Training simulator efficacy in developing thoracic and general surgical skills in a residency programme: a pilot study.

OBJECTIVES: Virtual training simulators have been introduced in several surgical disciplines to improve residents' abilities. Through the use of the LapSim® virtual training simulator (Surgical Science, Göteborg, Sweden), this study aims to plan an effective learning path in minimally invasive thoracic and general surgery. METHODS: All thoracic and general surgery trainees in their 1st and 2nd year of residency at the University of Insubria were enrolled and randomized into 2 groups: residents undergoing an intensive twice-a-week virtual training programme (group A: n = 8) and those undergoing a once-weekly non-intensive virtual training programme (group B: n = 9). The virtual training programme was divided into 4 modules, each of 12 weeks. In the 1st module, trainees repeated grasping, cutting, clip application, lifting and grasping, and fine dissection exercises during each training session. Seal-and-cut exercise was performed as the initial and final test. Data on surgical manoeuvres (time and on mistakes) were collected; intra- and inter-group comparisons were planned. RESULTS: No significant differences were observed between groups A and B at the 1st session, confirming that the 2 groups had similar skills at the beginning. After 12 weeks, both groups showed improvements, but comparing data between initial and final test, only Group A registered a significant reduction in total time (P-value = 0.0015), left (P-value = 0.0017) and right (P-value = 0.0186) instrument path lengths, and in left (P-value = 0.0010) and right (P-value = 0.0073) instrument angular path lengths, demonstrating that group A acquired greater precision in surgical manoeuvres. CONCLUSIONS: Virtual simulator training programme performed at least twice a week was effective for implementing basic surgical skills required for the trainee's professional growth. Additional virtual training modules focused on more complex exercises are planned to confirm these preliminary results.

Long-term follow-up of subthalamic nucleus deep brain stimulation in patients with Parkinson's disease: An analysis of survival and disability milestones.

BACKGROUND: Data on the long-term survival and incidence of disability milestones after subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD) is limited. OBJECTIVES: To estimate mortality and assess the frequency/time-to-development of disability milestones (falls, freezing, hallucinations, dementia, and institutionalization) among PD patients post STN-DBS. METHODS: A longitudinal retrospective study of patients undergoing STN-DBS. For mortality, Cox proportional hazards regression analysis was performed. For disease milestones, competing risk analyses were performed and cumulative incidence functions reported. The strength of association between baselines features and event occurrence was calculated based on adjusted hazard ratios. RESULTS: The overall mortality for the 109 patients was 16 % (62.1 ± 21.3 months after surgery). Falls (73 %) and freezing (47 %) were both the earliest (40.4 ± 25.4 and 39.6 ± 28.4 months, respectively) and most frequent milestones. Dementia (34 %) and hallucinations (32 %) soon followed (56.2 ± 21.2 and mean 60.0 ± 20.7 months after surgery, respectively). Higher ADL scores in the OFF state and higher age at surgery were associated with falls, freezing, dementia and institutionalization. CONCLUSIONS: Long-term mortality rate is low after STN-DBS. Disease milestones occur later during the disease course, with motor milestones appearing first and at a higher frequency than cognitive ones.

Video-assisted thoracoscopic surgery simulation and training: a comprehensive literature review.

BACKGROUND: Video-assisted thoracic surgery (VATS) has become the standard for lung cancer diagnosis and treatment. However, this surgical technique requires specific and dedicated training. In the past 20 years, several simulator systems have been developed to promote VATS training. Advances in virtual reality may facilitate its integration into the VATS training curriculum. The present review aims to first provide a comprehensive overview of the simulators for thoracoscopic surgery, focused especially on simulators for lung lobectomy; second, it explores the role and highlights the possible efficacy of these simulators in the surgical trainee curriculum. METHODS: A literature search was conducted in the PubMed, EMBASE, Science Direct, Scopus and Web of Science databases using the following keywords combined with Boolean operators "AND" and "OR": virtual reality, VR, augmented reality, virtual simulation, mixed reality, extended reality, thoracic surgery, thoracoscopy, VATS, video-assisted thoracoscopic surgery, simulation, simulator, simulators, training, and education. Reference lists of the identified articles were hand-searched for additional relevant articles to be included in this review. RESULTS: Different types of simulators have been used for VATS training: synthetic lung models (dry simulators); live animals or animal tissues (wet simulators); and simulators based on virtual or augmented reality. Their role in surgical training has been generally defined as useful. However, not enough data are available to ascertain which type is the most appropriate. CONCLUSIONS: Simulator application in the field of medical education could revolutionize the regular surgical training curriculum. Further studies are required to better define their impact on surgeons' training programs and, finally, on patients' quality of care.

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.

The surgical approach of late-onset tracheoesophageal fistula in a tracheostomized COVID-19 patient.

In the COVID-19 era the tracheal complications due to prolonged mechanical ventilation have significantly increased. Acquired tracheoesophageal fistula is one of those in ventilated COVID-19 patients. Thus, the knowledge of their management in such fragile patient is crucial. We report a case of tracheoesophageal fistula in a 56-year-old female under prolonged mechanical ventilation for COVID-19 bilateral pneumonia and discuss its management. A surgical approach was proposed. By a collar-shaped transverse cervicotomic access, we transected the trachea at level of fistula en-bloc with the tracheostoma. The esophageal lesion was longitudinally repaired in two-layers. Protective left strap muscle was sandwiched between esophagus and trachea. The tracheal end-to-end anastomosis was completed without a re-tracheostoma. Even if surgical approach of tracheoesophageal fistula in COVID-19 patients has not been tested before, surgery remains the treatment of choice according to the multidisciplinary board.

Impact of High-Grade Patterns in Early-Stage Lung Adenocarcinoma: A Multicentric Analysis.

OBJECTIVE: The presence of micropapillary and solid adenocarcinoma patterns leads to a worse survival and a significantly higher tendency to recur. This study aims to assess the impact of pT descriptor combined with the presence of high-grade components on long-term outcomes in early-stage lung adenocarcinomas. METHODS: We retrospectively collected data of consecutive resected pT1-T3N0 lung adenocarcinoma from nine European Thoracic Centers. All patients who underwent a radical resection with lymph-node dissection between 2014 and 2017 were included. Differences in Overall Survival (OS) and Disease-Free Survival (DFS) and possible prognostic factors associated with outcomes were evaluated also after performing a propensity score matching to compare tumors containing non-high-grade and high-grade patterns. RESULTS: Among 607 patients, the majority were male and received a lobectomy. At least one high-grade histological pattern was seen in 230 cases (37.9%), of which 169 solid and 75 micropapillary. T1a-b-c without high-grade pattern had a significant better prognosis compared to T1a-b-c with high-grade pattern (p = 0.020), but the latter had similar OS compared to T2a (p = 0.277). Concurrently, T1a-b-c without micropapillary or solid patterns had a significantly better DFS compared to those with high-grade patterns (p = 0.034), and it was similar to T2a (p = 0.839). Multivariable analysis confirms the role of T descriptor according to high-grade pattern both for OS (p = 0.024; HR 1.285 95% CI 1.033-1.599) and DFS (p = 0.003; HR 1.196, 95% CI 1.054-1.344, respectively). These results were confirmed after the propensity score matching analysis. CONCLUSIONS: pT1 lung adenocarcinomas with a high-grade component have similar prognosis of pT2a tumors.

Pathological and clinical features of multiple cancers and lung adenocarcinoma: a multicentre study.

OBJECTIVES: Lung cancer is increasingly diagnosed as a second cancer. Our goal was to analyse the characteristics and outcomes of early-stage resected lung adenocarcinomas in patients with previous cancers (PC) and correlations with adenocarcinoma subtypes. METHODS: We retrospectively reviewed data of patients radically operated on for stage I-II lung adenocarcinoma in 9 thoracic surgery departments between 2014 and 2017. Overall survival (OS) and time to disease relapse were evaluated between subgroups. RESULTS: We included 700 consecutive patients. PC were present in 260 (37.1%). Breast adenocarcinoma, lung cancer and prostate cancer were the most frequent (21.5%, 11.5% and 11.2%, respectively). No significant differences in OS were observed between the PC and non-PC groups (P = 0.378), with 31 and 75 deaths, respectively. Patients with PC had smaller tumours and were more likely to receive sublobar resection and to be operated on with a minimally invasive approach. Previous gastric cancer (P = 0.042) and synchronous PC (when diagnosed up to 6 months before lung adenocarcinoma; P = 0.044) were related, with a worse OS. Colon and breast adenocarcinomas and melanomas were significantly related to a lower incidence of high grade (solid or micropapillary, P = 0.0039, P = 0.005 and P = 0.028 respectively), whereas patients affected by a previous lymphoma had a higher incidence of a micropapillary pattern (P = 0.008). CONCLUSIONS: In patients with PC, we found smaller tumours more frequently treated with minimally invasive techniques and sublobar resection, probably due to a more careful follow-up. The impact on survival is not uniform and predictable; however, breast and colon cancers and melanoma showed a lower incidence of solid or micropapillary patterns whereas patients with lymphomas had a higher incidence of a micropapillary pattern.

Prognostic role of standard uptake value according to pathologic features of lung adenocarcinoma.

OBJECTIVE: To evaluate the influence of lung adenocarcinoma second predominant pattern on the maximal standard uptake value (SUVmax) and its prognostic effect in different histologic groups. METHODS: We retrospectively collected surgically resected pathologic stage I and II lung adenocarcinoma from nine European institutions. Only patients who underwent preoperative PET-CT and with available information regarding SUVmax of T (SUVmaxT) and N1 (SUVmaxN1) component were included. RESULTS: We enrolled 344 patients with lung adenocarcinoma. SUVmaxT did not show any significant relation according to the second predominant pattern (p = 0.139); this relationship remained nonsignificant in patients with similar predominant pattern. SUVmaxT influenced the disease-free survival in the whole cohort (p = 0.002) and in low- and intermediate-grade predominant pattern groups (p = 0.040 and p = 0.008, respectively). In the high-grade predominant pattern cohort and in the pathologic N1 cases, SUVmaxT lost its prognostic power. SUVmaxN1 did not show any significant correlation with predominant and second predominant patterns and did not have any prognostic impact on DFS. CONCLUSIONS: SUVmaxT is influenced only by the adenocarcinoma predominant pattern, but not by second predominant pattern. Concurrently, in high-grade predominant pattern and pN1 group the prognostic power of SUVmaxT becomes nonsignificant.

Surgical management of tracheal chondrosarcoma.

Background: Tracheal chondrosarcoma is an extremely rare, slow-growing, malignant tumour. This study aims to analyze the cases of tracheal chondrosarcoma published in the literature and our case report, in order to better define tracheal chondrosarcoma management.Methods: A systematic review of the English literature was carried out for fully described tracheal chondrosarcoma cases. Additionally, we reported a new case of a 58-year-old man undergoing tracheal resection and reconstruction for tracheal chondrosarcoma.Results: To date, 30 cases were published. This tumour predominantly involved male patients (93%; median age: 65 years), generally conditioning dyspnoea and cough. Most of the patients underwent tracheal resection with end-to-end anastomosis, without recurrence (median follow-up: 2 years). Tumours endoscopically treated recurred in half cases.Conclusion: Tracheal resection is the treatment of choice for chondrosarcoma, with an excellent prognosis. Endoscopic treatment and/or radiotherapy should be indicated for patients unfit for surgery.

Perioperative identifications of non-palpable pulmonary nodules: a narrative review.

Early detection of lung cancer is the key to improving treatment and prognosis of this disease, and the advent of advances in computed tomography (CT) imaging and national screening programs have improved the detection rate of very small pulmonary lesions. As such, the management of this sub-centimetric and often sub-solid lesions has become quite challenging for clinicians, especially for choosing the most suitable diagnostic method. In clinical practice, to fulfill this diagnostic yield, transthoracic needle biopsy (TTNB) is often the first choice especially for peripheral nodules. For lesions for which TTNB could present technical difficulties or failed, other diagnostic strategies are needed. In this case, video-assisted thoracic surgery (VATS) is the gold standard to reach the diagnosis of lung nodules suspect of being malignant. Nonetheless it's often not easy the identification of such lesions during VATS because of their little dimensions, non-firm consistency, deep localization. In literature various marking techniques have been described, in order to improve intraoperative nodules detection and to reduce conversion rate to thoracotomy: CT-guided hookwire positioning, methylene blue staining, intra-operative ultrasound and electromagnetic navigation bronchoscopy are the most used. The scientific evidence on this matter is weak because there are no randomized clinical trials but only case series on single techniques with no comparison on efficacy, so there are no guidelines to refer. From this standing, in this article we conducted a narrative review of the existing literature on the subject, with the aim of outlining a framework as complete as possible. We analyzed strengths and weaknesses of the main techniques reported, so as to allow the clinician to orient himself with greater ease.

Prognostic Value of 18F-FDG PET/CT Metabolic Parameters in Surgically Treated Stage I Lung Adenocarcinoma Patients.

PURPOSE OF THE REPORT: This article aims to explore the prognostic role of 18F-FDG PET/CT metabolic parameters in stage I lung adenocarcinoma patients. PATIENTS AND METHODS: One hundred eighty pathological stage I lung adenocarcinoma patients were retrospectively reviewed. Semiquantitative analysis of FDG tumor uptake was performed with TrueD software on the Siemens Leonardo workstation. SUVmean and MTV were calculated using SUV threshold of 41% of SUVmax; the total lesion glycolysis (TLG) was calculated as the product of SUVmean and MTV. Correlation was evaluated using Spearman correlation coefficient. Maximally selected rank statistics was performed to detect the optimal cutoff used for dichotomizing each PET parameter (6.5 for SUVmean, 9.6 for SUVmax, and 19.1 for TLG). RESULTS: Our main finding was the significant correlation between 18F-FDG PET/CT parameters (SUVmean, SUVmax, and TLG) and disease-free survival in pathologic stage I non-small cell lung cancer. SUVmean has the greatest accuracy in recurrence prediction (integrated area under the curve, 0.803; 95% confidence interval, 0.689-0.918). We run the maximally selected rank statistics to provide the classification of observations in 2 groups by a continuous predictor parameter; the free from recurrence rate was significantly greater in patients with SUVmean ≤6.5, SUVmax ≤9.6, and TLG ≤19.1. CONCLUSIONS: Our research supports the hypothesis that SUVmean, SUVmax, and TLG are well correlated with free from recurrence rate in stage I adenocarcinoma patients, subjected to pulmonary lobectomy. Our findings also indicate these markers as promising prognostic indicators.

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.

Energy devices safety and impact on video-assisted thoracoscopic lung lobectomy postoperative course: monopolar electrocautery versus ultrasonic dissector.

BACKGROUND: This study aims to compare safety and impact of monopolar electrocautery and ultrasonic dissector (Harmonic ACE Plus®) on postoperative short-term outcomes after video-assisted thoracoscopic (VATS) lobectomy and lymphadenectomy for lung cancer. METHODS: We analyzed the prospectively collected data of 140 consecutive patients [59% male; median age: 71(IQR:62-76) years] undergoing VATS lobectomy and lymphadenectomy in our institution between October 2016 and November 2019. Patients were divided in two groups based on device used: monopolar electric hook in 79 cases (Group A); ultrasonic dissector in 61(Group B). Energy instrument-related intraoperative accidents, hemothorax/chylothorax incidence, total pleural effusion volume at 48 postoperative hours and chest tube duration were compared between groups. Multivariable analysis was performed to test energy device as possible independent risk factor either for increased pleural effusion volume or for prolonged chest tube duration. RESULTS: No intraoperative accidents due to energy device occurred. No hemothorax was recorded. Postoperative chylothorax incidence was slightly higher in Group A (2.5% vs 0%; p-value = 0.21). Total pleural effusion volume at 48 h was significantly higher in Group B: 400 (285-500) vs 255 (150-459) ml (p-value = 0.005). Chest tube duration was similar in the two groups: 5 (3-9) vs 5 (3-8) days (p-value = 0.77). At multivariable analysis the energy device used was not associated with increased pleural effusion volume (p-value = 0.43) nor with prolonged chest tube duration (p-value = 0.28). CONCLUSIONS: Monopolar electrocautery and Harmonic ACE Plus® were safe and had a similar impact on short-term outcomes after VATS lobectomy and lymphadenectomy, suggesting that energy devices choice could be left to surgeon's preference.

Comparison of an expiratory flow accelerator device versus positive expiratory pressure for tracheobronchial airway clearance after lung cancer lobectomy: a preliminary study.

OBJECTIVE: A new type of device has recently been introduced in chest physiotherapy as an aid to tracheo-bronchial airway clearance: expiratory flow accelerator (EFA). It promotes mucus clearance without generating any pressure gradient, allowing patients to breathe at tidal volume against no resistance. DESIGN: Pilot randomized controlled study. SETTING: Tertiary hospital. PARTICIPANTS: Fifty adult patients who underwent lung cancer lobectomy were randomized to undergo chest physiotherapy with EFA (n=26) or PEP (n=24). INTERVENTIONS: EFA; PEP bottle. MAIN OUTCOMES: Incidence of postoperative pulmonary complications (PPC) and length of stay. SECONDARY OUTCOMES: trends in inspiratory capacity, respiratory rate, oxygen saturation, and dyspnoea. Patients rated user-friendliness of the two devices on a 5-point Likert scale. RESULTS: A slightly different incidence of PPCs was observed between the EFA and PEP group. Nevertheless, the length of stay was similar in the two groups. No substantial differences were seen in trends of inspiratory capacity, respiratory rate, oxygen saturation, dyspnoea between the two groups. Patient-reported user-friendliness of the two devices did not differ significantly, although the use of the EFA device appeared less strenuous. CONCLUSIONS: Results of this pilot study point to the use of EFA as an alternative treatment option rather than as a replacement for the PEP bottle in chest physiotherapy following lung cancer lobectomy. EFA may be preferable for weaker patients and/or with airway leakages in whom PEP has limited indications. Further investigation in a larger sample is required to statistically confirm the findings. Clinical Trial Registration Number ChiCTR-ONC-17013255.

Prognostic impact of lung adenocarcinoma second predominant pattern from a large European database.

BACKGROUND AND OBJECTIVES: Adenocarcinoma patterns could be grouped based on clinical behaviors: low- (lepidic), intermediate- (papillary or acinar), and high-grade (micropapillary and solid). We analyzed the impact of the second predominant pattern (SPP) on disease-free survival (DFS). METHODS: We retrospectively collected data of surgically resected stage I and II adenocarcinoma. SELECTION CRITERIA: anatomical resection with lymphadenectomy and pathological N0. Pure adenocarcinomas and mucinous subtypes were excluded. Recurrence rate and factors affecting DFS were analyzed according to the SPP focusing on intermediate-grade predominant pattern adenocarcinomas. RESULTS: Among 270 patients, 55% were male. The mean age was 68.3 years. SPP pattern appeared as follows: lepidic 43.0%, papillary 23.0%, solid 14.4%, acinar 11.9%, and micropapillary 7.8%. The recurrence rate was 21.5% and 5-year DFS was 71.1%. No difference in DFS was found according to SPP (p = .522). In patients with high-grade SPP, the percentage of SPP, age, and tumor size significantly influenced DFS (p = .016). In patients with lepidic SPP, size, male gender, and lymph-node sampling (p = .005; p = .014; p = .038, respectively) significantly influenced DFS. CONCLUSIONS: The impact of SPP on DFS is not homogeneous in a subset of patients with the intermediate-grade predominant patterns. The influence of high-grade SPP on DFS is related to its proportion in the tumor.

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.

Anterior Limb of Internal Capsule and Bed Nucleus of Stria Terminalis Stimulation for Gilles de la Tourette Syndrome with Obsessive-Compulsive Disorder in Adolescence: A Case of Success.

Gilles de la Tourette syndrome (GTS) is a neurobehavioral disorder comprising motor and vocal tics. In most cases it is associated with other disorders such as obsessive-compulsive disorder (OCD). In refractory cases deep brain stimulation (DBS) is a valid treatment option. This paper describes the case of a 15-year-old adolescent with an extremely refractory GTS with associated OCD. The patient developed catatonia associated with OCD, which partially remitted after electroconvulsive therapy. At the peak of the disease the Yale Global Tic Severity Scale (YGTSS) was 100 and the patient required sedation and intubation. All medical treatment options were unsuccessful. Bilateral DBS of the anterior limb of internal capsule (ALIC)/bed nucleus of stria terminalis (BST) region was performed, using a target below the BST and a trajectory through the ALIC, with stimulation of contacts 0 and 3. Two weeks after surgery sedatives were suspended and the patient was successfully extubated. One year after surgery the patient reached a YGTSS of 19, representing an 81% improvement. OCD completely resolved. Adverse events were a superficial infection and weight gain. In conclusion, this ALIC/BST stimulation appears to have been an effective and safe treatment for GTS with OCD in this case. Young age should not be an exclusion criterion for DBS in severe GTS and OCD. Further studies should be pursued for this target.

Staging System for Neuroendocrine Tumors of the Lung Needs to Incorporate Histologic Grade.

BACKGROUND: Neuroendocrine tumors of the lung are staged with the American Joint Committee on Cancer (AJCC) TNM system for non-small cell lung cancer. However neuroendocrine tumors have a distinct clinical behavior with grade providing critical prognostic information. We aim to determine components of a tumor-specific staging system. METHODS: We identified 12,415 of 58,736 neuroendocrine patients with complete 8th edition AJCC staging information in the National Cancer Database from 2004 to 2014. Data were randomized into training (n = 8324) and validation (n = 4091) sets and analyzed separately. Recursive partitioning followed by Cox regression was performed to classify by grade (G1, typical carcinoid; G2, atypical carcinoid; G3, large cell neuroendocrine), T category, and nodal status. Overall survival according to individual grade and an integrated grade-specific staging was compared by Kaplan-Meier analysis. RESULTS: Overall 7524 G1, 1211 G2, and 3680 G3 tumors were analyzed with no differences between sets. Each grade was separately classified by the AJCC TNM system with poor separation of the curves and clustered survival. Recursive partitioning identified grade as the most significant factor driving overall survival. Subsequent partitions identified nodal status and then T category as additional important factors, consistent with results from the Cox regression analysis (G2 hazard ratio, 3.05 [95% confidence interval, 2.65-3.5]; G3 hazard ratio, 9.03 [95% confidence interval, 8.22-9.92]). When grade was integrated with nodal status and T category to approximate a tumor-specific staging system, distinct overall survival stratification occurred at each proposed stage. CONCLUSIONS: Grade was the dominant driver of prognosis in patients with neuroendocrine tumors of the lung. Incorporation of grade with traditional TNM parameters better discriminates between stage categories compared with current AJCC staging. Future staging systems for neuroendocrine tumors of the lung should include histologic grade.

Serum miR-223: A Validated Biomarker for Detection of Early-Stage Non-Small Cell Lung Cancer.

BACKGROUND: The published circulating miRNA signatures proposed for early-stage non-small cell lung cancer (NSCLC) detection are inconsistent and difficult to replicate. Reproducibility and validation of an miRNA simple signature of NSCLC are prerequisites for translation to clinical application. METHODS: The serum level of miR-223 and miR-29c, emerging from published studies, respectively, as a highly sensitive and a highly specific biomarker of early-stage NSCLC, was measured with droplet digital PCR (ddPCR) technique in an Italian cohort of 75 patients with stage I-II NSCLC and 111 tumor-free controls. By ROC curve analysis we evaluated the miR-223 and miR-29c performance in discerning NSCLC cases from healthy controls. RESULTS: Reproducibility and robust measurability of the two miRNAs using ddPCR were documented. In a training set (40 stage I-II NSCLCs and 56 controls), miR-223 and miR-29c, respectively, showed an AUC of 0.753 [95% confidence interval (CI), 0.655-0.836] and 0.632 (95% CI, 0.527-0.729) in identifying NSCLC. Combination of miR-223 with miR-29c yielded an AUC of 0.750, not improved over that of miR-223 alone. Furthermore, in an independent blind set (35 stage I-II NSCLCs and 55 controls), we validated serum miR-223 as an effective biomarker of stage I-II NSCLC (AUC = 0.808; 95% CI, 0.712-0.884), confirming the miR-223 diagnostic performance reported by others in Chinese cohorts. CONCLUSIONS: Using ddPCR technology, miR-223 was externally validated as a reproducible, effective serum biomarker of early-stage NSCLC in ethnically different subjects. Combination with miR-29c did not improve the miR-223 diagnostic performance. IMPACT: Serum miR-223 determination may be proposed as a tool for refining NSCLC risk stratification, independent of smoking habit and age.