutic effects on VPM, and may not be appropriate for the larger VPM. Although we only studied one example in this article, this is the beginning of an intensive study into the detailed thermal behavior of pleural tissues under HIHP, and further analysis on more realistic cases is currently underway.

A Phase I Trial of Surgical Resection and Intraoperative Hyperthermic Cisplatin and Gemcitabine for Pleural Mesothelioma.

INTRODUCTION: The primary objective of this single-institution phase I clinical trial was to establish the maximum tolerated dose of gemcitabine added to cisplatin and delivered as heated intraoperative chemotherapy after resection of malignant pleural mesothelioma. METHODS: The extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D) treatment arms were based on investigators' assessment of patient fitness and potential for macroscopic complete resection. Previously established intracavitary dosing of cisplatin (range 175-225 mg/m2) with systemic cytoprotection was used in combination with escalating doses of gemcitabine, following a 3-plus-3 design from 100 mg/m2 in 100-mg increments. RESULTS: From 2007 to 2011, 141 patients were enrolled and 104 completed treatment. The median age of those completing treatment was 65 years (range 43-85 years), and 22 (21%) were female. In the EPP arm (n = 59), 31 patients (53%) had the epithelioid histologic type and the median radiographic tumor volume was 236 cm3 (range 16-4285 cm3). In the P/D arm (n = 41), 29 patients (71%) had the epithelioid histologic type and the median tumor volume was 79 cm3 (range 6-1107 cm3). The operative mortality rate was 2%, and 35 and 22 serious adverse events were encountered among 27 patients (46%) and 16 patients (39%) in the EPP and P/D arms, respectively. Dose-limiting toxicity (grade 3 leukopenia) was observed in two patients who were receiving 1100 mg/m2 of gemcitabine, thus establishing the maximum tolerated dose at 1000 mg/m2, in combination with 175 mg/m2 of cisplatin. The median overall and recurrence-free survival times in treated patients were 20.3 and 10.7 months, respectively. CONCLUSIONS: Combination cisplatin and gemcitabine heated intraoperative chemotherapy can be administered safely and feasibly in the context of complete surgical resection of malignant pleural mesothelioma by EPP or P/D.

Low-dose Pressurized Intrathoracic Aerosol Chemotherapy (PITAC) as an Alternative Therapy for Pleuropulmonary Involvement in Pseudomyxoma Peritonei.

BACKGROUND/AIM: Pseudomyxoma peritonei (PMP) is a rare disease characterized by mucinous ascites and widespread peritoneal implants. It usually originates from the rupture of an adenoma/adenocarcinoma of the appendix. Although this tumor is only superficially invasive and does not metastasize, it could be a fatal disease. Extra-abdominal spread of PMP is an unusual occurrence with few reports in medical literature. CASE REPORT: A 50-year-old man was diagnosed with PMP according to the findings of thorax and abdomen CT scan and cytologic and histological examinations. The radiological exam showed irregular thickening on the surface of left diaphragmatic and parietal pleura. RESULTS: First, cytoreductive surgery associated with hyperthermic intraperitoneal chemotherapy (HIPEC) for the abdominal disease was performed. Histopathological examination confirmed the diagnosis of low grade PMP. The radiological evaluation performed 5 months later showed a dimensional increase in pleural nodules. The treatment consisted of an extensive intrathoracic cytoreductive surgery in combination with pressurized intra-thoracic aerosol chemotherapy (PITAC). Postoperative course was uneventful. CONCLUSION: PMP with pleural extension is a rare phenomenon and carries an unfavourable prognosis. Due to the rarity of this presentation, its correct treatment is still unclear. We present a therapeutic approach to be applied in selected patients.

A review of bevacizumab in the treatment of malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is an aggressive cancer with poor prognosis. Systemic chemotherapy is the primary treatment modality for the majority of patients. VEGF plays a key mitogen for MPM cells physiopathology. Bevacizumab, a monoclonal anti-VEGF antibody, was a rational approach to be tested in MPM. Based on the results of the Phase III IFCT-0701 mesothelioma avastin cisplatin pemetrexed study, cisplatin-pemetrexed-bevacizumab is now the accepted standard in France. The National Comprehensive Cancer Network guidelines have also included this combination as an option for standard front-line therapy. This review summarized the efficacy and safety data of bevacizumab in the treatment of patients with MPM.

The inhibition of FGF receptor 1 activity mediates sorafenib antiproliferative effects in human malignant pleural mesothelioma tumor-initiating cells.

BACKGROUND: Malignant pleural mesothelioma is an aggressive cancer, characterized by rapid progression and high mortality. Persistence of tumor-initiating cells (TICs, or cancer stem cells) after cytotoxic drug treatment is responsible for tumor relapse, and represents one of the main reasons for the poor prognosis of mesothelioma. In fact, identification of the molecules affecting TIC viability is still a significant challenge. METHODS: TIC-enriched cultures were obtained from 10 human malignant pleural mesotheliomas and cultured in vitro. Three fully characterized tumorigenic cultures, named MM1, MM3, and MM4, were selected and used to assess antiproliferative effects of the multi-kinase inhibitor sorafenib. Cell viability was investigated by MTT assay, and cell cycle analysis as well as induction of apoptosis were determined by flow cytometry. Western blotting was performed to reveal the modulation of protein expression and the phosphorylation status of pathways associated with sorafenib treatment. RESULTS: We analyzed the molecular mechanisms of the antiproliferative effects of sorafenib in mesothelioma TIC cultures. Sorafenib inhibited cell cycle progression in all cultures, but only in MM3 and MM4 cells was this effect associated with Mcl-1-dependent apoptosis. To investigate the mechanisms of sorafenib-mediated antiproliferative activity, TICs were treated with epidermal growth factor (EGF) or basic fibroblast growth factor (bFGF) causing, in MM3 and MM4 cells, MEK, ERK1/2, Akt, and STAT3 phosphorylation. These effects were abolished by sorafenib only in bFGF-treated cells, while a modest inhibition occurred after EGF stimulation, suggesting that sorafenib effects are mainly due to FGF receptor (FGFR) inhibition. Indeed, FGFR1 phosphorylation was inhibited by sorafenib. Moreover, in MM1 cells, which release high levels of bFGF and showed autocrine activation of FGFR1 and constitutive phosphorylation/activation of MEK-ERK1/2, sorafenib induced a more effective antiproliferative response, confirming that the main target of the drug is the inhibition of FGFR1 activity. CONCLUSIONS: These results suggest that, in malignant pleural mesothelioma TICs, bFGF signaling is the main target of the antiproliferative response of sorafenib, acting directly on the FGFR1 activation. Patients with constitutive FGFR1 activation via an autocrine loop may be more sensitive to sorafenib treatment and the analysis of this possibility warrants further clinical investigation.

Is less also better? A single-institution experience on treatment of early stage Malignant Pleural Mesothelioma.

OBJECTIVES: No clear evidence of which surgical procedure should be performed for early stage mesothelioma is available to date. We analyzed our 10-year experience in the treatment of early stage mesothelioma with surgery and Hyperthermic IntraTHOracic Chemotherapy. METHODS: We retrospectively analyzed all cases of histologically proven epithelioid or biphasic IMIG stage I and II mesothelioma that we operated between 2005 and 2014. We performed an open pleurectomy and partial decortication of any visible lesion on the visceral pleura in all cases and both diaphragm and pericardium were always spared; Hyperthermic IntraTHOracic Chemotherapy was ran using Cisplatin 80 mg/m2 and Doxorubicin 25 mg/m2 at a target temperature of 42.5 °C for 60 min. RESULTS: We operated on 26 patients (23 male and 3 female); epithelioid tumor was diagnosed in 23 cases. Twelve patients were in IMIG stage I and 14 in IMIG stage II; median overall survival for all patients, stage I and II were 35.6, 46 and 23 months respectively and disease free survival was 18, 18 and 16 months respectively. Our results for stage I were better than those reported in literature and were similar for stage II. We observe no 30- and 90- mortality and the rate of severe complication (all CTCAE stage 3) were 30%; the median postoperative stay was 7.5 days. CONCLUSIONS: Our lung sparing approach for the treatment of pleural mesothelioma in early stages allows promising long term outcomes with a complete sparing of pulmonary and diaphragmatic function. Larger studies are needed to confirm our good results.

Chest wall resection for mesothelioma recurrence after surgery.

Malignant pleural mesothelioma is an aggressive and usually fatal disease, and its optimal management is still under debate. Surgery for recurrent malignant mesothelioma has been reported rarely in highly selected cases. We report a case of chest wall resection for local recurrence of epithelioid mesothelioma 3 years after cytoreductive surgery. Our patient experienced a 6-month disease-free survival after redo surgery, with complete resolution of his chest pain and discomfort.

Pleurectomy/decortication and hyperthermic intrapleural chemotherapy for malignant pleural mesothelioma: initial experience.

Cytoreductive surgery and hyperthermic intraoperative intrapleural chemotherapy (HITHOC) are a known option for malignant pleural mesothelioma (MPM). This prospective study was started to prove that pleurectomy/decortication and HITHOC could be successfully performed in a low volume center. Criteria of inclusion were a proven diagnosis of MPM, early-stage disease and good performance status. Six consecutive patients were enrolled. After pleurectomy/decortication, intrapleural cisplatin was administered for 60 min at 42.5 °C. Wedge resections and diaphragmatic reconstruction were added in two and one patient, respectively. Morbidity was 16.6%. Mortality was nil. Hospital stay was 7.8 days. Mean survival was 21.5 months (range: 6-30). This small experience confirms that pleurectomy/decortication and HITHOC are a good therapeutic option in the multimodality treatment of MPM. A randomized controlled trial is necessary.

Cynara scolymus affects malignant pleural mesothelioma by promoting apoptosis and restraining invasion.

Malignant pleural mesothelioma is a poorly treated neoplasia arising from the pleural mesothelial lining. Here we document that the leaf extract of Cynara scolymus exerts broad antitumoral effects both in vitro and in vivo on mesothelioma cell lines. We found that Cynara scolymus treatment affects strongly cell growth, migration and tumor engraftment of mesothelioma cell lines. Strikingly, dietary feeding with Cynara scolymus leaf extract reduces the growth of mesothelioma xenografted tumors similarly to pemetrexed, a commonly employed drug in the treatment of mesothelioma. In aggregate our findings suggest that leaf extract of Cynara scolymus holds therapeutic potential for the treatment of mesothelioma.