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Background: Video-assisted thoracoscopic surgery (VATS) is the recommended approach for the management of early-stage operable non-small cell lung carcinoma as well as for other pathologies of the thoracic cavity. Although VATS approaches have been largely adopted in Europe and North America, teaching the technique to novice thoracic surgery trainees remains challenging and non-standardized. Our objective was to assess the impact of a VATS simulation training program on the dexterity of thoracic surgery residents in a prospective single institution study., Methods: We developed a 6-month VATS simulation training program on two different dry-lab simulators (Johnson & Johnson Ethicon Stupnik ® lobectomy model; CK Surgical Simulation ® Crabtree perfused lobectomy model) and assessed the skills of first year thoracic surgery residents (study group, n=7) before and after this program using three standardized exercises on the Surgical Science Simball ® Box (peg placement on a board, rope insertion in loops, precision circle cutting). The results were compared to those of last-year medical students who performed the same Simball ® Box exercises at a 6-month interval without undergoing a training program (control group, n=5). For each participant, the travel distances of instruments, operation time and absences of periods of extreme motion were assessed for each exercise by the use of the computer-based evaluation of the Simball ® Box., Results: After the 6-month VATS training program, all residents revealed a significant increase of their performance status with respect to instrument travel distances operation times and absence of periods of extreme motion in all three exercises performed. The performance of the control group was not different from the study group prior to the training program and remained unchanged 6 months later, for all exercises and parameters assessed., Conclusions: Our results suggest that the implementation of a VATS simulation training program objectively increases the dexterity of thoracic surgery residents and could be an interesting training tool for their surgical education., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1288/coif). M.G. serves as an unpaid editorial board member of Journal of Thoracic Disease from February 2023 to January 2025. M.G. reports educational events (EMEA courses) sponsored by Johnson & Johnson. J.Y.P. reports educational events (EMEA courses) sponsored by Johnson & Johnson. The other authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Background: The inclusion of immune checkpoint inhibitors (ICIs) in the treatment of operable stage III non-small-cell lung cancer is becoming a new standard. Programmed death-ligand 1 (PD-L1) protein expression on tumor cells has emerged as the most important biomarker for sensitivity to ICIs targeting the programmed cell death protein 1 (PD-1)-PD-L1 axis. Little is known about the impact of neoadjuvant treatment on PD-L1 expression., Patients and Methods: We assessed PD-L1 expression by immunohistochemistry (Ventana SP263 assay) on tumor cells in treatment-naive diagnostic tumor samples and matched lung resections from patients with stage III non-small-cell lung cancer included in the Swiss Group for Clinical Cancer Research (SAKK) trials 16/96, 16/00, 16/01, and 16/14. All patients received neoadjuvant chemotherapy (CT) with cisplatin/docetaxel, either as single modality (CT), with sequential radiotherapy [chemoradiation therapy (CRT)] or with the PD-L1 inhibitor durvalumab (CT + ICI)., Results: Overall, 132 paired tumor samples were analyzed from patients with neoadjuvant CT (n = 69), CRT (n = 33) and CT + ICI (n = 30). For CT and CRT, PD-L1 expression before and after neoadjuvant treatment did not differ significantly (Wilcoxon test, P = 0.94). Likewise, no statistically significant difference was observed between CT and CRT for PD-L1 expression after neoadjuvant treatment (P = 0.97). For CT + ICI, PD-L1 expression before and after neoadjuvant treatment also did not differ significantly (Wilcoxon test, P > 0.99). Event-free survival and overall survival for patients with downregulation or upregulation of PD-L1 expression after neoadjuvant treatment were similar., Conclusions: In our cohort of patients neoadjuvant treatment did not influence PD-L1 expression, irrespective of the specific neoadjuvant treatment protocol. Dynamic change of PD-L1 expression did not correlate with event-free survival or overall survival., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Chest wall resections/reconstructions are a validated approach to manage tumors invading the thorax. However, how resection characteristics affect postoperative morbidity and mortality is unknown. We determined the impact of chest wall resection size and location on patient short and long-term postoperative outcomes., Methods: We reviewed all consecutive patients who underwent resections/reconstructions for chest wall tumors between 2003 and 2018. The impact of chest wall resection size and location and reconstruction on perioperative morbidity/mortality and oncological outcome were evaluated for each patient., Results: Ninety-three chest wall resections were performed in 88 patients for primary (sarcoma, breast cancer, n=66, 71%) and metastatic (n=27, 29%) chest wall tumors. The mean chest bony resection size was 107 (range, 15-375) cm 2 and involved ribs only in 57% (n=53) or ribs combined to sternal/clavicular resections in 43% of patients (n=40). Chest defect reconstruction methods included muscle flaps alone (14%) prosthetic material alone (25%) or a combination of both (61%). Early systemic postoperative complications included pneumonia (n=15, 16%), atelectasis (n=6, 6%), pleural effusion (n=15, 16%) and arrhythmia (n=6, 6%). The most frequent long-term reconstructive complications included wound dehiscence (n=4), mesh infection (n=5) and seroma (n=4). Uni- and multivariable analyses indicated that chest wall resection size (>114 cm 2 ) and location (sternum) were significantly associated with the occurrence of pneumonia and atelectasis [odds ratio (OR) =3.67, P=0.05; OR =78.92, P=0.02, respectively]. Disease-free and overall survival were 37±43 and 48±42 months for primary malignancy and of 24±33 and 48±53 months for metastatic chest wall tumors respectively with a mean follow-up of 46±44 months., Conclusions: Chest wall resections present good long-term oncological outcomes. A resection size above 114 cm 2 and the involvement of the sternum are significantly associated with higher rates of postoperative pneumonia/atelectasis. This subgroup of patients should have reinforced perioperative physical therapy protocols., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-21-2143/coif). The authors have no conflicts of interest to declare., (2022 Translational Cancer Research. All rights reserved.)

Background: Chemoradiotherapy with durvalumab consolidation has yielded excellent results in stage III non-small-cell lung cancer (NSCLC). Therefore, it is essential to identify patients who might benefit from a surgical approach., Material and Methods: Data from 437 patients with operable stage III NSCLC enrolled in four consecutive Swiss Group for Clinical Cancer Research (SAKK) trials (16/96, 16/00, 16/01, 16/08) were pooled and outcomes were analyzed in 431 eligible patients. All patients were treated with three cycles of induction chemotherapy (cisplatin/docetaxel), followed in some patients by neoadjuvant radiotherapy (44 Gy, 22 fractions) (16/00, 16/01, 16/08) and cetuximab (16/08)., Results: With a median follow-up time of 9.3 years (range 8.5-10.3 years), 5- and 10-year overall survival (OS) rates were 37% and 25%, respectively. Overall, 342 patients (79%) underwent tumor resection, with a complete resection (R0) rate of 80%. Patients (n = 272, 63%) with R0 had significantly longer OS compared to patients who had surgery but incomplete resection (64.8 versus 19.2 months, P < 0.001). OS for patients who achieved pathological complete remission (pCR) (n = 66, 15%) was significantly better compared to resected patients without pCR (86.5 versus 37.0 months, P = 0.003). For patients with pCR, the 5- and 10-year event-free survival and OS rates were 45.7% [95% confidence interval (CI) 32.8% to 57.7%] and 28.1% (95% CI 15.2% to 42.6%), and 58.2% (95% CI 45.2% to 69.2%) and 45.0% (95% CI 31.5% to 57.6%), respectively., Conclusion: We report favorable long-term outcomes in patients with operable stage III NSCLC treated with neoadjuvant chemotherapy with cisplatin and docetaxel ± neoadjuvant sequential radiotherapy from four prospective SAKK trials. Almost two-third of the patients underwent complete resection after neoadjuvant therapy. We confirm R0 resection and pCR as important predictors of outcome., Competing Interests: Disclosure DK: consulting or advisory role: AstraZeneca (AZ) (fee to institution). IO: grants (all fees to institution): Roche, Medtronic; honoraria (all fees to speakers bureau): AZ, Roche; advisory role: AZ, Merck, Sharp, and Dohme (MSD). WW: honoraria, consulting or advisory role, travel/accommodations: AZ, Medtronic. SIR: honoraria, consulting or advisory role (all fees to institution): AbbVie, Amgen, AZ, Boehringer Ingelheim, Bristol-Myers Squibb (BMS), Eli Lilly, Eisai, Janssen, MSD, Merck Serono, Novartis, PharmaMar, Pfizer, Roche, Takeda; travel/accommodations: Boehringer Ingelheim, BMS, Roche; Research support: AZ, Roche. AA: consulting or advisory role: AZ, Astella, BMS, MSD, Novartis, Roche; honoraria: AZ, Eli Lilly, Novartis. MM: consulting or advisory role: AZ (institution), BMS, Janssen, MSD, Roche. SP (all fees to institution): consulting or advisory role: AbbVie, Amgen, AZ, Bayer, Beigene, Biocartis, Boehringer Ingelheim, BMS, Clovis, Daiichi Sankyo, Debiopharm, ecancer, Eli Lilly, Elsevier, Fishawack, Foundation Medicine, Illumina, Imedex, IQVIA, Incyte, Janssen, Medscape, MSD, Merck Serono, Merrimack, Novartis, OncologyEducation, PharmaMar, Phosplatin Therapeutics, PER, Pfizer, PRIME, Regeneron, RMEI, Roche/Genentech, RTP, Sanofi, Seattle Genetics, Takeda, Talk: AZ, Boehringer Ingelheim, BMS, ecancer, Eli Lilly, Illumina, Imedex, Medscape, MSD, Novartis, PER, Pfizer, Prime, Roche/Genentech, RTP, Sanofi, Takeda; Grants/research support: Amgen, AZ, Biodesix, Boehringer Ingelheim, BMS, Clovis, GSK, Illumina, Lilly, MSD, Merck Serono, Mirati, Novartis, and Pfizer, Phosplatin Therapeutics, Roche/Genentech. MP: honoraria: Bayer, Janssen, Nestle; consulting or advisory role: AbbVie, Amgen, AZ, Bayer, Boehringer Ingelheim, BMS, Eisei, Janssen, MSD, Merck Serono, Nestle, Novartis, Pfizer, Roche, Sanofi, Takeda; travel/accommodations: AZ, Boehringer Ingelheim, BMS, Roche, Takeda, Vifor. MF: grants (all to institution): AZ, BMS; consulting or advisory role: AZ, Boehringer Ingelheim, BMS, MSD, Pfizer, Roche, Takeda; travel/accommodations: Merck Serono. All other authors have declared no conflicts of interest., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Ex vivo lung perfusion (EVLP) with pharmacological reconditioning may increase donor lung utilization for transplantation (LTx). 3-Aminobenzamide (3-AB), an inhibitor of poly(ADP-ribose) polymerase (PARP), reduces ex vivo lung injury in rat lungs damaged by warm ischemia (WI). Here we determined the effects of 3-AB reconditioning on graft outcome after LTx. Three groups of donor lungs were studied: Control (Ctrl): 1 hour WI + 3 hours cold ischemia (CI) + LTx; EVLP: 1 hour WI + 3 hours EVLP + LTx; EVLP + 3-AB: 1 hour WI + 3 hours EVLP + 3-AB (1 mg . mL -1 ) + LTx. Two hours after LTx, we determined lung graft compliance, edema, histology, neutrophil counts in bronchoalveolar lavage (BAL), mRNA levels of adhesion molecules within the graft, as well as concentrations of interleukin-6 and 10 (IL-6, IL-10) in BAL and plasma. 3-AB reconditioning during EVLP improved compliance and reduced lung edema, neutrophil infiltration, and the expression of adhesion molecules within the transplanted lungs. 3-AB also attenuated the IL-6/IL-10 ratio in BAL and plasma, supporting an improved balance between pro- and anti-inflammatory mediators. Thus, 3-AB reconditioning during EVLP of rat lung grafts damaged by WI markedly reduces inflammation, edema, and physiological deterioration after LTx, supporting the use of PARP inhibitors for the rehabilitation of damaged lungs during EVLP., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Vascular-targeted low-dose photodynamic therapy (L-PDT) was shown to improve chemotherapy distribution in malignant pleural tumors such as malignant pleural mesothelioma (MPM). However, the mechanisms triggered by L-PDT on the tumor vasculature are still debated. In pericyte and endothelial cell co-cultures, we show that pericytes exhibit enhanced sensitivity towards L-PDT compared to endothelial cells, displaying actin stress fibers and cellular contraction via Rho/ROCK kinase signaling myosin light chain and focal adhesion kinase phosphorylation (MLC-P, FAK-P). We then confirm, in two separate MPM models, in mice the phosphorylation of the MLC in pericytes specifically following L-PDT. Furthermore, while L-PDT does not affect tumor vascular density or diameter, we show that it enhances tumor vascular pericyte coverage, leads to a drop in tumor interstitial fluid pressure and enhances the transport of FITC-dextran throughout tumors. In conclusion, L-PDT has the potential to stabilize the tumor vascular bed which improves vascular transport. The mechanism described in the present study may help translate and optimize this approach in patients. Lasers Surg. Med. 51:550-561, 2019. © 2019 Wiley Periodicals, Inc., (© 2019 Wiley Periodicals, Inc.)

Objectives: A lung retransplant has been shown to be a valid option in selected patients with chronic lung allograft dysfunction (CLAD). However, a subgroup of patients may require, in addition to invasive mechanical ventilation, extracorporeal membrane oxygenation (ECMO) as a bridge to a retransplant. Overall and CLAD-free survival after ECMO-bridged retransplants are compared to first transplants with and without bridging ECMO and to retransplants without bridging ECMO., Methods: We reported a retrospective, single-institution experience based on a prospective data set of all patients undergoing lung transplants between January 2004 and December 2016 with a mean follow-up of 51 ± 41 months., Results: A total of 230 patients (96 men, 134 women, mean age 47.3 years) had lung transplants: 200 had first transplants without bridging ECMO; 13 had first transplants with bridging ECMO; 11 had retransplants without bridging ECMO; and 6 had retransplants with bridging ECMO. The 3- and 5-year survival rates were 81%/76%, 68%/68%, 69%/46% and 50%/25%, respectively. There was no significant difference in overall survival between those who had first transplants with and without bridging ECMO or retransplants without bridging ECMO. In contrast, patients undergoing ECMO-bridged retransplants had a significantly lower overall survival rate than those with a first transplant without bridging ECMO (P = 0.007). In addition, the post-transplant CLAD-free survival curves varied significantly among the 4 treatment groups (P = 0.041), paralleling overall survival., Conclusions: Patients requiring ECMO as a bridge to a retransplant had lower overall and CLAD-free survival rates compared to those who had a first transplant with and without bridging ECMO and a retransplant without bridging ECMO., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Introduction: Long-term data on outcomes of operable stage III NSCLC are scarce., Methods: Individual patient data from 368 patients enrolled in one phase III and two phase II trials were pooled and outcomes after applying the eighth (denoted with an asterisk [*]) versus the sixth TNM staging edition were compared. Patients were treated with either preoperative radiotherapy following 3 cycles of induction chemotherapy (trimodal) or neoadjuvant chemotherapy alone (bimodal)., Results: With the sixth version, the 5- and 10-year survival rates were 38% and 28% for stage IIIA, respectively, and 36% and 24% for stage IIIB, respectively. Factors associated with improved 5-year overall survival were younger age, R0 resection, and pathologic complete remission (pCR) (p = 0.043, p < 0.001 and p = 0.009). With the eighth TNM staging version, 162 patients were moved from stage IIIA to IIIB*. The 5- and 10-year survival rates were 41% and 29% for stage IIIA*, respectively, and 35% and 27% for stage IIIB* patients, respectively. There was no difference in the bi- versus trimodal group with regard to median overall survival (28 months [95% confidence interval (CI): 21-39 months] and 37 months [95% CI: 24-51 months], p = 0.9) and event-free survival (12 months [95% CI: 9-15 months] versus 13 months [95% CI: 10-22 months], p = 0.71)., Conclusions: We showed favorable 10-year survival rates of 29% and 27% in stage IIIA* and IIIB*, respectively. Younger age, R0 resection, and pathologic complete response were associated with improved long-term survival. Outcomes using the sixth versus eighth edition of the TNM classification were similar in operable stage III NSCLC., (Copyright © 2018 International Association for the Study of Lung Cancer. All rights reserved.)

Background: Enhanced recovery after surgery (ERAS) programs have been reported to decrease complications and shorten hospital stays after lung resections, but their implementation requires time and financial investment with dedicated staff. The aim of this study was to evaluate the clinical and economic outcomes of video-assisted thoracoscopic surgery (VATS) anatomical pulmonary resections before and after implementation of an ERAS program., Methods: The first 50 consecutive patients undergoing VATS lobectomy or segmentectomy for malignancy after implementation of an ERAS program were compared with 50 consecutive patients treated before its introduction. The ERAS protocol included preoperative counseling, reduced preoperative fasting with concomitant carbohydrate loading, avoidance of premedication, standardized surgery, anesthesia and postoperative analgesia, early removal of chest tube, nutrition and mobilization. Length of stay, readmissions and cardio-pulmonary complications within 30 days were compared. Total costs were collected for each patient and a cost-minimization analysis integrating ERAS-specific costs was performed., Results: Both groups were similar in terms of demographics and surgical characteristics. The ERAS group had significantly shorter postoperative length of stay (median: 4 vs . 7 days, P<0.0001), decreased pulmonary complications (16% vs. 38%; P=0.01) and decreased overall post-operative complications (24% vs . 48%, P=0.03). One patient in each group was readmitted and there was no 30-day mortality. ERAS-specific costs were calculated at €729 per patient including the clinical nurse and database costs. Average total hospitalization costs were significantly lower in ERAS group (€15,945 vs . €20,360, P<0.0001), mainly due to lower costs during the post-operative period (€7,449 vs. €11,454, P<0.0001) in comparison with the intra-operative period (€8,496 vs . €8,906, P=0.303). Cost-minimization analysis showed a mean saving in the ERAS group of €3,686 per patient., Conclusions: An ERAS program for VATS anatomical lung resection is cost-effective and is associated with a lower complication rate and a shorter postoperative hospitalization., Competing Interests: Conflicts of Interest: This work was presented at the 26th Annual Meeting of the European Society of Thoracic Surgery, Ljubljana, Slovenia, 26-29 May 2018.

Background: Pulmonary anatomical segmentectomies are increasingly being done via video-assisted thoracoscopic surgery (VATS). We analyzed clinical outcomes and risk factors for post-operative complications after pulmonary segmentectomy by VATS was introduced in two institutions., Methods: We retrospectively reviewed records of all patients who underwent anatomical pulmonary segmentectomy by VATS from 2014 to 2016 at the university hospitals of Geneva and Lausanne in Switzerland., Results: One hundred twenty-nine patients (64 men; median age 68 years, range, 29-85 years) underwent anatomical VATS segmentectomy for primary lung tumors (n=100), metastases (n=16) and benign lesions (n=13). The overall 30-day mortality and morbidity rates were 0.8% and 31%, respectively. The reoperation rate was 4.7% [indications: hemothorax 2, prolonged air leak (PAL) 2, segmental torsion 1, empyema 1]. Chest drainage lasted for a median of 2 days (range, 1-33 days) and patients were discharged from the hospital after a median of 6 days (range, 2-37 days). Postoperative complications were mainly associated with chronic obstructive pulmonary disease (COPD) [odds ratio (OR) 2.54 and 95% confidence interval (95% CI), 1.18-5.47], and smoking pack-years >50 units (OR 5.27; 95% CI, 1.68-16.55). Nine patients (9%) presented with distant recurrences. Nodule size >2 cm was associated with decreased disease-free survival (DFS) (P=0.04). There was no association between surgical experience in VATS segmentectomy and DFS or postoperative complications., Conclusions: Segmentectomies can be safely performed by VATS in an initial experience and result in favorable clinical outcome. COPD and smoking pack-years are associated with an increased risk of complications., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Human pleural mesothelioma is an incurable and chemoresistant cancer. Using a nude mouse xenograft model of human pleural mesothelioma, we show that RAPTA-T, a compound undergoing preclinical evaluation, enhances tumor vascular function by decreasing blood vessel tortuosity and dilation, while increasing the coverage of endothelial cells by pericytes and vessel perfusion within tumors. This in turn significantly reduces the interstitial fluid pressure and increases oxygenation in the tumor. Consequently, RAPTA-T pre-treatment followed by the application of cisplatin or liposomal cisplatin (Lipoplatin) leads to increased levels of the cytotoxin in the tumor and enhanced mesothelioma growth inhibition. We demonstrate that the vascular changes induced by RAPTA-T are related, in part, to the inhibition of poly-(ADP-ribose) polymerase 1 (PARP-1) which is associated to tumor vascular stabilization. These findings suggest novel therapeutic implications for RAPTA-T to create conditions for superior drug uptake and efficacy of approved cytotoxic anti-cancer drugs in malignant pleural mesothelioma and potentially other chemoresistant tumors.

Colorectal cancer (CRC) is a frequently occurring disease, yet diagnosed at a local stage in only 40% of cases. Lung metastases (LM) appear in 5-15% of patients and, left untreated, carry a very poor prognosis. Some CRC patients may benefit from a potentially curative LM resection, but success and benefit are difficult to predict. We discuss prognostic factors of survival after lung metastasectomy in CRC patients under several scenarios (with/ without prior liver metastases; repetitive pulmonary resections). We reviewed all studies (2005-2015) about pulmonary metastases surgical management with curative intent in CRC patients, with a minimum threshold on the number of patients reported (without prior liver metastases: n ≥ 100; with prior resection of liver metastases: n ≥ 50; repetitive thoracic surgery: n ≥ 30). The picture of the prognostic factors of survival is nuanced: surgical management demonstrates clear successes and steady progress, yet there is no single success criterion; stratification of patients and selection bias impact the conclusions. Surgical management of liver and lung metastases may prolong life or cure CRC patients, provided the lesions are fully resected and patients carefully selected. Repeat lung metastasectomy is a safe approach to treat patients in selected cases. In conclusion, there is no standard for surgical management in CRC patients with pulmonary metastases. Patients with isolated unilateral lung metastasis with normal CEA level and no lymph node involvement benefit the most from surgery. Most series report good results in highly selected patients, but instances of long-term disease-free survival remain exceptional., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: Volatile anaesthetics can provide significant protection against reperfusion injury in various experimental settings. The aim of this study was to assess the potential of sevoflurane treatment, the most commonly used volatile anaesthetic in modern anaesthesia, in rat lungs donated after circulatory death and reconditioned in an ex vivo lung perfusion (EVLP) system., Methods: Fifteen rats were sacrificed and divided into 3 groups. In the control and sevoflurane groups, the heart-lung blocks were exposed to 1 h of warm ischaemia and 2 h of cold ischaemia and were mounted on an EVLP circuit for 3 h, in the absence or in the presence of 2% sevoflurane. In the baseline group, heart-lung blocks were harvested immediately after euthanasia. Physiological data, lung nitro-oxidative stress, lactate dehydrogenase (LDH), expression of cytokines, oedema and histopathological findings were assessed during or post-EVLP., Results: The sevoflurane group showed significantly reduced LDH (8.82 ± 3.58 arbitrary unit vs 3.80 ± 3.02 arbitrary unit, P = 0.03), protein carbonyl (1.17 ± 0.44 nmol⋅mg-1 vs 0.55 ± 0.11 nmol⋅mg-1, P = 0.006), 3-nitrotyrosine (197.44 ± 18.47 pg⋅mg-1 vs 151.05 ± 23.54 pg⋅mg-1, P = 0.004), cytokine-induced neutrophil chemoattractant factor 1 (1.17 ± 0.32 ng⋅mg-1 vs 0.66 ± 0.28 ng⋅mg-1, P = 0.03) and tumour necrosis factor alpha (1.50 ± 0.59 vs 0.59 ± 0.38 ng⋅mg-1, P = 0.02) when compared with the control group. In addition, sevoflurane lungs gained significantly less weight (0.72 ± 0.09 g vs 0.72 ± 0.09 g, P = 0.044), had less perivascular oedema (0.58 ± 0.09 vs 0.47 ± 0.07, P = 0.036), and improved static pulmonary compliance (+0.215 ml⋅cmH2O-1, P = 0.003) and peak airways pressure (-1.33 cmH2O, P = 0.04) but similar oxygenation capacity (+1.61 mmHg, P = 0.77) and pulmonary vascular resistances (+0.078 mmHg⋅min⋅ml-1, P = 0.15) when compared with the control group., Conclusions: These findings suggest that the potential of sevoflurane in protecting the lungs donated after cardiac death and reconditioned using EVLP could improve the outcome of these lungs following subsequent transplantation.

Background: Extrathoracic muscle flaps can be used as airway substitutes for the closure of complex bronchopleural or tracheoesophageal fistulas or in the context of tracheocarinal reconstructions after resection for centrally localized tumors in order to alleviate excess anastomotic tension., Methods: Evaluation of all patients undergoing tracheocarinal reconstructions with extrathoracic muscle flap patches as airway substitutes in our institution from 1996 to 2016., Results: A total of 73 patients underwent tracheocarinal reconstructions using extrathoracic muscle flap patches as airway substitutes for the closure of bronchopleural fistulas (n = 17) and complex tracheoesophageal fistulas (n = 7), or in the context of airway reconstructions after carinal resections in combination with pneumonectomy/sleeve lobectomy for centrally localized lung tumors (n = 36) and noncircumferential tracheal resections for tracheal disease processes (n = 14). The size of airway defects replaced by muscle patches ranged from 2 × 2 to 8 × 4 cm and was at most 40% of the airway circumference. The postoperative 90-day mortality was 8.2% and was only observed after right-sided pneumonectomy. Complications at the airway reconstruction site occurred in 8 patients (10%): 4 airway dehiscence (5%) with uneventful healing after reoperation (n = 2) or temporary stenting (n = 2) and 4 airway stenosis (5%) that required repeated bronchoscopy and stenting. Overall, 63 of 67 surviving patients (94%) revealed intact airways without further bronchoscopic interventions or tracheal appliance during follow-up., Conclusions: Extrathoracic muscle flaps used as airway substitutes are an interesting and sometimes life-saving option to close difficult tracheocarinal airway defects or to reduce anastomotic tension in the context of complex tracheocarinal surgeries., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Introduction: Paraganglioma is a rare neuroendocrine tumor and may sometimes be located in the membranous part of the trachea., Presentation of Case: We report the case of a 52-year-old man presenting a paraganglioma just above the carina with obstructive symptoms. The patient successfully underwent a non-circumferential tracheal membranous resection, followed by latissimus dorsi muscle flap repair, under peripheral extra-corporeal membrane oxygenation (ECMO)., Discussion: Complex carinal resection can be avoided for tracheal membranous tumors and replaced with non-circumferential resection and direct reconstruction with a muscle flap. In addition, ECMO support may be used for airway resection and reconstruction., Conclusion: Tracheal membranous tumors can be managed without circumferential resection or direct anastomosis., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Solitary pulmonary nodules (SPN) are frequently detected in cancer patients. These lesions are often considered as pulmonary metastases and increasingly treated by non-surgical techniques without histological confirmation. The aim of this study is to determine the histological nature of SPN resected by thoracoscopy and to identify risk factors of malignancy., Methods: Single-institution retrospective analysis of all consecutive patients with previously known malignancies who underwent thoracoscopic resection of SPN with unknown diagnosis between 2001 and 2014., Results: One hundred and forty cancer patients underwent thoracoscopic resection of a SPN. The resected SPN was benign in 34 patients (24.3%) and malignant in 106 patients. The latter were metastasis in 70 patients (50%) and a primary lung cancer in 36 patients (25.7%). Upon univariate analysis, malignancy was significantly associated with age >60 years, disease-free interval ≥24 months, SPN size >8 mm, upper lobe localization and SUV max  > 2.5 on PET-CT. Upon multivariate analysis, upper lobe localization and SUV max  > 2.5 were associated with malignancy. Smoking was significantly associated with SPN containing primary lung cancer., Conclusion: In this series, only 50% of SPN in patients with known malignant disease were pulmonary metastases and 25% had a newly diagnosed NSCLC. Smoking was associated with primary lung cancer but no other predictor was found to allow the distinction between pulmonary metastasis and lung cancer. These results endorse the need of histological confirmation of SPN in patients with previous malignancies to avoid diagnostic uncertainty and suboptimal treatments.

Background: Low-dose photodynamic therapy PDT (photoinduction) can modulate tumor vessels and enhance the uptake of liposomal cisplatin (Lipoplatin®) in pleural malignancies. However, the photo-induction conditions must be tightly controlled as overtreatment shuts down tumor vessels and enhances normal tissue drug uptake., Material and Methods: In a pleural sarcoma and adenocarcinoma rat model (n = 12/group), we applied photoinduction (0.0625 mg/kg Visudyne®, 10 J/cm 2 ) followed by intravenous Lipoplatin® (5 mg/kg) administration. Tumor and normal tissue IFP were assessed before and up to 1 hour following photoinduction. Lipoplatin® uptake was determined 60 minutes following photoinduction. We then treated the pleura of tumor-free minipigs with high dose photodynamic therapy (PDT) (0.0625 mg/kg Visudyne®, 30 J/cm 2 , n = 5) followed by Lipoplatin (5 mg/kg) administration., Results: In rodents, photoinduction resulted in a significant decrease of IFP (P < 0.05) in both tumor types but not in the surrounding normal lung, equally exposed to light. Also, photoinduction resulted in a significant increase of Lipoplatin® uptake in both tumor types (P < 0.05) but not in normal lung. Tumor IFP variation and Lipoplatin® uptake fitted an inverted parabola. In minipigs, high dose photodynamic treatment resulted in pleural IFP increase of some animals which predicted higher Lipoplatin® uptake levels., Conclusion: Normal and tumor vasculatures react differently to PDT. Continuous IFP monitoring in normal and tumor tissues is a promising biomarker of vessel photoinduction. Moderate drop in tumor with no change in normal tissue IFP are predictive of specific Lipoplatin® uptake by cancer following PDT. Lasers Surg. Med. 49:773-780, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Objectives: Evaluation of complex, acquired, non-malignant tracheo/broncho-oesophageal fistulas (TEF) repaired by extrathoracic pedicled muscle flaps that were, in addition to their interposition between the airways and the gastro-intestinal tract, patched into gastro-intestinal or airway defects if primary closure seemed risky., Methods: A single institution experience of patients treated between 2003 and 2015. Twenty-two patients required TEF repair following oesophageal surgery (18), Boerhaave syndrome (1), chemotherapy for mediastinal lymphoma (1), carinal resection and irradiation (1) and laryngectomy (1); 64% of them underwent prior radio- or chemotherapy and 50% prior airway or oesophageal stenting., Results: Airway defects were closed by muscle flap patch ( n  = 12), lobectomy ( n  = 4), airway resection/anastomosis ( n  = 2), pneumonectomy ( n  = 1), segmentectomy ( n  = 2) or primary suture ( n  = 1). Gastro-intestinal defects were repaired by oesophageal diversion ( n  = 9), muscle flap patch ( n  = 8) or primary suture ( n  = 5). A muscle flap patch was used to close airway and gastro-intestinal defects in 55% and 36% of cases, respectively. The 90-day postoperative mortality and TEF recurrence rates were 18% and 4.5%. Airway healing and breathing without tracheal appliance was obtained in 95% of patients and gastro-intestinal healing in 77% of those without oesophageal diversion. Five of nine patients with oesophageal diversion underwent intestinal restoration by retrosternal colon transplants., Conclusions: Complex TEF arising after oesophageal surgery, radio-chemotherapy or failed stenting can be successfully closed using extrathoracic muscle flaps that can, in addition to their interposition between the airway and the gastro-intestinal tract, also be patched into gastro-oesophageal or airway defects if primary closure seems hazardous., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Damaged lung grafts obtained after circulatory death (DCD lungs) and warm ischemia may be at high risk of reperfusion injury after transplantation. Such lungs could be pharmacologically reconditioned using ex-vivo lung perfusion (EVLP). Since acute inflammation related to the activation of nuclear factor kappaB (NF-κB) is instrumental in lung reperfusion injury, we hypothesized that DCD lungs might be treated during EVLP by pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB. Rat lungs exposed to 1h warm ischemia and 2 h cold ischemia were subjected to EVLP during 4h, in absence (CTRL group, N = 6) or in presence of PDTC (2.5g/L, PDTC group, N = 6). Static pulmonary compliance (SPC), peak airway pressure (PAWP), pulmonary vascular resistance (PVR), and oxygenation capacity were determined during EVLP. After EVLP, we measured the weight gain of the heart-lung block (edema), and the concentration of LDH (cell damage), proteins (permeability edema) and of the cytokines IL-6, TNF-α and CINC-1 in bronchoalveolar lavage (BAL), and we evaluated NF-κB activation by the degree of phosphorylation and degradation of its inhibitor IκBα in lung tissue. In CTRL, we found significant NF-κB activation, lung edema, and a massive release of LDH, proteins and cytokines. SPC significantly decreased, PAWP and PVR increased, while oxygenation tended to decrease. Treatment with PDTC during EVLP inhibited NF-κB activation, did not influence LDH release, but markedly reduced lung edema and protein concentration in BAL, suppressed TNFα and IL-6 release, and abrogated the changes in SPC, PAWP and PVR, with unchanged oxygenation. In conclusion, suppression of innate immune activation during EVLP using the NF-κB inhibitor PDTC promotes significant improvement of damaged rat DCD lungs. Future studies will determine if such rehabilitated lungs are suitable for in vivo transplantation.

In the reported scenario, the patient known for a history of operated Bochdalek hernia or congenital diaphragmatic hernia (CDH) presented with new abdominal pain. The CT-scan suspected the presence of pancreas herniation through a recurrent CDH. Intraoperatively, the patient was found to have a recurrent CDH containing greater omentum concomitantly with a pulmonary sequestration (PS). This case report highlights the fact that intraoperative findings can be different from preoperative radiological diagnosis. In this patient the unusual diaphragmatic hernia content was not identified on preoperative CT., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: Donor lungs obtained after prolonged warm ischemia (WI) may be unsuitable for transplantation due to the risk of reperfusion injury, but could be reconditioned using ex-vivo lung perfusion (EVLP). Key processes of reperfusion injury include the formation of reactive oxygen species (ROS)/nitrogen species (RNS) and the activation of poly(adenosine diphosphate-ribose) polymerase (PARP). We explored whether rat lungs obtained after WI could be reconditioned during EVLP using the ROS/RNS scavenger Mn(III)-tetrakis (4-benzoic acid) porphyrin chloride (MnTBAP) or the PARP inhibitor 3-aminobenzamide (3-AB)., Methods: Rat lungs obtained after 3 hours cold ischemia (CI group, control), or 1 hour WI plus 2 hours CI (WI group) were placed in an EVLP circuit for normothermic perfusion for 3 hours. Lungs retrieved after WI were treated or not with 3-AB (1 mg/mL) or MnTBAP (0.3 mg/mL), added to the perfusate. Measurements included physiological variables (lung compliance, vascular resistance, oxygenation capacity), lung weight gain, levels of proteins, lactate dehydrogenase, protein carbonyl (marker of ROS), 3-nitrotyrosine (marker of RNS), poly(adenosine diphosphate-ribose) (PAR, marker of PARP activation) and IL-6, in the bronchoalveolar lavage or the lung tissue, and histology., Results: In comparison to the CI group, the lungs from the WI group displayed higher protein carbonyls, 3-nitrotyrosine, PAR, lactate dehydrogenase and proteins in bronchoalveolar lavage, lung weight gain, perivascular edema, as well as reduced static compliance, but similar oxygenation. All these alterations were markedly attenuated by 3-AB and MnTBAP., Conclusions: After EVLP, lungs obtained after WI exhibit oxidative stress, PARP activation, and tissue injury, which are suppressed by pharmacological inhibitors of ROS/RNS and PARP.

Spontaneous esophageal perforation (Boerhaave's syndrome) is an uncommon and challenging condition with significant morbidity and mortality. Surgical treatment is indicated in the large majority of cases and different procedures have been described in this respect. We present the results of a mono-institutional evaluation of the management of spontaneous esophageal perforation over a 20-year period. The charts of 25 patients with spontaneous esophageal perforation treated at the Surgical Department of the University Hospital of Lausanne were retrospectively studied. In the 25 patients, 24 patients were surgically treated and one was managed with conservative treatment. Primary buttressed esophageal repair was performed in 23 cases. Nine postoperative complications were recorded, and the overall mortality was 32%. Despite prompt treatment postoperative morbidity and mortality are still relevant. Early diagnosis and definitive surgical management are the keys for successful outcome in the management of spontaneous esophageal perforation. Primary suture with buttressing should be considered as the procedure of choice. Conservative approach may be applied in very selected cases.

Extracorporeal assistances are exponentially used for patients, with acute severe but reversible heart or lung failure, to provide more prolonged support to bridge patients to heart and/or lung transplantation. However, experience of use of extracorporeal assistance for pulmonary resection is limited outside lung transplantation. Airways management with standard mechanical ventilation system may be challenging particularly in case of anatomical reasons (single lung), presence of respiratory failure (ARDS), or complex tracheo-bronchial resection and reconstruction. Based on the growing experience during lung transplantation, more and more surgeons are now using such devices to achieve good oxygenation and hemodynamic support during such challenging cases. We review the different extracorporeal device and attempt to clarify the current practice and indications of extracorporeal support during pulmonary resection.

Background: Pulmonary metastasectomy is increasingly performed in selected patients by video-assisted thoracic surgery (VATS) on the base of thin-slice high-resolution CT-Scan (HRCT). This study determines the overall survival and ipsilateral recurrence rate and of patients undergoing after VATS lung metastasectomy., Patients and Method: Retrospective single institution study of all patients who underwent VATS pulmonary metastasectomy on the base of HRCT with curative intent between 2005 and 2014., Results: Seventy-seven patients (41 males, 36 females) underwent VATS pulmonary metastasectomy for solitary (n = 63) or multiple (n = 14) lung metastases in the context of colorectal carcinoma (n = 26), sarcoma (n = 17), melanoma (n = 16), or other primaries (n = 18). Nine patients had bilateral lung metastases and underwent synchronous (n = 4) or sequential (n = 5) VATS resections. Preoperative CT-guided hook wire localization of the lesions was performed in 65 patients (84 %). The postoperative mortality and morbidity rates were 0 and 5.2 %, respectively. During a mean follow-up time of 24 months (range 1–120 months), tumor progression occurred in 46 patients. Twenty-three patients (30 %) had pulmonary recurrence only, of them, eight patients (10 %) in the operated lungs. Seven of eight patients with recurrence in the operated lungs underwent a second metastasectomy by VATS (n = 5) or thoracotomy (n = 2). The overall 5-year survival rate was 54 % and without difference between patients without tumor recurrence and those with pulmonary recurrence treated by re-metastasectomy., Conclusion: Ipsilateral recurrence remains low after VATS pulmonary metastasectomy guided by preoperative HRCT and can be efficiently treated by re-metastasectomy.

Background: Video-assisted thoracic surgery (VATS) is currently performed to diagnose and treat solitary pulmonary nodules (SPN). However, the intra-operative identification of deep nodules can be challenging with VATS as the lung is difficult to palpate. The aim of the study was to report the utility and the results of pre-operative computed tomography (CT)-guided hook wire localization of SPN., Methods: All records of the patients undergoing CT-guided hook wire localization prior to VATS resection for SPN between 2002 and 2013 were reviewed. The efficacy in localizing the nodule, hook wire complications, necessity to convert VATS to thoracotomy and the histology of SPN are reported., Results: One hundred eighty-one patients (90 females, mean age 63 y, range 28-82 y) underwent 187 pulmonary resections after CT-guided hook wire localization. The mean SPN diameter was 10.3 mm (range: 4-29 mm). The mean distance of the lesion from the pleural surface was 11.6 mm (range: 0-45 mm). The mean time interval from hook wire insertion to VATS resection was 224 min (range 54-622 min). Hook wire complications included pneumothorax requiring chest tube drainage in 4 patients (2.1%) and mild parenchymal haemorrhage in 11 (5.9%) patients. Migration of the hook wire occurred in 7 patients (3.7%) although it did not affect the success of VATS resection (nodule location guided by the lung puncture site). Three patients underwent additional wedge resection by VATS during the same procedure because no lesion was identified in the surgical specimen. Conversion thoracotomy was required in 13 patients (7 %) for centrally localized lesions (6 patients) and pleural adhesions (7 patients). The mean operative time was 60 min (range 18-135 min). Pathological examination revealed a malignant lesion in 107 patients (59 %). The diagnostic yield was 98.3 %., Conclusion: VATS resection for SPN after CT-guided hook wire localization for SPN is safe and allows for proper diagnosis with a low thoracotomy conversion rate.

Background: Low-dose, Visudyne®-mediated photodynamic therapy (photo-induction) was shown to selectively enhance tumor vessel transport causing increased uptake of systemically administered chemotherapy in various tumor types grown on rodent lungs. The present experiments explore the efficacy of photo-induced vessel modulation combined to intravenous (IV) liposomal cisplatin (Lipoplatin®) on rodent lung tumors and the feasibility/toxicity of this approach in porcine chest cavities., Material and Methods: Three groups of Fischer rats underwent orthotopic sarcoma (n = 14), mesothelioma (n = 14), or adenocarcinoma (n = 12) implantation on the left lung. Half of the animals of each group had photo-induction (0.0625 mg/kg Visudyne®, 10 J/cm(2) ) followed by IV administration of Lipoplatin® (5 mg/kg) and the other half received Lipoplatin® without photo-induction. Then, two groups of minipigs underwent intrapleural thoracoscopic (VATS) photo-induction (0.0625 mg/kg Visudyne®; 30 J/cm(2) hilum; 10 J/cm(2) apex/diaphragm) with in situ light dosimetry in combination with IV Lipoplatin® administration (5 mg/kg). Protocol I (n = 6) received Lipoplatin® immediately after light delivery and Protocol II (n = 9) 90 minutes before light delivery. Three additional animals received Lipoplatin® and VATS pleural biopsies but no photo-induction (controls). Lipoplatin® concentrations were analyzed in blood and tissues before and at regular intervals after photo-induction using inductively coupled plasma mass spectrometry., Results: Photo-induction selectively increased Lipoplatin® uptake in all orthotopic tumors. It significantly increased the ratio of tumor to lung Lipoplatin® concentration in sarcoma (P = 0.0008) and adenocarcinoma (P = 0.01) but not in mesothelioma, compared to IV drug application alone. In minipigs, intrapleural photo-induction combined to systemic Lipoplatin® was well tolerated with no toxicity at 7 days for both treatment protocols. The pleural Lipoplatin® concentrations were not significantly different at 10 and 30 J/cm(2) locations but they were significantly higher in protocol I compared to II (2.37 ± 0.7 vs. 1.37 ± 0.7 ng/mg, P  < 0.001)., Conclusion: Visudyne®-mediated photo-induction selectively enhances the uptake of IV administered Lipoplatin® in rodent lung tumors. Intrapleural VATS photo-induction with identical treatment conditions combined to IV Lipoplatin chemotherapy is feasible and well tolerated in a porcine model. Lasers Surg. Med. 47:807-816, 2015. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Background: One of the standard options in the treatment of stage IIIA/N2 non-small-cell lung cancer is neoadjuvant chemotherapy and surgery. We did a randomised trial to investigate whether the addition of neoadjuvant radiotherapy improves outcomes., Methods: We enrolled patients in 23 centres in Switzerland, Germany and Serbia. Eligible patients had pathologically proven, stage IIIA/N2 non-small-cell lung cancer and were randomly assigned to treatment groups in a 1:1 ratio. Those in the chemoradiotherapy group received three cycles of neoadjuvant chemotherapy (100 mg/m(2) cisplatin and 85 mg/m(2) docetaxel) followed by radiotherapy with 44 Gy in 22 fractions over 3 weeks, and those in the control group received neoadjuvant chemotherapy alone. All patients were scheduled to undergo surgery. Randomisation was stratified by centre, mediastinal bulk (less than 5 cm vs 5 cm or more), and weight loss (5% or more vs less than 5% in the previous 6 months). The primary endpoint was event-free survival. Analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00030771., Findings: From 2001 to 2012, 232 patients were enrolled, of whom 117 were allocated to the chemoradiotherapy group and 115 to the chemotherapy group. Median event-free survival was similar in the two groups at 12·8 months (95% CI 9·7-22·9) in the chemoradiotherapy group and 11·6 months (8·4-15·2) in the chemotherapy group (p=0·67). Median overall survival was 37·1 months (95% CI 22·6-50·0) with radiotherapy, compared with 26·2 months (19·9-52·1) in the control group. Chemotherapy-related toxic effects were reported in most patients, but 91% of patients completed three cycles of chemotherapy. Radiotherapy-induced grade 3 dysphagia was seen in seven (7%) patients. Three patients died in the control group within 30 days after surgery., Interpretation: Radiotherapy did not add any benefit to induction chemotherapy followed by surgery. We suggest that one definitive local treatment modality combined with neoadjuvant chemotherapy is adequate to treat resectable stage IIIA/N2 non-small-cell lung cancer., Funding: Swiss State Secretariat for Education, Research and Innovation (SERI), Swiss Cancer League, and Sanofi., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Due to the underlying diseases and the need for immunosuppression, patients after lung transplantation are particularly at risk for gastrointestinal (GI) complications that may negatively influence long-term outcome. The present study assessed the incidences and impact of GI complications after lung transplantation and aimed to identify risk factors., Methods: Retrospective analysis of all 227 consecutively performed single- and double-lung transplantations at the University hospitals of Lausanne and Geneva was performed between January 1993 and December 2010. Logistic regressions were used to test the effect of potentially influencing variables on the binary outcomes overall, severe, and surgery-requiring complications, followed by a multiple logistic regression model., Results: Final analysis included 205 patients for the purpose of the present study, and 22 patients were excluded due to re-transplantation, multiorgan transplantation, or incomplete datasets. GI complications were observed in 127 patients (62%). Gastro-esophageal reflux disease was the most commonly observed complication (22.9%), followed by inflammatory or infectious colitis (20.5%) and gastroparesis (10.7%). Major GI complications (Dindo/Clavien III-V) were observed in 83 (40.5%) patients and were fatal in 4 patients (2.0%). Multivariate analysis identified double-lung transplantation (p = 0.012) and early (1993-1998) transplantation period (p = 0.008) as independent risk factors for developing major GI complications. Forty-three (21%) patients required surgery such as colectomy, cholecystectomy, and fundoplication in 6.8, 6.3, and 3.9% of the patients, respectively. Multivariate analysis identified Charlson comorbidity index of ≥3 as an independent risk factor for developing GI complications requiring surgery (p = 0.015)., Conclusion: GI complications after lung transplantation are common. Outcome was rather encouraging in the setting of our transplant center.

Video-assisted thoracoscopic surgery (VATS) is currently a routinely performed procedure for the management of early non small cell lung cancer. The oncological results of VATS in terms of local recurrence and overall survival are equivalent or superior to those of conventional thoracotomy with lower morbidity and hospital stay. In the field of pulmonary metastasectomy, current guidelines support a thoracotomy approach in order to properly palpate the lung and detect nodules too small to be identified on standard radiological examinations (typically less than 5mm in diameter). However, the oncological and clinical significance of these millimetric nodules is not known. This has led some thoracic surgeons to rethink the approach of solitary pulmonary metastasectomy: because of improvements in thin slice helical CT-scans, some support a VATS approach for solitary pulmonary nodules without formal bimanual palpation and suggest this allows equivalent oncological results and decreased surgical morbidity., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: The pre-conditioning of tumor vessels by low-dose photodynamic therapy (L-PDT) was shown to enhance the distribution of chemotherapy in different tumor types. However, how light dose affects drug distribution and tumor response is unknown. Here we determined the effect of L-PDT fluence on vascular transport in human mesothelioma xenografts. The best L-PDT conditions regarding drug transport were then combined with Lipoplatin(®) to determine tumor response., Methods: Nude mice bearing dorsal skinfold chambers were implanted with H-Meso1 cells. Tumors were treated by Visudyne(®) -mediated photodynamic therapy with 100 mW/cm(2) fluence rate and a variable fluence (5, 10, 30, and 50 J/cm(2) ). FITC-Dextran (FITC-D) distribution was assessed in real time in tumor and normal tissues. Tumor response was then determined with best L-PDT conditions combined to Lipoplatin(®) and compared to controls in luciferase expressing H-Meso1 tumors by size and whole body bioluminescence assessment (n = 7/group)., Results: Tumor uptake of FITC-D following L-PDT was significantly enhanced by 10-fold in the 10 J/cm(2) but not in the 5, 30, and 50 J/cm(2) groups compared to controls. Normal surrounding tissue uptake of FITC-D following L-PDT was significantly enhanced in the 30 J/cm(2) and 50 J/cm(2) groups compared to controls. Altogether, the FITC-D tumor to normal tissue ratio was significantly higher in the 10 J/cm(2) group compared others. Tumor growth was significantly delayed in animals treated by 10 J/cm2-L-PDT combined to Lipoplatin(®) compared to controls., Conclusions: Fluence of L-PDT is critical for the optimal distribution and effect of subsequently administered chemotherapy. These findings have an importance for the clinical translation of the vascular L-PDT concept in the clinics., (© 2015 Wiley Periodicals, Inc.)

Background: Infected postpneumonectomy chest cavities may be related to chronic postpneumonectomy empyema or arise in rare situations of necrotizing pneumonia with complete lung destruction where pneumonectomy and pleural debridement are required. We evaluated the safety and efficacy of an intrathoracic vacuum-assisted closure device (VAC) for the treatment of infected postpneumonectomy chest cavities., Method: A retrospective single institution review of all patients with infected postpneumonectomy chest cavities treated by VAC between 2005 and 2013. Patients underwent surgical debridement of the thoracic cavity, muscle flap closure of the bronchial stump when a fistula was present, and repeated intrathoracic VAC dressings until granulation tissue covered the entire chest cavity. After this, the cavity was obliterated by a Clagett procedure and closed., Results: Twenty-one patients (14 men and 7 women) underwent VAC treatment of their infected postpneumonectomy chest cavity. Twelve patients presented with a chronic postpneumonectomy empyema (10 of them with a bronchopleural fistula) and 9 patients with an empyema occurring in the context of necrotizing pneumonia treated by pneumonectomy. In-hospital mortality was 23%. The median duration of VAC therapy was 23 days (range, 4-61 days) and the median number of VAC changes per patient was 6 (range, 2-14 days). Infection control and successful chest cavity closure was achieved in all surviving patients. One adverse VAC treatment-related event was identified (5%)., Conclusions: The intrathoracic VAC application is a safe and efficient treatment of infected postpneumonectomy chest cavities and allows the preservation of chest wall integrity., (Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Lung volume reduction with valves is increasingly used to treat selected patients with severe emphysema. The indications for this procedure have been previously described; however, its contraindications have not yet been conclusively established. This case highlights the potentially severe complications of endobronchial one-way valve placement in the setting of a previous pleurodesis., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Most cases of emphysema are managed conservatively. However, in severe symptomatic emphysema associated with hyperinflation, lung volume reduction (LVR) may be proposed to improve dyspnea, exercice capacity, pulmonary functions, walk distance and to decrease long-term mortality. LVR may be achieved either surgically (LVRS) or endoscopically (EVLR by valves or coils) according to specific clinical criteria. Currently, the optimal approach is discussed in a multidisciplinary setting. The latter permits a personalized evaluation the patient's clinical status and allows the best possible therapeutic intervention to be proposed to the patient.

Introduction: Solid tumors are known to have an abnormal vasculature that limits the distribution of chemotherapy. We have recently shown that tumor vessel modulation by low-dose photodynamic therapy (L-PDT) could improve the uptake of macromolecular chemotherapeutic agents such as liposomal doxorubicin (Liporubicin) administered subsequently. However, how this occurs is unknown. Convection, the main mechanism for drug transport between the intravascular and extravascular spaces, is mostly related to interstitial fluid pressure (IFP) and tumor blood flow (TBF). Here, we determined the changes of tumor and surrounding lung IFP and TBF before, during, and after vascular L-PDT. We also evaluated the effect of these changes on the distribution of Liporubicin administered intravenously (IV) in a lung sarcoma metastasis model., Materials and Methods: A syngeneic methylcholanthrene-induced sarcoma cell line was implanted subpleurally in the lung of Fischer rats. Tumor/surrounding lung IFP and TBF changes induced by L-PDT were determined using the wick-in-needle technique and laser Doppler flowmetry, respectively. The spatial distribution of Liporubicin in tumor and lung tissues following IV drug administration was then assessed in L-PDT-pretreated animals and controls (no L-PDT) by epifluorescence microscopy., Results: L-PDT significantly decreased tumor but not lung IFP compared to controls (no L-PDT) without affecting TBF. These conditions were associated with a significant improvement in Liporubicin distribution in tumor tissues compared to controls (P < .05)., Discussion: L-PDT specifically enhanced convection in blood vessels of tumor but not of normal lung tissue, which was associated with a significant improvement of Liporubicin distribution in tumors compared to controls., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Tracheobronchial aspergillosis is a rare entity mainly observed in immune-compromised patients or those who have undergone transplantation. It may cause airway ulcerations or bleeding. We report the case of a 17-year-old patient receiving chemotherapy for acute lymphoblastic leukemia who presented with right-sided tension pneumothorax. Chest tube drainage revealed a massive air leak without reexpansion of the lung, and bronchoscopy showed a 15- × 15-mm defect of the distal trachea related to aspergillosis infection. The defect was closed by an intrathoracic transposition of a pedicled latissimus dorsi muscle flap, which was sutured into the debrided defect followed by temporary endotracheal stenting and antifungal medication., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Sleeve lobectomy is a valid alternative to pneumonectomy for the treatment of centrally located operable non-small cell lung cancer (NSCLC), but concern has been evoked regarding a potentially increased risk of bronchial anastomosis complications after induction therapy. This study examined the impact of induction therapy on airway healing after sleeve lobectomy for NSCLC., Methods: Bronchial anastomosis complications were recorded with respect to the induction regimen applied (neoadjuvant chemotherapy vs chemoradiotherapy) in a consecutive series of patients with sleeve lobectomy for NSCLC., Results: Ninety-nine patients underwent sleeve resection, 28 of them after induction therapy. Twelve patients received chemotherapy alone, and 16 patients had radiochemotherapy. There were no significant differences in postoperative 90-day mortality (3.6% vs 2.8%) and morbidity (54% vs 49%) for patients with and without induction therapy. Bronchial anastomosis complications occurred in 3 patients (10.8%) with neoadjuvant therapy and in 2 (2.8%) without (p = 0.3). In the induction therapy group, two bronchial stenoses occurred after radiochemotherapy and one bronchopleural fistula after chemotherapy alone. In patients without induction therapy, one bronchial stenosis and one bronchopleural fistula were observed. All bronchial stenoses were successfully treated by dilatation, and both bronchopleural fistulas occurring after right lower lobectomy were successfully treated by reoperation and completion sleeve bilobectomy with preservation of the upper lobe., Conclusions: Sleeve lobectomy for NSCLC can be safely performed after induction chemotherapy and radiochemotherapy with mortality and incidence of airway complications similar to that observed in nonpretreated patients. The treatment of airway complications does not differ for patients with and without induction therapy., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)