Pulmonary Lobectomy for Early-Stage Lung Cancer with Uniportal versus Three-Portal Video-Assisted Thoracic Surgery: Results from a Single-Centre Randomized Clinical Trial.

Video-assisted thoracic surgery (VATS) is a consolidated approach; however, there is no consensus on the number of ports leading to less postoperative pain. We compared early postoperative pain after uniportal and three-portal VATS lobectomy for early-stage NSCLC. In this randomized clinical trial, patients undergoing VATS lobectomy were randomly assigned to receive uniportal (U-VATS Group) or three-portal (T-VATS Group) VATS. The inclusion criteria were age ≤ 80 years and ASA < 4. The exclusion criteria were clinical T3, previous thoracic surgery, induction therapy, chest radiotherapy, connective tissue or vascular diseases, major organ failure, and analgesics or corticosteroids use. The postoperative analgesia protocol was based on NRS. Pain was measured as analgesic consumption; the secondary endpoints were intra- and postoperative complications, conversion rate, surgical time, dissected lymph nodes, hospital stay, and respiratory function. Out of 302 eligible patients, 120 were included; demographics were distributed homogeneously. The mean cumulative morphine consumption (CMC) in the U-VATS Group after 7 days was lower than in the T-VATS Group (77.4 mg vs. 90.1 mg, p = 0.003). Intraoperative variables and postoperative complications were comparable. The 30-day intercostal neuralgia rate was lower in the U-VATS Group, without reaching statistical significance. Patients undergoing U-VATS showed a lower analgesic consumption compared with the T-VATS Group; analgesic consumption was moderate in both groups.

Early outcomes of "low-risk" patients undergoing lung resection assessed by cardiopulmonary exercise testing: Single-institution experience.

Objective: Cardiopulmonary exercise testing (CPET) is currently recommended for all patients undergoing lung resection with either respiratory comorbidities or functional limitations. The main parameter evaluated is oxygen consumption at peak (VO2peak). Patients with VO2peak above 20 ml/kg/min are classified as low risk surgical candidates. The aims of this study were to evaluate postoperative outcomes of low-risk patients, and to compare their outcomes with those of patients without pulmonary impairment at respiratory function testing. Methods: Retrospective monocentric observational study was designed, evaluating outcomes of patients undergoing lung resection at San Paolo University Hospital, Milan, Italy, between January 2016 and November 2021, preoperatively assessed by CPET, according to 2009 ERS/ESTS guidelines. All low-risk patients undergoing any extent surgical lung resection for pulmonary nodules were enrolled. Postoperative major cardiopulmonary complications or death, occurring within 30 days from surgery, were assessed. A case-control study was nested, matching 1:1 for type of surgery the cohort population with control patients without functional respiratory impairment consecutively undergoing surgery at the same centre in the study period. Results: A total of 80 patients were enrolled: 40 subjects were preoperatively assessed by CPET and deemed at low risk, whereas 40 subjects represented the control group. Among the first, 4 patients (10%) developed major cardiopulmonary complications, and 1 patient (2.5%) died within 30 days from surgery. In the control group, 2 patients (5%) developed complications and none of the patients (0%) died. The differences in morbidity and mortality rates did not reach statistically significance. Instead, age, weight, BMI, smoking history, COPD incidence, surgical approach, FEV1, Tiffenau, DLCO and length of hospital stay resulted significantly different between the two groups. At a case-by-case analysis, CPET revealed a pathological pattern in each complicated patient, in spite of VO2peak above target for safe surgery. Conclusions: Postoperative outcomes of low-risk patients undergoing lung resections are comparable to those of patients without any pulmonary functional impairment; nonetheless the formers represent a dramatically different category of individuals from the latter and may harbour few patients with worse outcomes. CPET variables overall interpretation may add to the VO2peak in identifying higher risk patients, even in this subgroup.

Lobar size reduction in lung transplantation: A propensity score study.

OBJECTIVE: For small-sized recipients of lung transplantation, the time span for organ reception from standard donors is generally longer than for normal-sized patients. Despite its underuse, lobar reduction may be a concrete option for these patients. This study aims to assess early and long-term outcomes associated with lobar reduction in lung transplantation. METHODS: A retrospective study was performed on 608 consecutive lung transplantations at 2 centers between January 2005 and August 2019 (559 standard lung transplantations [standard transplantation] and 49 with lobar reduction [lung transplantation group]). A propensity-score weighting approach was used to account for potential confounding related to patients' nonrandom allocation to the 2 intervention groups. The effects of the intervention on postoperative outcomes were assessed with a weighted regression approach. RESULTS: The propensity score was estimated on 571 patients (522 in standard transplantation group and 49 in lung transplantation group). In terms of early outcomes, the lung transplantation group showed a higher percentage of severe primary graft dysfunction at 0 hours and reported longer intensive care unit stay than the standard transplantation group. No other differences in terms of morbidity, mortality, mechanical ventilation time, hospital stay, and anastomotic complications were observed. Although the lung transplantation group showed worse long-term pulmonary function, the 2 populations had comparable survival outcomes. CONCLUSIONS: The use of lobar reduction showed early and long-term results comparable to those after standard lung transplantation. Although a higher rate of early severe primary graft dysfunction and slightly reduced respiratory function were detected in the lobar group, these did not affect patients' morbidity and survival.

An Unusual Histology for a Lung Nodule: A Case Report of Primary Pulmonary Paraganglioma.

Introduction: Primary pulmonary paraganglioma is a rare tumor with few cases reported in literature and unspecific clinical presentation. Case Presentation: A 49-year-old woman presented to our department with an incidental finding of a pulmonary mass at chest X-ray and no associated clinical symptom. The CT scan and the FDG-PET showed mild uptake of contrast, but a definitive diagnosis was only possible after surgery through histopathological examination. Conclusion: Paragangliomas originating in the pulmonary tissue are generally non-functioning masses discovered incidentally in otherwise asymptomatic patients. Surgery appears to be the best treatment option, with only radiologic follow-up necessary afterwards.

Addition of 5% CO2 to Inspiratory Gas Prevents Lung Injury in an Experimental Model of Pulmonary Artery Ligation.

Rationale: Unilateral ligation of the pulmonary artery may induce lung injury through multiple mechanisms, which might be dampened by inhaled CO2. Objectives: This study aims to characterize bilateral lung injury owing to unilateral ligation of the pulmonary artery in healthy swine undergoing controlled mechanical ventilation and its prevention by 5% CO2 inhalation and to investigate relevant pathophysiological mechanisms. Methods: Sixteen healthy pigs were allocated to surgical ligation of the left pulmonary artery (ligation group), seven to surgical ligation of the left pulmonary artery and inhalation of 5% CO2 (ligation + FiCO2 5%), and six to no intervention (no ligation). Then, all animals received mechanical ventilation with Vt 10 ml/kg, positive end-expiratory pressure 5 cm H2O, respiratory rate 25 breaths/min, and FiO2 50% (±FiCO2 5%) for 48 hours or until development of severe lung injury. Measurements and Main Results: Histological, physiological, and quantitative computed tomography scan data were compared between groups to characterize lung injury. Electrical impedance tomography and immunohistochemistry analysis were performed in a subset of animals to explore mechanisms of injury. Animals from the ligation group developed bilateral lung injury as assessed by significantly higher histological score, larger increase in lung weight, poorer oxygenation, and worse respiratory mechanics compared with the ligation + FiCO2 5% group. In the ligation group, the right lung received a larger fraction of Vt and inflammation was more represented, whereas CO2 dampened both processes. Conclusions: Mechanical ventilation induces bilateral lung injury within 48 hours in healthy pigs undergoing left pulmonary artery ligation. Inhalation of 5% CO2 prevents injury, likely through decreased stress to the right lung and antiinflammatory effects.

Atelectasis, Shunt, and Worsening Oxygenation Following Reduction of Respiratory Rate in Healthy Pigs Undergoing ECMO: An Experimental Lung Imaging Study.

Rationale: Reducing the respiratory rate during extracorporeal membrane oxygenation (ECMO) decreases the mechanical power, but it might induce alveolar de-recruitment. Dissecting de-recruitment due to lung edema vs. the fraction due to hypoventilation may be challenging in injured lungs. Objectives: We characterized changes in lung physiology (primary endpoint: development of atelectasis) associated with progressive reduction of the respiratory rate in healthy animals on ECMO. Methods: Six female pigs underwent general anesthesia and volume control ventilation (Baseline: PEEP 5 cmH2O, Vt 10 ml/kg, I:E = 1:2, FiO2 0.5, rate 24 bpm). Veno-venous ECMO was started and respiratory rate was progressively reduced to 18, 12, and 6 breaths per minute (6-h steps), while all other settings remained unchanged. ECMO blood flow was kept constant while gas flow was increased to maintain stable PaCO2. Measurements and Main Results: At Baseline (without ECMO) and toward the end of each step, data from quantitative CT scan, electrical impedance tomography, and gas exchange were collected. Increasing ECMO gas flow while lowering the respiratory rate was associated with an increase in the fraction of non-aerated tissue (i.e., atelectasis) and with a decrease of tidal ventilation reaching the gravitationally dependent lung regions (p = 0.009 and p = 0.018). Intrapulmonary shunt increased (p < 0.001) and arterial PaO2 decreased (p < 0.001) at lower rates. The fraction of non-aerated lung was correlated with longer expiratory time spent at zero flow (r = 0.555, p = 0.011). Conclusions: Progressive decrease of respiratory rate coupled with increasing CO2 removal in mechanically ventilated healthy pigs is associated with development of lung atelectasis, higher shunt, and poorer oxygenation.

Case Report: Mediastinal Mass in SARS-COV-2 Pandemic: A Word of Caution.

Background: SARS-CoV-2 is a new disease with some manifestations not yet well-known. Sharing experiences in this topic is crucial for the optimal management of the patients. Case Presentation: Left upper extremity deep vein thrombosis (UEDVT) due to a mediastinal mass strongly suspected of lymphoproliferative disease in a patient affected by SARS-CoV-2, disappearing at the resolution of the viral infection. Conclusion: Before proceeding to surgical biopsy, mediastinal mass in SARS-CoV-2 patients must be revaluated after the resolution of the infection.

Uniportal and three-portal video-assisted thoracic surgery pulmonary lobectomy for early-stage lung cancer (UNIT trial): study protocol of a single-center randomized trial.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) lobectomy is currently the recommended approach for treating early-stage non-small cell lung cancer (NSCLC). Different VATS approaches have been proposed so far, and the actual advantages of one technique over the other are still under debate. The aim of our study is to compare postoperative pain and analgesic drug consumption in uniportal VATS and triportal VATS for pulmonary lobectomy in early-stage lung cancer patients. METHODS: This study is a single-center, prospective, two-arm, parallel-group, randomized controlled trial. It is designed to compare uniportal video-assisted thoracic surgery (u-VATS) and three-port video-assisted thoracic surgery (t-VATS) in terms of postoperative pain. The trial will enroll 120 patients with a 1:1 randomization. The primary outcome is the assessment of analgesic drug consumption. Secondary outcomes are postoperative pain measurement, evaluation of postoperative pulmonary function, and metabolic recovery after pulmonary lobectomy. DISCUSSION: The choice of which VATS approach to adopt for treating patients undergoing pulmonary resection mostly depends on the surgeon's preferences; therefore, it is hard to prove whether one VATS technique is superior to the other. Moreover, postoperative analgesic protocols vary consistently among different centers. To date, only a few studies have evaluated the effects of the most popular VATS techniques. There is no evidence about the difference between multiport VATS and u-VATS in terms of postoperative pain. We hope that the results of our trial will provide valuable information on the outcomes of these different surgical approaches. TRIAL REGISTRATION: ClinicalTrials.gov NCT03240250 . Registered on 07 August 2017; retrospectively registered.

The European experience.

Traditionally, pulmonary lobectomy has always been considered as the gold standard for the treatment of early stage non-small cell lung cancer (NSCLC); limited resections have been proposed in case of "compromised" patients, with relevant comorbidities. In the last years, the interest in anatomical segmentectomies among surgeons has been progressively growing, even for patients fit for lobectomy, in selected cases. In this article we debate the current trends in the treatment of early stage NSCLC around Europe.

Pulmonary Resection for Metastasis of Hepatocellular Carcinoma Recurring After Liver Transplant: An Italian Multicenter Experience.

Background and aim: Liver transplantation (LT) is a validated treatment for hepatocellular carcinoma (HCC). HCC recurrence occurred between 8 and 20% of patients and lung is the most frequent site. Pulmonary metastases resection (PMR) prolongs survival, however in LT-setting the impact on survival is unclear. To give new lights on this issue, we report the experience of three Italian LT Centers. Methods: All consecutive HCC transplanted patients in three Italian LT Centers, who developed pulmonary metastasis from HCC (PM-HCC), as first metastasis, from 2008 to 2018, were included whenever treated with PMR. Results: Twenty-five patients were enrolled (median age 58 yrs, 84% male, 3% cirrhotics). HCC recurred after 34 months (9-306) since LT and PMR was performed after 2.4 months (0-43.1). A total of 28 PMR (19 single resections; 9 multiple resections; 16 right; 2 left) have been performed on 24 patients while in one case percutaneous microwave ablation (MWA) was preferred. Four patients have been re-operated due to pulmonary HCC-recurrence after surgery. The majority of surgical resection type was wedge resection (26, 89%). Surgical access was: video-assisted thoracic surgery (VATS) in 17 cases (59%); thoracotomy in 11 (38%); MWA in 1 (3%). The 48% of nodule was in right lower lobe. Perioperative in-hospital mortality and 30 days mortality were nil; median surgical time 90 min (50-365); median post-operative overall stay 5 days (2-11). Post-operative ICU treatment was necessary in 1 case (3%) for 3 days; blood transfusions in 2 cases (7%). Overall, 5 complications (2 bleeding; 1 AKI; 1 major cardiac; 1 wound dehiscence) occurred, with an overall complications rate of 23%. Eight (32%) patients died during a follow-up after HCC recurrence of 32 months (7-213): 7 for HCC progression, 1 for severe liver failure due to chronic rejection. The 1 and 5 year cumulative probability of OS from recurrence were 100 and 43% (95%CI 12-74), respectively, with a median OS of 51 months (95%CI 24-78). Conclusion: Selected patients with isolated pulmonary HCC-recurrence after LT and with preserved hepatic function showed that a pulmonary metastasectomy could be efficacious in managing a PM-HCC and could give an opportunity for long-term survival.

Prognostic factors of lung cancer in lymphoma survivors (the LuCiLyS study).

BACKGROUND: Second cancer is the leading cause of death in lymphoma survivors, with lung cancer representing the most common solid tumor. Limited information exists about the treatment and prognosis of second lung cancer following lymphoma. Herein, we evaluated the outcome and prognostic factors of Lung Cancer in Lymphoma Survivors (the LuCiLyS study) to improve the patient selection for lung cancer treatment. METHODS: This is a retrospective multicentre study including consecutive patients treated for lymphoma disease that subsequently developed non-small cell lung cancer (NSCLC). Data regarding lymphoma including age, symptoms, histology, disease stage, treatment received and lymphoma status at the time of lung cancer diagnosis, and data on lung carcinoma as age, smoking history, latency from lymphoma, symptoms, histology, disease stage, treatment received, and survival were evaluated to identify the significant prognostic factors for overall survival. RESULTS: Our study population included 164 patients, 145 of which underwent lung cancer resection. The median overall survival was 63 (range, 58-85) months, and the 5-year survival rate 54%. At univariable analysis no-active lymphoma (HR: 2.19; P=0.0152); early lymphoma stage (HR: 1.95; P=0.01); adenocarcinoma histology (HR: 0.59; P=0.0421); early lung cancer stage (HR: 3.18; P<0.0001); incidental diagnosis of lung cancer (HR: 1.71; P<0.0001); and lung cancer resection (HR: 2.79; P<0.0001) were favorable prognostic factors. At multivariable analysis, no-active lymphoma (HR: 2.68; P=0.004); early lung cancer stage (HR: 2.37; P<0.0001); incidental diagnosis of lung cancer (HR: 2.00; P<0.0001); and lung cancer resection (HR: 2.07; P<0.0001) remained favorable prognostic factors. Patients with non-active lymphoma (n=146) versus those with active lymphoma (n=18) at lung cancer diagnosis presented better median survival (64 vs. 37 months; HR: 2.4; P=0.02), but median lung cancer specific survival showed no significant difference (27 vs. 19 months; HR: 0.3; P=0.17). CONCLUSIONS: The presence and/or a history of lymphoma should not be a contraindication to resection of lung cancer. Inclusion of lymphoma survivors in a lung cancer-screening program may lead to early detection of lung cancer, and improve the survival.

Uniportal and three-portal video-assisted thoracic surgery lobectomy: analysis of the Italian video-assisted thoracic surgery group database.

OBJECTIVES: This study compares the uniportal with the 3-portal video-assisted thoracic surgery (VATS) by examining the data collected in the Italian VATS Group Database. The primary end point was early postoperative pain; secondary end points were intraoperative and postoperative complications, surgical time, number of dissected lymph nodes and length of stay. METHODS: This was an observational, retrospective, cohort, multicentre study on data collected by 49 Italian thoracic units. Inclusion criteria were clinical stage I-II non-small-cell lung cancer, uniportal or 3-portal VATS lobectomy and R0 resection. Exclusion criteria were cT3 disease, previous thoracic malignancy, induction therapy, significant comorbidities and conversion to other techniques. The pain parameter was dichotomized: the numeric rating scale ≤3 described mild pain, whereas the numeric rating scale score >3 described moderate/severe pain. The propensity score-adjusted generalized estimating equation was used to compare the uniportal with 3-portal lobectomy. RESULTS: Among 4338 patients enrolled from January 2014 to July 2017, 1980 met the inclusion criteria; 1808 patients underwent 3-portal lobectomy and 172 uniportal surgery. The adjusted generalized estimating equation regression model using the propensity score showed that over time pain decreased in both groups (P < 0.001). There was a statistical difference on the second and third postoperative days; odds ratio (OR) 2.28 [95% confidence interval (CI) 1.62-3.21; P < 0.001] and OR 2.58 (95% CI 1.74-3.83; P < 0.001), respectively. The uniportal-VATS group had higher operative time (P < 0.001), shorter chest drain permanence (P < 0.001) and shorter length of stay (P < 0.001). CONCLUSIONS: Data from the Italian VATS Group Database showed that in clinical practice uniportal lobectomy seems to entail a higher risk of moderate/severe pain on second and third postoperative days.

VATS segmentectomy: an underused option?

It is well known that the "gold standard" procedure for surgically resectable early-stage non-small cell lung cancer (NSCLC), is pulmonary lobectomy. Even though sublobar resections (SLR), particularly segmentectomy, seem attractive as an alternative to lobectomy in early stage lung cancers, they are still debated procedures. The aim of this study is to answer to the question: "Is VATS lung segmentectomy an underused option?" To obtain an answer to this query, the authors carried out a review of the "state of the art" as follows: (I) performing a non-systematic review of the literature; (II) analyzing the review articles published; (III) looking at the ongoing studies, the results of which have not yet published; (IV) scanning the technical aspect of lung segmentectomy. After completing the multi-step revision, we can conclude that there is a lack of evidence about the oncological value of segmentectomy in early stage NSCLC. Although VATS segmentectomy is feasible and performed by many thoracic surgeons, it's currently not yet world-wide adopted. Among the trials now being recruited in some countries and, aimed to clarify the role of SLR in the treatment of early stage lung cancer, a European prospective randomized study is advocated to implement the scientific knowledge on this issue.

Minute ventilation to carbon dioxide output (V'E/V'CO2 slope) is the strongest death predictor before larger lung resections.

The minute ventilation to CO2 production ratio (V'E/V'CO2 slope) was recently identified as a mortality predictor after lung surgery, but the effect of the resection extent was not taken into account.  The aim of this study was to investigate the role of V'E/V'CO2 slope as preoperative mortality predictor depending on the type of surgery performed. Retrospective analysis was performed on 263 consecutive patients evaluated before surgery for lung cancer. Death within 30 days and serious respiratory complications were considered. Univariate and multivariate regression analyses were used to identify independent predictors of death. Lobectomy or bilobectomy were performed in 186 patients with 29/186 (15.6%) serious pulmonary complications and 6/186 (3.2%) deaths. Pneumonectomy was performed in 77 patients with 14/77 (18.2%) serious complications and 5/77 (6.5%) deaths.  Considering the whole group, the peak oxygen consumption (V'02peak, L/ min; z=-2.66, p<0.008, OR 0.007) and V'E/V'C02 slope (z=2.80, p<0.005, OR 1.14) were independent predictors of mortality whereas in pneumonectomies V'E/V'C02 slope (z=2.34, p<0.02, OR 1.22) was the only independent predictor of mortality. High V'E/V'CO2 slope, age and low V'02peak are predictors of death and severe complications after lung surgery. Before larger resections as pneumonectomies an increased V'E/V'CO2 slope represents the best mortality predictor.

Direct muscle neurotization after end-to end and end-to-side neurorrhaphy: An experimental study in the rat forelimb model.

The need for the continuous research of new tools for improving motor function recovery after nerve injury is justified by the still often unsatisfactory clinical outcome in these patients. It has been previously shown that the combined use of two reconstructive techniques, namely end-to-side neurorrhaphy and direct muscle neurotization in the rat hindlimb model, can lead to good results in terms of skeletal muscle reinnervation. Here we show that, in the rat forelimb model, the combined use of direct muscle neurotization with either end-to-end or end-to-side neurorrhaphy to reinnervate the denervated flexor digitorum muscles, leads to muscle atrophy prevention over a long postoperative time lapse (10 months). By contrast, very little motor recovery (in case of end-to-end neurorrhaphy) and almost no motor recovery (in case of end-to-side neurorrhaphy) were observed in the grasping activity controlled by flexor digitorum muscles. It can thus be concluded that, at least in the rat, direct muscle neurotization after both end-to-end and end-to-side neurorrhaphy represents a good strategy for preventing denervation-related muscle atrophy but not for regaining the lost motor function.