Human tracheal transplantation: A systematic review of case reports.

BACKGROUND: Patients with long-segment airway stenosis not amenable to conventional surgery may benefit from tracheal transplantation. However, this procedure has been only anecdotally reported, and its indications, techniques, and outcomes have not been extensively reviewed. METHODS: We conducted a systematic Literature search to identify all original articles reporting attempts at tracheal transplantation in humans. RESULTS: Of 699 articles found by the initial search, 11 were included in the systematic review, describing 14 cases of tracheal transplantation. Patients underwent transplantation for benign stenosis in nine cases, and for malignancies in five cases. In 12 cases blood supply to the trachea was provided by wrapping the graft in a vascularized recipient's tissue, while in 2 cases the trachea was directly transplanted as a vascularized composite allograft. The transplantation procedure was aborted before orthotopic transplantation in two patients. Among the remaining 12 patients, there was 1 operative mortality, while 4 patients experienced complications. Immunosuppressants drugs were administered to the majority of patients postoperatively, and only one group of authors attempted their withdrawal, in five patients. At the end of follow-up, all 11 patients surviving the operation were alive, but 2 had a recurrent tracheal stenosis requiring an airway appliance for breathing. CONCLUSION: Human tracheal transplantation is still at an embryonic phase. Studies available in the Literature report different surgical techniques, and information on long-term outcomes is still limited. Future research is needed in order to understand the clinical value of this procedure.

A prognostic score from a multicentric retrospective analysis of patients affected by sarcoma with metachronous lung metastases undergoing metastasectomy.

BACKGROUND: Despite the lack of evidence-based on prospective randomized studies, surgery has become the cornerstone of the treatment in patients with pulmonary oligometastatic sarcomas. Our study aimed to construct a composite prognostic score for metachronous oligometastatic sarcoma patients. METHODS: A retrospective analysis was performed on data patients who underwent radical surgery for metachronous metastases in six research institutes from January 2010 to December 2018. The log-hazard ratio (HR) obtained from the Cox model was used to derive weighting factors for a continuous prognostic index designed to identify differential outcome risks. RESULTS: A total of 251 patients were enrolled in the study. In the multivariate analysis, a longer disease-free interval (DFI) and a lower neutrophil-to-lymphocytes ratio (NLR) were predictive of a better overall survival (OS) and disease-free survival (DFS). A prognostic score was developed based on DFI and NLR data, identifying 2 risk class groups for DFS (3-years DFS 20.2% for the high-risk group [HRG]and 46.4% for the low-risk group [LRG] [<0.0001]) and 3 risk groups for OS (3 years OS 53.9% for the HRG vs. 76.9% for the intermediate-risk group and 100% of the LRG (p < 0.0001)). CONCLUSION: The proposed prognostic score effectively predicts outcomes for patients with lung metachronous oligo-metastases from the surgically treated sarcoma.

Three-Dimensional Imaging-Guided Lung Anatomic Segmentectomy: A Single-Center Preliminary Experiment.

Background and objectives: VATS segmentectomy has been proven to be effective in the treatment of stage I NSCLC, but its technical complexity remains one of the most challenging aspects for thoracic surgeons. Furthermore, 3D-CT reconstruction images can help in planning and performing surgical procedures. In this paper, we present our personal experience of 11 VATS anatomical resections performed after accurate pre-operative planning with 3D reconstructions. Materials and methods: A 3D virtual model of the lungs, airways, and vasculature was obtained, starting from a 1.25 mm 3-phase contrast CT scan, and the original images were used for the semi-automatic segmentation of the lung parenchyma, airways, and tumor. Results: Six males and five females were included in this study. The median diameter of the pulmonary lesion at the pre-operative chest CT scan was 20 mm. The surgical indication was confirmed in seven patients: in three cases, a lobectomy, instead of a segmentectomy, was needed due to intraoperative findings of nodal metastasis. Meanwhile, only in one case, we performed a lobectomy because of inadequate surgical resection margins. Skin-to-skin operative average time was 142 (IQR 1-3 105-182.5) min. The median post-operative stay was 6 (IQR 1-3 3.5-7) days. The mean value of the closest surgical margin was 13.7 mm. Conclusion: Image-guided reconstructions are a useful tool for surgeons to perform complex resections in order to spare healthy parenchyma and to ensure disease-free margins. Nevertheless, human skill and surgeon experience still remain fundamental for the final decisions regarding the proper resection to perform.

Surgical management of post-transplant bronchial stenoses: a single-center experience.

PURPOSE: Bronchial stenoses are challenging complications after lung transplantation and are associated with high rates of morbidity and mortality. We report a series of patients who underwent bronchoplasty or sleeve resection for bronchial stenoses that did not resolve with endoscopic treatment after lung transplantation. METHODS: Between 1995 and 2020, 497 patients underwent lung transplantation at our Institution. 35 patients (7.0%) experienced bronchial stenoses with a median time from transplantation of 3 months. Endoscopic management was effective in 28 cases (5.6%) while 1 patient required re-transplantation. Six patients (1.2%) underwent bronchoplasty or sleeve resection. RESULTS: The procedures of the six patients who underwent bronchoplasty or sleeve resection were as follows: lower sleeve bilobectomy (n = 3), wedge bronchoplasty of the bronchus intermedius (n = 1), isolated sleeve resection of the bronchus intermedius (n = 1), and isolated sleeve resection of the bronchus intermedius (n = 1), associated with a middle lobectomy. All patients were discharged after a median time of 11 days. At a median of 12 months from surgery, two patients remain alive with a preserved pulmonary function. Four patients died after a median time of 56 months from bronchoplasty of causes that were not related to surgery. CONCLUSIONS: Bronchial reconstructions are challenging procedures that can be performed in highly specialized centers. Despite this, they can be considered a good strategy to obtain a definitive resolution of stenosis after lung transplantation.

Adult Benign, Non-Iatrogenic Bronchoesophageal Fistulae: Systematic Review and Descriptive Analysis of Individual Patient Data.

BACKGROUND: Adult, benign, non-iatrogenic bronchoesophageal fistula (BEF) is a rare condition, which is occasionally described in single case reports. Therefore, little is known about its possible causes, presentation and management. METHODS: A systematic search of the literature in MEDLINE, PubMed Central and EMBASE databases between 1990 and 2020 was carried out to identify all cases of BEF. The initial database search identified 19,452 articles, of which 183 (251 individual patient cases) were included in the final analysis. RESULTS: Main causes of BEF were congenital malformations (97/251, 38.7%) and infections (82/251, 32.7%), while 33/251 (13.1%) fistulae were regarded as idiopathic and 39/251 (15.5%) attributed to other causes. Esophagograpy was the most sensitive method of diagnosis (97.4%) compared with esophagoscopy (78.9%), computed tomography (49.6%) and bronchoscopy (46.0%). Definitive treatment was surgical for 176 patients (70%), endoscopic for 25 (10%) and medical for 37 (14.7%). Compared with congenital BEFs, infective BEFs had shorter median symptom duration and were distributed more proximally over the bronchial tree. Definitive treatment was almost only surgical for congenital BEFs, while infective BEFs were treated also endoscopically (12%) and by medical therapy (38%). Morbidity, treatment failure and recurrence rates were higher for infective BEFs. CONCLUSIONS: BEFs are rare. Symptoms are non-specific and a high index of suspicion is necessary for diagnosis. Patients with infective BEF tend to have a more severe clinical picture than those with congenital BEF. Surgery is the main treatment for patients affected by congenital BEF, while infective BEFs may heal conservatively.

Postpneumonectomy bronchopleural fistula: analysis of risk factors and the role of bronchial stump coverage.

PURPOSE: Bronchopleural fistula (BPF) is a potentially fatal complication of pneumonectomy. We analyze its occurrence rate, risk factors, and the methods used for its prevention. METHODS: We reviewed the medical records of patients who underwent pneumonectomy at our Institution between January, 1990 and March, 2016. The risk factors for postoperative BPF were analyzed by univariate analysis and multiple logistic regression. RESULTS: Over the study period, 511 patients underwent pneumonectomy for non-small cell lung cancer (NSCLC) and had the bronchus closed by manual suturing. BPF developed in 23 patients (4.5%). Multiple logistic regression identified no coverage of the bronchial stump, right-sided pneumonectomy, residual tumor in the bronchial stump, postoperative ventilatory support, and completion pneumonectomy, as independent risk factors for BPF. The cumulative rate of BPF decreased significantly over time from 18% between 1990 and 1995 to 1% between 2011 and 2016 (p < 0.001). Concurrently, the data of several patients showed a significant positive trend over time, including bronchial stump coverage (BSC). DISCUSSION: Several known risk factors for BPF were confirmed. The more frequent usage of tissue flaps for coverage of the bronchial stump may have contributed to the reduction in the rate of postoperative BPF over time.

Correction to: Predictors of nodal upstaging in patients with cT1-3N0 non-small cell lung cancer (NSCLC): results from the Italian VATS Group Registry.

In the original publication, Carlo Curcio was not included in the author list. The correct author list is included in this Correction.

Predictors of nodal upstaging in patients with cT1-3N0 non-small cell lung cancer (NSCLC): results from the Italian VATS Group Registry.

PURPOSE: Accurate staging of early non-small cell lung cancer is fundamental for selecting the best treatment. The aim of this study was to identify risk factors for nodal upstaging after video-assisted thoracoscopic lobectomy for clinical T1-3N0 tumors. METHODS: From 2014 to 2017, 3276 thoracoscopic lobectomies were recorded in the prospective database "Italian VATS Group". Linear and multiple logistic regression models were adapted to identify independent predictors of nodal upstaging and factors associated with progression in postoperative N status. RESULTS: Nodal upstaging was found in 417 cases (12.7%), including 206 cases (6.2%) of N1-positive nodes, 81 cases of N2 nodes (2.4%), and 130 cases (4%) of involvement of both N1 + N2 nodes. A total of 241 (7.3%) patients had single-station nodal involvement, whereas 176 (5.3%) had multiple-station involvement. In the final regression model, the tumor grade, histology, pathologic T status, and > 12 resected nodes were independent predictors of nodal upstaging. CONCLUSIONS: The number of resected lymph nodes seems to predict nodal upstaging better than the type of intraoperative lymph node management. Other preoperative risk factors correspond to those for which the current guidelines of the European Society of Thoracic Surgery recommend more extensive preoperative mediastinal staging.

Does Induction Therapy Increase Anastomotic Complications in Bronchial Sleeve Resections?

BACKGROUND: Sleeve lobectomy represents a safe and effective treatment for central NSCLC to avoid the risks of pneumonectomy. Induction therapy (IT) may be indicated in advanced stages; however, the effect of IT on bronchial anastomoses remains uncertain. The purpose of the study was to evaluate the impact of IT on the complications of the anastomoses. METHODS: Between 2000 and 2012, 159 consecutive patients were submitted to sleeve lobectomy for NSCLC at our Institution. We retrospectively compared the results of patients who underwent IT before operation with those who received upfront surgery. RESULTS: In the study period, 49 (30.8%) patients received IT (37 chemotherapy, 1 radiotherapy and 11 chemo-radiotherapy) and 110 (69.2%) patients were directly submitted to surgery (S). The two groups were comparable for sex, age, comorbidities, ASA score, pulmonary function, side, type of procedure and histology. Pathological stage was statistically higher for IT group (p = 0.001). No differences between IT and S groups were observed in terms of post-operative mortality (2% vs 0%, p = NS), morbidity (45% vs 38%, p = NS), including early (6% vs 9%, p = NS) and long-term (16% vs 14%, p = NS) bronchial complication rates. Patients undergoing induction mediastinal radiotherapy, however, are at higher risk of bronchial complications. CONCLUSION: In our experience, the use of induction chemotherapy did not significantly increase mortality and morbidity rates, in particular, neither for early nor for late anastomotic complications. We, therefore, conclude that sleeve lobectomy after induction chemotherapy is safe and reliable procedure for the treatment of locally advanced NSCLC.

Long-Term Results and Prognostic Factors of Pulmonary Metastasectomy in Patients with Metastatic Transitional Cell Carcinoma.

Objective We wanted to assess the prognostic factors and the efficacy of the treatment in patients who underwent lung resections for transitional cell carcinoma metastases. Materials and Methods This is a retrospective, multicenter study. Between January 1995 and May 2014, 69 patients underwent lung metastasectomy with curative intent. We evaluated primary site of the tumor, the role of adjuvant chemotherapy after urological operation, disease-free interval (DFI; lower or higher than 24 months), type of lung resection, number of lung metastases, presence of metastatic lymph nodes, and diameter of the metastasis (less or more than 3 cm). Results Among 69 patients, 55 (79%) had bladder as primary site of disease and 12 of them received a transurethral bladder resection. Fourteen (21%) patients developed primary tumor in the renal pelvis or ureter; 53 (76%) patients presented with a single metastasis, 16 (24%) with multiple metastasis. The median DFI was 37 months and the median follow-up was 50 months. Sampling lymphadenectomy was done in 42 patients and nodal metastases were found in 7 patients. The overall 5-year survival was 52%, median 62 months. At univariate analysis, the DFI had a significant impact on survival (5-year survival of 58% for patients with DFI ≥ 24 months vs. 46%; p = 0.048) and diameter of metastasis (5-year survival of 59% for diameter less than 3 cm group vs. 33%; p = 0.001). The multivariate analysis confirmed metastasis' diameter as an independent prognostic factor (p = 0.001). Conclusion Our study found that, in addition to DFI that remains a common prognostic factor in patients with metastatic lung disease, in lung metastases by transitional cell carcinoma, the diameter of the lesion is another significant prognostic factor.

An Unusual Cause of Thoracic Outlet Syndrome.

Thoracic outlet syndrome (TOS) is a condition arising from compression of the subclavian vessels and/or brachial plexus. Many factors or diseases may cause compression of the neurovascular bundle at the thoracic outlet. We describe the case of a 41-year-old woman with TOS who presented with vascular venous symptoms. Chest computed tomography (CT) scan showed a cystic mass at the level of cervico-thoracic junction, located between the left subclavian artery and vein, which appeared compressed. The cystic mass was removed through a cervical approach and it was found to be a cyst arising from the thoracic duct compressing and anteriorly dislocating the left subclavian vein. After surgery symptoms promptly disappeared.

An alternative surgical access for posterior tracheal defects or fistulae situated between the cervical and thoracic region.

Posterior tracheal lesion defects between the cervical and the thoracic region represent a surgical challenge. Cervicotomy or median sternotomy might not allow a satisfactory exposure of the defect, and a history of prior neck surgeries could further complicate the procedure. We propose a high posterior right thoracotomic approach, by which the entire posterior aspect of the trachea is visible, up to the cervical region. We describe our experience with this approach, which is best suited for cases where a non-circumferential repair of the trachea is attempted.

Tracheal Tissue Engineering: Principles and State of the Art.

Patients affected by long-segment tracheal defects or stenoses represent an unsolved surgical issue, since they cannot be treated with the conventional surgery of tracheal resection and consequent anastomosis. Hence, different strategies for tracheal replacement have been proposed (synthetic materials, aortic allografts, transplantation, autologous tissue composites, and tissue engineering), each with advantages and drawbacks. Tracheal tissue engineering, on the other hand, aims at recreating a fully functional tracheal substitute, without the need for the patient to receive lifelong immunosuppression or endotracheal stents. Tissue engineering approaches involve the use of a scaffold, stem cells, and humoral signals. This paper reviews the main aspects of tracheal TE, starting from the choice of the scaffold to the type of stem cells that can be used to seed the scaffold, the methods for their culture and expansion, the issue of graft revascularization at the moment of in vivo implantation, and experimental models of tracheal research. Moreover, a critical insight on the state of the art of tracheal tissue engineering is also presented.

Surgery for tracheal and laryngotracheal stenosis: a historical case series.

OBJECTIVES: Benign (laryngo-)tracheal stenosis is a relatively rare pathology and its surgical treatment is performed only at few specialized centres. This study aims to investigate outcomes after (laryngo-)tracheal resection-anastomosis, to explore potential risk factors for postoperative complications and to assess whether, over a 33-year period, there were major changes in surgical indications, techniques or outcomes. METHODS: Retrospective, single-centre review of all consecutive patients who underwent tracheal or laryngo-tracheal resection/anastomosis for benign pathologies from 1990 to 2023. RESULTS: Overall, 211 patients underwent tracheal (149 patients, 70.6%) and laryngo-tracheal (62 patients, 29.4%) resection-anastomosis. Of these, 195 patients (93.8%) were affected by iatrogenic stenosis, while 13 (6.2%) suffered from idiopathic stenosis. The median length of stenosis was 25 mm (interquartile range 1-3, 20-30). The overall morbidity rate was 27.5%, while major morbidity occurred in 10.5% of cases. One patient (0.5%) died in the postoperative period. Glottic oedema (17 patients, 8.1%), granulations (12 patients, 5.7%) and restenosis (10 patients, 4.7%) were the main complications. The only independent risk factor for postoperative complications was the length of the resected airway (P = 0.019). In the latest half of the study period, an older median age was observed, and no patient with idiopathic tracheal stenosis underwent surgery. Postoperative outcomes were comparable between surgical eras. CONCLUSIONS: Surgical treatment of (laryngo-)tracheal stenosis is challenging and should be performed by specialized centres. In our experience, morbidity and mortality rates were satisfactory, and in most cases, patients could breathe without tracheostomy. The length of the stenosis was the most significant risk factor for postoperative complications.

Tumor inflammatory microenvironment contribution to survival in resected upstaged adenocarcinomas.

INTRODUCTION: Tumor Inflammatory microenvironment (TIME) encompasses several immune pathways modulating cancer development and escape that are not entirely uncoded. The results achieved with immunotherapy elicited the scientific debate on TIME also in non-small cell lung cancer (NSCLC). We aimed to investigate whether TIME (in terms of PD-L1 expression and/or Tumor Infiltrating Lymphocytes - TILs) played a separate role in terms of survival (OS) in resected upstaged lung adenocarcinomas (ADCs), excluding other perioperative variables as confounders. MATERIALS AND METHODS: This retrospective study included 50 patients with a clinically resectable lung ADC, undergoing surgery (lobectomy or segmentectomy) at the Thoracic Unit of Padova University Hospital between 2016 and 2022 and receiving an unexpected pathological upstaging (IIB or higher). RESULTS: Despite microscopical variables increasing from IIB to IIIB, survival was not significantly related to them. OS was better in TIME-active patients (defined as the presence of positive PD-L1 and/or TILs>10 %) than double negatives (PD-L1-/TILs-) (p = 0.01). In IIB or higher ADCs, TIME-active patients showed an improved survival compared to double negatives, merging the current TIME theories. CONCLUSION: TIME seems to be associated with survival independently from other microscopical parameter, even in case of resected upstaged adenocarcinomas.

Laser-assisted lung metastasectomy: a systematic review.

Laser-assisted resection (LAR) of pulmonary metastases offers several potential advantages compared to conventional surgical techniques. However, the technical details, indications and outcomes of LAR have not been extensively reviewed. We conducted a systematic literature search to identify all original articles reporting on LAR of pulmonary metastases. All relevant outcomes, including morbidity rate, R0 rate, pulmonary function tests, overall- (OS) and relapse-free survival (RFS) rates were collected. Additionally, a comparison between outcomes obtained by laser-assisted and conventional resection techniques was provided. Of 2629 articles found by the initial search, 12 were selected for the systematic review. Following LAR, the R0 rate ranged between 72 and 100% and the morbidity rate ranged from 0 to 27.5%. The postoperative decline in forced expiratory volume in 1 s varied between 3.4 and 11%. Median OS and RFS were 42-77.6 months and 9-34.1 months, respectively. Compared with patients treated by other resection techniques, patients treated by LAR frequently had a higher number of metastases and a higher rate of bilateral disease. Despite this, no significant differences were observed in R0 rate, morbidity rate, and median OS rate, while only 1 study found a lower RFS rate in the LAR cohort. Although selection bias limits the comparability of outcomes, the findings of this review suggest that LAR is a valid alternative to conventional procedures of lung metastasectomy. The main difficulties of this technique consist in the adoption of a video-assisted thoracoscopic approach, and in the pathologic assessment of resection margins.

Precision Surgery in NSCLC.

Non-small cell lung cancer (NSCLC) is still one of the leading causes of death worldwide. This is mostly because the majority of lung cancers are discovered in advanced stages. In the era of conventional chemotherapy, the prognosis of advanced NSCLC was grim. Important results have been reported in thoracic oncology since the discovery of new molecular alterations and of the role of the immune system. The advent of new therapies has radically changed the approach to lung cancer for a subset of patients with advanced NSCLC, and the concept of incurable disease is still changing. In this setting, surgery seems to have developed a role of rescue therapy for some patients. In precision surgery, the decision to perform surgical procedures is tailored to the individual patient; taking into consideration not only clinical stage, but also clinical and molecular features. Multimodality treatments incorporating surgery, immune checkpoint inhibitors, or targeted agents are feasible in high volume centers with good results in terms of pathologic response and patient morbidity. Thanks to a better understanding of tumor biology, precision thoracic surgery will facilitate optimal and individualized patient selection and treatment, with the goal of improving the outcomes of patients affected by NSCLC.

Impact of a standardized protocol for chest tube management after VATS pulmonary resections on post-operative outcomes and complications.

Chest tube management represents a major issue after lung surgery as no protocol is widely accepted and tube management is generally based on local or personal habits. Aim of this study is to evaluate the impact of a standardized protocol for chest tube management after pulmonary resections on the post-operative outcomes. We performed a single center retrospective analysis of all adult patients undergoing thoracoscopic pulmonary resection from January 2020 to December 2021. Starting from January 2021 a standardized protocol of chest tube management was applied after all procedures. Patients were divided into two groups according to the chest tube management strategy. he two groups had similar pre-operative characteristics and the extent of lung resection was comparable. Intervention group had significantly shorter time to chest tube removal (median 1 vs 3 days, p < 0.001) and post-operative length of stay (median 3 vs 4 days, p < 0.001). Despite earlier chest tube removal, there was not an increased incidence of post-removal complications. On multivariable analysis, the new chest drain management strategy was an independent predictor of earlier chest tube removal. A standardized protocol of chest tube management allows for an earlier chest tube removal and a shorter hospital stay, without an increase in post-operative complications.