Preoperative prognostic factors for 5-year survival following pulmonary metastasectomy from colorectal cancer: a systematic review and meta-analysis.

OBJECTIVES: We seek to identify preoperative prognostic factors and measure their effect on 5-year survival following pulmonary metastasectomy (PM) for Colorectal Cancer (CRC). METHODS: We systematically reviewed the databases of Cochrane Library, MEDLINE, Embase and Google Scholar from January 2000 to April 2021 to identify preoperative factors that have been investigated for their prognostic effect on survival following PM. Quality assessment was performed using the QUIPS tool. The prognostic effect of each identified factor on 5-year survival post-PM was estimated using random-effects meta-analyses. RESULTS: We identified 115 eligible articles which included 13 294 patients who underwent PM from CRC. The overall 5-year survival after resection of the lung metastasis was 54.1%. The risk of bias of the included studies was at least moderate in 93% (107/115). Seventy-seven preoperative factors had been investigated for their prognostic effect. Our analysis showed that 11 factors had favourable and statistically significant prognostic effect on 5-year survival post-PM. These included solitary metastasis, size <2 cm, unilateral location, N0 thoracic disease, no history of extra-thoracic or liver metastasis, normal carcinoembryonic antigen levels both before PM and CRC excision, no neo-adjuvant chemotherapy before PM, CRC T-stage < T4 and no p53 mutations on CRC. Disease-free interval at 24 months did not appear to affect 5-year survival. CONCLUSIONS: Despite the considerable risk of bias in the literature, our study consolidates the available evidence on preoperative prognostic factors for PM from CRC. These findings can complement both clinical practice and the design of future research on the field of PM.

Lymphoepithelioma-Like Carcinoma of the Lung Associated With Epstein-Barr Virus in a Caucasian Patient: A Case Report.

Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is a rare tumour that is histologically identical to the lymphoepithelioma originally described in the nasopharynx. It mostly occurs in endemic regions in Asia, where it is associated with Epstein-Barr virus (EBV) infection. The incidence of primary pulmonary LELC is even lower in the Western population, in which an association with EBV is not typically observed. In this report, we present the case of a 78-year-old Caucasian woman who was diagnosed with EBV-positive pulmonary LELC following lingulectomy and histopathological examination of the tumour. Metastasis from the nasopharynx was excluded clinically and radiologically. Due to the absence of regional lymph node involvement, the patient did not receive adjuvant therapy. She remained free of disease at the one-year follow-up. Reporting cases of primary pulmonary LELC in non-Asian patients can help to elucidate the association with EBV infection and its potential implications for diagnosis, treatment, and follow-up.

How effective is indocyanine green (ICG) in localization of malignant pulmonary nodules? A systematic review and meta-analysis.

Background: Video-Assisted and Robotic-Assisted techniques become constantly more prominent practice in thoracic surgery for lung cancer. Furthermore, the increased frequency in detection of small lung cancers makes the intra-operative identification of these cancers even more challenging. Indocyanine Green (ICG) is one of the most commonly used dyes that assists surgeons identify small lung cancers intra-operatively. Our study aimed to evaluate the effectiveness and safety of ICG in lung cancer detection. Methods: We performed a systematic review of the literature by screening the databases of MEDLINE, EMBASE, CENTRAL and Scopus until 30th April 2022 and the first 300 articles of Google Scholar for any suitable grey literature. We included any study that investigated the effectiveness of ICG in lung cancer detection. We excluded studies that explored the use of ICG only in identification of intersegmental planes, lymph node mapping, case reports and non-English articles. We aimed to perform a meta-analysis on test accuracy studies using hierarchical summary receiver operating characteristic (HSROC) and the bivariate random-effects models. In cases where the data for a localization technique was not sufficient for that analysis, it was presented with tables with narrative purposes. Each study was assessed for Risk of Bias (RoB) and Applicability using the QUADAS-2 tool. Results: We found 30 eligible studies that included a total of 1,776 patients who underwent ICG localization of pulmonary nodules. We identified three ICG localization techniques: CT-guided, endobronchial and intravenous. From the 30 studies, 13 investigated CT-guided localization, 12 explored an endobronchial method while 8 studies administered ICG intravenously the median reported success rate was 94.3% (IQR: 91.4%-100%) and 98.3% (IQR: 94%-100%) for the first two techniques respectively. Intravenous ICG lung cancer localization showed Sensitivity of 88% (95% CI: 59%-0.97%) and Specificity of 25% (95% CI: 0.04%-0.74%). There were 15.2% (150/989) patients who experienced complications from CT guided ICG localization. No ICG-related complications were reported in endobronchial or intravenous techniques. Conclusion: Our study provides a comprehensive review of the literature on ICG localization techniques for lung cancer. Current evidence suggests that ICG is boh effective and safe. Further prospective research with standardized protocols across multiple thoracic units is required in order to accurately validate these findings.

The Role of Surgery in Patients with COVID-19-Related Thoracic Complications.

Objective: Patients with several thoracic complications induced by SARS-CoV-2 infection may benefit from surgery, but its role in this condition is largely unknown, and many surgeons' advice against any surgical referrals. Our aim is to investigate the efficacy and safety of surgery in COVID-19 patients with thoracic complications requiring surgery. Methods: We designed a multicenter observational study, involving nine thoracic surgery departments, evaluating patients who developed thoracic complications in hospital, surgically managed from March 1, 2020, to May 31, 2021. An overall 30-day mortality was obtained by using the Kaplan-Meier method. Multivariable Cox regression model and logistic models were applied to identify the variables associated with mortality and postoperative complications. Results: Among 83 patients, 33 (40%) underwent surgery for complicated pneumothorax, 17 (20.5%) for pleural empyema, 13 (15.5%) for hemothorax, 8 (9.5%) for hemoptysis, 5 patients (6%) for lung abscess, 4 (5%) for infected pneumatoceles, and 3 (3.5%) for other causes. Within 30 days of surgery, 60 patients (72%) survived. At multivariable analysis, age (HR 1.05 [95% CI, 1.01, 1.09], p = 0.022), pulmonary hypertension (HR 3.98 [95% CI, 1.09, 14.5], p = 0.036), renal failure (HR 2.91 [95% CI, 1.19, 7.10], p-value 0.019), thoracotomy (HR 4.90 [95% CI, 1.84, 13.1], p-value 0.001) and infective affections (HR 0.17 [95% CI, 0.05, 0.58], p-value 0.004) were found to be independent prognostic risk factors for 30-day mortality. Age (OR 1.05 [95% CI, 1.01, 1.10], p = 0.023) and thoracotomy (OR 3.85 [95% CI, 1.35, 12.0] p = 0.014) became significant predictors for 30-day morbidity. Conclusion: Surgical management of COVID-19-related thoracic complications is affected by high mortality and morbidity rates, but a 72% survival rate still seems to be satisfactory with a rescue intent. Younger patients without pulmonary hypertension, without renal insufficiency and undergoing surgery for infectious complications appear to have a better prognosis.

Thoracic Outlet Syndrome: Single Center Experience on Robotic Assisted First Rib Resection and Literature Review.

Background: Thoracic outlet syndrome (TOS) is a pathological condition caused by a narrowing between the clavicle and first rib leading to a compression of the neurovascular bundle to the upper extremity. The incidence of TOS is probably nowadays underestimated because the diagnosis could be very challenging without a thorough clinical examination along with appropriate clinical testing. Beside traditional supra-, infraclavicular or transaxillary approaches, the robotic assisted first rib resection has been gaining importance in the last few years. Methods: We conducted a retrospective cohort analysis of all patients who underwent robotic assisted first rib resection due to TOS at Lucerne Cantonal Hospital and then we performed a narrative review of the English literature using PubMed, Cochrane Database of Systematic Reviews and Scopus. Results: Between June 2020 and November 2021, eleven robotic assisted first rib resections were performed due to TOS at Lucerne Cantonal Hospital. Median length of stay was 2 days (Standard Deviation: +/- 0.67 days). Median surgery time was 180 min (Standard Deviation: +/- 36.5). No intra-operative complications were reported. Conclusions: Robotic assisted first rib resection could represent a safe and feasible option in expert hands for the treatment of thoracic outlet syndrome.

Thymic tumours: a single center surgical experience and literature review on the current diagnosis and management of thymic malignancies.

OBJECTIVE: This study aimed to provide an extensive overview of clinical and pathological findings along with various therapeutic options analyzing in addiction, retrospectively, the surgical outcomes of a single center cohort. BACKGROUND: Thymic neoplasms are rare thoracic tumors which commonly are located in the anterior mediastinum and are associated with a wide spectrum of clinical presentations. They may run an indolent course or could present a very aggressive biologic progression with infiltration of mediastinal structures and presence of distant metastases. The pathogenesis of these tumors is so far not completely clear. Several treatment modalities in a multidisciplinary setting have to be considered in order to provide the best treatment for patients affected by thymic tumors. METHODS: We conducted a retrospective cohort analysis of all patients who underwent surgery due to thymic tumor in a university hospital located in Switzerland (Bern University Hospital) and then we performed a narrative review of the English literature using PubMed, Embase, Cochrane Database of Systematic Reviews and Scopus. CONCLUSIONS: Minimally invasive techniques play an important role in the treatment of thymic tumors. A careful patients selection in a multidisciplinary setting is mandatory in order to offer the best treatment for patients affected by thymic tumors.

Pneumonectomy for lung cancer in the elderly: lessons learned from a multicenter study.

BACKGROUND: 60% of patients diagnosed with lung cancer are older than 65 years and are at risk for substandard treatment due to a reluctance to recommend surgery. Pneumonectomy remains a high risk procedure especially in elderly patients. Nevertheless, the impact of age and neoadjuvant treatment on outcomes after pneumonectomy is still not well described. METHODS: We performed a multicentric retrospective study, analyzing outcomes of patients older than 70 years who underwent pneumonectomy for central primary lung malignancy between January 2009 and June 2019 in 7 thoracic surgery departments: Lucerne and Bern (Switzerland), Hamilton (Canada), Alicante (Spain), Monza (Italy), London (UK), Leuven (Belgium). Survival was estimated with Kaplan-Meier, and differences in survival were determined by log-rank analysis. We investigated pre- and post-operative prognostic factors using Cox proportional hazards regression model; multivariable analysis was performed only with variables, which were statistically significant at the invariable analysis. RESULTS: A total of 136 patients were included in the study. Mean age was 73.8 years (SD 3.6). 24 patients (17.6%) had an induction treatment (chemotherapy alone in 15 patients and chemo-radiation in 9). Mean length of stay (LOS) was 12.6 days (SD 10.39) and 74 patients (54.4%) had experienced a post-operative complication: 29 (21.3%) had a pulmonary complication, 33 (24.3%) had a cardiac complication and in 12 cases (8.8%) patients experienced both cardiac and pulmonary complications. 16 patients were readmitted [median LOS 13.7 days (range, 2-39 days)] and of those 14 (10.3%) required redo surgery. Median overall survival (OS) of the entire cohort was 38 months (95% CI: 29.9-46.1 months); in-hospital mortality was 1.5%, 30-day mortality rate was 3.7%, while 90-day mortality was 8.8% accounting for 5 and 12 patients respectively. Patients receiving neo-adjuvant therapy did not experience a higher incidence of postoperative complications (P=0.633), did not have a longer postoperative course (P=0.588), nor did they have an increased mortality rate (P=0.863). CONCLUSIONS: Age should not be considered an absolute contraindication for pneumonectomy in elderly patients even after neoadjuvant treatment. It has become apparent that especially in these patients, a patient-tailored approach with a careful selection should be used to define the risk-benefit balance.

Maintaining safe lung cancer surgery during the COVID-19 pandemic in a global city.

BACKGROUND: SARS-CoV-2 has challenged health service provision worldwide. This work evaluates safe surgical pathways and standard operating procedures implemented in the high volume, global city of London during the first wave of SARS-CoV-2 infection. We also assess the safety of minimally invasive surgery(MIS) for anatomical lung resection. METHODS: This multicentre cohort study was conducted across all London thoracic surgical units, covering a catchment area of approximately 14.8 Million. A Pan-London Collaborative was created for data sharing and dissemination of protocols. All patients undergoing anatomical lung resection 1st March-1st June 2020 were included. Primary outcomes were SARS-CoV-2 infection, access to minimally invasive surgery, post-operative complication, length of intensive care and hospital stay (LOS), and death during follow up. FINDINGS: 352 patients underwent anatomical lung resection with a median age of 69 (IQR: 35-86) years. Self-isolation and pre-operative screening were implemented following the UK national lockdown. Pre-operative SARS-CoV-2 swabs were performed in 63.1% and CT imaging in 54.8%. 61.7% of cases were performed minimally invasively (MIS), compared to 59.9% pre pandemic. Median LOS was 6 days with a 30-day survival of 98.3% (comparable to a median LOS of 6 days and 30-day survival of 98.4% pre-pandemic). Significant complications developed in 7.3% of patients (Clavien-Dindo Grade 3-4) and 12 there were re-admissions(3.4%). Seven patients(2.0%) were diagnosed with SARS-CoV-2 infection, two of whom died (28.5%). INTERPRETATION: SARS-CoV-2 infection significantly increases morbidity and mortality in patients undergoing elective anatomical pulmonary resection. However, surgery can be safely undertaken via open and MIS approaches at the peak of a viral pandemic if precautionary measures are implemented. High volume surgery should continue during further viral peaks to minimise health service burden and potential harm to cancer patients. FUNDING: This work did not receive funding.

Video-thoracoscopic left cardiac sympathetic denervation for long-QT syndrome.

BACKGROUND: Congenital long-QT syndrome represents the most common cardiac channelopathy and manifests as potentially lethal ventricular arrhythmias. Prevention strategies include beta-blockade pharmacotherapy, implantable cardioverter-defibrillators, and left cardiac sympathetic denervation, which can increase the threshold for ventricular fibrillation. Herein, we report our experience with video-assisted thoracoscopic left cardiac sympathetic denervation. METHODS: We performed a retrospective review of the electronic medical records of all patients with congenital long-QT syndrome who underwent video-assisted thoracoscopic left cardiac sympathetic denervation at our institution. RESULTS: From September 2009 to May 2016, 6 patients with a mean age of 30.5 years (range 20-47 years) underwent video-assisted thoracoscopic left cardiac sympathetic denervation for medically refractory long-QT syndrome. All patients had an uneventful recovery and were discharged 1-3 days after the operation. At a median follow-up of 14 months (range 12-60 months), 4 patients had no cardiac events while 2 experienced 1 episode of arrhythmic syncope and 1 episode of appropriate implantable cardioverter-defibrillator shock. Following surgery, the mean annual cardiac events in the study cohort decreased from 2.13 to 0.33 (p = 0.004) and the mean corrected QT interval reduced from 560 ms to 491 ms (p = 0.006). CONCLUSIONS: Video-assisted thoracoscopic left cardiac sympathetic denervation is a safe and effective therapy in patients with congenital long-QT syndrome who continue to suffer from recurrent life-threatening arrhythmias or frequent implantable cardioverter-defibrillator discharges despite maximum tolerated doses of beta blockers.

Focus on the pulmonary involvement and genetic patterns in Birt-Hogg-Dubè syndrome: Literature review.

INTRODUCTION: Brit-Hogg-Dubé syndrome (BHD) is a rare disorder that is estimated to affects about 600 families in the World. The disease-causing mutations is on FLCN gene which codes for folliculin. This protein has a role in different organs as skin, kidney and lung, thanks to the interaction with type I and II cadherins, RhoA activity and the regulation of AMPK, mTORC1 pathways and cell adhesion. The aim of our study is to focus on the manifestation of the syndrome, especially the pulmonary involvement, then on genetical analysis and on the available treatments. MATERIAL AND METHODS: We collected 15 previous studies where we found medical history information, clinical manifestations, radiological and histological diagnosis and genetical analysis. RESULTS: The prevalence of pneumothorax in patients with BHD syndrome was about 65%, but the lung involvement with multiple small cysts, localized especially in the lower part, was 85%. The prevalence of renal involvement in BHD patients ranged from 6.5% to 34%, while skin lesions ranged from 11% to 50%. More than 150 FLCN germline has been described, though the mutation in exon 11 is the most frequently detected, especially among Caucasian population. CONCLUSIONS: BHD syndrome is rare and usually the first manifestations appear in early age. In patients with these clinical and radiological characteristics we suggest taking a careful medical history, though the diagnosis of BHD syndrome should be confirmed with the analysis of FLCN gene.

Is systematic lymph node dissection mandatory or is sampling adequate in patients with stage I non-small-cell lung cancer?

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was: Is systematic lymph node dissection (SLND) mandatory or is sampling adequate in stage I non-small-cell lung cancer (NSCLC)? Two hundred and eleven papers were identified, of which 12 papers represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and the results of these papers are tabulated. There are 7 retrospective cohort reviews, 3 meta-analyses and 2 randomized controlled clinical trials (RCTs) to answer the clinical question. Four of the 7 retrospective studies demonstrated that the total number of resected lymph nodes and the number of lymph node stations sampled affected the accuracy of staging in patients with early-stage NSCLC and had an impact on overall survival and disease-free survival. Two RCTs, 1 meta-analysis and 1 cohort study revealed no significant benefit in overall survival and disease-free survival in patients undergoing SLND. One meta-analysis, which contained only 1 RCT, revealed significantly better 3- and 5-year survival with SLND. One further meta-analysis revealed improved survival with SLND in cohort studies but no significant difference in the 4 RCTs included. Two further studies identified specific subgroups of patients in whom LN sampling could be justified and SLND avoided. We conclude that there is no significant difference in the recurrence rate when performing either SLND or LN sampling in patients with stage I NSCLC. While retrospective cohort studies implied survival benefit with SLND, this was not borne out in RCTs and meta-analyses. However, there may be a potential survival benefit for patients who are upstaged by SLND identifying mediastinal nodal involvement.

Focus on specific disease-part 2: the European Society of Thoracic Surgery chest wall database.

BACKGROUND: Data collection has gained a great importance in numerous areas in the last years and also in the medical field. Collecting data is the key to knowledge and consequently improving data quality is fundamental, as the results of the data analysis can have a large impact on the clinical practice. METHODS: Collected data can be employed to assess the performance of surgeons or institutions and to implement hospital´s performance and productivity. The chest wall database is one of the satellites composing the European Society of Thoracic Surgery (ESTS) database and includes data on risk factors, surgical techniques, processes of care and outcomes related to chest wall pathologies. The participation to the registry is free and voluntary for the ESTS members. The ESTS chest wall database includes data on risk factors, surgical techniques, processes of care and outcomes related to chest wall pathologies. The collected data are designed for quality control and performance audit. Acquired data are anonymous, independently accessed and encrypted on a Dendrite platform, which provides data security and regular backups. The registry is managed by an external company (KData Clinicak Srl), which works together with the database committee in revising and updating periodically the database. RESULTS: The ESTS chest wall database is structured in four main sections: preoperative, intraoperative, postoperative and follow up. For each procedure registered in the database are collected a number of different variables regarding the patients' characteristics, the surgical technique, the postoperative course until the discharge and also follow up data. Correction of pectus excavatum is the most common procedures registered in 2017 (392 patients, 67% of all data), followed by pectus bar removal (159 patients, 27% of all procedures). CONCLUSIONS: The ESTS chest wall database is an ambitious European project, which aims to standardize all chest wall procedures in all their aspects.

Biologic Agents in the Treatment of Multicentric Castleman Disease.

Multicentric Castleman disease (MCD) causes an extensive range of systematic symptoms and can be life-threatening if not treated promptly and appropriately. The pathophysiology of the disease remains unclear; however, interleukin 6 (IL-6) pathway and human herpesvirus 8 infection appear to play an important role. As a result, the treatment of MCD remains complex and often insufficient, although a plethora of therapeutic approaches have been used. Between these, biological agents in the form of monoclonal antibodies against specific pathogenic processes of the disease have improved survival rates significantly. In the present study, we review the clinical results of rituximab, which targets B lymphocytes, siltuximab and tocilizumab, which target the IL-6 pathway, bortezomib, which is a selective proteasome inhibitor, and anakinra, which is an interleukin 1 receptor antagonist. The introduction of these biological agents in the treatment of MCD appears to be promising in the first studies performed. However, more clinical trials are required to assess the efficacy and safety of each agent and to form therapeutic strategies that will be widely accepted.

Surgical approach in oligometastatic non-small cell lung cancer.

The vast majority of lung cancer (80%) are non-small cell lung cancer (NSCLC) presenting in huge proportion of patients in a metastatic stage at the time of diagnosis with an overall survival (OS) of only 6 months. Standard treatment at this stage involves systemic platinum based chemotherapy improving the OS for only few months. For the vast majority of patients disease progression occurs and cure cannot achieved. An exception to this general rule is represented by patients with a limited number of metastasis (approximately 7% of patients with metastatic NSCLC): in 1995 Hellman and Weichselbaum introduced the term "oligometastatic" for a selected group of patients with metastatic disease. Several retrospective studies have been published and documented an improved outcome in patients managed surgically. The purpose of this narrative review is to gather all relevant information and present the various clinicopathological and generic aspects of diagnosis, management strategies and prognostic factors in patients with oligometastatic NSCLC. The key for long term survival includes radical treatment of the primary NSCLC, single organ site with either synchronous or metachronous presentation, a disease free interval to be as long as possible and the absence of intrathoracic lymph node spread (N0). A more accurate staging with combination of FDG-PET and CT scan can have on impact on the survival rates due to an increased accuracy in mediastinal staging and in the diagnosis of distant metastasis. No randomized data but only retrospective series are available to date to address this topic: in the future, additional prospective studies will be necessary to provide robust evidence to support the surgical resection as treatment of oligometastatic NSCLC.

The role of surgical resection in Unicentric Castleman's disease: a systematic review.

INTRODUCTION: Castleman's disease is a rare benign lymphoproliferative disorder of unknown etiology. The disease occurs in two clinical forms with different prognoses, treatments and symptoms: a unicentric form (UCD), which is solitary, localized, and a multicentric form characterized by generalized lymphadenopathy and systemic symptoms. This article aims to review the current literature to consolidate the evidence surrounding the curative potential of surgical treatment to the unicentric type. MATERIAL AND METHODS: A systematic review of English-language literature was performed and databases (Medline, Pubmed, the Cochrane Database and grey literature) were searched to identify articles pertaining to the treatment of unicentric form of Castleman's disease. Each article was critiqued by two authors using a structured appraisal tool, and stratified according to the level of evidence. RESULTS: After application of inclusion criteria, 14 studies were included. There were no prospective randomized control studies identified. One meta-analysis including 278 patients with UCD reported that resective surgery is safe and should be considered the gold standard for treatment. Seven retrospective studies enhance this standpoint. Radiotherapy (RT) has been used in six studies with controversial results. CONCLUSIONS: We conclude that surgical resection appears to be the most effective treatment for Unicentric Castleman's Disease of the thoracic cavity. Radiotherapy can also achieve clinical response and cure in selected patients.

Uniportal non-intubated thoracic surgery.

Uniportal video-assisted thoracoscopic surgery (VATS) is the most advanced evolution of the minimally invasive technique, which allows often the possibility to include patients in enhanced recovery programs in order to optimize the therapeutic pathway, shorten the length of stay and reduce hospital costs. Non-intubated VATS procedures allow the performance of surgeries with minimal sedation without general anesthesia, maintaining throughout the operation spontaneous breathing. The principle is to create an iatrogenic spontaneous pneumothorax, which can provide a good lung isolation without the need of a double lumen tube. A survey between the members of the European Society of Thoracic Surgery (ESTS) showed that non-intubated VATS procedures are already performed by a large number of ESTS members for minor procedures. With the publication of new data and the spreading of uniportal VATS in many centers worldwide in the last decades, the application of the non-intubated technique in major procedure like anatomic resections is expected to grow. This technique can potentially be beneficial for high-risk patients but also could be used for the routine procedures as well, but more data are needed to establish the real benefit for these groups of patients.