NSCLC Immunotherapy and Related Rare Toxicities: A Monocentric Real-Life Experience.

BACKGROUND: In the last years immunotherapy has revolutionized the treatment of non-small cell lung cancer (NSCLC) not supported by a driver mutation. Immunotherapy related adverse events (irAEs) have a unique toxicity profiles distinct from the toxicities of classical chemotherapy treatment relating to their mechanism of action. We analyzed some serious and uncommon life-threatening irAEs, needing a change in the therapeutic strategy. METHOD: Between October 2018 and October 2020, 63 NSCLC patients underwent immunotherapy. Thirty-eight patients underwent first-line Pembrolizumab, 200 mg every 21 days (Group A). Twenty patients were treated in second line with Pembrolizumab 200 mg every 21 days or Nivolumab 240 mg every 14 days or Atezolizumab 800 mg every 14 days (Group B). Five stage III patients treated after radio chemotherapy with Durvalumab 1500 mg every 14 days (Group C). RESULTS: We experienced: a) 2 bowel perforations (3.2%), necessitating Hartmann's resection. Only one of the two patients restored immunotherapy; b) 1 chronic renal insufficiency (1.6%, creatinine up to 8 mg/dL) and 2 severe hypertransaminasemias (3.2%, up to 65 U/L), requiring the immediate and definitive interruption of ICIs; c) 2 pericardial effusions (3.2%), of which one needed subxiphoid pericardiocentesis for cardiac tamponade. Patient restored immunotherapy after resolution of the acute event. CONCLUSIONS: Immunotherapy include monoclonal antibodies reducing the suppression of effector T cells and improving the tumor-specific immune responses. Most common irAEs are evident in mild and reversible form, but sometimes life-threatening irEAs show up. Therefore, further clinical trials needed to increase knowledge of drugs and prevent unexpected irAEs.

Is It Possible to Establish a Reliable Correlation between Maximum Standardized Uptake Value of 18-Fluorine Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography and Histological Types of Non-Small Cell Lung Cancer? Analysis of the Italian VATS Group Database.

BACKGROUND: Although positron emission tomography/computed tomography, often integrated with 2-deoxy-2-[fluorine-18] fluorine-D-glucose (18F-FDG-PET/CT), is fundamental in the assessment of lung cancer, the relationship between metabolic avidity of different histotypes and maximum standardized uptake value (SUVmax) has not yet been thoroughly investigated. The aim of the study is to establish a reliable correlation between Suvmax and histology in non-small cell lung cancer (NSCLC), in order to facilitate patient management. METHODS: We retrospectively assessed the data about lung cancer patients entered in the Italian Registry of VATS Group from January 2014 to October 2019, after establishing the eligibility criteria of the study. In total, 8139 patients undergoing VATS lobectomy were enrolled: 3260 females and 4879 males. The relationship between SUVmax and tumor size was also analyzed. RESULTS: The mean values of SUVmax in the most frequent types of lung cancer were as follows: (a) 4.88 ± 3.82 for preinvasive adenocarcinoma; (b) 5.49 ± 4.10 for minimally invasive adenocarcinoma; (c) 5.87 ± 4.18 for invasive adenocarcinoma; and (d) 8.85 ± 6.70 for squamous cell carcinoma. Processing these data, we displayed a statistically difference (p < 0.000001) of FDG avidity between adenocarcinoma and squamous cell carcinoma. Moreover, by classifying patients into five groups based on tumor diameter and after evaluating the SUVmax value for each group, we noted a statistical correlation (p < 0.000001) between size and FDG uptake, also confirmed by the post hoc analysis. CONCLUSIONS: There is a correlation between SUVmax, histopathology outcomes and tumor size in NSCLC. Further clinical trials should be performed in order to confirm our data.

Case Report: A New Tool for Anterior Chest Wall Reconstruction After Sternal Resection for Primary Or Secondary Tumors.

Sternal resection and anterior chest wall reconstruction techniques for malignant processes are not always standardized. We report an innovative method of sternal osteosynthesis in two patients, 65-year-old and 41-year-old women, with Ewing's sarcoma, and infiltrating thymoma, respectively. The first case manifested itself as a voluminous palpable mass while the second case was characterized for a paramediastinal mass widely extended to the anterior chest wall. Reconstruction with titanium mesh allowed the quick restoration of parietal stability, facilitating respiratory dynamic and recovery of patients.

Pleural empyema associated with alveolar-pleural fistulas in severe acute respiratory syndrome coronavirus 2.

Surgery in COVID-19 disease complicated by APF represents the last life-saving treatment option. The choice of the therapeutic period to indicate this approach is fundamental. In fact, the clinical stability of patient is necessary in order to allow single-lung ventilation and to minimize postoperative sequelae.

Plates versus struts versus an extracortical rib fixation in flail chest patients: Two-center experience.

PURPOSES: Notwithstanding advances in medical and surgical management of flail chest, its morbidity and mortality rates are still high. Aim of this study is to compare three approaches for parietal thoracic stabilization by analyzing both early and long-term patient outcomes. METHODS: A retrospective study from January 2006 to January 2018 involving sixty-five surgical flail chest (25 plates,11 struts and 29 wires fixations) was conducted. A mean Abbreviated Injury Scale (AIS) was 2.38±0.82 and a mean Injury Severity Score (ISS) was 32.02±8.21. RESULTS: Struts and plates stabilizations compared with wires fixation showed an immediate restoring of the partial pressure of oxygen (90.56 mmHg vs 91.90 mmHg vs 89.23 mmHg, p = 0.021), the carbon-dioxide levels (36.00 mmHg vs 35.03 mmHg vs 38.98 mmHg, p = 0.000) and the oxygen-blood saturation (97.71% vs 98.21% vs 92.12%, p = 0.000) in the early postoperative period. Furthermore, struts and plates ensured a better recovery of daily activities up to the 3rdmonth (QoL=1.0: p<0.001 in lateral flail chest and p<0.02 in anterior and antero-lateral flail chest). At the 12thmonth no difference in QoL was found between the different approaches. CONCLUSIONS: Plate and strut fixation revealed a lower rate of postoperative morbidity and mortality. Wires stabilization was characterized for a reduction of operative time.

Lobectomy versus sublobar resection in patients with non-small cell lung cancer: a systematic review.

Surgery is the gold standard treatment of lung cancer. The minimally invasive technique does not only concern access to the chest but also the limits of parenchymal resection. The study debates on the safety and oncological adequacy of sublobar resections in bronchogenic carcinoma patients. A systematic analysis of the data in the literature was carried out, comparing the outcomes of patients with resectable non-small lung cancer (NSCLC) who underwent lobectomy or sublobar resection. These last interventions include both segmentectomies and wedge resections taking into consideration the following parameters: complications, relapse rate and overall survival. The complication rate is higher in patients underwent lobectomy compared to sublobar resection, especially in presence of high comorbidity index or octogenarian patients (overall values respectively between 0 and 48% and 0 and 46.6%). Contrarily, the relapse rate (6.2% to 32% vs. 3.6% to 53.4%) and overall survival (50.2% to 93.8% vs. 38.6% to 100%) are more favorable in patients undergoing lobectomy. Sublobar resections are particularly indicated in elderly patients and in patients with high comorbidity index or reduced respiratory functional reserve. However, pulmonary lobectomy still remains the safest and oncologically correct method in patients with good performance status or higher risk of recurrence.

Video-assisted thoracoscopic sympathectomy versus modified Wittmoser method in surgical management of primary hyperhidrosis.

PURPOSES: We compared two different surgical methods evaluating the effectiveness of procedures and the quality of life (QoL) of patients. METHODS: From January 2010 to November 2017 we carried out 476 biportal video-assisted thoracoscopic surgery (VATS) approaches of sympathetic chain in 238 patients. One hundred and twenty-nine (54%) patients underwent conventional sympathectomy (CS) while 109 (46%) patients underwent sympathicotomy associated with the division of the rami communicantes (MWT). Quality of Life (QoL) was classified as follows: from 20 to 35 excellent; from 36 to 51 very good; from 52 to 68 good; from 69 to 84 poor; and > 84 very poor. RESULTS: We noticed statistical significant reduction of complications comparing CS with MWT approaches (chest pain from 36.4 to 4.5%; paresthesias from 8.5 to 3.6%; bradycardia from 28.6 to 10%, respectively). The preoperative and postoperative QoL index evaluation revealed a statistically significant improvement after surgery (CS: 86 ± 2 versus 35 ± 1, p = 0.00001; MWT: 85 ± 1 versus 33 ± 2, p = 0.00001), with general satisfaction of the two techniques. CONCLUSION: Modified Wittmoser method seems to be a valid alternative to conventional sympathectomy, minimizing the percentage rate of complications and showing significant effectiveness in the quality of life improvement.

Diagnostic performance of fluorine-18 fluorodeoxyglucose positron emission tomography in the management of solitary pulmonary nodule: a meta-analysis.

BACKGROUND: In the setting of solitary pulmonary nodules (SPNs), fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) is considered a useful non-invasive diagnostic tool though false positive (FP) and false negative (FN) results affects accuracy due to different conditions, such as inflammatory diseases or low-uptake neoplasms. Aim of this study is to evaluate overall diagnostic performance of 18F-FDG-PET/CT for malignant pulmonary nodules. METHODS: A computerized research, including published articles from 2012 and 2017, was carried out. 18F-FDG-PET/CT overall sensitivity (Se), specificity (Spe), positive likelihood ratio (PLR), negative likelihood ratio (NLR), positive predictive value (PPV), negative predictive value (NPV), diagnostic index and odds ratio were pooled. No selection-bias were found according to asymmetry test. RESULTS: A total of twelve studies were included in the meta-analysis. The pooled Se, Spe, PLR, NLR, PPV, NPV and accuracy index (AI) with relative 95% confidence intervals (CI) were 0.819 (95% CI: 0.794-0.843), 0.624 (95% CI: 0.582-0.665), 2.190 (95% CI: 1.950-2.440), 0.290 (95% CI: 0.250-0.330), 0.802 (95% CI: 0.783-0.819), 0.652 (95% CI: 0.618-0.684) and 0.649 (95% CI: 0.625-0.673), respectively. The diagnostic odds ratio (DOR) was 7.049 with a relative 95% CI between 5.550 and 8.944. CONCLUSIONS: The results suggest 18F-FDG-PET/CT has good diagnostic accuracy in SPNs evaluation; but, it should not be considered as a discriminatory test rather than a method to be included in a clinical and diagnostic pathway.

Endobronchial ultrasound-transbronchial needle aspiration (EBUS/TBNA): a diagnostic challenge for mediastinal lesions.

Lung cancer is one of the most frequent neoplastic diseases. To date, most lung cancer is diagnosed at an advanced stage, making it difficult to choose the diagnostic and therapeutic strategy. Surgical resection represents the best therapeutic solution. However, the best results are obtained only in the early stages of the disease. Lymph node involvement conditions the treatment (surgical or non-surgical approach). Mediastinoscopy is an effective and widely used method for mediastinal staging but does not allow us to reach many mediastinal lymph nodes. Endobronchial ultrasound/transbronchial needle aspiration (EBUS-TBNA) allows us to reach more lymph nodes and is referred to as a first-choice exam for mediastinal staging.

Surgical approach in the oligometastatic patient.

In the setting of a stage IV non-small cell lung cancer (NSCLC), oligometastatic patients represent a heterogeneous group whose incidence is increasing as far as with the adoption of new therapeutic regimens, the improvement of the molecular characterization assays and the increasing number of long-survivor patients. The oligometastatic state undergone a major revision with the introduction of the new TNM lung cancer staging system, being characterized by a different prognosis compared to multi-metastatic patients. Furthermore, the presence of a limited number of metastases imposes a local control especially when clonal selections occur during adjuvant therapy. In this regard, the review seeks to clarify the indications for surgical treatment by organ according to recent guidelines, by analyzing prognostic factors and outcome of patients. Although accurate patient stratification is mandatory, aggressive local control strategies represent a valid therapeutic approach in patients with oligometastatic NSCLC. At the same time, persevering with ablative strategies raises both medical and ethical issues about limits and reiteration, which certainly requires a deep reflection, being, on the other hand, in front of a metastatic disease.

National adoption of video-assisted thoracoscopic surgery (VATS) lobectomy: the Italian VATS register evaluation.

BACKGROUND: The expertise curve of video-assisted thoracoscopic surgery (VATS) lobectomies still stirs debate and controversy both because of the number of procedures to carry out and of the evaluation of the learning threshold. The purpose of our study was the examination of the variables related to the learning curve of the video-assisted approach, to establish what may be an expression of the technical maturity of the surgeon. METHODS: The National Register for VATS lobectomy built in 2013 was used to collect data from 65 Thoracic Surgery Units. Out of more than 3,700 patients enrolled, only information from Units with ≥100 VATS lobectomies were retrospectively analysed. Unpaired Student's t-tests, Fisher's exact tests, Pearson's χ2 were applied as needed. Cumulative summative analysis and one-way ANOVA were used to identify the expertise curve of VATS lobectomy. RESULTS: Ten institutions contributed a total of 1,679 patients, who were divided into three uniform groups according to the chronological sequence of surgery. The length of utility incision, the number of dissected lymph nodes and the operative time were not statistically significant (P=0.999, P=0.972 and P=0.307, respectively) among groups. Conversion to thoracotomy and postoperative air leaks occurred in 125 (7.44%) and 109 (6.49%) patients, gradually declined in Group 3 with statistical significance (P=0.048 and P=0.00086). CONCLUSIONS: The conversion rate and the percentage of air leaks seem to define the expertise of VATS lobectomy, being linked to the ability to manage more complicated surgical cases or intraoperative adverse events.

Basic statistics with Microsoft Excel: a review.

The scientific world is enriched daily with new knowledge, due to new technologies and continuous discoveries. The mathematical functions explain the statistical concepts particularly those of mean, median and mode along with those of frequency and frequency distribution associated to histograms and graphical representations, determining elaborative processes on the basis of the spreadsheet operations. The aim of the study is to highlight the mathematical basis of statistical models that regulate the operation of spreadsheets in Microsoft Excel.

Fluorine-18 fluorodeoxyglucose positron emission tomography in the management of solitary pulmonary nodule: a review.

Solitary pulmonary nodules are common radiologic findings and their detection has increased due to the introduction and improvement of diagnostics. Since a nodule can be an expression of early lung cancers, a proper classification and management are required because its treatment might lead to decreased morbidity and mortality. In this regard, prominent guidelines are available although they are characterized sometimes by discordant and misleading evidences. Furthermore, the same results of studies in the literature appear conflicting. Aim of this work is to evaluate the role of imaging through an extensive literature review but focusing on 18-fluorine fluorodeoxyglucose positron emission tomography combined with computed tomography (18F-FDG-PET/CT) in order to assess the limits and future perspectives of solitary pulmonary nodule characterization in early detection of lung cancer. Key messages Detection of solitary pulmonary nodules has increased. Management of solitary pulmonary nodules is still debated. Future perspectives of early solitary pulmonary nodule characterization.

Management of Bronchopleural Fistula Complicated by Skin Wound Necrosis after Thoracomyoplasty.

Skin necrosis is a rare complication after thoracomyoplasty and usually needs conservative treatment. We described positive findings with surgical approach. A 54-year-old man showed bronchopleural fistula after undergoing right pneumonectomy for lung cancer, treated with thoracomyoplasty. On the 20th postoperative day, a skin wound lesion was noted, whose deterioration required a skin flap transposition. Patient was discharged from hospital on the 7th postoperative day and did not show relapse at the 7th year follow-up. Surgery can be the most viable alternative to medical treatments in the management of a chest wall cutaneous complication even in high-risk patients.

Video-assisted thoracoscopic surgery lobectomy learning curve: what program should be offered in a residency course?

Video-assisted thoracoscopic (VAT) procedures are emerging for treatment of both benign and malignant thoracic diseases and substituting classical approaches, such as thoracotomies, thanks to several advantages concerning postoperative morbidity rates and overall patients' outcome (i.e., postoperative pain, chronic pain and quality of life). However, a VAT approach needs an established learning curve making procedures as safe as in open surgery. With regard of trainee surgeons, notwithstanding an increasing number of learning tools and strategies, such as simulation programs (i.e., black-boxes, wet labs, cadaver or animal labs, 3D virtual reality simulators) and direct observation both of live surgery and videos with a supportive evidence base from benchtop studies, there remains inconsistent adoption in surgical educations.

Can a standardised Ventilation Mechanical Test for quantitative intraoperative air leak grading reduce the length of hospital stay after video-assisted thoracoscopic surgery lobectomy?

We standardised a Ventilation Mechanical Test (VMT) after video-assisted thoracoscopic surgery (VATS) lobectomy that classifies intraoperative alveolar air leaks (IOAALs) in mild, moderate and severe. We assumed that mild IOAALs (<100 mL/min) are self-limiting, whereas severe IOAALs (>400 mL/min) must be treated. An IOAAL between 100 and 400 mL/min was defined moderate and constituted the study population of a prospective multicentre randomised trial on the use of a polymeric biodegradable sealant (ProgelTM Pleural Air Leak Sealant, Bard Davol, USA) in case of moderate IOAAL compared with no treatment. We assumed that the standardised VMT allows to accurately selected patients needing treatment, thus limiting unnecessary sealant use. We analysed data of the randomised trial to assess the cost-effectiveness of Progel treatment in VMT selected patients. This is a multicenter randomised controlled trial. Patients with moderate IOAAL were randomised to Progel (group A) or "no treatment" (group B).The primary efficacy endpoint of the study was the postoperative duration of air leakage. The secondary outcome measures included: mean time to chest drain removal, mean length of hospitalisation, the percentage of postoperative complications occurring within two months, and cost of treatment. Between January 2015 and January 2017, 255 VATS lobectomies were performed in 4 centres, 55 met the inclusion criteria, and they were randomly assigned to 2 different groups (28 in the Progel and 27 in the control group). The mean air leakage duration was statistically different between the two groups: in the group A was 1.60 vs. 5.04 days in group B (P<0.001). The average duration of chest drainage was statistically shorter in group A than in the control group (4.1 vs. 6.74 days; P=0.008). The mean time to hospital discharge was also statistically shorter in group A than in group B (5.75 vs. 7.85 days, P=0.026). In the Progel group, a statistically significant reduction of hospitalisation costs compared with the control group was observed (Progel group =12,905£, Control group =39,690£; P<0.001). Our standardised VMT helps in reducing the length of hospital stay after VATS lobectomy because in case of IOAALs between 100 and 400 mL/min the use of ProgelTM significantly reduces postoperative air leak, time to drain removal and length of hospitalisation compared with no treatment. This shorter hospital stays results in significant cost saving benefits. Selection of patients with standardised VMT is essential to limit unnecessary intraoperative sealant treatments, thus contributing to limit the costs.

Cost-effectiveness analysis of sealant impact in management of moderate intraoperative alveolar air leaks during video-assisted thoracoscopic surgery lobectomy: a multicentre randomised controlled trial.

BACKGROUND: Intraoperative alveolar air leak (IOAAL) is one of most common complications after video-assisted thoracoscopic surgery (VATS) lobectomy. The study aimed to evaluate if, in moderate IOAAL, intraoperative polymeric biodegradable sealant (ProgelTM) reduced postoperative air leak (PAL) and consequently was cost-effective. METHODS: Patients with moderate IOAAL were randomised in a multicentre trial to intraoperative use of a sealant (Sealant group) or standard management of air leaks (Control group). Primary endpoint was the postoperative duration of air leakage. Secondary outcomes included: time to drainage removal, length of hospital stay, postoperative complications within 2 months, and cost analysis. RESULTS: Between January 2015 and January 2017, 255 VATS lobectomies were performed in four centres. Fifty-five met inclusion criteria and were randomly assigned to Sealant group [28] and Control group [27]. The mean air leakage duration was statistically different between groups (Sealant group =1.60 days, Control group =5.04 days; P<0.001). The average length of drainage was significantly (P=0.008) shorter in Sealant group (4.1 days) than in Controls (6.74 days). The mean time of hospital stay was statistically shorter in sealant group (Sealant =5.75 days, Control =7.85 days; P=0.026). Sealant group observed a statistically significant reduction of costs. CONCLUSIONS: In moderate IOAAL after VATS lobectomy, polymeric biodegradable sealants are safe and efficient. Compared with standard treatments, sealant significantly reduces PAL, time to drain removal and length of hospital stay resulting in significant costs benefits.