LA CHEMIOTERAPIA IPERTERMICA INTRA-OPERATORIA NEL TRATTAMENTO DEL MESOTELIOMA PLEURICO MALIGNO: ESPERIENZA DI UN SINGOLO CENTRO

SCOPO DEL LAVORO. Il mesotelioma pleurico maligno (MPM) rappresenta la neoplasia primitiva più comune della pleura, con prognosi tutt’ora infausta. Nel tentativo di migliorare la sopravvivenza dei pazienti con MPM abbiamo associato alla chirurgia citoriduttiva la chemioterapia intra-cavitaria intra-operatoria ipertermica (HITHOC), seguite da chemioterapia sistemica adiuvante. MATERIALI E METODI. I principali criteri di inclusione sono stati: età 18-75, PS 0-2, istologia epiteliomorfo, stadio I-III. Tutti i pazienti sono stati sottoposti a chirurgia citoriduttiva (pleurectomia/decorticazione), seguita da HITHOC. Per quest’ultima abbiamo utilizzato una apparecchiatura dedicata (Performer LRT, RanD, Medolla, Italia) che permette il controllo automatico dei parametri di perfusione. Il cavo pleurico è stato riempito con soluzione salina portata alla temperatura di 42.5°C, quindi sono stati iniettati i farmaci antiblastici (Cisplatino a 80 mg/m2 ed Epirubicina a 25 mg/m2) e la perfusione protratta per 60 minuti. Tutti i pazienti sono poi stati sottoposti a CT adiuvante sistemica. RISULTATI. Da Aprile 2005 a Giugno 2013, abbiamo arruolato e trattato 51 pazienti. Successivamente 11 pazienti sono stati esclusi: 3 per istologia definitiva di bifasico, 8 persi al follow-up. Nei rimanenti 40 pazienti la procedura (chirurgia + HITHOC) è durata in media 225 min (range 160 – 335), non abbiamo registrato eventi avversi correlati alla HITHOC, ne vi è stata mortalità peri-operatoria. La morbilità è consistita in 9 casi di prolungata fuga aerea, 5 casi di sanguinamento post-operatorio che hanno richiesto utilizzo di emoderivati, 1 caso di embolia polmonare ed 1 deiscenza della toracotomia. La degenza media è stata di 9 giorni (range di 5 – 24). Ad un follow-up medio di 59 mesi (range di 6 – 104), la sopravvivenza mediana attuariale è di 24,5 mesi. Diciotto pazienti sono ancora in vita (45%), di cui uno solo libero da malattia. CONCLUSIONI. Nel MPM, la citoriduzione chirurgica in associazione con la HITHOC può essere eseguita con bassa morbilità e mortalità in pazienti ben selezionati. All’interno di un trattamento multimodale, la HITHOC sembra contribuire ad incrementare il periodo di sopravvivenza nei pazienti con MPM epiteliomorfo

Hypertermic Intrathoracic Chemotherapy (HITHOC) for thymoma: a narrative review on indications and results

Objective: With this narrative review, we retraced the history of hypertermic intrathoracic chemotherapy (HITHOC) since the beginning, analyzing literature on operative technique, feasibility and efficacy of this treatment. Moreover, we report the fifteen-year experience of our center in this relatively new technique, for what concerns both early postoperative results and long-term oncological outcomes. Background: Thymomas are frequently misdiagnosed and recognized in advanced stage, often with pleural dissemination, especially when not associated to Myasthenia Gravis that allows an early diagnosis during the initial assessment. Moreover, the natural history of locally advanced thymoma is characterized by a high rate of pleural or pericardial relapses. Surgery has always been considered a milestone in thymoma's treatment, even in case of serous dissemination or relapses, although his role as exclusive therapy does not guarantee an acceptable local disease control. In case of disseminated disease, different multidisciplinary protocols have been experimented, from chemotherapy to radiation therapy, alone or associated to surgery, in order to increase overall and disease-free survival, but the breakthrough happened in the early 90s with the introduction of HITHOC following surgery. Combination of surgery and HITHOC resulted in less toxic than systemic chemotherapy and providing a good local disease control in patients with stage IVa thymomas or thymoma's pleural recurrences. Methods: We searched PubMed for relevant literature, up to January 2020, on hypertermic intrapleural chemotherapy for thymomas (TPR or DNT), selecting only those reporting information about HITHOC protocol used, postoperative course and oncological outcomes. Conclusions: HITHOC is a safe and feasible procedure, with a very low complication rate and negligible systemic effects of chemotherapeutic agents, effective in controlling both TPR and DNT, in particular as regards local disease-free survival. Keywords: Hypertermic intrathoracic chemotherapy (HITHOC); thymoma; intracavitary chemotherapy; hyperthermia; redo-surgery

SARS-CoV-2 vaccination modelling for safe surgery to save lives: Data from an international prospective cohort study

Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population

EComment. Innovation for minimally invasive surgical treatment of pneumothorax

No abstract availabl

Pleural recurrence of thymoma: surgical resection followed by hyperthermic intrathoracic perfusion chemotherapy†

OBJECTIVES: Recurrences of thymoma are described in 10-30% of cases up to 10 years after surgical resection. Herein we report our experience with surgical removal of pleural recurrences followed by hyperthermic intrathoracic perfusion chemotherapy (HITHOC). METHODS: We prospectively collected data of patients with pleural recurrence of thymoma who underwent surgery followed by HITHOC. After thoracotomy had been closed, drainages were connected to a dedicated perfusion machine, pleural space was filled with saline solution, progressively heated up to 42.5°C. At this time, chemotherapeutic agents (Doxorubicin and Cisplatin) were injected and perfusion lasted 60 min. RESULTS: In the period 2005-2012, 13 consecutive patients have been treated (8 males, 5 females, mean age 46 years). Initial Masaoka-Koga stage was 2 IIa, 5 IIb, 5 III, 1 IVa. Disease-free interval was 47.2 months on average [standard deviation (SD): 25.5]. Nine patients presented paraneoplastic syndromes (8 myasthenia gravis and 1 red cell aplasia). Complete resection was achieved in all cases except one. HITHOC was successfully performed in all cases and no signs or symptoms of toxicity were recorded in the perioperative period. With a mean follow-up period of 64.6 months (SD: 32.5), 1 patient died for toxicity following systemic chemotherapy, another one died disease-free, 4 patients developed pleural relapses (2 ipsilateral, 2 contralateral) and 1 mediastinal and abdominal nodal metastases. Mean survival was 58 months [SD: 34.4), median survival by the Kaplan-Meier method was not reached while 5-year actuarial survival was 92%. CONCLUSIONS: HITHOC was shown to be feasible and safe. In terms of efficacy, it seems promising but multicentre studies and a longer follow-up period are required to ascertain its effectiveness

New Insights in Pleural Mesothelioma Classification Update: Diagnostic Traps and Prognostic Implications

The 2021 WHO Classification of Tumors of the Pleura has introduced significant changes in mesothelioma codification beyond the three current histological subtypes—epithelioid, sarcomatoid and biphasic. Major advances since the 2015 WHO classification include nuclear grading and the introduction of architectural patterns, cytological and stromal features for epithelioid diffuse mesothelioma. Mesothelioma in situ has been recognized as a diagnostic category. Demonstration of loss of BAP1 or MTAP by immunohistochemistry, or CDKN2A homozygous deletion by FISH, is valuable in establishing the diagnosis of epithelioid mesothelioma. Recent emerging data proved that grading and histological subtypes have prognostic implications and may be helpful to patient risk stratification and clinical management. Nevertheless, the latest mesothelioma classification increases the already non-negligible diagnostic pitfalls, especially concerning differential diagnosis of pre-invasive tumors. In this review, recent changes in histologic classification of mesothelioma and advances in molecular markers are presented and their relation to diagnostic challenges and prognostic implications is discussed