Comparison of frailty indexes as predictors of clinical outcomes after major thoracic surgery.

Background: Despite greater appreciation for the importance of frailty in surgical patients, due to improved understanding that frailty is often linked to poor outcomes, the optimal method of assessment remains unknown. In this study, we sought to evaluate the prevalence of frailty in patients considered for elective thoracic surgery and to test the ability of several frailty measurements to predict postoperative outcomes. Methods: Patients included were candidates for major elective thoracic surgery. Preoperative assessment of frailty included the Fried frailty phenotype, the Edmonton Frail Scale (EFS), the modified frailty index (mFI), the Clinical Frailty Scale (CFS), and additional components of frailty. Outcome data include days with chest drain, length of hospital stay, and postoperative adverse events. Results: According to the Fried frailty phenotype, 53% of 94 patients included were prefrail or frail. A significant association between frailty and postoperative complications was found (odds ratio 7.65; P=0.001). No association between CFS, mFI, EFS, and complications was observed. The Frailty Phenotype seemed the most accurate in predicting postoperative complications, with an area under the curve (AUC) of 0.77. Twenty-seven percent of patients meet the criteria for depression according to the Geriatric Depression Scale and they showed a higher risk of postoperative complications (OR 2.47; P=0.03). A lower psoas muscle index was associated with a higher risk of complications (OR 3.40; P=0.04). Conclusions: According to our results, the Fried frailty phenotype seems the most accurate tool to test frailty in patients undergoing thoracic resections. Surgeons should be aware that, although these aspects are not routinely tested, they are potential targets to improve clinical outcomes. Studies on additional interventions specifically targeting frail people in the setting of elective thoracic surgery are required.

Liquid Biopsy Detecting Circulating Tumor Cells in Patients with Non-Small Cell Lung Cancer: Preliminary Results of a Pilot Study.

Lung cancer is still the leading cause of cancer-related death worldwide. Interest is growing towards early detection and advances in liquid biopsy to isolate circulating tumor cells (CTCs). This pilot study aimed to detect epithelial CTCs in the peripheral blood of early-stage non-small cell lung cancer (NSCLC) patients. We used Smart BioSurface® (SBS) slide, a nanoparticle-coated slide able to immobilize viable nucleated cellular fraction without pre-selection and preserve cell integrity. Forty patients undergoing lung resection for NSCLC were included; they were divided into two groups according to CTC value, with a cut-off of three CTCs/mL. All patients were positive for CTCs. The mean CTC value was 4.7(± 5.8 S.D.) per ml/blood. In one patient, next generation sequencing (NGS) analysis of CTCs revealed v-raf murine sarcoma viral oncogene homolog B(BRAF) V600E mutation, which has also been identified in tissue biopsy. CTCs count affected neither overall survival (OS, p = 0.74) nor progression-free survival (p = 0.829). Multivariable analysis confirmed age (p = 0.020) and pNodal-stage (p = 0.028) as negative predictors of OS. Preliminary results of this pilot study suggest the capability of this method in detecting CTCs in all early-stage NSCLC patients. NGS on single cell, identified as CTC by immunofluorescence staining, is a powerful tool for investigating the molecular landscape of cancer, with the aim of personalized therapies.

The Overweight Paradox: Impact of Body Mass Index on Patients Undergoing VATS Lobectomy or Segmentectomy.

The aim of this study was to assess the impact of BMI on perioperative outcomes in patients undergoing VATS lobectomy or segmentectomy. Data from 5088 patients undergoing VATS lobectomy or segmentectomy, included in the VATS Group Italian Registry, were collected. BMI (kg/m2) was categorized according to the WHO classes: underweight, normal, overweight, obese. The effects of BMI on outcomes (complications, 30-days mortality, DFS and OS) were evaluated with a linear regression model, and with a logistic regression model for binary endpoints. In overweight and obese patients, operative time increased with BMI value. Operating room time increased by 5.54 minutes (S.E. = 1.57) in overweight patients, and 33.12 minutes (S.E. = 10.26) in obese patients (P < 0.001). Compared to the other BMI classes, overweight patients were at the lowest risk of pulmonary, acute cardiac, surgical, major, and overall postoperative complications. In the overweight range, a BMI increase from 25 to 29.9 did not significantly affect the length of stay, nor the risk of any complications, except for renal complications (OR: 1.55; 95% CI: 1.07-2.24; P = 0.03), and it reduced the risk of prolonged air leak (OR: 0.8; 95% CI: 0.71-0.90; P < 0.001). 30-days mortality is higher in the underweight group compared to the others. We did not find any significant difference in DFS and OS. According to our results, obesity increases operating room time for VATS major lung resection. Overweight patients are at the lowest risk of pulmonary, acute cardiac, surgical, major, and overall postoperative complications following VATS resections. The risk of most postoperative complications progressively increases as the BMI deviates from the point at the lowest risk, towards both extremes of BMI values. Thirty days mortality is higher in the underweight group, with no differences in DFS and OS.

Port Placement Strategies for Robotic Pulmonary Lobectomy: A Narrative Review.

BACKGROUND: Despite the use of robotics becoming increasingly popular among thoracic surgeons worldwide, there remains debate over the best robotic approach for lung resections. In this paper, we delineated the main port placement strategies and discussed their advantages and disadvantages. METHODS: A PubMed literature review was performed using key phrases such as "robotic lobectomy technique", "RATS lobectomy", and "port placement robotic lobectomy". After the final review, 22 articles were included as references, of which 10 described common robotic port mapping techniques. RESULTS: Several port strategies for robot-assisted pulmonary lobectomies have been proposed and described in the literature, each showing its own limitations and advantages. CONCLUSIONS: New robotic surgeons may choose their port strategy according to personal preference and previous surgical experience, especially regarding open or VATS resections. Robust data comparing different port placements in robotic surgery are lacking. Further research should be directed toward comparisons of clinical outcomes with different robotic approaches.

Lymph node isolated tumor cells and micrometastases in pathological stage I non-small cell lung cancer: prognostic significance.

OBJECTIVE: To determine the prevalence and prognostic significance of lymph node micrometastases and isolated tumor cells (ITC) in patients submitted for radical resection for pathological stage I non-small cell lung cancer (NSCLC). METHODS: From January 1998 through December 2005, 87 consecutive pT1-2, pN0 NSCLC patients were enrolled. Surgical specimens were submitted to pathological routine examinations to define histotype, grade, stage, vascular invasion, necrosis and tumor proliferative index. A total of 694 regional lymph nodes were examined by means of serial sections stained with hematoxylin and eosin and labelled by immunohistochemistry (antibody AE1/AE3, DAKO). Relationships between these parameters and patients' prognosis were investigated. RESULTS: By histological examination, there were 36 squamous-cell carcinoma, 38 adenocarcinoma and 13 large-cell carcinoma. Micrometastases and ITC were detected in 19 lymph nodes (2.7%) of 14 patients (16%). Significant correlation was observed between micrometastases or ITC and adenocarcinoma (p=0.03) and the absence of necrosis (p=0.05). No relationship was demonstrated between micrometastases or ITC and T-status, vascular invasion or proliferative index (p>0.05). Median follow-up was 3.2 (range 0.25-8.6) years. Two- and 5-year disease-free survival was similar for patients with and without micrometastases or ITC (79% and 64% vs 81% and 64%, respectively). Recurrence occurred in three patients with (two local, 66%) and in 21 patients without micrometastases or ITC (three local, 14%) (p=0.186). By multivariate analysis only T-status was demonstrated to be a significant prognostic factor. DISCUSSION: Micrometastases or ITC to regional lymph nodes are demonstrated to be not a rare aspect of pathological stage I resected lung cancer. In our series, the presence of lymph nodes micrometastases does not affect long-term disease-free survival.

The Redax® Coaxial Drain in pulmonary lobectomy: a study of efficacy.

BACKGROUND: Pleural drainage is required after pulmonary lobectomy to evacuate air-leak and fluid. We compared the performance of the new Redax® Coaxial Drain (CD) (Redax, Mirandola, Italy) with a standard chest tube (CT) in terms of fluid and air-leak evacuation. METHODS: Fifty-two patients receiving a 24-F CD under water-seal after pulmonary lobectomy through open surgery or video-assisted thoracic surgery (VATS) were matched according to demographic, clinical and pathological variables with 104 patients receiving a 24-F CT. Fluid evacuation and post-operative day 0 (POD0) fluid evacuation rate, air-leak rate, tension pneumothorax or increasing subcutaneous emphysema, tube occlusion at removal, visual analog scale (VAS) score at rest and during cough, chest drain duration, pleural fluid accumulation or residual pleural cavity after tube removal, post-operative morbidity and mortality rate were recorded and compared between the two groups. RESULTS: No differences were recorded in post-operative morbidity and mortality rates. Fluid drainage rates on POD0 were significantly higher in CD group (73% vs. 48%; P=0.004); air-leak occurrence was similar in both groups and no differences were recorded in terms of tension pneumothorax or increasing subcutaneous emphysema rates; VAS score was lower for CD when compared with CT and it reached significant difference in the subgroups of patients operated on by VATS; no cases of occlusion at removal were recorded in CD patient. CONCLUSIONS: Redax® CD is safe and efficient in air-leak and fluid evacuation; due to its design and constituting material it is superior to standard CTs in terms of fluid evacuation rate and patient post-operative comfort.

Metastasis to subsegmental and segmental lymph nodes in patients resected for non-small cell lung cancer: prognostic impact.

BACKGROUND: We investigated the prognostic significance of segmental and subsegmental (level 13 and 14) lymph nodes metastasis in patients with resected non-small cell lung cancer (NSCLC). METHODS: The pattern of lymph nodal metastasis was analyzed in 124 patients with pN1 NSCLC. Long-term outcomes were compared for 390 pN0, 124 pN1, and 82 pN2 consecutive patients submitted to planned pulmonary resection for NSCLC between 2000 and 2006. The pN1 status was stratified into 3 groups according to the highest level of lymph node involvement: level 10 (hilar); level 11+12 (lobar + interlobar); and level 13+14 (segmental + subsegmental). RESULTS: The 5-year overall survival (OS) rates for pN0, pN1, and pN2 patients were 93%, 66%, and 25%, respectively. The highest level of lymph node involvement was a significant prognostic indicator; the 5-year OS rate for level 13+14, level 11+12, level 10 pN1, and pN2 was 81%, 58%, 48%, and 25%, respectively. Significant differences were recorded in long-term outcome when pN0 and pN1 level 13+14, pN1 level 13+14, and pN1 level 11+12, pN1 level 11+12 and pN1 level 10 were compared (p < 0.05). The median number of examined level 13+14 lymph nodes was 2 (range 0 to 6) and 57% pN1 patients had metastasis at level 13+14 lymph nodes. CONCLUSIONS: The highest level of lymph node metastases may be used to stratify outcome of patients with pN1 disease. Routine examination of level 13+14 lymph nodes is to be recommended to correctly identify patients at risk of relapse and predict long-term prognosis.

Non-small cell lung cancer in surgically treated women.

AIM AND BACKGROUND: To determine whether female patients operated on for non-small cell lung cancer (NSCLC) have a survival advantage compared to male patients. METHODS AND STUDY DESIGN: We analyzed data from 1,426 prospectively collected patients submitted to lung resection for NSCLC between 1999 and 2008. RESULTS: Two groups, including 1,014 male and 412 female patients, were compared. Female patients were significantly younger, were more frequently asymptomatic, were less likely to be smokers, had better preoperative respiratory function, had a lower frequency of COPD, and were less commonly affected by cardiovascular comorbidity than men. Adenocarcinoma was more frequently present and early pathological stage (stage IA) more frequently detected in women at diagnosis. The operative mortality was significantly lower among women (1.6% vs 4.6%) (P = 0.012), and women underwent significantly more segmentectomies and fewer pneumonectomies (P = 0.001). The disease-related 5-year survival rate was significantly higher in women (66% vs 51%) (P = 0.0008). At univariate analysis the absence of symptoms at presentation, lower pathological stage, squamous cell type, and female gender were positive factors influencing long-term survival. At multivariate analysis low pathological stage, squamous cell type and female gender were confirmed as independent positive prognostic predictors. Women had a significant survival advantage irrespective of the histological subtype at pathological stage IA, IB, IIB and IIIA disease (P <0.05). CONCLUSIONS: Female gender was confirmed to be a particular subset amongst patients affected by NSCLC and exerted a positive effect on disease-related survival of patients submitted to surgical resection. This important effect of gender should be cautiously kept in mind in analyzing the results of current and future trials for lung cancer therapy.

Pulmonary aspergilloma: clinical aspects and surgical treatment outcome.

Aspergillomas are fungal balls within lung cavities. The natural history is variable. Hemoptysis is a dangerous sequela. Medical therapy is ineffective because of the lack of a lesion blood supply. Randomized trials are lacking. Surgery should be the treatment of choice in cases of hemoptysis, and even in asymptomatic patients, if lung function is not severely compromised. Cavernostomy and cavernoplasty may be options for high-risk patients. Percutaneous therapy should be reserved for patients who are not fit for surgery. Bronchial artery embolization is appropriate for symptomatic patients not suitable for surgery. Embolization could be considered a preoperative and temporary strategy.

Use of the proposals of the international association for the study of lung cancer in the forthcoming edition of lung cancer staging system to predict long-term prognosis of operated patients.

PURPOSE: To evaluate the utility of the proposals of the International Association for the Study of Lung Cancer (IASLC) in the forthcoming 7th edition of lung cancer staging system to classify patients submitted to radical surgical resection of non-small cell lung cancer and to compare their value in predicting long-term prognosis with the existing 6th edition of the American Joint Committee on Cancer (AJCC)/Union Internationale Contre le Cancer (UICC) TNM classification. METHODS: Nine hundred twenty-one patients received an anatomic resection and hilar-mediastinal dissection for primary non-small cell lung cancer during the period 1990 to 2005. Histopathologic staging following the actual AJCC/UICC TNM classification were as follows: 207 T1, 562 T2, 148 T3, and 4 T4; 570 N0, 149 N1, 198 N2, and 4 N3; 163 stage IA, 346 IB, 23 IIA, 157 IIB, 224 IIIA, and 8 IIIB. Stages reclassified using the proposals of IASLC for the new staging system were as follows: 101 T1a, 106 T1b, 400 T2a, 103 T2b, 210 T3, and 1 T4; 163 stage IA, 262 IB, 157 IIA, 106 IIB, 230 IIIA, and 4 IIIB. RESULTS: Follow-up was obtained for 836 patients. Mean follow-up was 46.5 +/- 48.9 months. N-status (unchanged between the 2 classifications) was confirmed to be a significant prognostic factor. Significant differences in 10-year disease-related survival were demonstrated between stages IIB and IIIA only (35% vs 14%) of the AJCC/UICC TNM classification and between stages IB and IIA (60% vs 46%) and stages IIB and IIIA (39% vs 15%) of the IASLC proposals for a new classification. DISCUSSION: The proposals of IASLC in the forthcoming 7th edition of the lung cancer staging system are demonstrated to be better able to separate prognostically distinct groups of patients operated for non-small cell lung cancer than the accepted existing 6th AJCC/UICC TNM classification.

Air-leak management after upper lobectomy in patients with fused fissure and chronic obstructive pulmonary disease: a pilot trial comparing sealant and standard treatment.

A pilot trial to compare the efficacy of two different procedures to prevent postoperative air-leak in chronic obstructive pulmonary disease (COPD) patients submitted to upper lobectomy for non-small cell lung cancer. Sixty patients with COPD and lung cancer at the upper pulmonary lobes eligible for lobectomy were enrolled and randomly assigned either to standard treatment (ST) with stapling device or to electrocautery dissection and application of a collagen patch coated with human fibrinogen and thrombin (TachoSil) (experimental treatment [ET]) for the intra-operative completion of their fused fissures. Thirty patients were enrolled in each group during a three-year period. Preoperative characteristics were similar between the two groups. Statistically significant reduction of air-leak was registered in the ET group when overall incidence of postoperative air-leak (55% vs. 96%; P=0.03), postoperative air-leak (mean 1.63+/-1.96 vs. 4.33+/-4.12 days; P=0.0018), chest-drain (mean 3.53+/-1.59 vs. 5.90+/-3.72 days; P=0.0021) and hospital stay duration (mean 5.87+/-1.07 vs. 7.50+/-3.20 days; P=0.01) were considered. The use of TachoSil to prevent postoperative air-leak after interlobar fissure completion in patients with COPD submitted to upper lobectomy seems to be safe and more effective than the ST based on stapling device application.

Open window thoracostomy for pleural empyema complicating partial lung resection.

BACKGROUND: Although an open-window thoracostomy (OWT) represents the ideal method for drainage of postpneumonectomy empyema, several controversies exist concerning its application to pleural empyema complicating pulmonary resections less than pneumonectomy. METHODS: Between January 1993 and December 2003, 19 patients (16 male and 3 female) were treated for a pleural empyema complicating partial lung resection. The median age was 62 years (range, 17 to 79). Five patients (26%) had a bronchopleural fistula. RESULTS: In 2 patients (10%), successful control of the infection was achieved with the OWT. In 10 patients (56%), the OWT was closed by obliteration of pleural cavity with antibiotic solution (2 patients) or intrathoracic muscle transposition (8 patients). OWT closure was successfully performed in all of 5 patients with postoperative pleural empyema due to bronchopleural fistula. Prolonged chest drainage was not successful in any patient with late onset postoperative pleural empyema. Univariate analysis revealed that previous left pulmonary resections (p < 0.05) and timing of OWT (p < 0.001) were significant predictors of empyema healing after pulmonary resections smaller than pneumonectomy. CONCLUSIONS: Immediate OWT is a significant predictor of empyema healing after partial lung resection. Smaller pleural cavities appeared to increase the likelihood of healing. Prolonged chest tube drainage failed to control the infection in late onset of postoperative pleural empyema due to entrapped lung.

Predictors of successful closure of open window thoracostomy for postpneumonectomy empyema.

BACKGROUND: Although the open window thoracostomy (OWT) represents the ideal method for drainage of postpneumonectomy empyema (PPE), several controversies exist concerning its closure. METHODS: Between January 1993 and December 2003, an OWT was created in 31 patients (29 male and 2 female) with PPE. The median age was 61 years (range, 32 to 76). In 26 patients (84%) a bronchial stump fistula developed. The OWT closure was correlated with characteristics of PPE and the timing of OWT. RESULTS: In 15 patients (48%), the OWT could be closed by obliteration of pleural cavity with antibiotic solution (3 patients) or intrathoracic muscle transposition (12 patients). A successful closure was observed in 13 of the 15 patients (87%). All patients closed by Clagett's procedure remained empyema free. Recurrent cancer (n = 4), poor functional status (n = 3), refusal of further operation (n = 2), and persistent tuberculous empyema (n = 2) were common causes of failure of OWT closure. Univariate analysis revealed that the timing of empyema development after surgery (p = 0.02) and the timing of OWT (p = 0.03) were significant predictors of thoracostomy closure. CONCLUSIONS: Late onset of PPE and immediate OWT creation are significant predictors of OWT closure. Smaller dimensions of the pleural cavity appeared to increase the likelihood of closure. When the pleural cavity shows healthy granulation tissue and no bronchopleural fistula, the Clagett's procedure is safe and effective to obliterate the pleural cavity. Obliteration by muscle flap transposition can be reserved for patients with persistent or recurrent bronchopleural fistula.