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Pleural mesothelioma (PM) is a rare but aggressive thoracic tumor with a poor prognosis. Multimodal treatment-including induction chemotherapy, aggressive surgical resection, radiotherapy and immunotherapy in selected cases-currently represents the best therapeutic option. Single-center studies advocate hyperthermic intrathoracic chemotherapy (HITHOC) during surgical resection as an additional therapeutic option, although its impact on post-operative morbidity and survival has not yet been evaluated on a larger scale. HITHOC can be applied not only in the case of mesothelioma, but also in the case of thymoma with pleural involvement or-in very selected cases-in patients with secondary pleural metastases. Despite favorable outcomes and reduced clinical risks, there is no uniform approach to HITHOC, and a wide variety of indications and technical applications are still reported. Based on available data, HITHOC seems to offer a clear benefit in regard to overall survival of all mesothelioma patients; however, multicenter randomized controlled trials are required to validate and standardize this approach. The aim of this review is to focus on the present role of HITHOC in thoracic tumors with pleural involvement as well as on future challenges, particularly in the light of possible combined therapy of thoracic tumors still presenting poor prognoses.
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(1) Background. Intracavitary hyperthermic chemotherapy (HITHOC) remains part of the complex mosaic that is the multimodal approach for advanced stage thymoma and pleural malignancies. However, robotic pleurectomy/removal of pleural lesions in combination with intrathoracic chemotherapy is not currently being investigated. The aim of this study is to evaluate the safety of robotic pleurectomy/removal of relapses and HITHOC in patients with pleural recurrence of thymoma or MPM. (2) Methods: The data of nine consecutive patients affected by thymoma relapses or MPM who underwent robotic surgery in combination with HITHOC from February 2017 to November 2022 were collected and analyzed. Surgery performed prior to intrathoracic infusion of high-temperature chemotherapy consisted of removal of recurrences (three patients) or pleurectomy (six patients). All surgeries were performed with a four-port, fully robotic technique. (3) Results: No intraoperative complications occurred. No renal complications related to infusion were recorded. One patient, who underwent pleurectomy for MPM, had a grade II Clavien-Dindo postoperative complication. Oncological follow-up showed results in line with the literature. (4) Conclusions: With the limitation of the small number of patients, robotic surgery in combination with HITHOC seems to be safe in patients with pleural relapses of thymoma and early-stage MPM.
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The current treatment for mesothelioma, in selected cases, consists of extended pleurodecortication and intrathoracic hyperthermic chemotherapy. This technique is laborious and detailed and must be followed step by step to achieve good results. We present the case of a patient with epithelioid mesothelioma meeting surgical criteria who underwent the mentioned technique, experiencing an adequate postoperative period and an early discharge. This experience demonstrates that the technique is safe when performed in centres with experience and the means to address this complex pathology.
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Hipertermia Inducida , Mesotelioma Maligno , Neoplasias Pleurales , Humanos , Neoplasias Pleurales/terapia , Mesotelioma Maligno/cirugía , Mesotelioma Maligno/terapia , Hipertermia Inducida/métodos , Terapia Combinada , Mesotelioma/terapia , Mesotelioma/patología , Mesotelioma/cirugía , Masculino , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/cirugía , Persona de Mediana EdadRESUMEN
Background: Cytoreductive surgery combined with hyperthermic intrathoracic chemotherapy (S-HITHOC) may be effective in treating thymic epithelial tumors (TETs) with pleural spread or recurrence. This study will evaluate the safety and efficacy of S-HITHOC in the treatment of TETs with pleural spread or recurrence. Methods: This study is an open, single-arm, prospective trial. Approximately 37 patients diagnosed with TETs with pleural spread or recurrence at the Zhongshan Hospital of Fudan University will be recruited and treated with S-HITHOC. The co-primary outcomes of the study are the length of postoperative hospital stay, complications, and overall quality of life (QoL). The secondary outcomes include drainage duration, volume, and cumulative pain scores. Discussion: This trial was approved by the Zhongshan Hospital Research Ethics Committee. The study findings will be actively disseminated through manuscript publications and conference presentations. Information sheets will be provided to each participant, and informed written consent will be obtained for each evaluation. This prospective study will evaluate the effectiveness of a surgical resection combined with the HITHOC procedure in treating TETs with pleural spread or recurrence in China and will support the standardization of the procedure. Registration: This trial was registered on Clinialtrial.gov (No. NCT05446935).
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OBJECTIVE: To compare the efficacy and safety of hyperthermic intrathoracic/intraperitoneal chemotherapy versus conventional intrapleural/intraperitoneal chemotherapy in the treatment of malignant pleural or peritoneal effusion. METHODS: A randomized clinical trial was carried out in 8 cancer centers across China. Patients with malignant pleural or peritoneal effusion were randomly assigned to the study group or control group. Patients in the study group were treated with cisplatin-based hyperthermic intrathoracic chemotherapy (HITHOC) or hyperthermic intraperitoneal chemotherapy (HIPEC), while the control group was treated with conventional intrapleural or intraperitoneal chemotherapy using same chemotherapeutic regime as the study group. The objective response rate (ORR) was analyzed as primary outcome. Quality-of-life (QOL) score was recorded as secondary outcome using the questionnaire 30 (QLQ-C30) of the European Organization for Research and Treatment of Cancer (EORTC). The efficacy and safety of the two treatments were compared. RESULTS: Total 135 patients were recruited and randomized in this study, with 67 patients in the study group and 68 patients in the control group. The ORR in the study group (80.70%) was significantly higher than that in the control group (31.03%, p < 0.001). However, neither changes of QOL scores, nor incidence rates of adverse events were significantly different between the two groups (p = 0.076 and 0.197, respectively). CONCLUSION: Efficacy of HITHOC or HIPEC is superior to that of conventional modality for the treatment of malignant effusion with comparable side effects.
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Hipertermia Inducida , Derrame Pleural Maligno , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Terapia Combinada , Calidad de Vida , Cisplatino/uso terapéutico , Derrame Pleural Maligno/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
Hyperthermic intrathoracic chemotherapy (HITHOC) adjunct to surgery for Malignant Pleural Mesothelioma (MPM) has no definite role. The primary objective of this pilot-trial was to evaluate the feasibility for future large studies. The study design was a prospective randomized three-centric pilot trial. We recruited patients diagnosed with MPM and prospectively assigned them to two groups: Group A: Video Assisted Thoracic Surgery (VATS) talc pleurodesis or Group B: Video-assisted P/D plus HITHOC. From November-2011 to July-2017 24 males and 3 females, with a median age of 68-years were enrolled (recruitment rate 5 patients/year). Preoperative stage was I-II, and 18 had epithelioid type. 14 patients were in the Group A. Operative mortality was 0. Follow-up ranged 6-80 months. The median overall survival time started to diverge at 20 months, being 19 months (95% CI 12-25) in Group A and 28 months (95% CI 0-56) in Group B. Survival rate for the epithelioid type was 15 months (95% CI 0-34) in Group A and 45 months (95% CI 0-107) in the Group B. These findings suggest that video-assisted P/D plus HITHOC may improve survival time in MPM patients undergoing surgical treatment and support the need for a larger multicenter randomized clinical trial.
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INTRODUCTION: Stage IVa thymoma is a rare disease without a standard of care. Subtotal pleurectomy and HITHOC introduced in highly selected patients may provide interesting oncologic results. The purpose of this study was to distinguish de novo stage IVa tumors (DNT) from distant relapse (DR) with respect to post-operative and long-term outcomes to provide the procedure efficacy. METHODS: From July 1997-December 2021, 40 patients with IVa pleural involvement were retrospectively analyzed. The surgical procedure was subtotal pleurectomy and HITHOC (cisplatin 50 mg/m2, mitomycin 25 mg/m2, 42 °C, 90 min). The post-operative outcome, disease-free interval (DFI) and overall survival (OS) were analyzed. RESULTS: Mean age was 52 ± 12 years. B2 and B3 thymomas were preponderant (27; 67.5%). The median number of pleural nodes were nine (4-81) vs. five (1-36); p = 0.004 * in DNT and DR, respectively. Hospital mortality rate was 2.5%. There were four specific HITHOC complications (10%). DFI were 49 and 85 months (p = 0.02 *), OS were 94 and 118 months (NS), in DNT and DR, respectively. CONCLUSIONS: Subtotal pleurectomy with HITHOC in IVa offers satisfying results in highly selected patients, for both DNT and DR. Due to the disease rarity, multicentric studies are needed to define HITHOC as a standard of care.
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Aim: Pleural dissemination of pseudomyxoma peritonei (PMP) is an extremely rare diagnosis, for which no standard therapy is available.Methods: We describe the successful treatment of a 67-year-old male diagnosed with left-sided intrapleural dissemination of PMP (low-grade appendiceal mucinous neoplasm), 2 years after treatment of abdominal PMP with cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy. Treatment consisted of extended pleural decortication (ePD) and oxaliplatin-based hyperthermic intrathoracic chemotherapy (HITHOC). The patient is doing well without complications or signs of recurrence, 26 months after thoracic surgery.Conclusion: ePD in combination with HITHOC is a valuable treatment for thoracic PMP.
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Neoplasias del Apéndice , Hipertermia Inducida , Neoplasias Peritoneales , Seudomixoma Peritoneal , Anciano , Neoplasias del Apéndice/terapia , Terapia Combinada , Procedimientos Quirúrgicos de Citorreducción , Humanos , Masculino , Neoplasias Peritoneales/diagnóstico por imagen , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/cirugía , Seudomixoma Peritoneal/diagnóstico por imagen , Seudomixoma Peritoneal/tratamiento farmacológico , Seudomixoma Peritoneal/cirugía , Estudios RetrospectivosRESUMEN
INTRODUCTION: Malignant Pleural Mesothelioma (MPM) is characterized by an aggressive behavior and an inevitably fatal prognosis, whose treatment is still far from being standardized. The role of surgery is questionable since a radical resection is unattainable in most cases. Hyperthermic IntraTHOracic Chemotherapy (HITHOC) combines the advantages of antitumoral effects together with those of high temperature on the exposed tissues with the aim to improve surgical radicality. MATERIAL AND METHODS: this is a narrative review on the role of HITHOC in the management of MPM patients. To provide data on the beginnings and the historical evolution of this technique, we searched the available literature by selecting the more exhaustive papers on this topic. RESULTS: from 1994 to date different authors experimented HITHOC following a cytoreductive surgery in MPM, obtaining in most cases a good local control and a better overall survival associated to very low complication rate. CONCLUSIONS: HITHOC may be considered as a safe, feasible and effective procedure although there is a high heterogeneity between different protocols adopted worldwide. More structured studies are needed to reach a unanimous consensus on this technique.
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Although the method of hyperthermic intrathoracic chemotherapy (HITHOC) after cytoreductive surgery is known for more than 20 years now, the interest of the scientific community has been growing especially in recent years with annually increasing numbers of publications. The feasibility and safety of HITHOC has already been demonstrated. The primary objective now is to reach a consent about the optimal implementation and standardization of the procedure. In the international clinical practice of HITHOC the parameters of temperature, duration, type and number of chemotherapeutic agents vary, making a comparison of the short- and long-term results difficult. For about ten years, the combination of surgical cytoreduction and HITHOC has been performed more routinely in several departments of thoracic surgery in Germany, especially in university hospitals. Recently, a group of experts for thoracic surgery of five departments of thoracic surgery elaborated recommendations for the HITHOC procedure in Germany. These recommendations represent a standardized and consistent implementation of HITHOC. Through this, postoperative complications associated to HITHOC should be reduced and a better comparison of the results should be enabled. This article is intended to give a brief overview of the literature, current recommendations in the implementation of HITHOC and also aims to show future perspectives of this procedure.
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Historically, patients with pleural malignant mesothelioma have had a poor prognosis and survival rate. Recently, new surgical approaches and chemotherapy delivery techniques have been developed. One of this treatment options is thoracic cytoreductive surgery and HITHOC (hyperthermic intrathoracic chemotherapy perfusion), a promising strategy in selected patients, offering significantly longer median survival length and tumour-free survival rate. However, there is little experience and little is known regarding the optimal perioperative management of this patients. Given that they usually present with poor preoperative status and the surgery is aggressive, prolonged and associated with significant hemodynamic repercussions, this procedure poses a true challenge to the anaesthesiologist. We will discuss optimal patient selection and optimization, as well as premedication, recommended monitoring aspects on top of the usual for any anaesthetic procedure, induction and anaesthetic agents, blood management and one lung ventilation. Also, we expose the importance of adequate pain control during the surgery and postoperatively, the hemodynamic disturbances that occur during the procedure and the potential complications that could occur afterwards. In a few words, this review intends to offer recommendations for the management of patients undergoing cytoreductive surgery and HITHOC for the perioperative care, based on the scarce evidence and our clinical experience.
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The traditional treatment of stage IV lung cancer is predominantly supportive or palliative. No current standardized guidelines promote the use of hyperthermic intrathoracic chemotherapy (HITHOC) in the treatment of advanced lung cancer with pleural involvement. Several small studies have examined the safety and utilization of HITHOC for this population, though the data is extremely limited. A review of the literature is presented in accordance with the Narrative Review checklist. The MEDLINE electronic database was searched for articles published in English from January 1999 - August 2020 using relevant keywords such as "hyperthermic intrathoracic chemotherapy", "hyperthermic intrapleural chemotherapy" and "HITHOC". This was supplemented by review and hand search of the reference lists. While data suggest a potential though controversial role for HITHOC for certain intrathoracic tumors such as malignant pleural mesothelioma and thymoma, there is insufficient evidence to confidently promote a role for hyperthermic intrathoracic chemotherapy in the treatment of advanced lung cancers. Existing studies are small, nonrandomized, and prone to bias. Hyperthermic intrathoracic chemotherapy is not a standardized treatment for advanced lung cancer, and is characterized by potentially serious side effects with little clinical benefit. Recent developments in targeted therapy and immunotherapy are unlikely to leave room for the development of large randomized controlled trials.
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Non-small cell lung cancer (NSCLC) with ipsilateral pleural dissemination (pM1a) is generally contraindicated for surgery owing to the extremely poor survival. However, some studies have demonstrated that primary tumor resection (PTR) may prolong the survival of these patients. Besides, with the development of systemic therapy, it is still hard to decide the best therapy model for pM1a patients. Thus, we reviewed essential studies about NSCLC with pleural disease and summarized the progress of new techniques in recent years, trying to provide promising new horizons about the management of pM1a patients. Firstly, we suggest performing PTR for highly selected pM1a patients, combined with appropriate systemic therapies and follow-up strategies. Secondly, hyperthermic intrathoracic chemotherapy (HITHOC) can control the symptoms and prolong the survival of NSCLC patients with malignant pleural effusion (MPE). It could also combine with PTR together. Finally, application of genetic testing and circulating tumor DNA (ctDNA) monitoring may furthermore make it possible for personalized management of pM1a patients in the future.
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This study was aimed at evaluating the safety and efficacy of hyperthermic intrathoracic chemotherapy in patients with Masaoka stage IVA thymoma. This is a retrospective comparative analysis between two groups of patients who were operated for Masaoka stage IVA thymoma. One group underwent complete parietal pleurectomy whereas other group received hyperthermic intrathoracic chemotherapy after complete pleurectomy. An analysis of all perioperative variables, complications and survival was carried out. A total of 13 patients had stage IVA disease during the study period. Initial 7 patients (March 2012-March 2015) underwent complete parietal pleurectomy, whereas next 6 patients (April 2015-December 2018) had undergone HITHOC after complete parietal pleurectomy. Both groups are comparable in terms of age, co-morbidities, tumor size and duration of symptoms. The duration of surgery and intra-operative blood loss, postoperative ICU stay, duration of ICD and total hospital stay was similar between two groups. The total number of post-operative complications was higher in HITHOC group (5 vs 2), however non-significant (p = 0.10). The median follow-up duration was 63 months in no HITHOC group and 49.5 months in HITHOC group. There was no peri-operative mortality. The overall survival (P = 0.06) and relapse-free survival (P = 0.36) were not significantly different in the both groups. Hyperthermic intrathoracic chemotherapy is a safe and feasible modality with no added morbidity or mortality. Multi-institutional prospective studies with large number of patients are required to accurately assess survival benefit.
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BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive malignancy with few long-term survivors. Despite the dismal prognosis, hyperthermic intrathoracic chemoperfusion (HITHOC) was shown to improve survival in a selective group of patients. We analyzed the influence of HITHOC following pleurectomy and decortication on postoperative morbidity and overall survival for patients suffering from localized mesothelioma. METHODS: From 2009 until 2013, 71 patients with localized pleural mesothelioma underwent pleurectomy and decortication followed by HITHOC with cisplatin and doxorubicin. We analyzed postoperative morbidity, age, overall survival and influence of macroscopic resection on survival. RESULTS: Median patient age was 70 years (range, 65-73 years). Patients having the sarcomatoid subtype of mesothelioma showed a poor median survival of 9.2 months. In contrast, patients having the epithelioid subtype had a median survival of 17.9 months. Patients following macroscopic complete resection had a significantly better survival with 28.2 months compared to 13.1 months in patients with incomplete resection of the mesothelioma (P<0.0001). HITHOC was performed in all patients after tumor resection using cisplatin and doxorubicin. CONCLUSIONS: Taken together, HITHOC following pleurectomy and decortication is supposed to be a safe therapeutic option for selected patients with localized epithelial pleural mesothelioma.
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Hyperthermic intrathoracic chemotherapy (HITHOC) has been used in addition to radical surgery for primary and secondary pleural malignancies to improve local control, prolong survival, and improve the quality of life. This study was performed to study the indications, methodology, perioperative outcomes, and survival in patients undergoing HITHOC at Indian centers. A retrospective analysis of prospectively collected demographic and clinical data, perioperative and survival data of patients undergoing surgery with or without HITHOC was performed. From January 2011 to May 2018, seven patients underwent pleurectomy/decortication (P/D) or extrapleural pneumonectomy (EPP) with HITHOC and four had P/D or EPP alone at three Indian centers. P/D was performed in two and EPP in nine patients. The primary tumor was pleural mesothelioma in eight, metastases from thymoma in one, germ cell tumor in one, and solitary fibrous tumor of the pleura in one. HITHOC was performed using cisplatin. Grade 3-4 complications were seen in one patient in the HITHOC group and none in the non-HITHOC group, and one patient in the non-HITHOC group died of complications. At a median follow-up of 9 months, five patients of the HITHOC group were alive, four without recurrence, and one with recurrence. One patient in the non-HITHOC group was alive and disease-free at 24 months, and two died of progression at 18 and 36 months. HITHOC can be performed without increasing the morbidity of P/D or EPP. Most of these patients require multimodality treatment and are best managed by multidisciplinary teams.
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BACKGROUND: In the treatment of malignant pleural mesothelioma the Hyperthermic Intra THOracic Chemotherapy (HITHOC) can improve the efficacy of pleurectomy and decortication with a local cytotoxic effect. However its biological impact in patient's hemodynamic and microcirculatory changes were rarely investigated. Aim of this study is to describe our experience with HITHOC after pleurectomy and decortication evaluating the role of sublingual video-microscopy in assessing the microcirculatory changes in the perioperative period. METHODS: This is a prospective and observational study concerning 10 consecutive patients undergoing extended P/D followed by HITHOC. These patients underwent sublingual microcirculatory monitoring, which was adopted as a routine procedure since 2012. Haemodynamic parameters were collected at eight consecutive times: the day before surgery (T1), induction of anaesthesia (T2), surgical phase before HITHOC beginning (T3), 5 and 30 minutes after HITHOC start (T4 and T5, respectively), 5 minutes from HITHOC end (T6), after the admission in ICU (T7), at discharge from the ICU (T8). Cardiac output (CO) was calculated with MostCare. Systemic vascular resistance (SVR), oxygen delivery (DO2), and oxygen extraction rate (O2ER) were calculated using standard formulas. Arterial blood pressure and central venous pressure (CVP) were obtained with standard arterial and venous catheters. At the same times we assessed the sublingual microcirculation with Sidestream Dark Field technique. RESULTS: Hemodynamic and microcirculatory data were collected in 10 patients, 8 male and 2 females (mean age 68.6±9.0, and body surface area of 1.9±0.1 m2). All patients had arterial hypertension, and one patient had diabetes. The mean arterial pressure significantly decreased at T2, with respect to T1 (P=0.05). CO, CVP, DO2, O2ER, and ScvO2, did not change significantly over the time. All patients needed infusion of noradrenalin from T4 to T6. TVD significantly decreased from T1 to T3, T5, and T8. Similarly, PVD significantly decreased from T1 to T3 and T8, and MFI from T1 to T6 and T8. PPV and HI did not change over the study period. No correlation was found between hemodynamic parameters (MAP, CO, CVP, DO2, O2ER, ScvO2) and microcirculatory data (TVD, PVD, PPV, MFI, HI), at any time of the study. CONCLUSIONS: In patients who receive HITHOC the fluid load can reduce the microvascular impairment restoring the normal tissue perfusion. This process takes days but is most evident in the first 72 h. The use of colloid and blood transfusion is much more effective in restoring microcirculation and reducing tissue damaging.
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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.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/cirugía , Mesotelioma/tratamiento farmacológico , Mesotelioma/cirugía , Neoplasias Pleurales/tratamiento farmacológico , Neoplasias Pleurales/cirugía , Anciano , Cisplatino/uso terapéutico , Terapia Combinada/métodos , Femenino , Humanos , Hipertermia Inducida/métodos , Neoplasias Pulmonares/patología , Masculino , Mesotelioma/patología , Mesotelioma Maligno , Persona de Mediana Edad , Neoplasias Pleurales/patología , Estudios Prospectivos , Procedimientos Quirúrgicos Torácicos/métodosRESUMEN
Cytoreductive surgery and hyperthermic-intraoperative-intrapleural-chemotherapy (HITHOC) is a known approach for malignant pleural diseases (MPD). This study was started to clarify the role of cytoreductive surgery and HITHOC in MPD. Criteria of inclusion were early-stage disease in malignant pleural mesothelioma (MPM), young age, good condition and selected stage-M1a lung cancer. Six patients with MPM and two patients with lung cancer were enrolled. After surgical debulking, intrapleural cisplatin was administered for 60 min at 42.5°C. Wedge, rib resection and repaired diaphragm were added in three, one and one patient, respectively. Morbidity, toxicity and mortality was nil. Hospital stay was 8 days. Mean survival is 13.6 months. This experience confirms that cytoreductive surgery and HITHOC is a good option in the treatment of MPD. A randomized controlled trial is necessary.