F-024TIME-TREND ANALYSIS OF THE PULMONARY FUNCTION AFTER SURGICAL TREATMENT FOR OESOPHAGEAL CANCER: POTENTIALITY AND ROLE OF PULMONARY REHABILITATION

n/

Farnesyltransferase inhibitors and human malignant pleural mesothelioma: a first-step comparative translational study.

It is known that the potential clinical use of farnesyltransferase inhibitors (FTI) could be expanded to include cancers harboring activated receptor tyrosine kinases. Approximately 70% of malignant pleural mesotheliomas (MPM) overexpress epidermal growth factor receptors (EGFR) and a subset express both EGFR and transforming growth factor A (TGF-A), suggesting an autocrine role for EGFR in MPM. We checked on MPM cells (10 human cell lines, 11 primary cultures obtained by human biopsies, and 7 short-term normal mesothelial cell cultures) concerning the following: (a) the relative overexpression of EGFR (Western blotting, flow cytometry, immunohistochemistry), (b) the relative expression of EGFR ligands (EGF, amphiregulin, TGF-A, ELISA), (c) the relative increase of the activated form of Ras (Ras-bound GTP) after EGF stimulation (Ras activation assay), (d) the efficacy of five different FTIs (HDJ2 prenylation, cell cytotoxicity, and apoptosis using ApopTag and gel ladder). EGFR was overexpressed in MPM cells compared with normal pleural mesothelial cells in equivalent levels as in non\u2013small cell lung cancer cells A549. MPM cells constitutively expressed EGFR ligands; however, Ras activation was attenuated at high EGF concentrations (100 ng/mL). Growth of MPM cells was substantially not affected by treatment with different FTIs (SCH66336, BMS- 214662, R115777, RPR-115135, and Manumycin). Among these, BMS-214662 was the only one moderately active. BMS-214662 triggered apoptosis in a small fraction of cells (not higher than 30%) that was paralleled by a slight decrease in the levels of TGF-A secreted by treated MPM cells. Our data highlighted the concept that the same signaling pathway can be regulated in different ways and these regulations can differ between different cells of different origin

Uniportal-VATS vs. open McKeown esophagectomy: Surgical and long-term oncological outcomes

Background: Till now there are very few reports about surgical results of Uniportal-VATS esophagectomy and no one about long-term outcomes. This study is the first comparing surgical and oncological outcomes of Uniportal-VATS with open McKeown esophagectomy, with the largest reported series and longest oncological follow-up. Methods: The prospectively collected clinical, surgical and oncological data of 75 patients, undergone McKeown esophagectomy at our Thoracic Surgery Department, from January 2012 to August 2022, were retrospectively analyzed. Nineteen patients underwent esophagectomy by thoracotomy and reconstruction according to McKeown technique while 56 by Uniportal-VATS approach. Gastric tubulization was performed totally laparoscopic or through a mini-laparatomic access and cervical anastomosis was made according to Orringer's technique. Results: The mean operative thoracic time was similar in both accesses (102.34 ± 15.21 min in Uniportal-VATS vs. 115.56 ± 23.12 min in open, p: 0.646), with a comparable number of mediastinal nodes retrieved (Uniportal-VATS:13.40 ± 8.12 vs. open:15.00 ± 6.86, p: 0.275). No case needed conversion from VATS to open. The learning curve in Uniportal-VATS was completed after 34 cases, while the Mastery was reached after 40. Both approaches were comparable in terms of minor post-operative complications (like pneumonia, lung atelectasis, anemization, atrial fibrillation, anastomotic-leak, left vocal cord palsy, chylothorax), while the number of re-operation for major complications (bleeding or mediastinitis) was higher in open group (21.0% vs. 3.6%, p: 0.04). Both techniques were also effective in terms of surgical radicality and local recurrence but VATS approach allowed a significantly lower chest tube length (11.89 ± 9.55 vs. 25.82 ± 24.37 days, p: 0.003) and post-operative stay (15.63 ± 11.69 vs. 25.53 ± 23.33, p: 0.018). The 30-day mortality for complications related to surgery was higher in open group (p: 0.002). The 2-, 5- and 8-year survival of the whole series was 72%, 50% and 33%, respectively. Combined 2- and 5-year OS in Uniportal-VATS group was 76% and 47% vs. 62% and 62% in open group, respectively (Log-rank, p: 0.286; Breslow-Wilcoxon: p: 0.036). No difference in DFS was recorded between the two approaches (5 year-DFS in Uniportal-VATS: 86% vs. 72%, p: 0.298). At multivariate analysis, only pathological stage independently affected OS (p: 0.02), not the surgical approach (p: 0.276). Conclusions: Uniportal-VATS seems to be a safe, feasible and effective technique for performing McKeown esophagectomy, with equivalent surgical and long-term oncological results to standard thoracotomy, but with a faster and unharmed recovery, and a quite short learning curve

Management of esophageal perforations and benign diseases

Page 1 of 2 © Annals of Esophagus. All rights reserved. Ann Esophagus 2022;5:1 | http://dx.doi.org/10.21037/aoe-2020-102 Editorial Management of esophageal perforations and benign diseases The Esophagus is a challenging and fascinating organ, whose disorders, both malignant and benign, may require a complex and demanding management by experts from several disciplines. If esophageal cancer still represents the sixth leading cause of death in the world (1), with a 5-year mortality of 80–85%, esophageal benign disease, like perforations, may also have a mortality rate that ranges up to 80% if not correctly managed (2). Indeed, despite diagnostic and surgical innovations and decades of clinical experience, the esophagus, with its functional complexity and its extension in three anatomical districts (neck, thorax and abdomen), still remains a challenge organ to be treated with devastating consequences in inexperienced hands. Few other pathologies require a prompt, correct and multidisciplinary approach by centers with high expertise like esophageal diseases. Therefore, also benign disorders and pathologies demand a proper management that could be difficult for centers with few experience and low cases per year and in the absence of well-codified guidelines on the topic. The aim of this special series is to discuss the management of esophageal perforations, injuries and other benign diseases, reviewing the last updates in literature and providing the experts’ experience in clinical practice. A panel of international thoracic surgeons, general surgeons and endoscopists, all expert in esophageal disease, was involved to present for each esophageal pathology the conservative/endoscopic and surgical treatments available. They also provided to the reader the best and the most appropriate approach to the specific cases on the basis of literature evidence and personal experiences. In particular, when technically and clinically feasible the conservative and endoscopic treatments are preferred and suggested by multidisciplinary teams, reserving surgery for all those cases in life-threatening conditions or unresponsive to or not manageable with minimally invasive treatments. Furthermore, innovative methods of cure are also presented and future directions explored. We hope this special series may be valuable to all medical doctors involved in the management of patients with rare but severe and unpredictable, if badly managed, benign esophageal diseases and perforations

Role of induction therapy in esophageal cancer

Esophageal cancer ranks sixth among the causes of death from cancer worldwide. Patients undergoing surgery have a median survival ranging from 13 to 19 months; 2-year survival rates range from 35 to 42 percent, and 5-year survival rates from 15 to 24 percent. In particular, the 3 year survival (= SVV) is about 26%, with a median survival of 17 months. An interesting point is that about 20-25% of the patients has only locoregional involvement as pattern of failure. At least two randomized studies reported about the combined use of radiotherapy and chemotherapy as sensibilization. They assessed that patients treated with chemoradiation had a longer median survival compared to patients receiving radiation therapy alone, both in early and advanced stages. Moreover radiochemotherapy seems able of achieving high rates of downstaging and of increasing overall and disease-free survival