Assessment of the 90-day mortality risk score after video-assisted thoracoscopic lobectomy in the Italian VATS Group cohort.

A five classes (A-E) aggregate risk score predicting 90-day mortality after video-assisted thoracoscopic lobectomy for lung cancer, including as independent factors male sex (3 points), DLCO <60% (1 point) and operative time >150 minutes (1 point), has been recently published. This study aims to assess the effectiveness and reliability of this risk model in a large, independent cohort of patients, to confirm its generalizability. From the Italian VATS Group Database, we selected 2,209 patients [60% males; median age 69 years (IQR:63-74)] who underwent video-assisted thoracoscopic lobectomy for non-small cell lung cancer. We calculated the aggregate risk score and the corresponding class of 90-day mortality risk for each patient. The correlation between risk classes and mortality rates was tested by Spearman's r-test. Model calibration was evaluated by Hosmer-Lemeshow goodness-of-fit test. Class A-E 90-day mortality rates were 0.33%, 0.51%, 1.39%, 1.31% and 2.56%, respectively. A strong uphill correlation was identified between risk classes and 90-day mortality (r=0.90; p=0.037), showing a positive correlation between increased mortality rate and class A to E. Hosmer-Lemeshow chi-squared value was 67.47 (p<0.001) with overall, Class D and E significantly lower 90-day mortality in our cohort than in the original one [1.04% vs 2.5% (p=0.018), 1.31% vs 5.65% (p=0.005) and 2.56% vs 18.75% (p=0.007), respectively]. Despite our data show a positive correlation between 90-day mortality and risk classes from A to E with modest discriminatory performance, the poor calibration suggests the need for model recalibration using local data to better manage and counsel lung cancer patients eligible for video-assisted thoracoscopic lobectomy.

Air leak and intraoperative bleeding in thoracic surgery: a Delphi consensus among the members of Italian society of thoracic surgery.

Background: Persistent air leak and the management of intraoperative blood loss are common threats in thoracic surgical practice. The availability of new procedures, technology and materials is constantly evolving topical hemostats and surgical sealants must be added to this toolkit. Topical hemostats and surgical sealants differ according to their chemical nature and physical characteristics, to their origin and mechanism of action, regulatory/registration and vigilance paths. A Delphi consensus was set to highlight the different points of view on the use of topical haemostatic products and sealants among the members of Italian Society of thoracic surgery. Methods: The board was formed by a group of five Italian experts; in the first phase after a careful review of the scientific literature and two rounds, the board finally generated 16 consensus statements for testing across a wider audience. During the second phase, the statements were collated into a questionnaire, which was electronically sent to a panel of 46 Italian surgeons, experts in the field. Results: Out of 46 Italian surgeons, 33 (72%) panel members responded to the Delphi questionnaire. All the items reached a positive consensus, with elevated levels of agreement, as demonstrated by the presence of a 100% consensus for nine items. For the remaining 7 statements the minimum level of consent was 88% (29 participants approved the statement and 4 disagreed) and the maximum was 97% (32 participants approved the statement and 1 was in disagreement). Conclusions: The present Delphi analysis shows that air leak and intraoperative bleeding are clinical problems well known among thoracic surgeons. Nevertheless, the aim of the scientific societies and of the group of experts is to execute the education activities in the surgery community. This Delphi survey suggest the need of wider and updated scientific information about technical and registration characteristics of most recent technologic solutions, such as the of topical hemostats and surgical sealants to provide healthcare and administrative staff with the opportunity to work and interact through a common and shared language and eventually to guarantee minimal requirements of assistance.

Nephrobronchial fistula a case report and review of the literature.

Nephrobronchial fistula is an extremely rare complications of renal infections. We present a case of nephrobronchial fistula in a middle age immunocompetent woman who complained cough and weight loss, with underlying asymptomatic nephrolithiasis. She underwent a chest X-ray that showed left lower lobe infiltrate and abdominal ultrasound. Abdominal ultrasound showed a complicated pyonephrosis ; CT of chest-abdomen-pelvis with intravenous contrast was performed in order to stage and define the extension of the pathology. At CT, a suspected diagnosis of stage III xanthogranulomatous pyelonephritis complicated with pyonephrosis and a nephrobronchial fistula was formulated. A nephrostomy tube was placed, and the patient was treated with antibiotics. Follow up CT, performed after 15 days, showed the healing of the fistulous connection between the perinephric abscess and bronchi; the patient underwent nephrectomy with no airway complication during intubation. Histopathological diagnosis confirmed the presence on complicated xanthogranulomatous pyelonephritis.

Pleural empyema secondary to nephropleural fistula in complicated pyonephrosis.

Pleural empyema of extra pulmonary origin is uncommon and empyema secondary to a fistula between the urinary tract and thorax is extremely rare. We report a case of nephropleural fistula causing massive pleural empyema in a 64-year-old woman with a long history of urological problems, including nephrolitiasis and urinary tract infection. She was admitted with sepsis, fever, chills, tachypnea, productive cough and pyuria. At clinical examination, breath sounds were reduced over the left hemithorax. CT revealed a fistulous connection from the upper left calyceal group and the pleural space. Drainage of thoracic and perinephric collection was carried out, but nephrectomy and pleural decortication were required due to haemopurulent urine and decreased hemoglobin levels during the hospitalization. This case demonstrates the unusual and prolonged evolution of an obstructive hydroureteronephrosis complicated by pyonephrosis, culminating in retroperitoneal abscess that fistulized into the pleural space, leading to empyema.

INSL4 as prognostic marker for proliferation and invasiveness in Non-Small-Cell Lung Cancer.

Non-small-cell-lung cancer accounts for 80-85% of all forms of lung cancer as leading cause of cancer-related death in human. Despite remarkable advances in the diagnosis and therapy of lung cancer, no significant improvements have thus far been achieved in terms of patients' prognosis. Here, we investigated the role of INSL4 - a member of the relaxin-family - in NSCLC. We overexpressed INSL4 in NSCLC cells to analyse in vitro the growth rate and the tumourigenic features. We investigated the signalling pathways engaged in INSL4 overexpressing cells and the tumour growth ability by studying the tumour development in a patient derived tumour xenograft mouse model. We found an INSL4 cell growth promoting effect in vitro in H1299 cells and in vivo in NOD/SCID mice. Surprisingly, in NSCLC-A549 cells, INSL4 overexpression has not similar effect, despite huge basal INSL4-mRNA expression respect to H1299. The INSL4-mRNA analysis of eight different NSCLC-derived cell lines, revealed highly difference in the INSL4-mRNA amount. Transfection of NSCLC lines with INSL4-Myc showed huge level of INSL4-mRNA with a very low amount of protein expressed. Notably, similar discrepancy has been observed in NSCLC patients. However, in a cohort of NSCLC patients analysing a database, we found a significant inverse correlation between INSL4 expression and Overall Survival. By combining the in vitro and in vivo results, suggest that in patients whose NSCLC adenocarcinoma spontaneously expressed high levels of INSL4 post-transcriptional modifications affecting INSL4 do not allow to assess precision therapy in selected patients without consider protein INSL4 amount.

Rescue Tracheostomy for Patients With Unresectable Large Growing Neck Masses.

Most patients with undifferentiated thyroid cancer have unresectable disease with a very high rate of airway compromise. Tracheostomy typically entails technical issues in these cases. In fact, it can be very difficult to expose or simply locate the trachea beneath the mass, and the extensive soft tissue involvement can force the surgeon to cut the tumor to place the tracheostomy tube. The combined use of rigid bronchoscopy and percutaneous tracheostomy techniques, applied in an open surgical procedure, can greatly simplify the procedure. Furthermore, by this method, the airways are quickly secured and the risk of intraoperative bleeding is reduced.

Chronic chest pain and paresthesia after video-assisted thoracoscopy for primary pneumothorax.

BACKGROUND: This study aims to identify clinical and surgical risk factors for chronic chest pain and paresthesia after video thoracoscopic surgery for primary spontaneous pneumothorax. METHODS: We retrospectively collected the data of 1,178 consecutive patients <40-years-old undergoing video thoracoscopic surgery for primary spontaneous pneumothorax in 9 Italian centers in 2007-2017. Cases with <2-month follow-up were excluded, leaving 920 patients [80% male; median age: 21 (IQR, 18-27) years] for statistical analysis. The following risk factors for chronic chest pain and chronic paresthesia were assessed by univariable and multivariable Cox regression model: age, gender, cannabis smoking, video thoracoscopy ports number, pleurodesis technique (partial pleurectomy/pleural electrocauterization/pleural abrasion/talc poudrage), chest tube size (24/28 F), postoperative chest tube stay. RESULTS: Blebs/bullae resection with pleurodesis was performed in 732 (80%) cases; pleurodesis alone in 188 (20%). During a median follow-up of 68 (IQR: 42-95) months, chronic chest pain developed in 8% of patients, chronic chest paresthesia in 22%; 0.5% of patients regularly assumed painkillers. Chronic chest pain was independently associated with partial pleurectomy/pleura abrasion (P<0.001) and postoperative chest tube stay (P=0.019). Chronic chest paresthesia was independently associated with pleurodesis by partial pleurectomy (P<0.001), chest tube stay (P=0.035) and 28 F chest tube (P<0.001). CONCLUSIONS: After video thoracoscopic surgery for primary spontaneous pneumothorax, the incidence of chronic chest pain and paresthesia was significantly lower when pleurodesis was performed by pleural electrocauterization or talc poudrage, and chest tube was removed early. A 24 F chest tube was associated with lower risk of chronic chest paresthesia.

Indoleamine 2,3-Dioxygenase 2 Immunohistochemical Expression in Resected Human Non-small Cell Lung Cancer: A Potential New Prognostic Tool.

Indoleamine 2,3-dioxygenase 2 (IDO2) is an analog of the tryptophan degrading and immunomodulating enzyme indoleamine 2,3-dioxygenase 1 (IDO1). Although the role of IDO1 is largely understood, the function of IDO2 is not yet well-elucidated. IDO2 overexpression was documented in some human tumors, but the linkage between IDO2 expression and cancer progression is still unclear, in particular in non-small cell lung cancer (NSCLC). Immunohistochemical expression and cellular localization of IDO2 was evaluated on 191 formalin-fixed and paraffin-embedded resected NSCLC. Correlations between IDO2 expression, clinical-pathological data, tumor-infiltrating lymphocytes (TILs), immunosuppressive tumor molecules (IDO1 and programmed cell death ligand-1 - PD-L1 -) and patients' prognosis were evaluated. IDO2 high expression is strictly related to high PD-L1 level among squamous cell carcinomas group (p = 0.012), to either intratumoral or mixed localization of TILs (p < 0.001) and to adenocarcinoma histotype (p < 0.001). Furthermore, a significant correlation between IDO2 high expression and poor non-small cell lung cancer prognosis was detected (p = 0.011). The current study reaches interesting knowledge about IDO2 in non-small cell lung cancer. The close relationship between IDO2 expression, PD-L1 increased levels, TILs localization and NSCLC poor prognosis, assumed IDO2 as a potential prognostic biomarker to be exploited for optimizing innovative combined therapies with immune checkpoint inhibitors.

Analysis of pneumothorax recurrence risk factors in 843 patients who underwent videothoracoscopy for primary spontaneous pneumothorax: results of a multicentric study.

OBJECTIVES: Risk factors for pneumothorax recurrence after videothoracoscopy for primary spontaneous pneumothorax are still being debated. The goal of this study was to assess whether the pleurodesis technique and other variables are possibly associated with the postoperative ipsilateral recurrence of pneumothorax. METHODS: We retrospectively collected data of 1178 consecutive ≤40-year-old patients who underwent videothoracoscopy for primary spontaneous pneumothorax in 9 centres between 2007 and 2017. We excluded patients with hybrid pleurodesis and/or incomplete follow-up, leaving for analysis 843 cases [80% men; median age (interquartile range) 22 (18-28) years]. Univariable and multivariable analyses were performed by logistic regression and tested by Cox regression model to assess factors related to ipsilateral pneumothorax recurrence including age, gender, body mass index, smoking habit, cannabis smoking, respiratory comorbidity, dystrophic severity score, surgical indication, videothoracoscopy port number and side, lung resection, pleurodesis technique and postoperative prolonged air leak (>5 days). RESULTS: Blebs/bullae resection was performed in 664 (79%) patients. Pleurodesis was achieved by partial pleurectomy in 228 (27%) cases; by pleural electrocauterization in 176 (21%); by pleural abrasion in 121 (14%); and by talc poudrage in 318 (38%). During a median follow-up period of 70.0 months (95% confidence interval 66.6-73.4), pneumothorax recurred in 79 patients (9.4%); among these, 29 underwent redo surgery; 34, chest drain/talc slurry; and 16, clinicoradiological observation. The only independent risk factor for recurrence was postoperative prolonged air leak (P < 0.001) that was significantly related to blebs/bullae resection (P = 0.03). CONCLUSIONS: In this multicentric series, postoperative ipsilateral pneumothorax recurrence was remarkable and independently related to prolonged postoperative air leak; besides the retrospective study setting, the pleurodesis method did not have an impact on recurrence. To prevent prolonged air leak, blebs/bullae treatment should be accurate and performed only if indicated.

Microalbuminuria assessment after thoracic surgery: Early identification of complication risks.

INTRODUCTION: Microalbuminuria (MA) is considered a reflection of systemic capillary leak and an early marker of acute stress reaction to the surgical insult, proportional to the severity of the initiating condition and predictive of the individual response to surgical stress. OBJECTIVES: We conducted a prospective study to assess for the variation of MA within 4 days after thoracic surgery. We correlated observed MA levels with both their respective PaO2 /FiO2 respiratory ratio and the onset of postoperative complications. METHODS: This single-centre study enrolled 255 consecutive patients having an American Society of Anaesthesiologists (ASA) score ≤ 3. The mean age was 62 years with 67% male. All patients were scheduled for elective pulmonary resection. MA was measured in urine samples as the albumin-to-creatinine ratio (A/C), prior to, at and after extubation up to 96 hours. PaO2 /FiO2 was measured at extubation and on the first postoperative day. RESULTS: Overall, preoperative A/C levels resulted normal, with a significant average increase at extubation which peaked 6 hours later (P < 0.001). Larger postoperative A/C increases were observed in patients who developed postoperative complications, compared to those without these complications (P < 0.019). Moreover, patients undergoing major open pulmonary resections had larger postoperative A/C increases, compared to those undergoing minor video-assisted thoracic surgery resections (P < 0.006). At the time of extubation, A/C was inversely related to the PaO2 /FiO2 ratio (r = -0.25; P = 0.038). Peak A/C > 61 mg/g (P = 0.0003) was associated with postoperative cardio-pulmonary complications (OR 3.85; P = 0.003). CONCLUSION: Within 6 hours after extubation, MA assessment may be a rapid and relatively inexpensive method for better predicting perioperative risk in an ASA score ≤ 3 population.

An Alternative Method for Airway Management With Combined Tracheal Intubation and Rigid Bronchoscope.

An innovative technique for airway management, using a small-diameter, short-cuffed orotracheal tube for assisting rigid bronchoscopy in critical airway obstruction is reported. The device, part of the translaryngeal tracheostomy kit, "Fantoni method" (DAR TLT, Covidien, Minneapolis, MN), was placed beyond the stenosis and used in combination with the rigid bronchoscope. This procedure improves safety during the management of critical tracheal stenoses because the airway is constantly under the anesthesiologist's control. Consequently, inhalation anesthesia is feasible, use of neuromuscular blockade is possible, end-tidal carbon dioxide monitoring is reliable, and the distal airway is protected from blood and debris soilage during tumor debulking. Surgery is faster because it is uninterrupted.

Is Myotomy Plus Diverticulopexy Suitable for Symptomatic Zenker's Diverticula?

The aim of the study was to prospectively evaluate the outcome of myotomy plus diverticulopexy over short and long-terms. A prospectively collected consecutive series (2007-2017) of 37 patients undergoing myotomy plus diverticulopexy was analyzed for clinical condition, operative information, peri-operative events, and follow-up by means of interview and physical examination. Diverticulopexy was scheduled regardless of the diverticulum's features and patient condition, other than operability. There was no choice or selection between possible treatment options. Patients were evaluated pre-operatively, at post-operative day 30 and after 1 year. Follow-up aimed at assessing the subjective condition following treatment. During the interview, patients were asked to self-assess their ability to swallow before and after surgery. No patient had peri-operative events, complications associated with the procedure, wound infection or impaired swallowing. All patients could start drinking the day after operation, could return to solid diet on post-operative day 2 and be discharged on post-operative days 3-4. Barium swallowing was not necessary before discharge. Full solid diet was resumed according to patient's compliance from post-operative day 2 (some patients refused solid diet soon after the operation even if asymptomatic). Follow-up ranged between 1 and 8 years. No patient was lost at follow-up. No disease recurrence was observed. Finally, no patient needed or sought for a clinical examination between the follow-up calls. Patients reported at least 50% improvement of symptomatology after 1 year. Diverticulopexy appears to be clinically safe, methodologically reproducible, and an effective procedure; it avoids suturing and offers good outcome results along with high patient satisfaction.

Assessment of TILs, IDO-1, and PD-L1 in resected non-small cell lung cancer: an immunohistochemical study with clinicopathological and prognostic implications.

Several cancers, especially non-small cell lung cancer (NSCLC), are able to escape the immunosurveillance of tumor-infiltrating lymphocytes (TILs); among the molecules involved, the indoleamine 2,3-dioxygenase 1 (IDO-1) and the programmed cell death ligand-1 (PD-L1) play a crucial role. These aspects are of great interest in the current immunotherapeutic era, therefore the current study analyses the TILs, IDO-1, and PD-L1 interactions and their correlations with clinicopathological parameters and prognosis in NSCLC. One hundred ninety-three NSCLC surgical specimens, formalin-fixed, and paraffin-embedded were assessed for TILs density, TILs localization, IDO-1 (clone 4.16H1), and PD-L1 (clone E1L3N) immunohistochemical expressions. This data was correlated with clinicopathological parameters, disease free, and overall survivals. IDO-1 and PD-L1 high expressions were related to the solid pattern of adenocarcinomas (respectively p = 0.036 and p = 0.026); high PD-L1 expression was correlated with squamous histotype (p = 0.048). IDO-1 overexpression correlated with former smokers (p = 0.041), higher adenocarcinoma stages (p = 0.039), and with both higher TILs density and PD-L1 expression (respectively p = 0.025 and p = 0.0003). A better prognosis was associated with TILs intratumoral or mixed localizations (p = 0.029). TILs localization affects NSCLC prognosis; the higher expression of IDO-1 and PD-L1 in poorly differentiated and more aggressive lung adenocarcinomas, as well as the correlation between high PD-L1 expression and squamous cell histotype, confirm the more efficient immunoescaping of these NSCLC subgroups.

Interatrial Shunting Through an Asymptomatic Patent Foramen Ovale in Thoracic Surgery.

BACKGROUND: Patent foramen ovale (PFO) is present in as many as 25% of the general population and is considered an irrelevant condition in healthy subjects. Here, we sought to determine an association between an asymptomatic PFO at baseline and postoperative short-term adverse events in patients undergoing major pulmonary resection for lung cancer. In addition, we evaluated for the rate of PFO after pulmonary resections. METHODS: This prospective, observational study assessed patients by transcranial Doppler with contrast at baseline and discharge. To confirm interatrial shunting, patients with positive transcranial Doppler at baseline also underwent contrast transthoracic echocardiography. Multivariate logistic regression models were adopted to investigate for independent factors that could have been associated with complications. Backward stepwise procedure was used for model selection. RESULTS: Median age was 67.7 ± 9.2 years (range, 36 to 86), and 67% were men. Overall, 18 patients underwent pneumonectomy, 11 bilobectomy, and 118 lobectomy; 54% underwent right-sided procedure and 46%, left-sided. One perioperative death was recorded, and 34 patients had one or more cardiopulmonary complications. At baseline, PFO was positive in 25% (37 of 147) and negative in 75% (110 of 147); of the latter, 11% were positive at discharge. Detection of PFO at baseline, on multivariate analysis, was significantly associated with a risk of postoperative complications (odds ratio 2.5; 95% confidence interval: 1.1 to 5.8). Specifically, we observed a significant association between atrial fibrillation and positive PFO at baseline (odds ratio 3.5; 95% confidence interval: 1.4 to 9.0). CONCLUSIONS: Preoperative asymptomatic PFO was independently associated with postoperative adverse events. Moreover, 11% of patients who had negative transcranial Doppler studies at baseline had asymptomatic PFOs at discharge. Larger prospective studies are needed to further investigate for a prognostic impact of PFO in thoracic surgery.

Bedside sonography assessment of extravascular lung water increase after major pulmonary resection in non-small cell lung cancer patients.

BACKGROUND: Extra vascular lung water (EVLW) following pulmonary resection increases due to fluid infusion and rises in capillary surface and permeability of the alveolar capillary membranes. EVLW increase clinically correlates to pulmonary oedema and it may generate impairments of gas exchanges and acute lung injury. An early and reliable assessment of postoperative EVLW, especially following major pulmonary resection, is useful in terms of reducing the risk of postoperative complications. The currently used methods, though satisfying these criteria, tend to be invasive and cumbersome and these factors might limit its use. The presence and burden of EVLW has been reported to correlate with sonographic B-line artefacts (BLA) assessed by lung ultrasound (LUS). This observational study investigated if bedside LUS could detect EVLW increases after major pulmonary resection. Due to the clinical association between EVLW increase and impairment of gas exchange, secondary aims of the study included investigating for associations between any observed EVLW increases and both respiratory ratio (PaO2/FiO2) and fluid retention, measured by brain natriuretic peptide (BNP). METHODS: Overall, 74 major pulmonary resection patients underwent bedside LUS before surgery and at postoperative days 1 and 4, in the inviolate hemithorax which were divided into four quadrants. BLA were counted with a four-level method. The respiratory ratio PaO2/FiO2 and fluid retention were both assessed. RESULTS: BLA resulted being increased at postoperative day 1 (OR 9.25; 95% CI, 5.28-16.20; P<0.0001 vs. baseline), and decreased at day 4 (OR 0.50; 95% CI, 0.31-0.80; P=0.004 vs. day 1). Moreover, the BLA increase was associated with both increased BNP (OR 1.005; 95% CI, 1.003-1.008; P<0.0001) and body weight (OR 1.040; 95% CI, 1.008-1.073; P=0.015). Significant inverse correlations were observed between the BLA values and the PaO2/FiO2 respiratory ratios. CONCLUSIONS: Our results suggest that LUS, due to its non-invasiveness, affordability and capacity to detect increases in EVLW, might be useful in better managing postoperative patients.

Lobectomy with angioplasty: which is the best technique for pulmonary artery reconstruction?

Lobectomies with bronchial and/or vascular reconstruction are conservative procedures aimed at managing locally advanced lung cancer, avoiding a pneumonectomy. Considering morbidity, mortality and the functional consequences of a pneumonectomy, such procedures must be in the technical armamentarium of every thoracic surgeon. Vascular reconstruction of the pulmonary artery (PA) is seldom performed with or without the bronchial sleeve resection. Both functional and oncologic outcomes have been reported to be better than after a pneumonectomy. Different technical options are now available but some aspects and technical details are not standardized. Indications, possible complications, planning and even definitions need to be more solid to allow for definitive improvement in such procedures. This analysis is aimed at assessing the acquired technical data with special emphasis on the PA reconstruction with autologous tissues.

Targeting autophagy sensitises lung cancer cells to Src family kinase inhibitors.

Lung cancer is the main cancer killer in both men and women, mostly due to the rapid development of drug resistant metastatic disease. Here, we evaluate the potential involvement of SRC family kinases (SFK) in lung cancer biology and assess the possible benefits of their inhibition as a therapeutic approach. We demonstrated that various SRC family members, including LYN and LCK, normally expressed solely in hematopoietic cells and neural tissues, are overexpressed and activated in a panel of SCLC and NSCLC cell lines. This was clinically relevant as LYN and FYN are also overexpressed in lung cancer clinical specimens. Moreover, LYN overexpression correlated with decreased patient survival on univariate and multivariate analysis. Dasatinib (BMS-354825), a SRC/ABL inhibitor, effectively blocked SFK activation at nanomolar concentrations which correlated with a significant decrease in cell numbers of multiple lung cancer cell lines. This effect was matched by a decrease in DNA synthesis, but only moderate induction of apoptosis. Indeed, dasatinib as well as PP2, another SFK inhibitor, strongly induced autophagy that likely prevented apoptosis. However, inhibition of this autophagic response induced robust apoptosis and sensitised lung cancer cells to dasatinib in vitro and in vivo. Our results provide an explanation for why dasatinib failed in NSCLC clinical trials. Furthermore, our data suggest that combining SFK inhibitors with autophagy inhibitors could provide a novel therapeutic approach in this disease.