Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Mesothelioma: Outcomes from a Tertiary Cancer Care Center in Northern India

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Mesothelioma: Outcomes from a Tertiary Cancer Care Center in Northern India | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Mesothelioma: Outcomes from a Tertiary Cancer Care Center in Northern India Mukurdipi Ray, Bhawani Pathak, Ravi Venugopal, Shwetal Sonvane This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4063777/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Malignant peritoneal mesothelioma (MPM) is a rare and aggressive form of cancer originating from the peritoneum. The prognosis for MPM has historically been poor, and treatment options are limited. This study evaluated the impact of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) as a treatment modality for MPM, although optimal management is still evolving. Materials and Methods: This retrospective analysis included fifteen patients diagnosed with MPM between 2012 and 2023 at a tertiary referral cancer care center in North India. Patients underwent CRS followed by HIPEC. The study assessed outcomes based on overall survival (OS) and postoperative morbidity rates. Results: Demographic analysis revealed a female preponderance (60%) and a majority of younger patients, 80% of whom were younger than the age of 50. Neoadjuvant chemotherapy was infrequent (13.33%), while the most common histopathological subtype was epithelioid (66.67%). The mean peritoneal cancer index (PCI) was 14.0, with 60% of patients having a PCI above the mean. The completeness of cytoreduction (CC) varied, with 40% achieving CC0, 33.33% CC1, and 26.67% CC2. Adjuvant chemotherapy was administered to 60% of the patients. The mean blood loss was 577 ml, and the mean operation duration was 350 minutes. Postoperative complications ranged from mild to life-threatening, with a mortality rate of 6.67%. The median follow-up period was 25 months, revealing an overall median survival of 27.0 months, with 1- and 3-year survival rates of 86.7% and 33.3%, respectively. On univariate analysis, only histological subtype emerged as a predictive factor for overall survival. Conclusion : CRS combined with HIPEC is a viable and effective treatment option for patients with MPM and offers improved survival rates and an acceptable safety profile. These findings support the integration of this treatment modality into the management plan for select patients with MPM, although optimal management is still evolving. Malignant peritoneal mesothelioma HIPEC CRS Introduction Malignant peritoneal mesothelioma (MPM) is a rare but aggressive malignancy originating from the peritoneal lining and has a historically dire prognosis. The incidence of this disease is increasing, particularly in industrialized nations, posing significant challenges to oncological care.( 1 ) It primarily affects the pleura (60%-70%) and peritoneum (20%-30%), with less common involvement of the pericardium (1%-2%) and tunica vaginalis (1%).( 2 ) Although asbestos remains the most recognized etiologic factor, its role in MPM is less definitive than that in pleural mesothelioma, suggesting that other pathogenic mechanisms may contribute to its development.( 3 ) The clinical manifestations of MPM are often nonspecific, leading to late-stage diagnosis and a median survival of merely 6 to 12 months without intervention. ( 4 ) Traditional treatments such as systemic chemotherapy and palliative surgery have shown limited efficacy and have not significantly improved patient survival. ( 5 ) Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have emerged as promising modalities for the management of peritoneal surface malignancies. CRS aims to resect all visible tumor deposits and, combined with the locoregional application of chemotherapy via HIPEC, has shown improved survival outcomes in select patient populations. ( 6 , 7 ) HIPEC utilizes the cytotoxic effects of heat treatment to target residual microscopic disease, which can potentially be enhanced by the synergy of hyperthermia with chemotherapeutic agents. ( 8 ) The rationale behind HIPEC lies in its dual mechanism of direct cytotoxicity and heat-induced augmentation of chemotherapeutic effects. Regional delivery allows for higher local drug concentrations, which might be more effective against peritoneal disease than systemic chemotherapy, potentially leading to a reduced systemic toxicity profile. ( 9 ) Studies have shown varying results with this approach, but a consistent observation is the prolonged survival of patients with complete cytoreduction (CC-0) and favourable histological subtypes, such as epithelioid mesothelioma. ( 5 , 10 ) Despite these advancements, the literature on the role of HIPEC in treating peritoneal mesothelioma remains limited and consists primarily of retrospective analyses, small case series, and observational studies. ( 4 , 9 ) Furthermore, assessments of perioperative morbidity and long-term quality of life post-CRS and HIPEC treatment have become subjects of increasing interest, with recent research suggesting an acceptable safety profile and improved patient-reported outcomes. ( 11 , 12 ) This study aimed to expand the literature by providing a comprehensive analysis of outcomes following CRS and HIPEC in the treatment of MPM at our institution. Materials and Methods Study Design A retrospective analysis of a prospectively maintained computerized database extending from 2012 to 2023 was performed. The study was carried out within the Department of Surgical Oncology at a tertiary referral cancer care centre in North India. Patient Selection and Evaluation Evaluation of the suitability of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) was performed during weekly multidisciplinary meetings. The team, consisting of surgical oncologists, medical oncologists, and radiologists, assessed patient performance status, comorbidities, extent of disease on computed tomography (CT) scans, and feasibility of maximal cytoreduction. Patient population Fifteen patients with MPM were included in the observational study. All patients had a histological diagnosis of MPM and provided signed informed consent. Treatment Protocol All patients underwent CRS and HIPEC as per a standard protocol. The exclusion criteria included poor performance status, inability to perform major surgical intervention based on preanaesthetic evaluation, and unresectable disease determined during laparotomy. Preoperative assessment Before treatment, patients underwent physical examination; blood tests (including full blood count; serum electrolytes, creatinine, liver function test, and tumor marker levels); and imaging tests (oral and intravenous contrast CT scans of the chest, abdomen, and pelvis). Mechanical bowel preparation was performed, and prophylactic antibiotics were administered at the time of incision; this process was repeated every 4 hours. Surgical Procedure Patients were placed in the supine or low lithotomy position, and a midline incision was made from the xiphisternum to the pubic symphysis. Tumor deposits were documented using the peritoneal cancer index (PCI), and all visible intraperitoneal tumor deposits were excised with CRS.( 13 ) The completeness of cytoreduction (CC) score was recorded to document residual disease.( 14 ) Hyperthermic intraperitoneal chemotherapy (HIPEC) After surgery, HIPEC was administered for 90 minutes utilizing cisplatin (50 mg/m2) and pemetrexed (500 mg/m2) dissolved in 2 litres of dextrose peritoneal dialysis solution. Pelvic and right paracolic gutter drains were inserted before closure of the abdomen. Postoperative Management Patients were managed in the intensive care unit (ICU) until clinically stable (usually 24–48 hours) and then transferred to the surgical ward. Postoperative complications were graded based on the Clavien‒Dindo classification, and patients received continued follow-up care from medical and surgical oncologists upon discharge.( 15 ) Statistical analysis Data analysis was conducted using SPSS for Windows version 25.0 (SPSS, Munich, Germany). Patient characteristics were described using frequency distributions and descriptive analyses. Survival analysis was performed using the Kaplan‒Meier method, with differences between survival curves assessed using the log-rank test. P < 0.05 indicated statistical significance. RESULTS The demographic analysis highlighted a preponderance of females, accounting for 60% (n = 9) of the patients, while males composed 40% (n = 6) of the patients. The majority of patients in the cohort were younger than 50 years, 80% (n = 12) of whom were younger. The average age of the patients was 40.5 years, with a standard deviation of 14.0 years. Notably, all patients (100%, n = 15) had no history of asbestos exposure, a known risk factor for mesothelioma. Neoadjuvant chemotherapy was administered infrequently and was evident in 13.33% (n = 2) of the patients, with the majority (86.67%, n = 13) not receiving such treatment. Histopathological analysis revealed that the most common subtype was epithelioid, which was found in 66.67% (n = 10) of the patients, followed by the mixed subtype in 26.67% (n = 4) and the sarcomatoid subtype in 6.67% (n = 1). The Peritoneal Cancer Index (PCI), a measure of disease extent, exhibited a mean value of 14.0 (SD = 8.4), with a division in the cohort between those with a PCI below the mean (40%, n = 6) and those above (60%, n = 9). Complete cytoreduction (CC0) was achieved in 40.00% (n = 6) of patients, 33.33% (n = 5) had minimal residual disease (CC1), and 26.67% (n = 4) had residual disease up to 2.5 cm from 2.5 mm (CC2). Hyperthermic intraperitoneal chemotherapy (HIPEC) was the standard treatment for all patients, underscoring its established role in the management protocol (100%, n = 15). Additionally, a significant proportion of patients received adjuvant chemotherapy (60%, n = 9). Total peritonectomy was performed in 11 patients, disease-specific peritonectomy in 4 patients, and total omentectomy in all patients. Total abdominal hysterectomy with bilateral salpingo-oophorectomy was carried out in 7 patients. Low anterior resection and appendectomy were both conducted in 1 patient. Pelvic lymph node dissection was performed in 3 patients. The mean blood loss during the operative procedures was 577 ml, with a standard deviation (SD) of 590 ml. The mean operative duration was 350 minutes, with a mean operative duration of 168 minutes. The median intensive care unit (ICU) stay for the patient cohort was 1 day, with a range from 1 to 5 days. The median hospital stay was 8 days, with a range from 5 to 17 days. Seven patients experienced no significant postoperative complications. The postoperative complication profile of our patient cohort post-CRS and HIPEC reflects the inherent risks associated with aggressive management of MPM. The observed complications ranged from mild, self-limiting conditions such as pancreatitis, nausea, and fever (Grade I) in 26.67% of patients to more severe events such as sepsis and acute renal failure (Grade II) and even life-threatening complications such as pleural effusion (Grade III) and peritonitis (Grade IV). The mortality rate was 6.67%, with one patient succumbing to a myocardial infarction postoperatively. These findings are consistent with the literature, where the severity and range of complications post-CRS and HIPEC are well documented, with morbidity rates comparable to those in our study, suggesting that CRS and HIPEC, despite their risks, remain viable treatment options for selected patients with MPM. ( 10 , 16 – 19 ) The median follow-up period from the time of surgery was 25 months (range 0.2–112 months). The overall median survival of patients with MPM analysed using the Kaplan‒Meier method was 27.0 months (Figs. 1 & 2 ). The 1- and 3-year survival rates were 86.7% (71.1%-100.0%) and 33.3% (16.3%-68.2%), respectively. According to the univariate analysis, only histological subtype was a significant predictive factor for overall survival. DISCUSSION MPM, a malignancy arising from the lining of the abdominal cavity, remains a therapeutic challenge and has a historically poor prognosis. Predominantly linked to asbestos exposure, its epidemiology suggests a changing pattern, with a subset of patients presenting without any known exposure to this carcinogen. This shift necessitates re-examination of the disease's risk factors and pathogenesis. The demographic distribution within our study, notably a female majority and a prevalence of patients under the age of 50, raises questions about the typical profile of mesothelioma patients and suggests that other environmental or genetic factors may contribute to disease development. The absence of asbestos exposure in our patient cohort is particularly striking and aligns with emerging research suggesting alternative etiological pathways.( 20 ) The limited size of the sample could have influenced the outcomes. Traditionally, the treatment of MPM involves systemic chemotherapy and palliative care, with limited success in improving patient survival. ( 21 ) However, the advent of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has revolutionized the treatment landscape, offering the potential for extended survival in selected patients. ( 13 ) HIPEC involves the circulation of heated chemical agents within the peritoneal cavity postcytoreduction, aiming to eliminate residual microscopic disease. The rationale for hyperthermia is twofold: it enhances the cytotoxicity of chemotherapeutic agents and facilitates deeper penetration into tissues. ( 22 ) Studies have demonstrated that HIPEC combined with complete cytoreduction can lead to median survival rates that significantly exceed those achieved with traditional therapies. ( 23 ) Despite these promising developments, the administration of HIPEC remains complex, with considerable debate regarding its indications, optimal timing, and patient selection criteria. The procedure is associated with significant morbidity and requires careful patient evaluation and management by a multidisciplinary team. ( 24 ) The administration of neoadjuvant chemotherapy in our study was reserved, and only 13.33% (n = 2) of patients received this treatment. This percentage is comparatively low when juxtaposed with other studies, where neoadjuvant chemotherapy is more commonly used as a part of multimodal treatment.( 5 ) The rationale behind this conservative approach to neoadjuvant chemotherapy in our cohort could be multifaceted and potentially influenced by factors such as the timing of presentation, the burden of disease, and the perceived responsiveness of the tumor to systemic therapy. In our series, epithelial mesothelioma was the most common histological subtype (66.67%), which is associated with a better prognosis than are the sarcomatoid and mixed subtypes.( 25 ) The distribution of subtypes in our study aligns with the established literature that also reports that epithelioids are the most common subtype of peritoneal mesothelioma. Among our patients, 26.67% (n = 4) had the mixed subtype, followed by the sarcomatoid subtype (n = 1). When addressing the clinical management outcomes detailed in the provided data, it is essential to consider the peritoneal cancer index (PCI) and the completeness of cytoreduction (CC), both of which are well-established prognostic indicators for MPM. Our cohort presented a mean PCI of 14.0, which is a pivotal finding considering that a higher PCI is correlated with poorer outcomes, as indicated in studies where cytoreductive surgery combined with HIPEC was evaluated. ( 5 ) The fact that 60% of our patients had a PCI above the mean might reflect an advanced disease stage at presentation and could influence survival outcomes, despite the aggressive treatment approach adopted. Our cohort achieved a CC0 rate of 40%, which compares favourably with the published literature. For instance, Sugarbaker and colleagues reported CC0 rates varying from approximately 40–50% in selected patient groups undergoing CRS and HIPEC, confirming the importance of complete cytoreduction in improving outcomes.( 6 ) Other studies have reported CC0 rates ranging between 30–60%, with higher rates associated with specialized centers that frequently perform these complex treatments.( 5 , 23 ) The CC1 and CC2 rates, representing minimal and more extensive residual disease, respectively, were 33.33% and 26.67%. These findings underscore the inherent challenges in achieving complete cytoreduction and align with broader clinical experience, where complete macroscopic clearance is not always feasible due to tumor spread and patient factors.( 26 ) The universal application of HIPEC in our cohort reinforces its role as a cornerstone in the current standard of care for MPM, as it has been shown to improve survival in patients who underwent complete cytoreductive surgery.( 23 ) The high rate of adjuvant chemotherapy usage (60%) further exemplifies the aggressive therapeutic strategy employed in our center, although the impact on survival remains to be conclusively determined. The surgical procedures, ranging from total resection to organ-specific resection and lymph node dissection, reflect the tailored approach to the extent of disease, aiming to achieve the best possible cytoreductive outcomes. However, the relatively extensive surgeries performed may contribute to variability in postoperative recovery and morbidity, factors that require careful preoperative assessment. When interpreting the operative and postoperative data of MPM patients in our study, surgical management was considered to be appropriate, as reflected by the mean blood loss and operative duration. The average blood loss of 577 ml, though significant, is within acceptable limits for major abdominal surgeries, and the mean operative time of 350 minutes indicates the complexity and extent of the procedures performed, such as peritonectomy and organ resections. These operative parameters are consistent with those of other specialized centers performing similar extensive cytoreductive surgeries. ( 27 ) A median ICU stay of 1 day and a hospital stay of 8 days are indicative of an efficient postoperative care protocol, optimizing patient recovery and resource utilization. These durations are comparable to or better than those reported in larger series, where the complexity of the surgery can lead to longer ICU and hospital stays.( 5 ) The relatively short ICU stay also suggested a high level of surgical and anaesthetic expertise, as well as effective postoperative management protocols. Postoperative complications occur in a pattern that is not uncommon in high-risk abdominal surgeries. The spectrum of complications observed, ranging from mild (grade I) to more severe (grade IV), provides a real-world snapshot of the potential risks associated with aggressive surgical management of MPM. Notably, the incidences of Grade III and IV complications, as well as single-stage mortality, underscore the necessity of careful patient selection and the inherent risks of the disease and its treatment. The overall median survival of 27.0 months, with 1- and 3-year survival rates of 86.7% and 33.3%, respectively, offers a meaningful addition to the literature on MPM, which generally reports a median survival ranging from 12 to 27 months.( 23 ) On univariate analysis, only histological subtype emerged as a predictive factor for overall survival, while PCI and CC were not significant. This could be attributed to the small sample size of our study. The limitations of this study include its retrospective nature, reliance on data from a single center, limited sample size, and absence of Ki67 reporting in the histopathological analysis. CONCLUSION MPM is a rare disease group but represents a unique entity. The standard of care is CRS combined with HIPEC. However, the potential benefit of chemotherapy in the adjuvant or neoadjuvant setting is uncertain. Nevertheless, in specialized centres, extensive surgical procedures involving HIPEC have been observed to improve survival outcomes, as evidenced by our institution's experience, although optimal management is still evolving. Abbreviations MPM - Malignant Peritoneal Mesothelioma CRS - Cytoreductive Surgery HIPEC - Hyperthermic Intraperitoneal Chemotherapy CC - Completeness of Cytoreduction OS - Overall Survival PCI - Peritoneal Cancer Index ICU - Intensive Care Unit Declarations Ethics approval and consent to participate The study protocol was approved by the Institute Ethics Committee, AIIMS, New Delhi, India, in accordance with the Declaration of Helsinki. Consent for publication Not applicable Availability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests Funding No funding was required for this study. Authors' contributions We express gratitude to MDR for their editorial contributions and assistance in crafting the final manuscript. RV's support in data collection is greatly appreciated. BP's diligent analysis and preparation of the results are acknowledged with thanks. Finally, we acknowledge the collaborative efforts of BP and SS in finalizing the manuscript. Acknowledgements All authors were involved in the preparation, revision, and writing of this manuscript References BIANCHI C, BIANCHI T. Malignant Mesothelioma: Global Incidence and Relationship with Asbestos. Ind Health [Internet]. 2007;45(3):379–87. Available from: http://dx.doi.org/10.2486/indhealth.45.379 Ray MD, Dhall K. Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in the management of peritoneal surface malignancies – An evidence-based review. Curr Probl Cancer. 2021 Dec 1;45(6):100737. Boffetta P. Epidemiology of peritoneal mesothelioma: a review. Annals of Oncology [Internet]. 2007 Jun;18(6):985–90. 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Annals of Oncology [Internet]. 2007 Dec;18(12):1943–50. Available from: http://dx.doi.org/10.1093/annonc/mdm137 Tables TABLE 1. Characteristics of Patients Who Underwent Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Mesothelioma Category Number Percentage (%) Gender Male 6 40.00% Female 9 60.00% Age 45 Years 7 46.67% Mean (SD) 40.5 (14.0) History of asbestos exposure Yes 0 No 15 100.00% Neoadjuvant chemotherapy Yes 2 13.33% No 13 86.67% Histopathological subtypes Epitheloid 10 66.67% Sarcomatoid 1 6.67% Mixed 4 26.67% PCI Mean (SD) 14.0 (8.4) Low (mean) 9 60.00% Completeness of cytoreduction CC0 6 40.00% CC1 5 33.33% CC2 4 26.67% Adjuvant chemotherapy Yes 9 60.00% No 6 40.00% TABLE 2. Univariate Analysis Comparing Prognostic Variables Prognostic variables P value Age 45 year CC 0 0.18 1 2 Histology Epitheloid 0.01 Sarcomatoid Mixed PCI Low 0.91 High Sex Male 0.33 Female Adjuvant CT Yes 0.11 No NACT Yes 0.1 No Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4063777","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":285067985,"identity":"89a58ecc-e93d-4793-a339-1a173334e94a","order_by":0,"name":"Mukurdipi Ray","email":"data:image/png;base64,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","orcid":"","institution":"All India Institute of Medical Sciences, New Delhi","correspondingAuthor":true,"prefix":"","firstName":"Mukurdipi","middleName":"","lastName":"Ray","suffix":""},{"id":285067986,"identity":"9d7655c5-8876-41b8-94ac-bb76139c62ee","order_by":1,"name":"Bhawani Pathak","email":"","orcid":"","institution":"All India Institute of Medical Sciences, New Delhi","correspondingAuthor":false,"prefix":"","firstName":"Bhawani","middleName":"","lastName":"Pathak","suffix":""},{"id":285067987,"identity":"7383090d-8504-4a50-bae5-e9a0ed79d58a","order_by":2,"name":"Ravi Venugopal","email":"","orcid":"","institution":"All India Institute of Medical Sciences, New Delhi","correspondingAuthor":false,"prefix":"","firstName":"Ravi","middleName":"","lastName":"Venugopal","suffix":""},{"id":285067988,"identity":"8bf54561-e507-4f50-a7a9-c8cd08750abd","order_by":3,"name":"Shwetal Sonvane","email":"","orcid":"","institution":"All India Institute of Medical Sciences, New Delhi","correspondingAuthor":false,"prefix":"","firstName":"Shwetal","middleName":"","lastName":"Sonvane","suffix":""}],"badges":[],"createdAt":"2024-03-10 09:44:48","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4063777/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4063777/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":58449074,"identity":"f52a3809-4947-47e2-ba91-f83a5baff4d5","added_by":"auto","created_at":"2024-06-16 16:03:29","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":503088,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4063777/v1/230c9361-16de-4db3-8550-3fa84ff4afa4.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Mesothelioma: Outcomes from a Tertiary Cancer Care Center in Northern India","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMalignant peritoneal mesothelioma (MPM) is a rare but aggressive malignancy originating from the peritoneal lining and has a historically dire prognosis. The incidence of this disease is increasing, particularly in industrialized nations, posing significant challenges to oncological care.(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) It primarily affects the pleura (60%-70%) and peritoneum (20%-30%), with less common involvement of the pericardium (1%-2%) and tunica vaginalis (1%).(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) Although asbestos remains the most recognized etiologic factor, its role in MPM is less definitive than that in pleural mesothelioma, suggesting that other pathogenic mechanisms may contribute to its development.(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eThe clinical manifestations of MPM are often nonspecific, leading to late-stage diagnosis and a median survival of merely 6 to 12 months without intervention. (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) Traditional treatments such as systemic chemotherapy and palliative surgery have shown limited efficacy and have not significantly improved patient survival. (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eCytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have emerged as promising modalities for the management of peritoneal surface malignancies. CRS aims to resect all visible tumor deposits and, combined with the locoregional application of chemotherapy via HIPEC, has shown improved survival outcomes in select patient populations. (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) HIPEC utilizes the cytotoxic effects of heat treatment to target residual microscopic disease, which can potentially be enhanced by the synergy of hyperthermia with chemotherapeutic agents. (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eThe rationale behind HIPEC lies in its dual mechanism of direct cytotoxicity and heat-induced augmentation of chemotherapeutic effects. Regional delivery allows for higher local drug concentrations, which might be more effective against peritoneal disease than systemic chemotherapy, potentially leading to a reduced systemic toxicity profile. (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e) Studies have shown varying results with this approach, but a consistent observation is the prolonged survival of patients with complete cytoreduction (CC-0) and favourable histological subtypes, such as epithelioid mesothelioma. (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eDespite these advancements, the literature on the role of HIPEC in treating peritoneal mesothelioma remains limited and consists primarily of retrospective analyses, small case series, and observational studies. (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e) Furthermore, assessments of perioperative morbidity and long-term quality of life post-CRS and HIPEC treatment have become subjects of increasing interest, with recent research suggesting an acceptable safety profile and improved patient-reported outcomes. (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eThis study aimed to expand the literature by providing a comprehensive analysis of outcomes following CRS and HIPEC in the treatment of MPM at our institution.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eStudy Design\u003c/p\u003e \u003cp\u003eA retrospective analysis of a prospectively maintained computerized database extending from 2012 to 2023 was performed. The study was carried out within the Department of Surgical Oncology at a tertiary referral cancer care centre in North India.\u003c/p\u003e \u003cp\u003ePatient Selection and Evaluation\u003c/p\u003e \u003cp\u003eEvaluation of the suitability of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) was performed during weekly multidisciplinary meetings. The team, consisting of surgical oncologists, medical oncologists, and radiologists, assessed patient performance status, comorbidities, extent of disease on computed tomography (CT) scans, and feasibility of maximal cytoreduction.\u003c/p\u003e \u003cp\u003ePatient population\u003c/p\u003e \u003cp\u003eFifteen patients with MPM were included in the observational study. All patients had a histological diagnosis of MPM and provided signed informed consent.\u003c/p\u003e \u003cp\u003eTreatment Protocol\u003c/p\u003e \u003cp\u003eAll patients underwent CRS and HIPEC as per a standard protocol. The exclusion criteria included poor performance status, inability to perform major surgical intervention based on preanaesthetic evaluation, and unresectable disease determined during laparotomy.\u003c/p\u003e \u003cp\u003ePreoperative assessment\u003c/p\u003e \u003cp\u003eBefore treatment, patients underwent physical examination; blood tests (including full blood count; serum electrolytes, creatinine, liver function test, and tumor marker levels); and imaging tests (oral and intravenous contrast CT scans of the chest, abdomen, and pelvis). Mechanical bowel preparation was performed, and prophylactic antibiotics were administered at the time of incision; this process was repeated every 4 hours.\u003c/p\u003e \u003cp\u003eSurgical Procedure\u003c/p\u003e \u003cp\u003ePatients were placed in the supine or low lithotomy position, and a midline incision was made from the xiphisternum to the pubic symphysis. Tumor deposits were documented using the peritoneal cancer index (PCI), and all visible intraperitoneal tumor deposits were excised with CRS.(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e) The completeness of cytoreduction (CC) score was recorded to document residual disease.(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eHyperthermic intraperitoneal chemotherapy (HIPEC)\u003c/p\u003e \u003cp\u003eAfter surgery, HIPEC was administered for 90 minutes utilizing cisplatin (50 mg/m2) and pemetrexed (500 mg/m2) dissolved in 2 litres of dextrose peritoneal dialysis solution. Pelvic and right paracolic gutter drains were inserted before closure of the abdomen.\u003c/p\u003e \u003cp\u003ePostoperative Management\u003c/p\u003e \u003cp\u003ePatients were managed in the intensive care unit (ICU) until clinically stable (usually 24\u0026ndash;48 hours) and then transferred to the surgical ward. Postoperative complications were graded based on the Clavien‒Dindo classification, and patients received continued follow-up care from medical and surgical oncologists upon discharge.(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e)\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eData analysis was conducted using SPSS for Windows version 25.0 (SPSS, Munich, Germany). Patient characteristics were described using frequency distributions and descriptive analyses. Survival analysis was performed using the Kaplan‒Meier method, with differences between survival curves assessed using the log-rank test. P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 indicated statistical significance.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003eThe demographic analysis highlighted a preponderance of females, accounting for 60% (n\u0026thinsp;=\u0026thinsp;9) of the patients, while males composed 40% (n\u0026thinsp;=\u0026thinsp;6) of the patients. The majority of patients in the cohort were younger than 50 years, 80% (n\u0026thinsp;=\u0026thinsp;12) of whom were younger. The average age of the patients was 40.5 years, with a standard deviation of 14.0 years. Notably, all patients (100%, n\u0026thinsp;=\u0026thinsp;15) had no history of asbestos exposure, a known risk factor for mesothelioma. Neoadjuvant chemotherapy was administered infrequently and was evident in 13.33% (n\u0026thinsp;=\u0026thinsp;2) of the patients, with the majority (86.67%, n\u0026thinsp;=\u0026thinsp;13) not receiving such treatment. Histopathological analysis revealed that the most common subtype was epithelioid, which was found in 66.67% (n\u0026thinsp;=\u0026thinsp;10) of the patients, followed by the mixed subtype in 26.67% (n\u0026thinsp;=\u0026thinsp;4) and the sarcomatoid subtype in 6.67% (n\u0026thinsp;=\u0026thinsp;1).\u003c/p\u003e \u003cp\u003eThe Peritoneal Cancer Index (PCI), a measure of disease extent, exhibited a mean value of 14.0 (SD\u0026thinsp;=\u0026thinsp;8.4), with a division in the cohort between those with a PCI below the mean (40%, n\u0026thinsp;=\u0026thinsp;6) and those above (60%, n\u0026thinsp;=\u0026thinsp;9). Complete cytoreduction (CC0) was achieved in 40.00% (n\u0026thinsp;=\u0026thinsp;6) of patients, 33.33% (n\u0026thinsp;=\u0026thinsp;5) had minimal residual disease (CC1), and 26.67% (n\u0026thinsp;=\u0026thinsp;4) had residual disease up to 2.5 cm from 2.5 mm (CC2). Hyperthermic intraperitoneal chemotherapy (HIPEC) was the standard treatment for all patients, underscoring its established role in the management protocol (100%, n\u0026thinsp;=\u0026thinsp;15). Additionally, a significant proportion of patients received adjuvant chemotherapy (60%, n\u0026thinsp;=\u0026thinsp;9).\u003c/p\u003e \u003cp\u003eTotal peritonectomy was performed in 11 patients, disease-specific peritonectomy in 4 patients, and total omentectomy in all patients. Total abdominal hysterectomy with bilateral salpingo-oophorectomy was carried out in 7 patients. Low anterior resection and appendectomy were both conducted in 1 patient. Pelvic lymph node dissection was performed in 3 patients.\u003c/p\u003e \u003cp\u003eThe mean blood loss during the operative procedures was 577 ml, with a standard deviation (SD) of 590 ml. The mean operative duration was 350 minutes, with a mean operative duration of 168 minutes. The median intensive care unit (ICU) stay for the patient cohort was 1 day, with a range from 1 to 5 days. The median hospital stay was 8 days, with a range from 5 to 17 days. Seven patients experienced no significant postoperative complications.\u003c/p\u003e \u003cp\u003eThe postoperative complication profile of our patient cohort post-CRS and HIPEC reflects the inherent risks associated with aggressive management of MPM. The observed complications ranged from mild, self-limiting conditions such as pancreatitis, nausea, and fever (Grade I) in 26.67% of patients to more severe events such as sepsis and acute renal failure (Grade II) and even life-threatening complications such as pleural effusion (Grade III) and peritonitis (Grade IV). The mortality rate was 6.67%, with one patient succumbing to a myocardial infarction postoperatively. These findings are consistent with the literature, where the severity and range of complications post-CRS and HIPEC are well documented, with morbidity rates comparable to those in our study, suggesting that CRS and HIPEC, despite their risks, remain viable treatment options for selected patients with MPM. (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan additionalcitationids=\"CR17 CR18\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eThe median follow-up period from the time of surgery was 25 months (range 0.2\u0026ndash;112 months). The overall median survival of patients with MPM analysed using the Kaplan‒Meier method was 27.0 months (Figs.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e \u0026amp; \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The 1- and 3-year survival rates were 86.7% (71.1%-100.0%) and 33.3% (16.3%-68.2%), respectively. According to the univariate analysis, only histological subtype was a significant predictive factor for overall survival.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eMPM, a malignancy arising from the lining of the abdominal cavity, remains a therapeutic challenge and has a historically poor prognosis. Predominantly linked to asbestos exposure, its epidemiology suggests a changing pattern, with a subset of patients presenting without any known exposure to this carcinogen. This shift necessitates re-examination of the disease's risk factors and pathogenesis.\u003c/p\u003e \u003cp\u003eThe demographic distribution within our study, notably a female majority and a prevalence of patients under the age of 50, raises questions about the typical profile of mesothelioma patients and suggests that other environmental or genetic factors may contribute to disease development. The absence of asbestos exposure in our patient cohort is particularly striking and aligns with emerging research suggesting alternative etiological pathways.(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e) The limited size of the sample could have influenced the outcomes.\u003c/p\u003e \u003cp\u003eTraditionally, the treatment of MPM involves systemic chemotherapy and palliative care, with limited success in improving patient survival. (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e) However, the advent of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has revolutionized the treatment landscape, offering the potential for extended survival in selected patients. (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eHIPEC involves the circulation of heated chemical agents within the peritoneal cavity postcytoreduction, aiming to eliminate residual microscopic disease. The rationale for hyperthermia is twofold: it enhances the cytotoxicity of chemotherapeutic agents and facilitates deeper penetration into tissues. (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e) Studies have demonstrated that HIPEC combined with complete cytoreduction can lead to median survival rates that significantly exceed those achieved with traditional therapies. (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eDespite these promising developments, the administration of HIPEC remains complex, with considerable debate regarding its indications, optimal timing, and patient selection criteria. The procedure is associated with significant morbidity and requires careful patient evaluation and management by a multidisciplinary team. (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eThe administration of neoadjuvant chemotherapy in our study was reserved, and only 13.33% (n\u0026thinsp;=\u0026thinsp;2) of patients received this treatment. This percentage is comparatively low when juxtaposed with other studies, where neoadjuvant chemotherapy is more commonly used as a part of multimodal treatment.(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) The rationale behind this conservative approach to neoadjuvant chemotherapy in our cohort could be multifaceted and potentially influenced by factors such as the timing of presentation, the burden of disease, and the perceived responsiveness of the tumor to systemic therapy.\u003c/p\u003e \u003cp\u003eIn our series, epithelial mesothelioma was the most common histological subtype (66.67%), which is associated with a better prognosis than are the sarcomatoid and mixed subtypes.(\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e) The distribution of subtypes in our study aligns with the established literature that also reports that epithelioids are the most common subtype of peritoneal mesothelioma. Among our patients, 26.67% (n\u0026thinsp;=\u0026thinsp;4) had the mixed subtype, followed by the sarcomatoid subtype (n\u0026thinsp;=\u0026thinsp;1).\u003c/p\u003e \u003cp\u003eWhen addressing the clinical management outcomes detailed in the provided data, it is essential to consider the peritoneal cancer index (PCI) and the completeness of cytoreduction (CC), both of which are well-established prognostic indicators for MPM. Our cohort presented a mean PCI of 14.0, which is a pivotal finding considering that a higher PCI is correlated with poorer outcomes, as indicated in studies where cytoreductive surgery combined with HIPEC was evaluated. (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) The fact that 60% of our patients had a PCI above the mean might reflect an advanced disease stage at presentation and could influence survival outcomes, despite the aggressive treatment approach adopted.\u003c/p\u003e \u003cp\u003eOur cohort achieved a CC0 rate of 40%, which compares favourably with the published literature. For instance, Sugarbaker and colleagues reported CC0 rates varying from approximately 40\u0026ndash;50% in selected patient groups undergoing CRS and HIPEC, confirming the importance of complete cytoreduction in improving outcomes.(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) Other studies have reported CC0 rates ranging between 30\u0026ndash;60%, with higher rates associated with specialized centers that frequently perform these complex treatments.(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e) The CC1 and CC2 rates, representing minimal and more extensive residual disease, respectively, were 33.33% and 26.67%. These findings underscore the inherent challenges in achieving complete cytoreduction and align with broader clinical experience, where complete macroscopic clearance is not always feasible due to tumor spread and patient factors.(\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eThe universal application of HIPEC in our cohort reinforces its role as a cornerstone in the current standard of care for MPM, as it has been shown to improve survival in patients who underwent complete cytoreductive surgery.(\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e) The high rate of adjuvant chemotherapy usage (60%) further exemplifies the aggressive therapeutic strategy employed in our center, although the impact on survival remains to be conclusively determined.\u003c/p\u003e \u003cp\u003eThe surgical procedures, ranging from total resection to organ-specific resection and lymph node dissection, reflect the tailored approach to the extent of disease, aiming to achieve the best possible cytoreductive outcomes. However, the relatively extensive surgeries performed may contribute to variability in postoperative recovery and morbidity, factors that require careful preoperative assessment.\u003c/p\u003e \u003cp\u003eWhen interpreting the operative and postoperative data of MPM patients in our study, surgical management was considered to be appropriate, as reflected by the mean blood loss and operative duration. The average blood loss of 577 ml, though significant, is within acceptable limits for major abdominal surgeries, and the mean operative time of 350 minutes indicates the complexity and extent of the procedures performed, such as peritonectomy and organ resections. These operative parameters are consistent with those of other specialized centers performing similar extensive cytoreductive surgeries. (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eA median ICU stay of 1 day and a hospital stay of 8 days are indicative of an efficient postoperative care protocol, optimizing patient recovery and resource utilization. These durations are comparable to or better than those reported in larger series, where the complexity of the surgery can lead to longer ICU and hospital stays.(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e) The relatively short ICU stay also suggested a high level of surgical and anaesthetic expertise, as well as effective postoperative management protocols.\u003c/p\u003e \u003cp\u003ePostoperative complications occur in a pattern that is not uncommon in high-risk abdominal surgeries. The spectrum of complications observed, ranging from mild (grade I) to more severe (grade IV), provides a real-world snapshot of the potential risks associated with aggressive surgical management of MPM. Notably, the incidences of Grade III and IV complications, as well as single-stage mortality, underscore the necessity of careful patient selection and the inherent risks of the disease and its treatment.\u003c/p\u003e \u003cp\u003eThe overall median survival of 27.0 months, with 1- and 3-year survival rates of 86.7% and 33.3%, respectively, offers a meaningful addition to the literature on MPM, which generally reports a median survival ranging from 12 to 27 months.(\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e) On univariate analysis, only histological subtype emerged as a predictive factor for overall survival, while PCI and CC were not significant. This could be attributed to the small sample size of our study.\u003c/p\u003e \u003cp\u003eThe limitations of this study include its retrospective nature, reliance on data from a single center, limited sample size, and absence of Ki67 reporting in the histopathological analysis.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eMPM is a rare disease group but represents a unique entity. The standard of care is CRS combined with HIPEC. However, the potential benefit of chemotherapy in the adjuvant or neoadjuvant setting is uncertain. Nevertheless, in specialized centres, extensive surgical procedures involving HIPEC have been observed to improve survival outcomes, as evidenced by our institution's experience, although optimal management is still evolving.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003col\u003e\n \u003cli\u003eMPM - Malignant Peritoneal Mesothelioma\u003c/li\u003e\n \u003cli\u003eCRS - Cytoreductive Surgery\u003c/li\u003e\n \u003cli\u003eHIPEC - Hyperthermic Intraperitoneal Chemotherapy\u003c/li\u003e\n \u003cli\u003eCC - Completeness of Cytoreduction\u003c/li\u003e\n \u003cli\u003eOS - Overall Survival\u003c/li\u003e\n \u003cli\u003ePCI - Peritoneal Cancer Index\u003c/li\u003e\n \u003cli\u003eICU - Intensive Care Unit\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study protocol was approved by the Institute Ethics Committee, AIIMS, New Delhi, India, in accordance with the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding was required for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe express gratitude to MDR for their editorial contributions and assistance in crafting the final manuscript. RV\u0026apos;s support in data collection is greatly appreciated. BP\u0026apos;s diligent analysis and preparation of the results are acknowledged with thanks. Finally, we acknowledge the collaborative efforts of BP and SS in finalizing the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors were involved in the preparation, revision, and writing of \u0026nbsp; \u0026nbsp;this manuscript\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eBIANCHI C, BIANCHI T. Malignant Mesothelioma: Global Incidence and Relationship with Asbestos. Ind Health [Internet]. 2007;45(3):379\u0026ndash;87. Available from: http://dx.doi.org/10.2486/indhealth.45.379\u003c/li\u003e\n \u003cli\u003eRay MD, Dhall K. Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in the management of peritoneal surface malignancies \u0026ndash; An evidence-based review. Curr Probl Cancer. 2021 Dec 1;45(6):100737.\u003c/li\u003e\n \u003cli\u003eBoffetta P. Epidemiology of peritoneal mesothelioma: a review. Annals of Oncology [Internet]. 2007 Jun;18(6):985\u0026ndash;90. Available from: http://dx.doi.org/10.1093/annonc/mdl345\u003c/li\u003e\n \u003cli\u003eAcherman YIZ, Welch LS, Bromley CM, Sugarbaker PH. Clinical Presentation of Peritoneal Mesothelioma. Tumori Journal [Internet]. 2003 May;89(3):269\u0026ndash;73. Available from: http://dx.doi.org/10.1177/030089160308900307\u003c/li\u003e\n \u003cli\u003eYan TD, Welch L, Black D, Sugarbaker PH. A systematic review on the efficacy of cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for diffuse malignancy peritoneal mesothelioma. Annals of Oncology [Internet]. 2007 May;18(5):827\u0026ndash;34. Available from: http://dx.doi.org/10.1093/annonc/mdl428\u003c/li\u003e\n \u003cli\u003eSugarbaker PH. Peritoneal Metastases from Adrenal Cortical Carcinoma Treated by Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy. Tumori Journal [Internet]. 2016 Sep;102(6):588\u0026ndash;92. Available from: http://dx.doi.org/10.5301/tj.5000567\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eGonz\u0026aacute;lez-Moreno S. Peritoneal Surface Oncology: A progress report. European Journal of Surgical Oncology (EJSO) [Internet]. 2006 Aug;32(6):593\u0026ndash;6. Available from: http://dx.doi.org/10.1016/j.ejso.2006.03.001\u003c/li\u003e\n \u003cli\u003eWitkamp AJ, De Bree E, Van Goethem R, Zoetmulder FAN. Rationale and techniques of intraoperative hyperthermic intraperitoneal chemotherapy. Cancer Treat Rev [Internet]. 2001 [cited 2024 Feb 11];27(6):365\u0026ndash;74. Available from: https://pubmed.ncbi.nlm.nih.gov/11908929/\u003c/li\u003e\n \u003cli\u003eDeraco M, Kusamura S, Baratti D, Casali P, Gronchi A, Zaffaroni N. Peritoneal mesothelioma treated by cytoreductive surgery and intra peritoneal hyperthermic perfusion: Clinical and translational study. Journal of Clinical Oncology [Internet]. 2004 Jul;22(14_suppl):9729. Available from: http://dx.doi.org/10.1200/jco.2004.22.14_suppl.9729\u003c/li\u003e\n \u003cli\u003eBrigand C, Monneuse O, Mohamed F, Sayag-Beaujard AC, Isaac S, Gilly FN, et al. Peritoneal Mesothelioma Treated by Cytoreductive Surgery and Intraperitoneal Hyperthermic Chemotherapy: Results of a Prospective Study. Ann Surg Oncol [Internet]. 2006 Jan;13(3):405\u0026ndash;12. Available from: http://dx.doi.org/10.1245/aso.2006.05.041\u003c/li\u003e\n \u003cli\u003eMcquellon R, Gavazzi C, Piso P, Swain D, Levine E. Quality of life and nutritional assessment in peritoneal surface malignancy (PSM): recommendations for care. J Surg Oncol [Internet]. 2008 Sep 15 [cited 2024 Feb 11];98(4):300\u0026ndash;5. Available from: https://pubmed.ncbi.nlm.nih.gov/18726903/\u003c/li\u003e\n \u003cli\u003eSchmidt C, Moritz S, Rath S, Grossmann E, Wiesenack C, Piso P, et al. Perioperative management of patients with cytoreductive surgery for peritoneal carcinomatosis. J Surg Oncol [Internet]. 2009 Sep 15 [cited 2024 Feb 11];100(4):297\u0026ndash;301. Available from: https://pubmed.ncbi.nlm.nih.gov/19697426/\u003c/li\u003e\n \u003cli\u003eJacquet P, Sugarbaker PH. Clinical research methodologies in diagnosis and staging of patients with peritoneal carcinomatosis. Cancer Treat Res [Internet]. 1996 [cited 2024 Feb 12];82:359\u0026ndash;74. Available from: https://pubmed.ncbi.nlm.nih.gov/8849962/\u003c/li\u003e\n \u003cli\u003eSugarbaker PH. Peritonectomy procedures. Ann Surg [Internet]. 1995 [cited 2024 Feb 12];221(1):29\u0026ndash;42. Available from: https://pubmed.ncbi.nlm.nih.gov/7826158/\u003c/li\u003e\n \u003cli\u003eClavien PA, Barkun J, De Oliveira ML, Vauthey JN, Dindo D, Schulick RD, et al. The Clavien‒Dindo classification of surgical complications: five-year experience. Ann Surg [Internet]. 2009 Aug [cited 2024 Feb 12];250(2):187\u0026ndash;96. Available from: https://pubmed.ncbi.nlm.nih.gov/19638912/\u003c/li\u003e\n \u003cli\u003eChua TC, Yan TD, Morris DL. Outcomes of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal mesothelioma: The Australian experience. J Surg Oncol [Internet]. 2008 Nov;99(2):109\u0026ndash;13. Available from: http://dx.doi.org/10.1002/jso.21177\u003c/li\u003e\n \u003cli\u003eSpiliotis J, Halkia E, Lianos E, Kalantzi N, Grivas A, Efstathiou E, et al. Cytoreductive Surgery and HIPEC in Recurrent Epithelial Ovarian Cancer: A Prospective Randomized Phase III Study. Ann Surg Oncol [Internet]. 2014 Nov;22(5):1570\u0026ndash;5. Available from: http://dx.doi.org/10.1245/s10434-014-4157-9\u003c/li\u003e\n \u003cli\u003eAhmed S, Stewart JH, Shen P, Votanopoulos KI, Levine EA. Outcomes with cytoreductive surgery and HIPEC for peritoneal metastasis. J Surg Oncol [Internet]. 2014 Aug;110(5):575\u0026ndash;84. Available from: http://dx.doi.org/10.1002/jso.23749\u003c/li\u003e\n \u003cli\u003eKooby DA. Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma of the Extremity and Trunk Wall: Importance of Histological Subtype With Treatment Recommendations. Ann Surg Oncol [Internet]. 2003 Dec;11(1):78\u0026ndash;84. Available from: http://dx.doi.org/10.1245/aso.2004.03.058\u003c/li\u003e\n \u003cli\u003eGibbs AR. Determination of Asbestos Exposure by Pathology and Clinical History. In: Malignant Mesothelioma [Internet]. Springer-Verlag; p. 259\u0026ndash;66. Available from: http://dx.doi.org/10.1007/0-387-28274-2_16\u003c/li\u003e\n \u003cli\u003eManzini V de P, Recchia L, Cafferata M, Porta C, Siena S, Giannetta L, et al. Malignant peritoneal mesothelioma: a multicenter study on 81 cases. Annals of Oncology [Internet]. 2010 Feb;21(2):348\u0026ndash;53. Available from: http://dx.doi.org/10.1093/annonc/mdp307\u003c/li\u003e\n \u003cli\u003eHelm CW, Richard SD, Pan J, Bartlett D, Goodman MD, Hoefer R, et al. Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer: First Report of the HYPER-O Registry. International Journal of Gynecological Cancer [Internet]. 2010 Jan;20(1):61\u0026ndash;9. Available from: http://dx.doi.org/10.1111/igc.0b013e3181c50cde\u003c/li\u003e\n \u003cli\u003eYan TD, Deraco M, Baratti D, Kusamura S, Elias D, Glehen O, et al. Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Malignant Peritoneal Mesothelioma: Multi-Institutional Experience. Journal of Clinical Oncology [Internet]. 2009 Dec;27(36):6237\u0026ndash;42. Available from: http://dx.doi.org/10.1200/jco.2009.23.9640\u003c/li\u003e\n \u003cli\u003eKusamura S, Younan R, Baratti D, Costanzo P, Favaro M, Gavazzi C, et al. Cytoreductive surgery followed by intraperitoneal hyperthermic perfusion: Analysis of morbidity and mortality in 209 peritoneal surface malignancies treated with closed abdomen technique. Cancer [Internet]. 2006 Feb;106(5):1144\u0026ndash;53. Available from: http://dx.doi.org/10.1002/cncr.21708\u003c/li\u003e\n \u003cli\u003eAlexander HR, Bartlett DL, Pingpank JF, Libutti SK, Royal R, Hughes MS, et al. Treatment factors associated with long-term survival after cytoreductive surgery and regional chemotherapy for patients with malignant peritoneal mesothelioma. Surgery [Internet]. 2013 Jun [cited 2024 Feb 13];153(6):779\u0026ndash;86. Available from: https://pubmed.ncbi.nlm.nih.gov/23489943/\u003c/li\u003e\n \u003cli\u003eFeldman AL, Libutti SK, Pingpank JF, Bartlett DL, Beresnev TH, Mavroukakis SM, et al. Analysis of Factors Associated With Outcome in Patients With Malignant Peritoneal Mesothelioma Undergoing Surgical Debulking and Intraperitoneal Chemotherapy. Journal of Clinical Oncology [Internet]. 2003 Dec;21(24):4560\u0026ndash;7. Available from: http://dx.doi.org/10.1200/jco.2003.04.150\u003c/li\u003e\n \u003cli\u003eBijelic L, Jonson A, Sugarbaker PH. Systematic review of cytoreductive surgery and heated intraoperative intraperitoneal chemotherapy for treatment of peritoneal carcinomatosis in primary and recurrent ovarian cancer. Annals of Oncology [Internet]. 2007 Dec;18(12):1943\u0026ndash;50. Available from: http://dx.doi.org/10.1093/annonc/mdm137\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTABLE 1. Characteristics of Patients Who Underwent Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Mesothelioma\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"50.78534031413613%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCategory\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19720767888307%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNumber\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.017452006980804%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePercentage (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50.78534031413613%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGender\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19720767888307%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.017452006980804%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50.78534031413613%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Male\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19720767888307%\" valign=\"top\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.017452006980804%\" valign=\"top\"\u003e\n \u003cp\u003e40.00%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50.78534031413613%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Female\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19720767888307%\" valign=\"top\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.017452006980804%\" valign=\"top\"\u003e\n \u003cp\u003e60.00%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50.78534031413613%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19720767888307%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.017452006980804%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50.78534031413613%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026lt;45 Years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19720767888307%\" valign=\"top\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.017452006980804%\" valign=\"top\"\u003e\n \u003cp\u003e53.33%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50.78534031413613%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026gt;45 Years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19720767888307%\" valign=\"top\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.017452006980804%\" valign=\"top\"\u003e\n \u003cp\u003e46.67%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50.78534031413613%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19720767888307%\" valign=\"top\"\u003e\n \u003cp\u003e40.5 (14.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.017452006980804%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50.78534031413613%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHistory of asbestos exposure\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19720767888307%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.017452006980804%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50.78534031413613%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Yes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19720767888307%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.017452006980804%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50.78534031413613%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;No\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19720767888307%\" valign=\"top\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.017452006980804%\" valign=\"top\"\u003e\n \u003cp\u003e100.00%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50.78534031413613%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNeoadjuvant chemotherapy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19720767888307%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.017452006980804%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50.78534031413613%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Yes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19720767888307%\" valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.017452006980804%\" valign=\"top\"\u003e\n \u003cp\u003e13.33%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50.78534031413613%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;No\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19720767888307%\" valign=\"top\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.017452006980804%\" valign=\"top\"\u003e\n \u003cp\u003e86.67%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50.78534031413613%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHistopathological subtypes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19720767888307%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.017452006980804%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50.78534031413613%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Epitheloid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19720767888307%\" valign=\"top\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.017452006980804%\" valign=\"top\"\u003e\n \u003cp\u003e66.67%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50.78534031413613%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Sarcomatoid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19720767888307%\" valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.017452006980804%\" valign=\"top\"\u003e\n \u003cp\u003e6.67%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50.78534031413613%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Mixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19720767888307%\" valign=\"top\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.017452006980804%\" valign=\"top\"\u003e\n \u003cp\u003e26.67%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50.78534031413613%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePCI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19720767888307%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.017452006980804%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50.78534031413613%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19720767888307%\" valign=\"top\"\u003e\n \u003cp\u003e14.0 (8.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.017452006980804%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50.78534031413613%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Low (\u0026lt;mean)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19720767888307%\" valign=\"top\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.017452006980804%\" valign=\"top\"\u003e\n \u003cp\u003e40.00%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50.78534031413613%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;High (\u0026gt;mean)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19720767888307%\" valign=\"top\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.017452006980804%\" valign=\"top\"\u003e\n \u003cp\u003e60.00%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50.78534031413613%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCompleteness of cytoreduction\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19720767888307%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.017452006980804%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50.78534031413613%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;CC0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19720767888307%\" valign=\"top\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.017452006980804%\" valign=\"top\"\u003e\n \u003cp\u003e40.00%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50.78534031413613%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;CC1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19720767888307%\" valign=\"top\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.017452006980804%\" valign=\"top\"\u003e\n \u003cp\u003e33.33%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50.78534031413613%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;CC2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19720767888307%\" valign=\"top\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.017452006980804%\" valign=\"top\"\u003e\n \u003cp\u003e26.67%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50.78534031413613%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdjuvant chemotherapy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19720767888307%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.017452006980804%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50.78534031413613%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Yes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19720767888307%\" valign=\"top\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.017452006980804%\" valign=\"top\"\u003e\n \u003cp\u003e60.00%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"50.78534031413613%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;No\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.19720767888307%\" valign=\"top\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.017452006980804%\" valign=\"top\"\u003e\n \u003cp\u003e40.00%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTABLE 2. Univariate Analysis Comparing Prognostic Variables\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"98%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003ePrognostic variables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;45 year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.48\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026gt;45 year\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHistology\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eEpitheloid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSarcomatoid\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePCI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.91\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.33\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAdjuvant CT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.11\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNACT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Malignant peritoneal mesothelioma, HIPEC, CRS","lastPublishedDoi":"10.21203/rs.3.rs-4063777/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4063777/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003eMalignant peritoneal mesothelioma (MPM) is a rare and aggressive form of cancer originating from the peritoneum. The prognosis for MPM has historically been poor, and treatment options are limited. This study evaluated the impact of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) as a treatment modality for MPM, although optimal management is still evolving.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMaterials and Methods:\u003c/strong\u003e This retrospective analysis included fifteen patients diagnosed with MPM between 2012 and 2023 at a tertiary referral cancer care center in North India. Patients underwent CRS followed by HIPEC. The study assessed outcomes based on overall survival (OS) and postoperative morbidity rates.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003eDemographic analysis revealed a female preponderance (60%) and a majority of younger patients, 80% of whom were younger than the age of 50. Neoadjuvant chemotherapy was infrequent (13.33%), while the most common histopathological subtype was epithelioid (66.67%). The mean peritoneal cancer index (PCI) was 14.0, with 60% of patients having a PCI above the mean. The completeness of cytoreduction (CC) varied, with 40% achieving CC0, 33.33% CC1, and 26.67% CC2. Adjuvant chemotherapy was administered to 60% of the patients. The mean blood loss was 577 ml, and the mean operation duration was 350 minutes. Postoperative complications ranged from mild to life-threatening, with a mortality rate of 6.67%. The median follow-up period was 25 months, revealing an overall median survival of 27.0 months, with 1- and 3-year survival rates of 86.7% and 33.3%, respectively. On univariate analysis, only histological subtype emerged as a predictive factor for overall survival.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: CRS combined with HIPEC is a viable and effective treatment option for patients with MPM and offers improved survival rates and an acceptable safety profile. These findings support the integration of this treatment modality into the management plan for select patients with MPM, although optimal management is still evolving.\u003c/p\u003e","manuscriptTitle":"Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Mesothelioma: Outcomes from a Tertiary Cancer Care Center in Northern India","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-29 10:05:34","doi":"10.21203/rs.3.rs-4063777/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5ba7bde7-23ab-410f-bba6-20770ab66a41","owner":[],"postedDate":"March 29th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-06-16T15:55:22+00:00","versionOfRecord":[],"versionCreatedAt":"2024-03-29 10:05:34","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4063777","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4063777","identity":"rs-4063777","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}