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Grading lung squamous cell carcinoma (LUSC) is controversial and not universally accepted. The histomorphologic feature of tumor budding (TB) is an established independent prognostic factor in colorectal cancer, and its importance is growing in other solid cancers, making it a candidate for inclusion in tumor grading schemes. We aimed to compare TB between preoperative biopsies and resection specimens in pulmonary squamous cell carcinoma and assess interobserver variability. A retrospective cohort of 249 consecutive patients primarily resected with LUSC in Bern (2000-2013, n = 136) and Lausanne (2005-2020, n = 113) with available preoperative biopsies was analyzed for TB and additional histomorphologic parameters, such as spread through airspaces and desmoplasia, by 2 expert pathologists (M.M., C.N.). Results were correlated with clinicopathologic parameters and survival. In resection specimens, peritumoral budding (PTB) score was low (0-4 buds/0.785 mm2) in 47.6%, intermediate (5-9 buds/0.785 mm2) in 27.4%, and high (≥10 buds/0.785 mm2) in 25% of cases (median bud count, 5; IQR, 0-26). Both the absolute number of buds and TB score were similar when comparing tumor edge and intratumoral zone (P = .192) but significantly different from the score obtained in the biopsy (P < .001). Interobserver variability was moderate, regardless of score location (Cohen kappa, 0.59). The discrepant cases were reassessed, and consensus was reached in all cases with identification of causes of discordance. TB score was significantly associated with stage (P = .002), presence of lymph node (P = .033), and distant metastases (P = .020), without significant correlation with overall survival, tumor size, or pleural invasion. Desmoplasia was significantly associated with higher PTB (P < .001). Spread through airspaces was present in 34% and associated with lower PTB (P < .001). To conclude, despite confirming TB as a reproducible factor in LUSC, we disclose areas of scoring ambiguity. Preoperative biopsy evaluation was insufficient in establishing the final TB score of the resected tumor.
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Since the late 1990s, and Henrik Kehlet's hypothesis that a reduction of the body's stress response to major surgeries could decrease postoperative morbidity, "Enhanced Recovery After Surgery" (ERAS) care pathways have been streamlined. They are now well accepted and considered standard in many surgical disciplines. Yet, to this day, there is no specific ERAS protocol for chest wall resections (CWRs), the removal of a full-thickness portion of the chest wall, including muscle, bone and possibly skin. This is most unfortunate because these are high-risk surgeries, which carry high morbidity rates. In this review, we propose an overview of the current key elements of the ERAS guidelines for thoracic surgery that might apply to CWRs. A successful ERAS pathway for CWR patients would entail, as is the standard approach, three parts: pre-, peri- and postoperative elements. Preoperative items would include specific information, targeted patient education, involvement of all members of the team, including the plastic surgeons, smoking cessation, dedicated nutrition and carbohydrate loading. Perioperative items would likely be standard for thoracotomy patients, namely carefully selective pre-anesthesia sedative medication only in some rare instances, low-molecular-weight heparin throughout, antibiotic prophylaxis, minimization of postoperative nausea and vomiting, avoidance of fluid overload and of urinary drainage. Postoperative elements would include early mobilization and feeding, swift discontinuation of intravenous fluid supply and chest tube removal as soon as safe. Optimal pain management throughout also appears to be critical to minimize the risk of respiratory complications. Together, all these items are achievable and may hold the key to successful introduction of ERAS pathways to the benefit of CWR patients.
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Objective: Malignant pleural mesothelioma is a fatal disease and a clinical challenge, as few effective treatment modalities are available. Previous evidence links the gut microbiome to the host immunoreactivity to tumors. We thus evaluated the impact of a novel microbiome modulator compound (MMC) on the gut microbiota composition, tumor immune microenvironment, and cancer control in a model of malignant pleural mesothelioma. Methods: Age- and weight-matched immunocompetent (n = 23) or athymic BALB/c mice (n = 15) were randomly assigned to MMC or no treatment (control) groups. MMC (31 ppm) was administered through the drinking water 14 days before AB12 malignant mesothelioma cell inoculation into the pleural cavity. The impact of MMC on tumor growth, animal survival, tumor-infiltrating leucocytes, gut microbiome, and fecal metabolome was evaluated and compared with those of control animals. Results: The MMC delayed tumor growth and significantly prolonged the survival of immunocompetent animals (P = .0015) but not that of athymic mice. The improved tumor control in immunocompetent mice correlated with increased infiltration of CD3+CD8+GRZB+ cytotoxic T lymphocytes in tumors. Gut microbiota analyses indicated an enrichment in producers of short chain fatty acids in MMC-treated animals. Finally, we observed a positive correlation between the level of fecal short chain fatty acids and abundance of tumor-infiltrating cytotoxic T cells in malignant pleural mesothelioma. Conclusions: MMC administration boosts antitumor immunity, which correlates with a change in gut microbiome and metabolome. MMC may represent a valuable treatment option to combine with immunotherapy in patients with cancer.
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Introduction: The pulmonary endothelium is the primary target of lung ischemia-reperfusion injury leading to primary graft dysfunction after lung transplantation. We hypothesized that treating damaged rat lungs by a transient heat stress during ex-vivo lung perfusion (EVLP) to elicit a pulmonary heat shock response could protect the endothelium from severe reperfusion injury. Methods: Rat lungs damaged by 1h warm ischemia were reperfused on an EVLP platform for up to 6h at a constant temperature (T°) of 37°C (EVLP37°C group), or following a transient heat stress (HS) at 41.5°C from 1 to 1.5h of EVLP (EVLPHS group). A group of lungs exposed to 1h EVLP only (pre-heating conditions) was added as control (Baseline group). In a first protocol, we measured lung heat sock protein expression (HSP70, HSP27 and Hsc70) at selected time-points (n=5/group at each time). In a second protocol, we determined (n=5/group) lung weight gain (edema), pulmonary compliance, oxygenation capacity, pulmonary artery pressure (PAP) and vascular resistance (PVR), the expression of PECAM-1 (CD31) and phosphorylation status of Src-kinase and VE-cadherin in lung tissue, as well as the release in perfusate of cytokines (TNFα, IL-1ß) and endothelial biomarkers (sPECAM, von Willebrand Factor -vWF-, sE-selectin and sICAM-1). Histological and immunofluorescent studies assessed perivascular edema and formation of 3-nitrotyrosine (a marker of peroxinitrite) in CD31 lung endothelium. Results: HS induced an early (3h) and persisting expression of HSP70 and HSP27, without influencing Hsc70. Lungs from the EVLP37°C group developed massive edema, low compliance and oxygenation, elevated PAP and PVR, substantial release of TNFα, IL-1ß, s-PECAM, vWF, E-selectin and s-ICAM, as well as significant Src-kinase activation, VE-cadherin phosphorylation, endothelial 3-NT formation and reduced CD31 expression. In marked contrast, all these alterations were either abrogated or significantly attenuated by HS treatment. Conclusion: The therapeutic application of a transient heat stress during EVLP of damaged rat lungs reduces endothelial permeability, attenuates pulmonary vasoconstriction, prevents src-kinase activation and VE-cadherin phosphorylation, while reducing endothelial peroxinitrite generation and the release of cytokines and endothelial biomarkers. Collectively, these data demonstrate that therapeutic heat stress may represent a promising strategy to protect the lung endothelium from severe reperfusion injury.
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Resposta ao Choque Térmico , Pulmão , Perfusão , Animais , Pulmão/patologia , Pulmão/metabolismo , Ratos , Masculino , Perfusão/métodos , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/prevenção & controle , Transplante de Pulmão/efeitos adversos , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismoRESUMO
Lung cancer is responsible for one in five cancer-related deaths. Screening for lung cancer using low-dose chest CT (LDCT) is supported by several international studies targeting the at-risk population as part of an organised programme. Given the organisational challenges for the healthcare systems of the countries concerned, this involves setting up pilot screening projects. This requires close collaboration between the players involved, with a multidisciplinary approach structured around the participant, aiming to offer the expertise of the pulmonologist and the radiologist on the LDCT performed, interpreted with the help of artificial intelligence. Here we set out the elements needed to develop a screening programme, starting with the implementation of a pilot project.
Le cancer pulmonaire est responsable d'un décès lié au cancer sur cinq. Le dépistage du cancer pulmonaire par le scanner thoracique à faible dose (LDCT) est soutenu par plusieurs études internationales ciblant la population à risque dans le cadre d'un programme organisé. Vu les enjeux organisationnels pour le système de santé des pays concernés, cela passe par la mise en place de projets pilotes de dépistage. Cela requiert une collaboration étroite entre les différents acteurs, avec une approche multidisciplinaire structurée autour du participant visant à offrir l'expertise du pneumologue et du radiologue sur le LDCT effectué, interprété avec l'aide de l'intelligence artificielle. Nous exposons ici les éléments nécessaires à l'élaboration d'un programme de dépistage, en passant d'abord par la mise en place d'un projet pilote.
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Detecção Precoce de Câncer , Neoplasias Pulmonares , Humanos , Programas de Rastreamento , Projetos Piloto , Suíça/epidemiologia , Inteligência Artificial , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/epidemiologiaRESUMO
Ex vivo lung perfusion (EVLP) may serve as a platform for the pharmacologic repair of lung grafts before transplantation (LTx). We hypothesized that EVLP could also permit nonpharmacologic repair through the induction of a heat shock response, which confers stress adaptation via the expression of heat shock proteins (HSPs). Therefore, we evaluated whether transient heat application during EVLP (thermal preconditioning [TP]) might recondition damaged lungs before LTx. TP was performed during EVLP (3 hours) of rat lungs damaged by warm ischemia by transiently heating (30 minutes, 41.5 °C) the EVLP perfusate, followed by LTx (2 hours) reperfusion. We also assessed the TP (30 minutes, 42 °C) during EVLP (4 hours) of swine lungs damaged by prolonged cold ischemia. In rat lungs, TP induced HSP expression, reduced nuclear factor κB and inflammasome activity, oxidative stress, epithelial injury, inflammatory cytokines, necroptotic death signaling, and the expression of genes involved in innate immune and cell death pathways. After LTx, heated lungs displayed reduced inflammation, edema, histologic damage, improved compliance, and unchanged oxygenation. In pig lungs, TP induced HSP expression, reduced oxidative stress, inflammation, epithelial damage, vascular resistance, and ameliorated compliance. Collectively, these data indicate that transient heat application during EVLP promotes significant reconditioning of damaged lungs and improves their outcomes after transplantation.
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Transplante de Pulmão , Ratos , Suínos , Animais , Pulmão , Reperfusão , Resposta ao Choque Térmico , Inflamação/patologia , PerfusãoRESUMO
OBJECTIVES: The aim of this study was to compare short-term outcomes and local control in pT1c pN0 non-small-cell lung cancer that were intentionally treated by video-assisted thoracoscopic surgery (VATS) lobectomy or segmentectomy. METHODS: Multicentre retrospective study of consecutive patients undergoing VATS lobectomy (VL) or VATS segmentectomy (VS) for pT1c pN0 non-small-cell lung cancer from January 2014 to October 2021. Patients' characteristics, postoperative outcomes and survival were compared. RESULTS: In total, 162 patients underwent VL (n = 81) or VS (n = 81). Except for age [median (interquartile range) 68 (60-73) vs 71 (65-76) years; P = 0.034] and past medical history of cancer (32% vs 48%; P = 0.038), there was no difference between VL and VS in terms of demographics and comorbidities. Overall 30-day postoperative morbidity was similar in both groups (34% vs 30%; P = 0.5). The median time for chest tube removal [3 (1-5) vs 2 (1-3) days; P = 0.002] and median postoperative length of stay [6 (4-9) vs 5 (3-7) days; P = 0.039] were in favour of the VS group. Significantly larger tumour size (mean ± standard deviation 25.1 ± 3.1 vs 23.6 ± 3.1 mm; P = 0.001) and an increased number of lymph nodes removal [median (interquartile range) 14 (9-23) vs 10 (6-15); P < 0.001] were found in the VL group. During the follow-up [median (interquartile range) 31 (14-48) months], no statistical difference was found for local and distant recurrence in VL groups (12.3%) and VS group (6.1%) (P = 0.183). Overall survival (80% vs 80%) was comparable between both groups (P = 0.166). CONCLUSIONS: Despite a short follow-up, our preliminary data shows that local control is comparable for VL and VS.
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Primary ciliary dyskinesia, with or without situs abnormalities, is a rare lung disease that can lead to an irreversible lung damage that may progress to respiratory failure. Lung transplant can be considered in end-stage disease. This study describes the outcomes of the largest lung transplant population for PCD and for PCD with situs abnormalities, also identified as Kartagener's syndrome. Retrospectively collected data of 36 patients who underwent lung transplantation for PCD from 1995 to 2020 with or without SA as part of the European Society of Thoracic Surgeons Lung Transplantation Working Group on rare diseases. Primary outcomes of interest included survival and freedom from chronic lung allograft dysfunction. Secondary outcomes included primary graft dysfunction within 72 h and the rate of rejection ≥A2 within the first year. Among PCD recipients with and without SA, the mean overall and CLAD-free survival were 5.9 and 5.2 years with no significant differences between groups in terms of time to CLAD (HR: 0.92, 95% CI: 0.27-3.14, p = 0.894) or mortality (HR: 0.45, 95% CI: 0.14-1.43, p = 0.178). Postoperative rates of PGD were comparable between groups; rejection grades ≥A2 on first biopsy or within the first year was more common in patients with SA. This study provides a valuable insight on international practices of lung transplantation in patients with PCD. Lung transplantation is an acceptable treatment option in this population.
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Síndrome de Kartagener , Transplante de Pulmão , Humanos , Síndrome de Kartagener/cirurgia , Estudos Retrospectivos , Biópsia , Coleta de DadosRESUMO
We aimed to evaluate whether computed tomography (CT)-derived preoperative sarcopenia measures were associated with postoperative outcomes and survival after video-assisted thoracoscopic (VATS) anatomical pulmonary resection in patients with early-stage non-small cell lung cancer (NSCLC). We retrospectively reviewed all consecutive patients that underwent VATS anatomical pulmonary resection for NSCLC between 2012 and 2019. Skeletal muscle mass was measured at L3 vertebral level on preoperative CT or PET/CT scans to identify sarcopenic patients according to established threshold values. We compared postoperative outcomes and survival of sarcopenic vs. non-sarcopenic patients. A total of 401 patients underwent VATS anatomical pulmonary resection for NSCLC. Sarcopenia was identified in 92 patients (23%). Sarcopenic patients were predominantly males (75% vs. 25%; p < 0.001) and had a lower BMI (21.4 vs. 26.5 kg/m2; p < 0.001). The overall postoperative complication rate was significantly higher (53.2% vs. 39.2%; p = 0.017) in sarcopenic patients and the length of hospital stay was prolonged (8 vs. 6 days; p = 0.032). Two factors were associated with postoperative morbidity in multivariate analysis: BMI and American Society of Anesthesiologists score >2. Median overall survival was comparable between groups (41 vs. 46 months; p = 0.240). CT-derived sarcopenia appeared to have a small impact on early postoperative clinical outcomes, but no effect on overall survival after VATS anatomical lung resection for NSCLC.
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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.
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Pulmonary transplantation remains the ultimate therapeutic option for selected patients with an advanced pulmonary disease and terminal respiratory insufficiency when all other therapeutic options have been exhausted. The optimal time-frame to proceed to a first discussion and evaluation about lung transplantation may be difficult to determine. This article describes the pathway of a patient towards lung transplantation and summarizes the criteria, which may help to timely identify eligibility for this therapeutic modality. We will focus mainly on the 2021 update of the International Society for Heart and Lung Transplantation (ISHLT) recommendations for the selection of lung transplant candidates.
La transplantation pulmonaire reste l'ultime option thérapeutique pour des patients sélectionnés présentant une maladie pulmonaire avancée au stade d'insuffisance respiratoire terminale, une fois les autres traitements reconnus épuisés. Le moment idéal pour une première discussion et l'évaluation d'une transplantation pulmonaire peut être difficile à identifier. Cet article décrit le parcours d'un patient vers la transplantation pulmonaire et résume les différents facteurs qui permettent d'identifier son éligibilité pour ce traitement. Nous nous focalisons notamment sur les recommandations pour la sélection des receveurs de transplantation pulmonaire mises à jour en 2021 par l'International Society for Heart and Lung Transplantation (ISHLT).
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Transplante de Coração , Pneumopatias , Transplante de Pulmão , Humanos , Seleção de PacientesRESUMO
BACKGROUND: Persistent pain and disability following rib fractures result in a large psycho-socio-economic impact for health-care system. Benefits of rib osteosynthesis are well documented in patients with flail chest that necessitates invasive ventilation. In patients with uncomplicated and simple rib fractures, indication for rib osteosynthesis is not clear. The aim of this trial is to compare pain at 2 months after rib osteosynthesis versus medical therapy. METHODS: This trial is a pragmatic multicenter, randomized, superiority, controlled, two-arm, not-blinded, trial that compares pain evolution between rib fixation and standard pain medication versus standard pain medication alone in patients with uncomplicated rib fractures. The study takes place in three hospitals of Thoracic Surgery of Western Switzerland. Primary outcome is pain measured by the brief pain inventory (BPI) questionnaire at 2 months post-surgery. The study includes follow-up assessments at 1, 2, 3, 6, and 12 months after discharge. To be able to detect at least 2 point-difference on the BPI between both groups (standard deviation 2) with 90% power and two-sided 5% type I error, 46 patients per group are required. Adjusting for 10% drop-outs leads to 51 patients per group. DISCUSSION: Uncomplicated rib fractures have a significant medico-economic impact. Surgical treatment with rib fixation could result in better clinical recovery of patients with uncomplicated rib fractures. These improved outcomes could include less acute and chronic pain, improved pulmonary function and quality of life, and shorter return to work. Finally, surgical treatment could then result in less financial costs. TRIAL REGISTRATION: ClinicalTrials.gov NCT04745520 . Registered on 8 February 2021.
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Tórax Fundido , Fraturas das Costelas , Tórax Fundido/etiologia , Tórax Fundido/cirurgia , Fixação Interna de Fraturas/efeitos adversos , Fixação Interna de Fraturas/métodos , Humanos , Estudos Multicêntricos como Assunto , Dor , Ensaios Clínicos Pragmáticos como Assunto , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Fraturas das Costelas/complicações , Fraturas das Costelas/diagnóstico , Fraturas das Costelas/cirurgia , CostelasRESUMO
BACKGROUND: Survival predictors are not established for cystic fibrosis (CF) patients listed for lung transplantation (LT). Using the deficit accumulation approach, we developed a CF-specific frailty index (FI) to allow risk stratification for adverse waitlist and post-LT outcomes. METHODS: We studied adult CF patients listed for LT in the Toronto LT Program (development cohort 2005-2015) and the Swiss LT centres (validation cohort 2008-2017). Comorbidities, treatment, laboratory results and social support at listing were utilized to develop a lung disease severity index (LI deficits, d = 18), a frailty index (FI, d = 66) and a lifestyle/social vulnerability index (LSVI, d = 10). We evaluated associations of the indices with worsening waitlist status, hospital and ICU length of stay, survival and graft failure. RESULTS: We studied 188 (Toronto cohort, 176 [94%] transplanted) and 94 (Swiss cohort, 89 [95%] transplanted) patients. The median waitlist times were 69 and 284 days, respectively. The median follow-up post-transplant was 5.3 and 4.7 years. At listing, 44.7% of patients were frail (FI ≥ 0.25) in the Toronto and 21.3% in the Swiss cohort. The FI was significantly associated with all studied outcomes in the Toronto cohort (FI and post-LT mortality, multivariable HR 1.74 [95%CI:1.24-2.45] per 0.1 point of the FI). In the Swiss cohort, the FI was associated with worsening waitlist status, post-LT mortality and graft failure. CONCLUSIONS: In CF patients listed for LT, FI risk stratification was significantly associated with waitlist and post-LT outcomes. Studying frailty in young populations with advanced disease can provide insights on how frailty and deficit accumulation impacts survival.
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Fibrose Cística , Fragilidade , Transplante de Pulmão , Adulto , Humanos , Fragilidade/complicações , Fibrose Cística/complicações , Fibrose Cística/cirurgia , Listas de Espera , Estudos de CoortesRESUMO
Background: Video-assisted thoracic surgery (VATS) is now the preferred approach for standard anatomical pulmonary resections. This study evaluates the impact of operative time (OT) on post-operative outcomes after VATS anatomical pulmonary resection for non-small cell lung cancer (NSCLC). Methods: We retrospectively reviewed all consecutive patients undergoing VATS lobectomy or segmentectomy for NSCLC between November 2010 and December 2019. Postoperative outcomes were compared between short (<150 minutes) and long (≥150 minutes) OT groups. A multivariable analysis was performed to identify predictors of long OT and overall post-operative complications. Results: A total of 670 patients underwent lobectomy (n=496, 74%) or segmentectomy (n=174, 26%) for NSCLC. Mediastinal lymph node dissection was performed in 621 patients (92.7%). The median OT was 141 minutes (SD: 47 minutes) and 387 patients (57.8%) were operated within 150 minutes. Neoadjuvant chemotherapy was given in 25 patients (3.7%). Conversion thoracotomy was realized in 40 patients (6%). Shorter OT was significantly associated with decreased post-operative overall complication rate (30% vs. 41%; P=0.003), shorter median length of drainage (3 vs. 4 days; P<0.001) and shorter median length of hospital stay (6 vs. 7 days; P<0.001). On multivariable analysis, long OT (≥150 minutes) (OR 1.64, P=0.006), ASA score >2 (OR 1.87, P=0.001), FEV1 <80% (OR 1.47, P=0.046) and DLCO <80% (OR 1.5, P=0.045) were significantly associated with postoperative complications. Two predictors of long OT were identified: neoadjuvant chemotherapy (OR 3.11, P=0.01) and lobectomy (OR 1.5, P=0.032). Conclusions: A prolonged OT is significantly associated with postoperative complications in our collective of patients undergoing VATS anatomical pulmonary resection.
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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) cm2 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 cm2) 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 cm2 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.
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OBJECTIVE: Surgical treatment of locally advanced non-small cell lung cancer including single or multilevel N2 remains a matter of debate. Several trials demonstrate that selected patients benefit from surgery if R0 resection is achieved. We aimed to assess resectability and outcome of patients with locally advanced clinical T3/T4 (American Joint Committee on Cancer 8th edition) tumors after induction treatment followed by surgery in a pooled analysis of 3 prospective multicenter trials. METHODS: A total of 197 patients with T3/T4 non-small cell lung cancer of 368 patients with stage III non-small cell lung cancer enrolled in the Swiss Group for Clinical Cancer Research 16/96, 16/00, 16/01 trials were treated with induction chemotherapy or chemoradiation therapy followed by surgery, including extended resections. Univariable and multivariable analyses were applied for analysis of outcome parameters. RESULTS: Patients' median age was 60 years, and 67% were male. A total of 38 of 197 patients were not resected for technical (81%) or medical (19%) reasons. A total of 159 resections including 36 extended resections were performed with an 80% R0 and 13.2% pathological complete response rate. The 30- and 90-day mortality were 3% and 7%, respectively, without a difference for extended resections. Morbidity was 32% with the majority (70%) of minor grading complications. The 3-, 5-, and 10-year overall survivals for extended resections were 61% (95% confidence interval, 43-75), 44% (95% confidence interval, 27-59), and 29.5% (95% confidence interval, 13-48), respectively. R0 resection was associated with improved overall survival (hazard ratio, 0.41; P < .001), but pretreatment N2 extension (177/197) showed no impact on overall survival. CONCLUSIONS: Surgery after induction treatment for advanced T3/T4 stage including single and multiple pretreatment N2 disease resulted in 80% R0 resection rate and 7% 90-day mortality. Favorable overall survival for extended and not extended resection was demonstrated to be independent of pretreatment N status.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Estudos Prospectivos , Estadiamento de Neoplasias , Quimiorradioterapia , Resultado do Tratamento , Pneumonectomia/efeitos adversos , Pneumonectomia/métodosRESUMO
Background: Ex vivo lung perfusion (EVLP) may allow therapeutic reconditioning of damaged lung grafts before transplantation. This study aimed to develop relevant rat models of lung damage to study EVLP therapeutic reconditioning for possible translational applications. Methods: Lungs from 31 rats were exposed to cold ischemia (CI) or warm ischemia (WI), inflated at various oxygen fractions (FiO2), followed by 3 h EVLP. Five groups were studied as follow: (1) C21 (control): 3 h CI (FiO2 0.21); (2) C50: 3 h CI (FiO2 0.5); (3) W21: 1 h WI, followed by 2 h CI (FiO2 0.21); (4) W50: 1 h WI, followed by 2 h CI (FiO2 0.5); and (5) W2h: 2 h WI, followed by 1 h CI (FiO2 0.21). Following 3 h EVLP, we measured static pulmonary compliance (SPC), pulmonary vascular resistance, lung weight gain (edema), oxygenation capacity (differential partial pressure of oxygen), and protein carbonyls in lung tissue (oxidative stress), as well as lactate dehydrogenase (LDH, lung injury), nitrotyrosine (nitro-oxidative stress), interleukin-6 (IL-6, inflammation), and proteins (permeability edema) in bronchoalveolar lavage (BAL). Perivascular edema was quantified by histology. Results: No significant alterations were noted in C21 and C50 groups. W21 and W50 groups had reduced SPC and disclosed increased weight gain, BAL proteins, nitrotyrosine, and LDH. These changes were more severe in the W50 group, which also displayed greater oxidative stress. In contrast, both W21 and W50 showed comparable perivascular edema and BAL IL-6. In comparison with the other WI groups, W2h showed major weight gain, perivascular edema, SPC reduction, drop of differential partial pressure of oxygen, and massive increases of BAL LDH and proteins but comparable increase of IL-6 and biomarkers of oxidative stress. Conclusions: These models of lung damage of increasing severity might be helpful to evaluate new strategies for EVLP therapeutic reconditioning. A model combining 1 h WI and inflation at FiO2 of 0.5 seems best suited for this purpose by reproducing major alterations of clinical lung ischemia-reperfusion injury.
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Background: Lung cancer is the worldwide leading oncological cause of death in both genders combined and accounts for around 40-50% of brain metastases in general. In early-stage lung cancer, the incidence of brain metastases is around 3%. Since the early detection of asymptomatic cerebral metastases is of prognostic value, the aim of this study was to analyze the incidence of brain metastases in early-stage lung cancer and identify possible risk factors. Methods: We conducted a retrospective multicentric analysis of patients with Stage I (based on T and N stage only) Non-Small Cell Lung Cancer (NSCLC) who had received preoperative cerebral imaging in the form of contrast-enhanced CT or MRI. Patients with a history of NSCLC, synchronous malignancy, or neurological symptoms were excluded from the study. Analyzed variables were gender, age, tumor histology, cerebral imaging findings, smoking history, and tumor size. Results were expressed as mean with standard deviation or median with range. Results: In total, 577 patients were included in our study. Eight (1.4%) patients were found to have brain metastases in preoperative brain imaging. Tumor histology was adenocarcinoma in all eight cases. Patients were treated with radiotherapy (five), surgical resection (two), or both (one) prior to thoracic surgical treatment. Other than tumor histology, no statistically significant characteristics were found to be predictive of brain metastases. Conclusion: Given the low incidence of brain metastases in patients with clinical Stage I NSCLC, brain imaging in this cohort could be avoided.
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Repeated exposure to antigens via inhalation is the primary cause of hypersensitivity pneumonitis, a form of interstitial pneumonia. The chronic form of hypersensitivity pneumonitis leads to progressive loss of respiratory function; lung transplantation is the only therapeutic option for chronically ill patients. The ESTS Lung Transplantation Working Group conducted a retrospective multicentred cohort study to increase the body of knowledge available on this rare indication for lung transplantation. Data were collected for every patient who underwent lung transplant for hypersensitivity pneumonitis in participating centres between December 1996 and October 2019. Primary outcome was overall survival; secondary outcome was freedom from chronic lung allograft dysfunction. A total of 114 patients were enrolled from 9 centres. Almost 90% of patients were diagnosed with hypersensitivity pneumonitis before transplantation, yet the antigen responsible for the infection was identified in only 25% of cases. Eighty per cent of the recipients received induction therapy. Survival at 1, 3, and 5 years was 85%, 75%, and 70%, respectively. 85% of the patients who survived 90 days after transplantation were free from chronic lung allograft dysfunction after 3 years. The given study presents a large cohort of HP patients who underwent lung transplants. Overall survival rate is higher in transplanted hypersensitivity pneumonitis patients than in those suffering from any other interstitial lung diseases. Hypersensitivity pneumonitis patients are good candidates for lung transplantation.
Assuntos
Alveolite Alérgica Extrínseca , Doença Enxerto-Hospedeiro , Doenças Pulmonares Intersticiais , Transplante de Pulmão , Alveolite Alérgica Extrínseca/diagnóstico , Alveolite Alérgica Extrínseca/cirurgia , Biópsia , Estudos de Coortes , Humanos , Doenças Pulmonares Intersticiais/patologia , Estudos RetrospectivosRESUMO
OBJECTIVES: We assessed the accuracy of 3 validated lobectomy scoring systems to predict prolonged air leak (PAL) in patients undergoing video-assisted thoracoscopic surgery (VATS) segmentectomy. METHODS: We reviewed all consecutive patients who had a VATS segmentectomy between January 2016 and October 2020. We determined PALs on postoperative day 5. These findings were correlated with the calculated Brunelli (gender, age, body mass index [BMI], forced expiratory volume in 1 s < 80 and pleural adhesion), Epithor (gender, location, dyspnoea score, BMI, type of resection and pleural adhesion) and European Society of Thoracic Surgeons (ESTS) (gender, BMI and forced expiratory volume in 1 s) scores of each patient. RESULTS: A total of 453 patients (mean age: 66.5 years, female/male sex ratio: 226/227) underwent a VATS segmentectomy for malignant (n = 400) and non-malignant (n = 53) disease. Postoperative cardiopulmonary complications and in-hospital mortality rates were 19.6% and 0.4%, respectively. Median chest tube drainage duration and hospital stay were 2 (interquartile range: 1-4) and 4 (interquartile range: 3-7) days, respectively. On day 5, the prevalence of PAL was 14.1%. The ESTS, Brunelli and Epithor scores for the treated population were, respectively, class A (6.8%), class B (3.2%), class C (10.8%) and class D (28.2%); very low and low (0%), moderate (5%), high (6.3%) and very high (21%); and class A (7%), class B (13.2%), class C (24%) and class D (27.8%). All scores correlated with PAL (p ≤ 0.001). The areas under the receiver operating characteristic (ROC) curve were 0.686, 0.680 and 0.644, respectively. CONCLUSIONS: All 3 scoring systems were correlated with PAL > 5 days following the VATS segmentectomies. ESTS scores seem easier to introduce in clinical practice, but validation by a multicentre cohort is mandatory.