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Thymic epithelial tumors (TETs) are rare mediastinal cancers originating from the thymus, classified in two main histotypes: thymoma and thymic carcinoma (TC). TETs affect a primary lymphoid organ playing a critical role in keeping T-cell homeostasis and ensuring an adequate immunological tolerance against “self”. In particular, thymomas and not TC are frequently associated with autoimmune diseases (ADs), with Myasthenia Gravis being the most common AD present in 30% of patients with thymoma. This comorbidity, in addition to negatively affecting the quality and duration of patients’ life, reduces the spectrum of the available therapeutic options. Indeed, the presence of autoimmunity represents an exclusion criteria for the administration of the newest immunotherapeutic treatments with checkpoint inhibitors. The pathophysiological correlation between TETs and autoimmunity remains a mystery. Several studies have demonstrated the presence of a residual and active thymopoiesis in adult patients affected by thymomas, especially in mixed and lymphocytic-rich thymomas, currently known as type AB and B thymomas. The aim of this review is to provide the state of art in regard to the histological features of the different TET histotype, to the role of the different immune cells infiltrating tumor microenvironments and their impact in the break of central immunologic thymic tolerance in thymomas. We discuss here both cellular and molecular immunologic mechanisms inducing the onset of autoimmunity in TETs, limiting the portfolio of therapeutic strategies against TETs and greatly impacting the prognosis of associated autoimmune diseases.

Primary malignant melanoma isa rare lesion, that accounts for only 0.1 % of primary esophageal malignant neoplasms. The tumor is polypoid, pedunculated and sometimes ulcerated. Symptoms are similar to those of squamous cell carcinoma and the preoperative differential diagnosis is important. Surgical resection is the treatment of choice. In tracavitary radiotherapy may be a useful form of adjuvant therapy in selected patients. Here we record the case of a 67 years old man with a primary malignant melanama of the esophagus. He underwent an esophagectomy, and is stili alive 5 months aftnr lhe procedure.

Background: Tracheal stenosis represents a fearsome complication that substantially impairs quality of life. The recent SARS-CoV-2 pandemic increased the number of patients requiring invasive ventilation through prolonged intubation or tracheostomy, increasing the risk of tracheal stenosis. Study design and methods: In this prospective, observational, multicenter study performed in Lombardy (Italy), we have exanimated 281 patients who underwent prolonged intubation (more than 7 days) or tracheostomy for severe COVID-19. Patients underwent CT scan and spirometry 2 months after hospital discharge and a subsequent clinical follow-up after an additional 6 months (overall 8 months of follow-up duration) to detect any tracheal lumen reduction above 1%. The last follow-up evaluation was completed on 31 August 2022. Results: In the study period, 24 patients (8.5%, CI 5.6–12.4) developed tracheal stenosis in a median time of 112 days and within a period of 200 days from intubation. Compared to patients without tracheal stenosis, tracheostomy was performed more frequently in patients that developed stenosis (75% vs 54%, p = 0.034). Tracheostomy and alcohol consumption (1 unit of alcohol per day) increased risk of developing tracheal stenosis of 2.6-fold (p = 0.047; IC 0.99–6.8) and 5.4-fold (p = 0.002; CI 1.9–16), respectively. Conclusions: In a large cohort of patients, the incidence of tracheal stenosis increased during pandemic, probably related to the increased use of prolonged intubation. Patients with histories of prolonged intubation should be monitored for at least 200 days from invasive ventilation in order to detect tracheal stenosis at early stage. Alcohol use and tracheostomy are risk factors for developing tracheal stenosis.

Background: The identification of small lung nodules is challenging during mini-invasive thoracic surgery. Unable to palpate them directly, surgeons have developed several methods to preoperatively localize pulmonary nodules, including the computed tomography-guided positioning of coils or metallic landmarks (hook wire) or bronchoscopic marking. Methods: We present a series of patients scheduled for the video-assisted thoracoscopic sublobar resection of small pulmonary nodules, in which we performed preoperative percutaneous computed tomography (CT)-guided nodule localization through the injection of a mixture of indocyanine green and human albumin. Results: A total of 40 patients underwent a preoperative CT-guided injection of indocyanine green followed by VATS resection within 24 h. Patients tolerated the procedure well, no pain medication was administrated, and no complications were observed during the marking procedure. All pulmonary nodules were easily detected and successfully resected. Conclusion: the near-infrared dye marking solution of indocyanine green (ICG) with diluted human albumin was safe, effective, and easy to perform. The ICG solution has the potential to facilitate the accurate localization and resection of pulmonary nodules during VATS surgery, avoiding the risk of marker displacement/migration.

The use of extracorporeal lung support (ECLS) during thoracic surgery is a recent concept that has been gaining increasing approval. Firstly introduced for lung transplantation, this technique is now increasingly adopted also in oncological thoracic surgical procedures. In this review, we focus on the cutting-edge application of extracorporeal membrane oxygenation (ECMO) during oncological thoracic surgery. Therefore, we report the most common surgical procedures in oncological thoracic surgery that can benefit from the use of ECMO. They will be classified and discussed according to the aim of ECMO application. In particular, the use of ECMO is usually limited to certain lung surgery procedures that can be resumed such as in procedures in which an adequate ventilation is not possible such as in single lung patients, procedures where conventional ventilation can cause conflict with the surgical field such as tracheal or carinal surgery, and conventional procedures requiring both ventilators and hemodynamic support. So far, all available evidence comes from centers with large experience in ECMO and major thoracic surgery procedures.

Abstract Neuroendocrine tumors (NETs) are epithelial neoplasms with predominant neuroendocrine differentiation that arise in most organs of the body. Mediastinal NETs are very rare, and account for no more than 5% of all mediastinal tumors. R0 surgery represents the milestone of treatment. Here, we describe a case of a locally advanced primary atypical carcinoid of the mediastinum. This was initially considered inoperable due to infiltration of a great vessel and was successfully resected after neoadjuvant treatment as a result of very extensive surgery. Only through an accurate preoperative diagnosis and good radiological planning is it possible to obtain satisfactory oncological results.

Abstract Small cell lung cancer (SCLC) is an aggressive malignancy with a poor prognosis that accounts for 10% of all cases of clinical lung cancer. Due to its high growth fraction and rapid doubling time it is usually diagnosed as extensive local or metastatic disease in 60%–70% of cases. Combined small cell lung cancer (C‐SCLC) is a relatively rare subtype of SCLC and is defined as SCLC combined with any elements of non‐small cell lung cancer (NSCLC). Clinical presentation of SCLC as an isolated pedunculated endotracheal lesion is an especially rare occurrence. Here, we report for the first time the occurrence of a C‐SCLC as a polypoid tumor of the trachea diagnosed in an 80‐year‐old woman admitted to the emergency department with a principal complaint of cough and wheezing.

Background: Intraoperative localisation of nodal disease in non-small cell lung cancer (NSCLC) can be challenging. Lymph node localisation via radiopharmaceuticals is used in many conditions; we tested the feasibility of this approach in NSCLC. Methods: NSCLC patients were prospectively recruited. Intraoperative peri-tumoral injections of [99mTc]Tc-albumin nanocolloids were performed, followed by removing the tumour and locoregional lymph nodes. These were examined ex vivo with a gamma probe and labelled sentinel lymph nodes (SLNs) if they showed any activity or non-sentinel lymph nodes (nSLNs) if they did not. Thereafter, the surgical field was scanned with the probe; any further radioactive lymph node was removed and labelled as “extra” SLNs (eSLNs). All specimens were sent to histology, and metastatic status was recorded. Results: 48 patients were enrolled, and 290 nodal stations were identified: 179 SLNs, 87 nSLNs, and 24 eSLNs. A total of 44 nodal metastases were identified in 22 patients, with 36 of them (82%) located within SLNs. Patients with nSLNs metastases had at least a co-existing positive SLN. No metastases were found in eSLNs. Conclusions: The technique shows high sensitivity for intraoperative nodal metastases identification. This information could allow selective lymphadenectomies in low-risk patients or more aggressive approaches in high-risk patients.

Abstract Primary lung signet‐ring cell carcinomas are a rare entity and only a few cases of pure signet‐ring cell carcinomas of the lung are reported in the English literature. They usually have an aggressive behavior and a poor prognosis because in most cases they are identified at an advanced stage. We present a unique case of primary signet‐ring cell carcinoma of the lung because the patient was HIV positive, a heavy smoker, and also the tumor, discovered incidentally during chest x‐ray, was a pure type of signet‐ring cell carcinoma. Surgical therapy associated with chemoradiotherapy represents the gold standard in the care of these patients.

Localization of small-sized pulmonary nodules is challenging during video-assisted thoracoscopic surgery. Several preoperative strategies have been developed to mark these targets. We describe our localization strategy using a preoperative computed tomography-guided near-infrared dye marking.

Pulmonary metastasectomy is an established treatment that can provide improved long- term survival for patients with metastatic tumor(s) in the lung. In this mini-review, we discuss the state of the art of thoracic surgery in surgical management of lung metastases which actually occurs for a large part of surgical activity in thoracic surgery department. We describe the principles of surgical therapy that have been defined across the time, and that should remain the milestones of lung metastases treatment: a radical surgery and an adequate lymphadenectomy. We then focus on current surgical indications and report the oncological results according to the surgical approach (open vs. mini-invasive), the histological type and number of lung metastases, and in case of re-metastasectomy. Finally, we conclude with a brief overview about the future perspectives in thoracic surgery in treatment of lung metastases.

The thymus is widely recognized as an immunological niche where autoimmunity against the acetylcholine receptor (AChR) develops in myasthenia gravis (MG) patients, who mostly present thymic hyperplasia and thymoma. Thymoma-associated MG is frequently characterized by autoantibodies to the muscular ryanodine receptor 1 (RYR1) and titin (TTN), along with anti-AChR antibodies. By real-time PCR, we analyzed muscle—CHRNA1, RYR1, and TTN—and muscle-like—NEFM, RYR3 and HSP60—autoantigen gene expression in MG thymuses with hyperplasia and thymoma, normal thymuses and non-MG thymomas, to check for molecular changes potentially leading to an altered antigen presentation and autoreactivity. We found that CHRNA1 (AChR-α subunit) and AIRE (autoimmune regulator) genes were expressed at lower levels in hyperplastic and thymoma MG compared to the control thymuses, and that the RYR1 and TTN levels were decreased in MG versus the non-MG thymomas. Genes encoding autoantigens that share epitopes with AChR-α (NEFM and HSP60), RYR1 (neuronal RYR3), and TTN (NEFM) were up-regulated in thymomas versus hyperplastic and control thymuses, with distinct molecular patterns across the thymoma histotypes that could be relevant for autoimmunity development. Our findings support the idea that altered muscle autoantigen expression, related with hyperplastic and neoplastic changes, may favor autosensitization in the MG thymus, and that molecular mimicry involving tumor-related muscle-like proteins may be a mechanism that makes thymoma prone to developing MG.

Despite the adoption of enhanced recovery programs, the reported postoperative length of stay after robotic surgery is 4 days even in highly specialized centers. We report preliminary results of a pilot study for a new protocol of early discharge (on day 2) with telehealth home monitoring after robotic lobectomy for lung cancer. All patients with a caregiver were discharged on postoperative day 2 with a telemonitoring device if they satisfied specific discharge criteria. Teleconsultations were scheduled once in the afternoon of post-operative day 2, twice on postoperative day 3, and then once a day until the chest tube removal. Post-discharge vital signs were recorded by patients at least four times daily through the device and were available for consultation by two surgeons through phone application. In case of sudden variation of vital signs or occurrence of adverse events, a direct telephone line was available for patients as well as a protected re-hospitalization path. Primary outcome was the safety evaluated by the occurrence of post-discharge complications and readmissions. Secondary outcome was the evaluation of resources optimization (hospitalization days) maintaining the standard of care. During the study period, twelve patients satisfied all preoperative clinical criteria to be enrolled in our protocol. Two of twelve enrolled patients were successively excluded because they did not satisfy discharge criteria on postoperative day 2. During telehealth home monitoring a total of 27/427 vital-sign measurements violated the threshold in seven patients. Among the threshold violations, only 1 out of 27 was a critical violation and was managed at home. No postoperative complication occurred neither readmission was needed. A mean number of three hospitalization days was avoided and an estimated economic benefit of about EUR 500 for a single patient was obtained if compared with patients submitted to VATS lobectomy in the same period. These preliminary results confirm that adoption of telemonitoring allows, in selected patients, a safe discharge on postoperative day 2 after robotic surgery for early-stage NSCLC. A potential economic benefit could derive from this protocol if this data will be confirmed in larger sample.

(1) Background: Once lung lesions are identified on CT scans, they must be characterized by assessing the risk of malignancy. Despite the promising performance of computer-aided systems, some limitations related to the study design and technical issues undermine these tools’ efficiency; an “intelligent agent” to detect and non-invasively characterize lung lesions on CT scans is proposed. (2) Methods: Two main modules tackled the detection of lung nodules on CT scans and the diagnosis of each nodule into benign and malignant categories. Computer-aided detection (CADe) and computer aided-diagnosis (CADx) modules relied on deep learning techniques such as Retina U-Net and the convolutional neural network; (3) Results: Tests were conducted on one publicly available dataset and two local datasets featuring CT scans acquired with different devices to reveal deep learning performances in “real-world” clinical scenarios. The CADe module reached an accuracy rate of 78%, while the CADx’s accuracy, specificity, and sensitivity stand at 80%, 73%, and 85.7%, respectively; (4) Conclusions: Two different deep learning techniques have been adapted for CADe and CADx purposes in both publicly available and private CT scan datasets. Experiments have shown adequate performance in both detection and diagnosis tasks. Nevertheless, some drawbacks still characterize the supervised learning paradigm employed in networks such as CNN and Retina U-Net in real-world clinical scenarios, with CT scans from different devices with different sensors’ fingerprints and spatial resolution. Continuous reassessment of CADe and CADx’s performance is needed during their implementation in clinical practice.

BackgroundPersistent air leak is a common complication occurring from 6% to 23% of cases after extended pleurectomy/decortication for malignant pleural mesothelioma. Treatment options for this complication after major lung resection are well documented in literature; nevertheless, lines of evidence in extended pleurectomy/decortication for malignant pleural mesothelioma are absent. The aim of the study is to evaluate the efficacy of intraoperative administration of 50% hypertonic glucose solution in reducing duration of air leak following extended pleurectomy/decortication for malignant pleural mesothelioma.Materials and MethodsIn this retrospective case–control study, we analyzed our electronic health record and selected those patients with a histological diagnosis of malignant pleural mesothelioma who underwent extended pleurectomy/decortication in the period 2013–2021. From 2018, we introduced a lavage with 500 ml of glucose solution at 50% concentration into the chest cavity at the end of the surgical procedure. Patients operated before 2018 were used as the control group. Postoperative glycemia was measured, and patients were followed after hospital discharge until the air leak resolved and the chest tube was removed. Statistical analysis was performed using R software.ResultsA total of 71 patients met our criteria. Treatment and control groups were similar for age, sex, smoking status, number of comorbidities, tumor histotype, and side of disease. Use of hypertonic glucose solution resulted in shorter chest tube maintenance after hospital discharge (p = 0.0028). A statistically significant difference (p = 0.02) was also found in postoperative glycemia between the treatment (103 g/dl ± 8.9) and control group (98.8 g/dl ± 8.6). Days of hospitalization and chest tube maintenance during hospitalization did not significantly differ between the groups.InterpretationIntraoperative administration of 50% hypertonic glucose solution reduced the duration of air leak after hospital discharge. An increase in postoperative glycemia was found in the treatment group, but with no clinical effect. Hypertonic glucose solution is an effective and safe method to manage persistent air leak after extended pleurectomy/decortication for malignant pleural mesothelioma.

Objective(s): There is still limited data in the literature concerning the survival of patients with tumors of the thoracic spine. In this study, we analyzed clinical features, perioperative and long-term outcomes in patients who underwent vertebrectomy for cancer. Furthermore, we evaluated the survival and surgical complications. Methods: We retrospectively reviewed all cases of thoracic spinal tumors treated by the same team between 1998 and 2018. We divided them into three groups according to type of tumor (primary vertebral, primary lung and metastases) and compared outcomes. For each patient, Overall Survival (OS) and Cumulative Incidence of Relapse (CIR) were estimated. Complications and survival were analyzed using a logistic model. Results: Seventy-two patients underwent thoracic spine surgery (40 in group 1, 16 in each group 2 and 3). Thirty patients died at the end of the observation at a mean follow up time of 60 months (41%). The 5-year overall survival was 72% (95% CI: 0.52–0.84), 20% (95% CI: 0.05–0.43) and 27% (95% CI: 0.05–0.56) for each group, respectively. CIR of group 3 was higher (HR 2.57, 95% CI: 1.22–5.45, p = 0.013). The logistic model revealed that age was related to complications (p = 0.04), while surgery for a type 3 tumor was related to mortality (p = 0.02). Conclusions: Although the cohort size was limited, primary vertebral tumors displayed the best 5-y-OS with an acceptable complications rate. The indication of surgery should be advised by a multidisciplinary team and only for selected cases. Finally, the use of a combined approach does not increase the risk of complications.

IntroductionWe report the results of the first prospective international randomized control trial to compare the perioperative outcome and surgical radicality of the robotic approach with those of traditional video-assisted surgery in the treatment of early-stage lung cancer.MethodsPatients with clinical stage T1–T2, N0–N1 non-small cell lung cancer (NSCLC) were randomly assigned to robotic-assisted thoracoscopic surgery (RATS) or video-assisted thoracic surgery (VATS) resection arms. The primary objective was the incidence of adverse events including complications and conversion to thoracotomy. The secondary objectives included extent of lymph node (LN) dissection and other indicators.ResultsThis trial was closed at 83 cases as the probability of concluding in favor of the robot arm for the primary outcome was null according to the observed trend. In this study, we report the results of the analysis conducted on the patients enrolled until trial suspension. Thirty-nine cases were randomized in the VATS arm and 38 in the robotic arm. Six patients were excluded from analysis. Despite finding no difference between the two arms in perioperative complications, conversions, duration of surgery, or duration of postoperative stay, a significantly greater degree of LN assessment by the robotic technique was observed in regards to the median number of sampled LN stations [6, interquartile range (IQR) 4–6 vs. 4, IQR 3–5; p = 0.0002], hilar LNs (7, IQR 5–10 vs. 4, IQR 2–7; p = 0.0003), and mediastinal LNs (7, IQR 5–10 vs. 5, IQR 3–7; p = 0.0001).ConclusionsThe results of this trial demonstrated that RATS was not superior to VATS considering the perioperative outcome for early-stage NSCLC, but the robotic approach allowed an improvement of LN dissection. Further studies are suggested to validate the results of this trial.Clinical Trial Registrationclinicaltrials.gov, identifier NCT02804893.

Objectives: We examined a series of malignant pleural mesothelioma (MPM) patients who consecutively underwent surgery in our institution during the last 20 years. Across this period, we changed our surgical approach to MPM, adopting extended pleurectomy and decortication (eP/D) instead of extrapleural pneumonectomy (EPP). In this study, we compare the perioperative outcomes and long-term survival of patients who underwent EPP vs. eP/D. Methods: A retrospective analysis was carried out of all the MPM patients identified from our departmental database who underwent EPP or P/D from 2000 to 2021. Clavien–Dindo criteria was adopted to score postoperative complications, while Kaplan–Meier methods and a Cox multivariable analysis were used to perform the survival analysis. Results: Of 163 patients, 78 (48%) underwent EPP and 85 (52%) eP/D. Induction chemotherapy was significantly administrated more often in the eP/D group (88% vs. 51%). Complete trimodality treatment including induction chemotherapy, radical surgery, and adjuvant radiotherapy was administered in 74% of the eP/D group versus 32% of the EPP group (p < 0.001). The postoperative morbidity rate was higher in the eP/D group (54%) compared to the EPP group (36%) (p = 0.02); no statistically significant differences were identified concerning major complications (EPP 43% vs. eP/D 24%, p = 0.08). No statistical differences were identified in 30-day mortality, 90-day mortality, median disease-free, and overall survival statistics between the two groups. The Cox multivariable analysis confirmed no induction chemotherapy (HR, 0.5; p = 0.002), RDW (HR, 1.08; p = 0.02), and the presence of pathological nodal disease (HR, 1.99; p = 0.001) as factors associated with worse survival in the entire series. Conclusions: Our data support that eP/D is a well-tolerated procedure allowing the implementation of a trimodality strategy (induction chemotherapy, surgery, and radiotherapy) in most MPM patients. When eP/D is offered in this setting, the oncological results are comparable to EPP. To obtain the best oncological results, the goal of surgical resection should be macroscopic complete resection (R0) in carefully selected patients (clinical N0).

Background: Persistent air leak is a common complication after lung resection causing prolonged length of stay and increased healthcare costs. Surgical intervention can be an option, but other more conservative approaches should be considered first. Here, we describe the use of flexible bronchoscopy to apply fibrin glue and autologous blood sequentially to the damaged lung. We named the technique “flexible thoracoscopy”. Methods: Medical records from patients with persistent air leaks after lung resection were collected retrospectively. Depending on the type of aerostasis that was performed, two groups were created: flexible thoracoscopy and surgery (thoracotomy). Flexible thoracoscopy was introduced at our institution in 2013. We entered the pleural space with a bronchoscope following the same surgical pathway that was used for tube thoracostomy. Perioperative characteristics and outcomes were analyzed using R software (ver. 3.4.4). Results: From 1997 to 2021, a total of 23 patients required an intervention for persistent air leaks. Aerostasis was performed via flexible thoracoscopy in seventeen patients (69%) and via thoracotomy in six patients (31%). The median age was 70 years (22–82). Twenty patients were males (87%). There was no difference in age, sex distribution, BMI, comorbidities and FEV1%. An ASA score of 3 was more represented in the flexible thoracoscopy group; however, no evidence of a difference was found when compared to the thoracotomy group (p = 0.124). Length of in-hospital stay and chest tube duration was also similar between groups (p = 1 and p = 0.68, respectively). Conclusions: Aerostasis achieved either by flexible thoracoscopy or by thoracotomy showed similar results. We believe that flexible thoracoscopy could be a valid alternative to facilitate minimally invasive treatments for persistent air leaks. Further studies are needed to confirm these results.

Backgrounds: Since the application of mini-invasive surgery to pulmonary lobectomy, various studies confirmed the feasibility and the safety of the technique, with equivalent oncological standards. However, there are no studies that compare long-term postoperative pain in minimally invasive thoracic surgery. Methods: Between 1 January 2019 and 28 February 2020, we analysed pain scores at 2 weeks, 3 months, 6 months, and 1 year after the operation, where 50 patients underwent a VATS lobectomy and 50 underwent a RATS lobectomy. Pain scores are obtained through a telephone questionnaire, according to a Numerical Rating Scale (NRS). Results: The medias of the NRS scores, at 2 weeks, 3 months, 6 months, and 1 year after the operation were similar in both groups. Group I was composed of 50 patients who underwent a video-assisted lobectomy, while Group II was composed of 50 patients who underwent a robotic-assisted lobectomy. Two weeks after surgery Group I had a NRS value of 2.96 and in Group II it was 2.86; three months after in Group I the value was 2.16 and in Group II it was 2.06; six months after Group I ‘s value was 1.62 and Group II’s was 1.56; one year after in Group I the value was 1.30 and in the Group II was 1.24. For each time interval, no statistically significant differences were found (p > 0.05). Conclusions: In our analysis, RATS and VATS did not have significant differences in post-operative and long-term pain.

Background: We analysed a series of malignant pleural mesothelioma (MPM) patients who consecutively underwent extended Pleurectomy/Decortication (eP/D) in a centre with a high level of thoracic surgery experience (IRCCS Humanitas Research Hospital) to explore postoperative morbidity and mortality, pattern of recurrence and survival. Methods: A retrospective analysis was performed on MPM patients underwent eP/D in our centre from 2010 to 2021. All patients were identified from our departmental database. Postoperative complications were scored according to Clavien–Dindo criteria. Survival analysis was performed by the Kaplan–Meier methods and Cox multivariable analysis. Results: Eighty-five patients underwent extended pleurectomy decortication (eP/D) during study period. Macroscopical residual disease (R2) was reported in one case. A neoadjuvant chemotherapy regiment was administrated in 88% of the surgical cohort. A complete trimodality treatment including induction with platinum agents and pemetrexed, radical cytoreductive surgery and volumetric modulated arc therapy technology (VMAT) could be administered in 63 patients (74%). Postoperative morbidity rate was 54.11%, major complications (defined as Clavien–Dindo ≥ 3) were reported in 11 patients (12.9%). Thirty-day mortality and 90-day mortality were, respectively, 2.35% and 3.53%. Median disease-free and overall survival were, respectively, 13.7 and 25.5 months. The occurrence of major complications (Clavien–Dindo ≥ 3), operative time, pT3–T4, pathological node involvement (pN+) were prognostic factors associated with worse survival. Conclusions: In our experience, eP/D is a well-tolerated procedure with acceptable mortality and morbidity, allowing for the administration of trimodality regimens in most patients. eP/D offered in a multimodality treatment setting have satisfactory long term oncological results. To obtain best oncological results the goal of surgery should be macroscopic complete resection in carefully selected patients (clinical N0).

Abstract Background Pseudoangiomatous stromal hyperplasia is an uncommon mesenchymal breast neoplasm. Case presentation Here we present a case of an 11-year old hispanic girl affected by bilateral mammary nodular pseudoangiomatous stromal hyperplasia, an uncommon breast disease, with a review of the literature related to diagnostic workup, differential diagnosis, and management. A rapidly growing mass in the breast may be stressful for both parents and child as the suspicion of malignancy arises. Multiple wide excisions of both breasts were performed. Conclusions The purpose of this case report is to draw attention to the fact that most emerging lesions of the breast in girls during puberty are benign diseases.

Background: Non-small cell lung cancer (NSCLC) frequently presents when surgical intervention is no longer feasible. Despite local treatment with curative intent, patients might experience disease recurrence. In this context, accurate non-invasive biomarkers are urgently needed. We report the results of a pilot study on the diagnostic and prognostic role of circulating tumor cells (CTCs) in operable NSCLC. Methods: Blood samples collected from healthy volunteers (n = 10), nodule-negative high-risk individuals enrolled in a screening program (n = 7), and NSCLC patients (n = 74) before surgery were analyzed (4 mL) for the presence of cells with morphological features of malignancy enriched through the ISET® technology. Results: CTC detection was 60% in patients, while no target cells were found in lung cancer-free donors. We identified single CTCs (sCTC, 46%) and clusters of CTCs and leukocytes (heterotypic clusters, hetCLU, 31%). The prevalence of sCTC (sCTC/4 mL ≥ 2) or the presence of hetCLU predicted the risk of disease recurrence within the cohort of early-stage (I–II, n = 52) or advanced stage cases (III–IVA, n = 22), respectively, while other tumor-related factors did not inform prognosis. Conclusions: Cancer cell hematogenous dissemination occurs frequently in patients with NSCLC without clinical evidence of distant metastases, laying the foundation for the application of cell-based tests in screening programs. CTC subpopulations are fine prognostic classifiers whose clinical validity should be further investigated in larger studies.

We compare the perioperative course, postoperative pain, and quality-of-life (QOL) in patients undergoing anatomic resections of early-stage lung cancer by means of robotic surgery (RATS), video-assisted thoracic surgery (VATS), or muscle-sparing thoracotomy (OPEN); 169 consecutive patients with known/suspected lung cancer, candidates to anatomic resection, were enrolled in a single-center prospective study from April 2016 to December 2018. EORTC QLQ-C30 and QLQ-LC13 scores were obtained preoperatively and, at three time points, postoperatively. RATS and VATS groups were matched for ASA scores, while RATS and open surgery were matched for gender, ASA score, cancer stage, and tumor size; 58 patients underwent open surgery, 58 had VATS, and 53 had RATS. Hospital stay was shorter after RATS than OPEN (median 4.5 versus 5; p = 0.047). Comparing matched RATS and VATS groups, the number of hilar lymph nodes and nodal stations removed was significantly higher in the former approach (p = 0.01 vs. p < 0.0001); conversely, pain at 2 weeks was slightly lower after VATS (p = 0.004). No significant difference was observed in conversions, complications, duration of surgery, and postoperative hospitalization. The robotic approach was superior to OPEN in terms of QOL, pain, and length of postoperative stay and showed improved lymph node dissection compared to VATS.

BACKGROUND:Lung adenocarcinoma (LUAD) is the most common histologic subtype of lung cancer and has a high risk of distant metastasis at every disease stage. We aimed to characterize the genomic landscape of LUAD and identify mutation signatures associated with tumor progression. METHODS AND FINDINGS:We performed an integrative genomic analysis, incorporating whole exome sequencing (WES), determination of DNA copy number and DNA methylation, and transcriptome sequencing for 101 LUAD samples from the Environment And Genetics in Lung cancer Etiology (EAGLE) study. We detected driver genes by testing whether the nonsynonymous mutation rate was significantly higher than the background mutation rate and replicated our findings in public datasets with 724 samples. We performed subclonality analysis for mutations based on mutant allele data and copy number alteration data. We also tested the association between mutation signatures and clinical outcomes, including distant metastasis, survival, and tumor grade. We identified and replicated two novel candidate driver genes, POU class 4 homeobox 2 (POU4F2) (mutated in 9 [8.9%] samples) and ZKSCAN1 (mutated in 6 [5.9%] samples), and characterized their major deleterious mutations. ZKSCAN1 was part of a mutually exclusive gene set that included the RTK/RAS/RAF pathway genes BRAF, EGFR, KRAS, MET, and NF1, indicating an important driver role for this gene. Moreover, we observed strong associations between methylation in specific genomic regions and somatic mutation patterns. In the tumor evolution analysis, four driver genes had a significantly lower fraction of subclonal mutations (FSM), including TP53 (p = 0.007), KEAP1 (p = 0.012), STK11 (p = 0.0076), and EGFR (p = 0.0078), suggesting a tumor initiation role for these genes. Subclonal mutations were significantly enriched in APOBEC-related signatures (p < 2.5×10-50). The total number of somatic mutations (p = 0.0039) and the fraction of transitions (p = 5.5×10-4) were associated with increased risk of distant metastasis. Our study's limitations include a small number of LUAD patients for subgroup analyses and a single-sample design for investigation of subclonality. CONCLUSIONS:These data provide a genomic characterization of LUAD pathogenesis and progression. The distinct clonal and subclonal mutation signatures suggest possible diverse carcinogenesis pathways for endogenous and exogenous exposures, and may serve as a foundation for more effective treatments for this lethal disease. LUAD's high heterogeneity emphasizes the need to further study this tumor type and to associate genomic findings with clinical outcomes.

A workshop of experts from France, Germany, Italy and the United States took place at Humanitas Research Hospital Milan, Italy, on 10-11 February 2016, to examine techniques for and applications of robotic surgery to thoracic oncology. The main topics of presentation and discussion were: robotic surgery for lung resection; robot-assisted thymectomy; minimally invasive surgery for esophageal cancer; new developments in computer-assisted surgery and medical applications of robots; the challenge of costs; and future clinical research in robotic thoracic surgery. The following article summarizes the main contributions to the workshop. The Workshop consensus was that, since video-assisted thoracoscopic surgery (VATS) is becoming the mainstream approach to resectable lung cancer in North America and Europe, robotic surgery for thoracic oncology is likely to be embraced by an increasing numbers of thoracic surgeons, since it has technical advantages over VATS, including intuitive movements, tremor filtration, more degrees of manipulative freedom, motion scaling, and high definition stereoscopic vision. These advantages may make robotic surgery more accessible than VATS to trainees and experienced surgeons, and also lead to expanded indications. However the high costs of robotic surgery and absence of tactile feedback remain obstacles to widespread dissemination. A prospective multicentric randomized trial (NCT02804893) to compare robotic and VATS approaches to stage I and II lung cancer will start shortly.