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.

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.

Surgical management of chronic diaphragmatic hernias.

Chronic diaphragmatic hernia (CDH) is an uncommon disease which may be associated with significant morbidity and mortality. Antecedent (even many months or years before CDH development) blunt or penetrating thoracic/thoraco-abdominal trauma is generally recognized. A wide spectrum of different mechanisms of injury, timing in presentation, size of the diaphragmatic defect, types and amount of abdominal viscera herniated into the chest cavity, clinical symptoms are observed in CDHs. Thoracic and abdominal CT scan (with coronal, axial and sagittal reconstructions) is the best diagnostic tool; sometimes thoracic MRI is needed to better define the extent of the diaphragmatic defect and the number of abdominal organs displaced into the chest cavity. Surgery (sometimes urgent) represents the treatment of choice for CDH; diaphragmatic hernia direct repair with a tension-free suture is generally attempted; in case of very large defects or when a tension-free suture is deemed unfeasible, the use of prosthesis is recommended. This review article will discuss about CDH aetiology, clinical presentation diagnosis and surgical treatment.

Management of Chest Drains After Thoracic Resections.

Immediately after lung resection, air tends to collect in the retrosternal part of the chest wall (in supine position), and fluids in its lower part (costodiaphragmatic sinus). Several general thoracic surgery textbooks currently recommend the placement of 2 chest tubes after major pulmonary resections, one anteriorly, to remove air, and another into the posterior and basilar region, to drain fluids. Recently, several authors advocated the placement of a single chest tube. In terms of air and fluid drainage, this technique demonstrated to be as effective as the conventional one after wedge resection or uncomplicated lobectomy.

Primary lung tumors invading the chest wall.

Chest wall (CW) involvement occurs in approximately 5% of all primary lung neoplasms. According to the most recent TNM classification, lung tumors invading CW are classified as T3, and they represent approximately 45% of all T3 lung cancers. The most common clinical symptom at presentation is chest pain (>60%), which is highly specific of CW infiltration (>90%). Dyspnoea and hemoptysis are also described, especially in case of large lesions. A realistic chance to cure locally advanced tumors invading CW is a surgical resection, consisting in the excision of the primary lung cancer along with the involved CW (sometimes an "en-bloc" resection) and an appropriate lymph-nodal dissection. However, such patients are at high-risk of facing postoperative complications; prognosis mainly depends on: (I) the completeness of resection; and (II) the lymph-nodal involvement. Hence, due to these reasons (incidence, symptoms, prognosis, post-operative complications), such category of patients are to be carefully assessed preoperatively and if deemed practicable, surgery should be taken into consideration. In this view, the aim of this paper is to critically review the most recent series of lung tumors invading the CW, with a particular focus on patients' preoperative evaluation, surgical techniques, postoperative complications and overall outcome.

Surgery of colorectal cancer lung metastases: analysis of survival, recurrence and re-surgery.

BACKGROUND: Surgery is considered an effective therapeutic option for patients with lung metastasis (MTS) of colorectal cancer (CRC). The purpose of the study was to evaluate efficacy and feasibility of lung metastasectomy in CRC patients and to explore factors of prognostic relevance. METHODS: This is a retrospective study of patients operated for lung MTS of CRC from 2004 to 2012 in a single Institution. Overall survival (OS) was the primary endpoint. Secondary endpoints were progression free survival (PFS) in resection status R0 and OS in in patients submitted to re-resections. In order to evaluate prognostic factors, a multivariable Cox proportional hazard model was performed. RESULTS: One-hundred eighty-eight consecutive patients were included in the final analysis. The median follow-up (FU) was 45 months. The 5-year OS and PFS were 53% (95% CI: 44-60%) and 33% (95% CI: 25-42%), respectively. Two- and 5-year survival after re-resection were 79% (95% CI: 63-89%) and 49% (95% CI: 31-65%), respectively. Multivariate adjusted analysis showed that primary CRC pathological TNM stages (P=0.019), number of resected MTS ≥5 (P=0.009) and lymph nodal involvement (P<0.0001) are independent predictors of poor prognosis. CONCLUSIONS: Patients operated and re-operated for lung MTS from CRC cancers showed encouraging survival rates. Our results indicated that primary CRC stage, number of MTS and lymph nodal involvement are strong predictive factors. Prognosis after surgery remained comforting up to four resected MTS. Adjuvant chemotherapy seems to have a benefit on survival in patients affected by multiple metastases. Finally, according to the high rate of unidentified lymph node involvement in pre-operative setting, lymph node sampling should be advisable for a correct staging.

When size matters: changing opinion in the management of pleural space-the rise of small-bore pleural catheters.

Tube thoracostomy is usually the first step to treat several thoracic/pleural conditions such as pneumothorax, pleural effusions, haemothorax, haemo-pneumothorax and empyema. Today, a wide range of drains is available, ranging from small to large bore ones. Indications for an appropriate selection remains yet matter of debate, especially regarding the use of small bore catheters. Through this paper, we aimed to retrace the improvements of drains through the years and to review the current clinical indications for chest drain placement in pleural/thoracic diseases, comparing the effectiveness of small-bore drains vs. large-bore ones.

Efficacy and safety of human fibrinogen-thrombin patch (Tachosil(®)) in the management of diffuse bleeding after chest wall and spinal surgical resection for aggressive thoracic neoplasms.

Diffuse bleeding after chest wall and spine resection represents a major problem in General Thoracic Surgery. Several fibrin sealants (FS) have been developed over the years and their use has been gradually increasing over time, becoming an important aid to the surgeons, justifying their use across numerous fields of surgery due to its valid haemostatic properties. Among the several FS available, TachoSil(®) (Takeda Austria GmbH, Linz, Austria) stands out for its haemostatic and aerostatic properties, the latter being demonstrated even in high-risk patients after pulmonary resections for primary lung cancers. Several papers available in literature demonstrated TachoSil(®)'s effectiveness in controlling intraoperative and postoperative bleeding in different surgical branches, including hepatic and pancreatic surgery, as well as cardiac and thoracic surgery. However, the use of TachoSil(®) to control diffuse bleeding following major resections for advanced lung cancers, with requirement of chest wall and vertebral body resection for oncological radicality, was never published so far. In this paper, we report three cases of pulmonary lobectomy associated to chest wall resection and haemivertebrectomy for primary malignant lung neoplasms and for a recurrence of malignant solitary fibrous tumour of the pleura in which we used TachoSil(©), which demonstrated its efficacy in controlling diffuse bleeding following resection.

Bronchopulmonary Carcinoids causing Cushing Syndrome: Results from a Multicentric Study Suggesting a More Aggressive Behavior.

OBJECTIVE: Cushing syndrome (CS) caused by bronchopulmonary carcinoids (BCs) is a very rare entity. The aim of this study was to revisit the features of a multicenter clinical series to identify significant prognostic factors. METHODS: From January 2002 to December 2013, the clinical and pathological data of 23 patients (treated in five different institutions) were retrospectively reviewed. Survival analysis was performed to explore the relative weight of potential prognostic factors. RESULTS: Median age and male/female ratio were 48 years and 14/9, respectively. Most (> 80%) of the patients presented with CS-related symptoms at diagnosis. Tumor location was peripheral in 13 patients (57%) and central in 10 (43%). All patients but two (treated with chemotherapy) underwent surgical resection with curative intent. Definitive cyto/histology was indicative of typical carcinoid (TC) in 16 cases (70%) and atypical carcinoid (AC) in 7 cases (30%). A complete remission of CS was obtained in 16 cases (70%). Lymph nodal involvement was detected in 11 cases (48%), with N2 disease occurring in 7 (∼ 30% of all cases). Four patients (22%) experienced a relapse of the disease after radical surgery. Overall 5-year survival (long-term survival, LTS) was 60%, better in TCs when compared with AC (LTS: 66 v s. 48%, p = 0.28). Log-rank analysis identified ECOG performance status, cTNM and cN staging, pTNM and pN staging, persistence of CS and relapses (local p = 0.006; distant p = 0.001) as significant prognostic factors in this cohort of patients. CONCLUSION: BCs causing CS are characterized by a high rate of lymph-nodal involvement, a suboptimal prognosis (5-year survival = 60%, 66% in TCs) and a remarkable risk of relapse even after radical resection. Advanced stage, lymph-nodal involvement and the persisting of the CS after treatment correlate with a poor prognosis.

Digital versus traditional air leak evaluation after elective pulmonary resection: a prospective and comparative mono-institutional study.

BACKGROUND: The increased demand to reduce costs and hospitalization in general pushed several institution worldwide to develop fast-tracking protocols after pulmonary resections. One of the commonest causes of protracted hospital stay remains prolonged air leaks (ALs). We reviewed our clinical practice with the aim to compare traditional vs. digital chest drainages in order to evaluate which is the more effective to correctly manage the chest tube after pulmonary resection. METHODS: All patients submitted to elective pulmonary resection for lung malignancies, between April to December, 2014 in our General Thoracic Surgery Department were included in the study. The primary outcome was the chest tube duration, the secondary the postoperative overall hospitalization. Significant differences between traditional and digital groups were investigated with logistic regression models. Numerical variables between the groups were compared by means of the unpaired Wilcoxon-Mann-Whitney test. RESULTS: Both series of patients were comparable for clinical, surgical and pathological characteristics. Chest tube duration showed to be significantly shorter in the digital group (3 vs. 5 days, P=0.0009), while the hospitalization was longer in traditional one [8 vs. 7 days in digital drainage (DD); P=0.0385]. No chest drainage replacement was required at 30-day, in both groups. CONCLUSIONS: We were able to demonstrate that patients managed with a digital system experienced a shorter chest tube duration as well as a lower overall hospital length of stay, compared to those who received the traditional drainage (TD).

Extended transcervical thymectomy with partial upper sternotomy: results in non-thymomatous patients with myasthenia gravis.

OBJECTIVES: Thymectomy is a recognized treatment for myasthenia gravis (MG), but the optimal surgical approach is yet to be determined. This study analysed the results in non-thymomatous MG patients treated at our institution using an extended transcervical access with partial upper sternotomy (TC-US), in order to describe cumulative incidence of remission and its predictors. METHODS: In the period 1988-2012, 215 non-thymomatous MG patients underwent thymectomy using the TC-US approach. There were 61 males and 154 females (median age: 33 years). Primary end points were complete stable remission (CSR) and pharmacological remission (PR). Clinico-pathological predictors of CSR/PR were analysed including age, gender, preoperative MG symptom duration, preoperative immunosuppression therapy and disease severity. RESULTS: The median follow-up period was 127 months. The median preoperative duration of MG symptoms was 9 months (interquartile range 4-13). The median operative time was 65 min (range: 45-135). There was no postoperative death. Morbidity rate was 7% (14 patients, no major complication). Ten patients died at the follow-up (3 of MG). MG symptoms improved in 85% (150/176) of the patients. CSR rate was 34%, PR rate was 4%. Cumulative incidence of CSR/PR was 27, 37 and 46% at 5, 10 and 15 years, respectively. Independent predictors of increased CSR/PR rate were age (P = 0.028) and MG symptom duration <6 months (P = 0.013). CONCLUSIONS: Our data suggest that in patients with non-thymomatous MG, thymectomy by TC-US has a remission rate not inferior to those reported after trans-sternal or video-assisted thoracic surgery techniques. The short duration of MG symptoms before thymectomy is a predictor of remission. The technique strikes a reasonable balance between the extent of thymic resection, operative and anaesthesia time, patient acceptance, neurological outcome and costs.

Clinical management of atypical carcinoid and large-cell neuroendocrine carcinoma: a multicentre study on behalf of the European Association of Thoracic Surgeons (ESTS) Neuroendocrine Tumours of the Lung Working Group†.

OBJECTIVES: In 2012, the European Society of Thoracic Surgeons (ESTS) created the Lung Neuroendocrine Tumors Working Group (NETs-WG) with the aim to develop scientific knowledge on clinical management of such rare neoplasms. This paper outlines the outcome and prognostic factors of two aggressive NETs: atypical carcinoids (ACs) and large-cell neuroendocrine carcinomas (LCNCs). METHODS: Using the ESTS NETs-WG database, we retrospectively collected data on 261 patients in seven institutions in Europe, between 1994 and 2011. We used a Cox regression model to evaluate variables affecting patient survival and disease-free survival. Univariate and multivariate analysis were also carried out. RESULTS: Five-year overall survival rates for ACs and LCNCs were 77 vs 28% (P < 0.001), respectively. We found that for ACs, age (P < 0.001), tumour size (P = 0.015) and sub-lobar surgical resection (P = 0.005) were independent negative prognostic factors; for LCNCs, only pTNM stage III tumours (P = 0.016) negatively affected outcome in the multivariate analysis. Local recurrences and distant metastases developed in 93 patients and were statistically more frequent in LCNCs (P = 0.02). CONCLUSIONS: The biological aggressiveness of ACs and LCNCs has been demonstrated with this study. Our aim is to confirm these results with enhanced data collection through the ESTS NETs database.

Does the World Health Organization histological classification predict outcomes after thymomectomy? Results of a multicentre study on 750 patients.

OBJECTIVES: The World Health Organization (WHO) thymoma histological classification clinical value remains a controversy. In this study, we evaluated its prognostic significance in patients with thymoma treated with radical intent. METHODS: Six high-volume Italian Thoracic Surgery Institutions collaborated with their own retrospective anonymized datasets. Demographic, clinical, pathological and treatment data were examined. A WHO histological classification (WHO-HC) collapsed scheme (A/AB and B1/B2 types merged) was proposed and compared with the traditional one. Predictors of survival were assessed using a Cox model with shared frailty. Competing-risk regression models were performed to identify the association between individual factors and freedom from recurrence. RESULTS: Between 1990 and 2011, 750 thymomas were operated on in participating centres. Myasthenia gravis was observed in 363 (48%) patients. A complete resection was achieved in 676 (91%) cases. One hundred and nine patients (15%) had a WHO-HC A type, 166 (22%) AB, 179 (24%) B1, 158 (21%) B2 and 135 (18%) B3. The rate of 5-year OS and cumulative incidence of recurrence for all cases was 91% and 0.11, respectively. Five-year survival rates by WHO-HC in the collapsed scheme were A/AB 93%, early-B 90% and advanced-B 85%. Masaoka stage only was demonstrated to be an independent predictor for survival and recurrence. The WHO-collapsed scheme showed a trend in influencing recurrence overall survival development (hazard ratio: 1.32; P = 0.16). CONCLUSIONS: Our results show evidence of lack of significance by WHO-HC in influencing prognosis, even though the proposed collapsed scheme revealed a fair stratification of risk to relapses and better correlation with patients' clinical characteristics.

Exploring Stage I non-small-cell lung cancer: development of a prognostic model predicting 5-year survival after surgical resection†.

OBJECTIVES: Despite impressive results in diagnosis and treatment of non-small-cell lung cancer (NSCLC), more than 30% of patients with Stage I NSCLC die within 5 years after surgical treatment. Identification of prognostic factors to select patients with a poor prognosis and development of tailored treatment strategies are then advisable. The aim of our study was to design a model able to define prognosis in patients with Stage I NSCLC, submitted to surgery with curative intent. METHODS: A retrospective analysis of two surgical registries was performed. Predictors of survival were investigated using the Cox model with shared frailty (accounting for the within-centre correlation). Candidate predictors were: age, gender, smoking habit, morbidity, previous malignancy, Eastern Cooperative Oncology Group performance status, clinical N stage, maximum standardized uptake value (SUV(max)), forced expiratory volume in 1 s, carbon monoxide lung diffusion capacity (DLCO), extent of surgical resection, systematic lymphadenectomy, vascular invasion, pathological T stage, histology and histological grading. The final model included predictors with P < 0.20, after a backward selection. Missing data in evaluated predictors were multiple-imputed and combined estimates were obtained from 10 imputed data sets. RESULTS: Analysis was performed on 848 consecutive patients. The median follow-up was 48 months. Two hundred and nine patients died (25%), with a 5-year overall survival (OS) rate of 74%. The final Cox model demonstrated that mortality was significantly associated with age, male sex, presence of cardiac comorbidities, DLCO (%), SUV(max), systematic nodal dissection, presence of microscopic vascular invasion, pTNM stage and histological grading. The final model showed a fair discrimination ability (C-statistic = 0.69): the calibration of the model indicated a good agreement between observed and predicted survival. CONCLUSIONS: We designed an effective prognostic model based on clinical, pathological and surgical covariates. Our preliminary results need to be refined and validated in a larger patient population, in order to provide an easy-to-use prognostic tool for Stage I NSCLC patients.

Prognostic factors in neuroendocrine tumours of the lung: a single-centre experience.

OBJECTIVES: To assess the independent prognostic role of histological subtypes, tumour size and lymph nodal involvement upon survival in lung neuroendocrine tumours (NETs). METHODS: A retrospective search of the database of the Department of Thoracic Surgery (Turin, Italy) identified 157 patients operated on for a newly diagnosed NET between January 1995 and December 2011. Multivariable Cox models were used to analyse predictors of overall survival and progression-free survival. RESULTS: According to histology, 71 (45.2%) were typical carcinoids (TCs), 35 (22.3%) atypical carcinoids (ACs), 37 (23.6%) large-cell neuroendocrine carcinomas (LCNCs) and 14 (8.9%) small-cell lung carcinomas (SCLCs). After a median follow-up time of 6.5 years, 60 patients died and 73 had a recurrence or died. The overall 5-, 10- and 15-year survival rates were 64%, 53% and 46%, respectively. Older age, histology (ACs, LCNCs and SCLCs vs TCs) and lymph nodal involvement were confirmed to be independent negative prognostic factors in the multivariable models for overall survival and progression-free survival. CONCLUSIONS: Tumour histology and lymph nodal involvement are definitively the predominant and relevant factors influencing survival. ACs showed an intermediate prognosis between TCs and poorly differentiated NETs.

Outcome of surgically resected thymic carcinoma: a multicenter experience.

OBJECTIVE: Thymic carcinoma (TC) is a rare and invasive mediastinal tumor, with poor prognosis. Most of the previous published papers are single-institution based, reporting small series of patient, sometimes including palliative resection. This study collected patients with TC treated in 5 high-volume Italian Thoracic Surgery Institutions. METHODS: A multicenter retrospective study of patients operated for TC between 2000 and 2011 was conducted. Exclusion criteria were: Neuroendocrine thymic neoplasms, debulking/palliative resection and tumor biopsy. Cause specific survival (CSS) was the primary endpoint. RESULTS: Four hundred and seventy-eight patients underwent surgery for thymic malignancies: 40 of them (8.4%) had TC. Eleven (27.5%) received induction chemotherapy because of their radiological invasiveness. A complete resection (R0) was achieved in 36 (90%; 9/11 submitted to induction chemotherapy). Adjuvant radio/chemotherapy was offered to 37 patients, according to the type of surgical resection and tumor invasiveness. Three, 5 and 10-year survival rates were 79%, 75% and 58%. Recurrences developed in 10 patients. R0 resection (p<0.0003) and absence of tumor recurrences (p=0.03) resulted significant prognostic factors at univariate analysis. Independent CSS predictor was the achievement of a complete resection (p<0.05). CONCLUSIONS: TC is a rare and invasive mediastinal tumor. A multimodal approach is indicated especially in TC invasive forms. The achievement of a complete surgical resection is fundamental to improve survival.

Outcome and prognostic factors in bronchial carcinoids: a single-center experience.

INTRODUCTION: The aim of this study is to assess factors influencing survival in patients with bronchial carcinoids (BCs). METHODS: A retrospective review of our surgical database of patients operated for primary lung cancer with a final histologic diagnosis of BC in the period from January 1, 1995 to December 31, 2010 was carried out. RESULTS: There were 126 patients (74 women): 83 had a typical carcinoid and 43 an atypical one (AC). All patients received a radical resection; systematic lymphadenectomy was accomplished in 120. Lymph nodal metastases were observed in 26 cases (12 N2) and were more frequent in ACs (p = 0.009). Twelve patients received adjuvant therapy (chemo/radio/biological). Distant metastases (DM) and local tumor recurrence occurred in 28 (22%) and 8 (6.3%) cases, respectively: DM were more frequent in ACs (p = 0.0001) and in N2 patients (p = 0.0001). Smoke, atypical histology, lymph nodal metastases, and high cellular proliferative index demonstrated to be statistically negative prognostic factors. CONCLUSION: Even if characterized by an indolent behavior, BCs may spread to lymph node or distant or present with local recurrence. Amid all prognostic factors, the presence of DM demonstrated to be the strongest negative one.