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

Pathological and clinical features of multiple cancers and lung adenocarcinoma: a multicentre study

OBJECTIVES: Lung cancer is increasingly diagnosed as a second cancer. Our goal was to analyse the characteristics and outcomes of early-stage resected lung adenocarcinomas in patients with previous cancers (PC) and correlations with adenocarcinoma subtypes.METHODS: We retrospectively reviewed data of patients radically operated on for stage I-II lung adenocarcinoma in 9 thoracic surgery departments between 2014 and 2017. Overall survival (OS) and time to disease relapse were evaluated between subgroups.RESULTS: We included 700 consecutive patients. PC were present in 260 (37.1%). Breast adenocarcinoma, lung cancer and prostate cancer were the most frequent (21.5%, 11.5% and 11.2%, respectively). No significant differences in OS were observed between the PC and non-PC groups (P = 0.378), with 31 and 75 deaths, respectively. Patients with PC had smaller tumours and were more likely to receive sublobar resection and to be operated on with a minimally invasive approach. Previous gastric cancer (P = 0.042) and synchronous PC (when diagnosed up to 6 months before lung adenocarcinoma; P = 0.044) were related, with a worse OS. Colon and breast adenocarcinomas and melanomas were significantly related to a lower incidence of high grade (solid or micropapillary, P = 0.0039, P = 0.005 and P = 0.028 respectively), whereas patients affected by a previous lymphoma had a higher incidence of a micropapillary pattern (P = 0.008).CONCLUSIONS: In patients with PC, we found smaller tumours more frequently treated with minimally invasive techniques and sublobar resection, probably due to a more careful follow-up. The impact on survival is not uniform and predictable; however, breast and colon cancers and melanoma showed a lower incidence of solid or micropapillary patterns whereas patients with lymphomas had a higher incidence of a micropapillary pattern

Impact of High‑Grade Patterns in Early‑Stage Lung Adenocarcinoma: A Multicentric Analysis

Objective The presence of micropapillary and solid adenocarcinoma patterns leads to a worse survival and a signifcantly higher tendency to recur. This study aims to assess the impact of pT descriptor combined with the presence of high-grade components on long-term outcomes in early-stage lung adenocarcinomas. Methods We retrospectively collected data of consecutive resected pT1-T3N0 lung adenocarcinoma from nine European Thoracic Centers. All patients who underwent a radical resection with lymph-node dissection between 2014 and 2017 were included. Diferences in Overall Survival (OS) and Disease-Free Survival (DFS) and possible prognostic factors associated with outcomes were evaluated also after performing a propensity score matching to compare tumors containing non-highgrade and high-grade patterns. Results Among 607 patients, the majority were male and received a lobectomy. At least one high-grade histological pattern was seen in 230 cases (37.9%), of which 169 solid and 75 micropapillary. T1a-b-c without high-grade pattern had a signifcant better prognosis compared to T1a-b-c with high-grade pattern (p=0.020), but the latter had similar OS compared to T2a (p=0.277). Concurrently, T1a-b-c without micropapillary or solid patterns had a signifcantly better DFS compared to those with high-grade patterns (p=0.034), and it was similar to T2a (p=0.839). Multivariable analysis confrms the role of T descriptor according to high-grade pattern both for OS (p=0.024; HR 1.285 95% CI 1.033–1.599) and DFS (p=0.003; HR 1.196, 95% CI 1.054–1.344, respectively). These results were confrmed after the propensity score matching analysis. Conclusions pT1 lung adenocarcinomas with a high-grade component have similar prognosis of pT2a tumors

Il ruolo della chirurgia timica nel controllo della miastenia gravis

I timomi si ritrovano in circa il 10-15% dei pazienti affetti da Miastenia Gravis, mentre in oltre il 65% dei casi si osserva un’iperplasia timica non neoplastica. Entrambe le patologie timiche vengono trattate mediante la chirurgia. L’efficacia della timectomia nel raggiungimento di un miglioramento clinico, così come della remissione totale, nei pazienti miastenici, è stata largamente dimostrata. Con questa tesi, si vuole studiare come l’intervento di timectomia per via sternotomica influenzi il decorso clinico neurologico dei pazienti affetti da Miastenia Gravis. Metodi: sono state analizzate retrospettivamente, in seguito a un follow-up di almeno tre anni, le condizioni cliniche dei pazienti miastenici sottoposti a intervento di timectomia per via sternotomica presso l’U.O. Chirurgia Toracica di Pisa, sia per timoma che per iperplasia timica, tra il 1990 e il 2012

Trattamento chirurgico delle stenosi tracheali durante la pandemia da SARS-CoV2 e confronto con l'esperienza precedente.

Tracheal stenosis is a life-threatening condition, often secondary to invasive mechanical ventilation, which needs multidisciplinary management in referral centers. Tracheal resection with primary end-to-end anastomosis (R/A) is a valid therapeutic option although related to a challenging post-operative care. During the SARS-CoV2 pandemic, the large use of invasive mechanical ventilation determined a marked increase of post-intubation or post-tracheostomy stenosis requiring surgical treatment. Data of those patients operated on for tracheal stenosis in our tertiary referral Center during the pandemic were collected, analyzed, and compared with previous series. In the biennium 2020-2021, 11 patients underwent tracheal R/A. All benign stenosis were iatrogenic complications of mechanical ventilation. Six(75%) patients had previously been affected by severe respiratory failure due to SARS-CoV2 pneumonia. There were no differences between patients who have had Covid-19 and patients who did not, regarding intra-and postoperative outcomes. At the endoscopic exam in 30th postoperative day no anastomosis complication was detected. Prevention of SARS CoV2 diffusion is fundamental to avoid the rise of tracheal stenosis incidence. However, although tracheal R/A still remains a complex surgical procedure with potentially high morbidity rates, it has proved to be safe and effective even in the more challenging subset of Covid-19 patients, in referral high-volume Centers

Thymectomy in myasthenic patients with thymoma: killing two birds with one stone

BACKGROUND: Thymoma and Myasthenia Gravis share several pathogenetic aspects including the role of surgery as therapeutic option. Extended thymectomy is associated with excellent survival and good local control, especially in early stages, while its role for the neurological disease has been recently validated. The aim of this study is evaluating oncological and neurological outcomes of myasthenic patients with thymoma underwent extended thymectomy.METHODS: We retrospectively collected surgical, oncological and neurological data of all myasthenic patients with thymoma underwent extended thymectomy at our department from January 1994 to December 2016. Clinical and pathological data, neurological remission rate as well as overall survival and disease-free interval were analyzed.RESULTS: Two hundred-nineteen patients underwent extended thymectomy. The B2 histotype was the most represented thymoma (24.2%), while the most prevalent pathological Masaoka stage was IIB (37.9%). The Overall Survival and Disease-Free Survival were statistically different between early- and advanced-stage. During the surveillance, 33 patients (15.1%) developed recurrences, treated in 21 cases with iterative surgery. Regarding neurological outcomes, 75 patients (34.2%) reached a complete stable remission, 84 (38.4%) a pharmacologic remission, 51 (23.3%) had an improvement of their symptoms while in 9 (4.1%) patients Myasthenia was unchanged or worsened.CONCLUSIONS: Surgery is a cornerstone in the treatment of patients with both thymoma and Myasthenia Gravis. Extended thymectomy, as proposed by Masaoka, offers considerable oncological outcomes with an excellent survival and a low recurrence-rate of thymoma; moreover, surgery leads to remarkable neurological results

Nerve sparing surgery in advanced stage thymomas

Phrenic nerve infiltration has been described in up to 33% of advanced thymomas; en-bloc resection causes diaphragmatic loss of function, with detrimental effects on pulmonary function. We report the outcomes of selected patients operated on for invasive thymoma with a "nerve sparing" technique

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

Hyperthermic Intrathoracic Chemotherapy for Malignant Pleural Mesothelioma: The Forefront of Surgery-Based Multimodality Treatment

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