Colorectal Cancer Pulmonary Metastasectomy: When, Why and How.

Colorectal cancer is the third-most-diagnosed cancer in males and in females, representing 8% of estimated new cases, and the third cause of cancer-related death in both sexes, accounting for 9% of cancer deaths in men and 8% in women. About 20% of patients diagnosed with CRC present metastatic disease. Although lung metachronous or synchronous metastatic spread without other involved sites has been reported in only a small proportion of patients, considering that this tumor is frequently diagnosed, the clinical approach to CRC pulmonary metastases represents a major issue for thoracic surgeons and CRC oncologists. Among patients diagnosed with pulmonary metastases from CRC, about 9-12% are eligible for local treatments with radical intent, including surgical resection, SBRT (stereotactic body radiation therapy) and ablation therapy. Due to the lack of randomized controlled trials among different local strategies, there is no definitive evidence about the optimal approach, although surgical resection is considered the most effective therapeutic option in this clinical scenario. Oncological achievement of primary radical resection, the biology of primary tumor and metastatic sites, disease free interval and or progression free survival are independent prognostic factors which make it possible to define a cohort of patients which might significantly benefit from pulmonary metastasectomy.

Pleural mesothelioma in situ: a comprehensive review.

Pleural mesothelioma is a rare and aggressive cancer that affects the pleura. In recent years, there has been increasing interest and attention in detecting and diagnosing early-stage or precancerous forms of mesothelioma because of its severe prognosis and short life expectancy at the time of diagnosis. Mesothelioma in situ represents a clear opportunity to improve and innovate the diagnostic approach and the multimodality treatment of mesothelioma: the diagnosis of pleural mesothelioma at the 'in-situ phase' means early disease detection and thus paves the way to new possible curable strategies. Since 2021, when mesothelioma in situ was finally identified and described as a new histological entity, its diagnosis and management became a challenge and the subject of ongoing research; several aspects remain open and still outstanding as regards diagnostic techniques, time and probability of progression, need for and methods of follow up, aggressive and early surgery. This narrative review aims to provide a comprehensive overview of mesothelioma in situ covering its definition, risk factors, diagnostic criteria, and tricky aspects of early detection. It also highlights its clinical significance, new perspectives, and potential future indications in the context of pleural mesothelioma multidisciplinary management.

Stem cell technology for antitumor drug loading and delivery in oncology.

The main aim of antineoplastic treatment is to maximize patient benefit by augmenting the drug accumulation within affected organs and tissues, thus incrementing drug effects and, at the same time, reducing the damage of non-involved tissues to cytotoxic agents. Mesenchymal stromal cells (MSC) represent a group of undifferentiated multipotent cells presenting wide self-renewal features and the capacity to differentiate into an assortment of mesenchymal family cells. During the last year, they have been proposed as natural carriers for the selective release of antitumor drugs to malignant cells, thus optimizing cytotoxic action on cancer cells, while significantly reducing adverse side effects on healthy cells. MSC chemotherapeutic drug loading and delivery is an encouraging new area of cell therapy for several tumors, especially for those with unsatisfactory prognosis and limited treatment options available. Although some experimental models have been successfully developed, phase I clinical studies are needed to confirm this potential application of cell therapy, in particular in the case of primary and secondary lung cancers.

Mesenchymal Stromal Cell Therapy for Thoracic Surgeons: An Update.

Stem cells are undifferentiated cells presenting extensive self-renewal features and the ability to differentiate "in vitro" and "in vivo" into a range of lineage cells, like chondrogenic, osteogenic and adipogenic lineages when cultured in specific inducing media. Two major domains of clinical applications of stem cells in thoracic surgery have been investigated: regenerative medicine, which is a section of translational research in tissue engineering focusing on the replacement, renewal or regeneration of cells, tissues and organs to re-establish damaged physiologic functions; drug loading and delivery, representing a new branch proposing stem cells as carriers to provide selected districts with anti-cancer agents for targeted treatments.

Multi-level analysis and evaluation of organizational improvements in thoracic surgery according to a Value-Based HealthCare approach.

Background: Value-Based HealthCare (VBHC), designed by Harvard University, is an evolving model of healthcare delivery that achieves better patient outcomes and greater financial sustainability for the healthcare professionals. According to this innovative approach, the value is determined by a panel of indicators and the ratio between results and costs. Our goal was to develop a panel of thoracic-fashioned key-performance indicators (KPIs) creating a model that could be applied in thoracic surgery for the first time, reporting our early experience. Methods: Fifty-five indicators were developed based on literature review: 37 for outcomes and 18 for costs. Outcomes were measured by a 7 level Likert scale, while overall costs were defined through the sum of the individual economic performance on each resource indicator. An observational retrospective cross-sectional study was designed to make a cost-effective evaluation of the indicators. Therefore, the Patient Value in Thoracic Surgery (PVTS) score calculated value gained for every lung cancer patient undergoing lung resection at our surgical department. Results: A total of 552 patients were enrolled. From 2017 to 2019 mean outcome indicators per patient were 109, 113 and 110 while mean costs per patient were 7.370, 7.536 and 7.313 euros respectively. Hospital stay and waiting time from consultation to surgery for lung cancer patients decreased from 7.3 to 5 and from 25.2 to 21.9 days, respectively. On the contrary, number of patients increased but overall costs decreased, despite cost of consumables has gone from 2.314 to 3.438 euros, since cost of hospitalization and occupancy of the operating room (OR) improved (from 4.288 to 3.158 euros). Variables analyzed showed that overall value delivered grew from 14.8 to 15. Conclusions: Introducing a new concept of value, the VBHC theory applied to thoracic surgery may revolutionize traditional organizational management in lung cancer patients, showing how value delivered can increase in accordance with outcomes, despite the growth of part of the costs. Our panel of indicators has been created to provide an innovative score to successfully identify improvements needed and quantify their effectiveness in Thoracic Surgery and our early experience reports encouraging results.

Surgical management of compensatory sweating: A systematic review.

Endoscopic thoracic sympathectomy (ETS) surgery is a highly effective treatment of primary hyperhidrosis (PH) for the palms, face, axillae. Compensatory sweating (CS) is the most common and feared side effect of thoracic sympathectomy. CS is a phenomenon characterized by increased sweating in sites distal to the level of sympathectomy. Compensatory sweating is the main problem for which many patients give up surgery, losing the chance to solve their problem and accepting a poor quality of life. There are still no treatments that offer reliable solutions for compensatory sweating. The treatments proposed in the literature are scarce, with low case histories, and with uncertain results. Factors associated with CS are extension of manipulation of the sympathetic chain, level of sympathetic denervation, and body mass index. Therapeutic options include non surgical treatment and surgical treatment. Non surgical treatments include topical agents, botulinum toxin, systemic anticholinergics, iontophoresis. Surgical treatments include clip removal, extended sympathectomy and sympathetic chain reconstruction, although the efficacy is not well-established for all the methods. In this review we provide an overview of the treatments and outcomes described in the literature for the management of compensatory CS, with focus on surgical treatment.

Management of COVID-19 related tracheal stenosis: The state of art.

Tracheal stenosis (TS) is a debilitating disease promoted by pathologic narrowing of the trachea. The acute respiratory distress syndrome caused by COVID-19 has been demonstrated to trigger enhanced inflammatory response and to require prolonged invasive mechanical ventilation as well as high frequency of re-intubation or emergency intubation, thus increasing the rate and complexity of TS. The standard-of-care of COVID-19-related tracheal complications has yet to be established and this is a matter of concern. This review aims at collecting latest evidence on this disease, providing an exhaustive overview on its distinctive features and open issues, and investigating different diagnostic and therapeutic strategies to handle COVID-19-induced TS, focusing on endoscopic versus open surgical approach. The former encompasses bronchoscopic procedures: electrocautery or laser-assisted incisions, ballooning dilation, submucosal steroid injection, endoluminal stenting. The latter consists of tracheal resection with end-to-end anastomosis. As a rule, traditionally, the endoscopic management is restricted to short, low-grade, and simple TS, whereas the open techniques are employed in long, high-grade, and complex TS. However, the critical conditions or extreme comorbidities of several COVID-19 patients, as well as the marked inflammation in tracheal mucosa, have led some authors to apply endoscopic management also in complex TS, recording acceptable results. Although severe COVID-19 seems to be an issue of the past, its long-term complications are still unknown and considering the increased rate and complexity of TS in these patients, we strongly believe that it is worth to focus on it, attempting to find the best management strategy for COVID-19-related TS.

Post-intubation iatrogenic tracheobronchial injuries: The state of art.

Iatrogenic tracheobronchial injury (ITI) is an infrequent but potentially life-threatening disease, with significant morbidity and mortality rates. Its incidence is presumably underestimated since several cases are underrecognized and underreported. Causes of ITI include endotracheal intubation (EI) or percutaneous tracheostomy (PT). Most frequent clinical manifestations are subcutaneous emphysema, pneumomediastinum and unilateral or bilateral pneumothorax, even if occasionally ITI can occur without significant symptoms. Diagnosis mainly relies on clinical suspicion and CT scan, although flexible bronchoscopy remains the gold standard, allowing to identify location and size of the injury. EI and PT related ITIs more commonly consist of longitudinal tear involving the pars membranacea. Based on the depth of tracheal wall injury, Cardillo and colleagues proposed a morphologic classification of ITIs, attempting to standardize their management. Nevertheless, in literature there are no unambiguous guidelines on the best therapeutic modality: management and its timing remain controversial. Historically, surgical repair was considered the gold standard, mainly in high-grade lesions (IIIa-IIIb), carrying high morbi-mortality rates, but currently the development of promising endoscopic techniques through rigid bronchoscopy and stenting could allow for bridge treatment, delaying surgical approach after improving general conditions of the patient, or even for definitive repair, ensuring lower morbi-mortality rates especially in high-risk surgical candidates. Our perspective review will cover all the above issues, aiming at providing an updated and clear diagnostic-therapeutic pathway protocol, which could be applied in case of unexpected ITI.

Uniportal-VATS vs. open McKeown esophagectomy: Surgical and long-term oncological outcomes.

Background: Till now there are very few reports about surgical results of Uniportal-VATS esophagectomy and no one about long-term outcomes. This study is the first comparing surgical and oncological outcomes of Uniportal-VATS with open McKeown esophagectomy, with the largest reported series and longest oncological follow-up. Methods: The prospectively collected clinical, surgical and oncological data of 75 patients, undergone McKeown esophagectomy at our Thoracic Surgery Department, from January 2012 to August 2022, were retrospectively analyzed. Nineteen patients underwent esophagectomy by thoracotomy and reconstruction according to McKeown technique while 56 by Uniportal-VATS approach. Gastric tubulization was performed totally laparoscopic or through a mini-laparatomic access and cervical anastomosis was made according to Orringer's technique. Results: The mean operative thoracic time was similar in both accesses (102.34 ± 15.21 min in Uniportal-VATS vs. 115.56 ± 23.12 min in open, p: 0.646), with a comparable number of mediastinal nodes retrieved (Uniportal-VATS:13.40 ± 8.12 vs. open:15.00 ± 6.86, p: 0.275). No case needed conversion from VATS to open. The learning curve in Uniportal-VATS was completed after 34 cases, while the Mastery was reached after 40. Both approaches were comparable in terms of minor post-operative complications (like pneumonia, lung atelectasis, anemization, atrial fibrillation, anastomotic-leak, left vocal cord palsy, chylothorax), while the number of re-operation for major complications (bleeding or mediastinitis) was higher in open group (21.0% vs. 3.6%, p: 0.04). Both techniques were also effective in terms of surgical radicality and local recurrence but VATS approach allowed a significantly lower chest tube length (11.89 ± 9.55 vs. 25.82 ± 24.37 days, p: 0.003) and post-operative stay (15.63 ± 11.69 vs. 25.53 ± 23.33, p: 0.018). The 30-day mortality for complications related to surgery was higher in open group (p: 0.002). The 2-, 5- and 8-year survival of the whole series was 72%, 50% and 33%, respectively. Combined 2- and 5-year OS in Uniportal-VATS group was 76% and 47% vs. 62% and 62% in open group, respectively (Log-rank, p: 0.286; Breslow-Wilcoxon: p: 0.036). No difference in DFS was recorded between the two approaches (5 year-DFS in Uniportal-VATS: 86% vs. 72%, p: 0.298). At multivariate analysis, only pathological stage independently affected OS (p: 0.02), not the surgical approach (p: 0.276). Conclusions: Uniportal-VATS seems to be a safe, feasible and effective technique for performing McKeown esophagectomy, with equivalent surgical and long-term oncological results to standard thoracotomy, but with a faster and unharmed recovery, and a quite short learning curve.

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.

Sneaky Diagnosis of Pleural Malignant Mesothelioma in Thoracic Surgery: All That Glitters Is Not Gold.

Malignant Pleural Mesothelioma (MPM) is a highly aggressive disease whose diagnosis could be challenging and confusing. It could occur with atypical presentations on every examined level. Here, we present three unconventional cases of the complex diagnostic process of MPM that we have experienced during routine practice: a patient with reactive mesothelial hyperplasia mimicking MPM, an unexpected presentation of MPM with persistent unilateral hydropneumothorax, a rare case of MPM in situ. Then, we review the relevant literature on each of these topics. Definitive biomarkers to confidently distinguish MPM from other pleural affections are still demanded. Patients presenting with persistent hydropneumothorax must always be investigated for MPM. MPM in situ is now a reality, and this raises questions about its management.

COVID-19 After Lung Resection in Northern Italy.

We reviewed surgical cases from 4 Thoracic Surgery departments in the Lombardia region of Italy, the area mostly affected by Coronavirus pandemic in Europe, with the aim to describe the impact of COVID-19 on the treatment of thoracic surgical patients. Clinical, radiological and laboratory data from patients who underwent lung resection from December 2019 to March 2020 were retrospectively collected until June 2020. Univariable Cox regression models were estimated to evaluate potential prognostic factors for developing COVID-19 and to investigate postoperative mortality among patients who developed symptomatic COVID-19 infection. We examined data from 107 patients. (74 lobectomies, 32 wedge/segmentectomies and 1 pneumonectomy). Twelve patients developed COVID-19 (Group 1), whereas 95 patients were not infected (Group 2). In Group 1, 6 patients (50%) died from complications related to infection; in Group 2, one patient (1%) died because of non-COVID-19-related causes. Median days from surgery to first symptoms, CT confirmation, clinical confirmation and PCR positivity was 48.1, 54.3, 55.1, and 55.2 respectively. At univariable analysis, DLCO/VA% (P = 0.008), duration of the surgery (P = 0.009), smoking history (pack/year) (P < 0.001), BMI (P< 0.001) and number of segments resected (P = 0.010) were associated with COVID-19 onset. Moreover, CCI (P < 0.001), DLCO/VA% (P = 0.002), cigarette pack/year (P < 0.001), BMI (P < 0.001) and COVID-19 (P < 0.001) were associated with death. Patients who undergo lung resection and then develop symptomatic COVID-19 infection are at higher risk of developing severe respiratory complications and postoperative death. Insidious symptoms' onset may lead to a delay in diagnosis. We suggest two mitigating strategies: (1) Improve symptoms surveillance and isolation during recovery period, (2) Be aware of a potential greater risk of developing symptomatic COVID-19 and death correlated with elevated CCI, BMI, smoking history, DLCO/VA%, number of resected segments and duration of surgery.

Standardization of Procedures to Contain Cost and Reduce Variability of Care After the Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has changed many aspects of our private and professional routine. In particular, the lockdowns have severely affected the entire healthcare system and hospital activities, forcing it to rethink the protocols in force. We suggest that this scenario, in spite of the new challenges involving so far complex healthcare providers, may lead to the unique opportunity to rethink pathways and management of patients. Indeed, having to resume institutional activity after a long interruption that has completely canceled the previously existing schemes, healthcare providers have the unique opportunity to overcome obsolete and "we have always done in this way" model on the wave of the general desire to resume a normal life. Furthermore, the pandemic has highlighted some flaws in our health system, highlighting those critical issues that most need to be addressed. This article is a review of pre-pandemic literature addressing the use of Lean Six Sigma (LSS) and standardization processes in thoracic surgery to improve efficiency. Our goal is to identify the main issues that could be successfully improved along the entire pathway of a patient from the first referral to diagnosis, hospitalization, and surgical operation up to convalescence. Furthermore, we aim to identify the standardization processes that have been implemented to achieve significant improvements in patient outcomes while reducing costs. The methods and goals that could be used in the near future to modernize our healthcare systems are drawn up from a careful reading and interpretation in light of the pandemic of the most significant review articles in the literature.