A prospective randomized trial comparing stapler and laser techniques for interlobar fissure completion during pulmonary lobectomy.

Alveolar air leaks, often resulting from lung tissue traumatization during dissection of fissures, still remain a challenging problem in lung surgery. Several tools and techniques have been used to reduce air leakage, but none was judged ideal. This prospective, randomized trial was designed to evaluate the feasibility, safety, and effectiveness of completion of fissures during pulmonary lobectomy by using a laser system. A standard stapler technique was used for comparison; the primary goal was to reach at least a comparable result. Forty-four patients were enrolled, 22 were treated with standard technique by using staplers (S) and 22 underwent laser (L) dissection. Randomization to one of the two groups was intraoperative after evaluating the presence of incomplete fissure (grade 3-4 following Craig's classification). A Thulium laser 2010 nm (Cyber TM, Quanta System, Italy) was used at power of 40 W. Outcome primary measures were the evaluation and duration of intra- and postoperative air leaks, the rate of complications, and the hospital stay. Air leaks (2.1 ± 4.2 vs 3.6 ± 7.2 days; p = 0.98) and chest tube duration (6.4 ± 4.2 vs 7.5 ± 6.3 days, p = 0.44) were lower in L compared with S group even if these were not statistically significant. Complications (36.4 vs 77.3 %; p = 0.006), hospital stay (6.9 ± 3.8 vs 9.9 ± 6.9 days; p = 0.03), hospitalization costs (5,650 vs 8,147 euros; p = 0.01), and procedure costs (77 % of difference; p < 0.0001) were significantly lower for L group, while operative time was longer (197 ± 34 vs 158 ± 41 min; p = 0.004). The use of laser dissection to prevent postoperative air leaks is effective and comparable with stapler technique. Aero-haemostatic laser properties (by sealing of small blood vessels and checking air leaks) allow a safe application during pulmonary lobectomy in interlobar fissure completion avoiding stapler use.

Should all patients receive extended thromboprophylaxis after resection of primary lung cancer?

OBJECTIVE: The optimal duration of thromboprophylaxis in patients undergoing resection of primary lung cancer is not known. We investigated the incidence of pulmonary emboli and venous thromboembolism in patients undergoing early-stage lung cancer resection and the impact of change from short duration to extended thromboprophylaxis. METHODS: We reviewed the outcomes of consecutive patients who underwent resection of early-stage primary lung cancer following a change in protocol from inpatient-only to extended thromboprophylaxis to 28 days. Propensity-score matching of control (routine inpatient pharmacologic thromboprophylaxis) and treatment group (extended pharmacologic thromboprophylaxis) was performed. Adjustment for covariates based on the Caprini risk assessment model was undertaken. Thromboembolic outcomes were compared between the 2 groups. RESULTS: Seven hundred fifty consecutive patients underwent resection of primary lung cancer at Oxford University Hospitals NHS Foundation Trust between January 2013 and December 2018. Six hundred patients were included for analysis and propensity-score matching resulted in 253 matched pairs. Extended prophylaxis was associated with a significant reduction in pulmonary emboli (10 of 253 patients [4%] vs 1 of 253 patients [0.4%], P = .01). One patient (0.4%) developed a bleeding complication within the treatment cohort. Multivariable logistic regression model demonstrated that extended thromboprophylaxis was independently associated with a reduction in postoperative pulmonary emboli. CONCLUSIONS: Patients undergoing lung cancer resection surgery are at moderate-to-high risk of postoperative thromboembolic disease. Extended dalteparin for 28 days is safe and is associated with reduced incidence of pulmonary embolus in patients undergoing resection of early-stage primary lung cancer.

Optimal resection rate for lung cancer in the UK: how high should we go?

BACKGROUND: The optimal resection rate for institutions managing early-stage primary lung cancer is not known. Whether the prognosis of patients who do not proceed to operation is determined by their comorbidities for which they were deemed at prohibitively high-operative risk, or disease progression, is uncertain. We investigated the outcomes of patients with early-stage lung cancer who were considered for surgical management. METHODS: We reviewed the outcomes of consecutive patients who were considered for resection of early-stage primary lung cancer at Oxford University Hospitals National Health Service Foundation Trust between 2012 and 2017. RESULTS: Between 29 November 2012 and 31 March 2017, 467 consecutive patients underwent resection with curative intent for primary lung cancer (operative group), while 81 patients were deemed resectable but either inoperable or did not wish to proceed to operation (non-operative group). Reason for not proceeding to resection was cardiovascular in 16 patients (19.8%), respiratory in 21 (25.9%), cardiorespiratory in 11 (13.6%), performance status in 8 (9.9%) and patient choice in 25 (30.9%) patients. Sixty-six patients (81.5%) received an alternative radical treatment. Median follow-up was 169 weeks (IQR 119-246 weeks) in the operative group and 118 weeks (IQR 74-167 weeks) in the non-operative group. Median survival of patients with early-stage lung cancer who did not proceed to operation was 2.5 years; median survival of patients undergoing lung cancer resection was undefined (p<0.0001). Lung cancer was documented as directly or indirectly leading to or contributing to death in 40 patients (76.9%). In 11 patients, the cause of death was due to comorbidities (21.2%). CONCLUSIONS: Patients turned down for operation in a high-resection rate UK unit have limited survival due to lung cancer progression. We conclude that 'optimal' resection rates may not have been reached in the UK even in high-resection rate centres.

Mitochondrial Inhibitor Atovaquone Increases Tumor Oxygenation and Inhibits Hypoxic Gene Expression in Patients with Non-Small Cell Lung Cancer.

PURPOSE: Tumor hypoxia fuels an aggressive tumor phenotype and confers resistance to anticancer treatments. We conducted a clinical trial to determine whether the antimalarial drug atovaquone, a known mitochondrial inhibitor, reduces hypoxia in non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with NSCLC scheduled for surgery were recruited sequentially into two cohorts: cohort 1 received oral atovaquone at the standard clinical dose of 750 mg twice daily, while cohort 2 did not. Primary imaging endpoint was change in tumor hypoxic volume (HV) measured by hypoxia PET-CT. Intercohort comparison of hypoxia gene expression signatures using RNA sequencing from resected tumors was performed. RESULTS: Thirty patients were evaluable for hypoxia PET-CT analysis, 15 per cohort. Median treatment duration was 12 days. Eleven (73.3%) atovaquone-treated patients had meaningful HV reduction, with median change -28% [95% confidence interval (CI), -58.2 to -4.4]. In contrast, median change in untreated patients was +15.5% (95% CI, -6.5 to 35.5). Linear regression estimated the expected mean HV was 55% (95% CI, 24%-74%) lower in cohort 1 compared with cohort 2 (P = 0.004), adjusting for cohort, tumor volume, and baseline HV. A key pharmacodynamics endpoint was reduction in hypoxia-regulated genes, which were significantly downregulated in atovaquone-treated tumors. Data from multiple additional measures of tumor hypoxia and perfusion are presented. No atovaquone-related adverse events were reported. CONCLUSIONS: This is the first clinical evidence that targeting tumor mitochondrial metabolism can reduce hypoxia and produce relevant antitumor effects at the mRNA level. Repurposing atovaquone for this purpose may improve treatment outcomes for NSCLC.

Imaging of congenital chest wall deformities.

To identify the anatomy and pathology of chest wall malformations presenting for consideration for corrective surgery or as a possible chest wall "mass", and to review the common corrective surgical procedures. Congenital chest wall deformities are caused by anomalies of chest wall growth, leading to sternal depression or protrusion, or are related to failure of normal spine or rib development. Cross-sectional imaging allows appreciation not only of the involved structures but also assessment of the degree of displacement or deformity of adjacent but otherwise normal structures and differentiation between anatomical deformity and neoplasia. In some cases, CT is also useful for surgical planning. The use of three-dimensional reconstructions, utilizing a low-dose technique, provides important information for the surgeon to discuss the nature of anatomical abnormalities and planned corrections with the patient and often with their parents. In this pictorial essay, we discuss the radiological features of the commonest congenital chest wall deformities and illustrate pre- and post-surgical appearances for those undergoing surgical correction.

Surgical and neurologic outcomes after robotic thymectomy in 100 consecutive patients with myasthenia gravis.

OBJECTIVE: Thymectomy is a well-defined therapeutic option for patients with myasthenia gravis; however, controversies still exist about the surgical approach, indication, and timing for surgery. We reviewed our experience reporting surgical and neurologic results after robotic thymectomy in patients with myasthenia gravis. METHODS: Between 2002 and 2010, 100 patients (74 female and 26 male; median age, 37 years) underwent left-sided robotic thymectomy using the da Vinci robotic system (Intuitive Surgical, Inc, Sunnyvale, Calif). The Myasthenia Gravis Foundation of America classification was adopted for pre- and postoperative evaluation. Preoperative Myasthenia Gravis Foundation of America class was I in 10% of patients, II in 35% of patients, III in 39% of patients, and IV in 16% of patients. RESULTS: Median operative time was 120 (60-300) minutes. No death or intraoperative complications occurred. Postoperative complications were observed in 6 patients (6%) (bleeding requiring blood transfusions in 3, chylothorax in 1, fever in 1, and myasthenic crisis in 1). Median hospital stay was 3 days (range, 2-14 days). Histologic analysis revealed 76 patients (76%) with hyperplasia, 7 patients (7%) with atrophy, 8 patients (8%) with small thymomas, and 9 patients (9%) with normal thymus; ectopic thymic tissue was found in 26 patients (26%). Clinical follow-up showed a 5-year probability of complete stable remission and overall improvement of 28.5% and 87.5%. Remission was significantly associated with preoperative I to II Myasthenia Gravis Foundation of America class (P = .02). A significant improvement rate was found in Myasthenia Gravis Foundation of America class I to II (P = .03) and AbAchR+ (P = .04). A high percentage of patients interrupted or reduced their medications. CONCLUSIONS: Robotic thymectomy is a safe and effective procedure. We observed a neurologic benefit in a great number of patients. A better clinical outcome was obtained in patients with early Myasthenia Gravis Foundation of America class.

Changes in pulmonary function tests predict radiological response to chemotherapy in malignant pleural mesothelioma.

OBJECTIVES: Response to chemotherapy in malignant pleural mesothelioma (MPM) is usually evaluated by radiological criteria, but no common agreement exists on their validity, yet. The cytoreductive effect of chemotherapy on pleural thickening may make the lung more expansible, reducing the restrictive ventilatory impairment. The aim of this study was to evaluate the changes in pulmonary function following chemotherapy in patients with MPM and to correlate these findings with radiological changes. METHODS: Between 2004 and 2011, 62 consecutive patients (74% males, median age 63 years) were prospectively investigated. Modified RECIST criteria were used for radiological evaluation of response to chemotherapy. All patients underwent pulmonary function tests before and after three cycles of platinum-based chemotherapy. Changes between baseline and post-chemotherapy pulmonary function values (Δ) and their differences were assessed by means of Student's paired and unpaired t-test, respectively. Receiver operating characteristic (ROC) curve analysis was performed on spirometric parameters significantly associated with response. RESULTS: Thirty (48.4%) patients had a radiological stable disease (S), 23 (37.1%) a partial response (R) and 9 (14.5%) a progressive disease (P). ΔFEV1%pred (R: 18.1 ± 18.5%; S: 0.5 ± 9.3%; P: -11 ± 13.5%; P < 0.0001), ΔFVC%pred (R: 16.1 ± 11.8%; S: 0.4 ± 11.2%; P: -9.2 ± 14.6%; P < 0.0001) and ΔVC%pred (R: 12.9 ± 15.7%; S: 1.5 ± 12.1%; P: -6.1 ± 13.2%; P = 0.001) were significantly associated with radiological response. A significant correlation was observed between ΔFEV1%pred (r = 0.46, P = 0.01), ΔFVC%pred (r = 0.43, P = 0.02) and % change in linear tumour measurement. ROC curve analysis using dichotomized radiological response (P/S vs R) as classification variables showed AUC = 0.88 (95%CI: 0.77-0.95) for ΔFEV1%pred (optimal cut-off value: +7%, sensitivity: 83%, specificity: 82%, PPV: 73%, NPV: 89%) and AUC = 0.86 (95%CI: 0.75-0.94) for ΔFVC%pred (optimal cut-off value: +6%, sensitivity: 82%, specificity: 74%, PPV: 64%, NPV: 88%). CONCLUSIONS: Dynamic lung volumes and radiological changes after chemotherapy seem directly related. Lung function changes could be an additional tool to better evaluate the response to chemotherapy in MPM.

Prosthetic azygo-atrial bypass for palliation of superior vena cava syndrome.

We report a case of locally advanced excavated non-small cell lung cancer with superior vena cava (SVC) syndrome that underwent four cycles of induction chemotherapy. Due to early treatment failure and the impossibility applying radical radiotherapy, a decision was made to perform surgery. The patient underwent right intrapericardial pneumonectomy with en-bloc resection of the SVC, azygos vein and mediastinal lymph nodes. Prosthetic azygo-atrial bypass was then performed. The patient enjoys one year progression-free survival with patent graft and symptomatic relief of SVC syndrome.

Robot-aided thoracoscopic thymectomy for early-stage thymoma: a multicenter European study.

OBJECTIVE: Minimally invasive thymectomy for stage I to stage II thymoma has been suggested in recent years and considered technically feasible. However, because of the lack of data on long-term results, controversies still exist on surgical access indication. We sought to evaluate the results after robot-assisted thoracoscopic thymectomy in early-stage thymoma. METHODS: Data were collected from 4 European centers. Between 2002 and 2011, 79 patients (38 men and 41 women; median age, 57 years) with early-stage thymoma were operated by left-sided (82.4%), right-sided (12.6%), or bilateral (5%) robotic thoracoscopic approach. Forty-five patients (57%) had associated myasthenia gravis. RESULTS: Average operative time was 155 minutes (range, 70-320 minutes). One patient needed open conversion, in 1 patient a standard thoracoscopy was performed after robotic system breakdown, and in 5 patients an additional access was required. No vascular and nervous injuries were recorded, and no perioperative mortality occurred. Ten patients (12.7%) had postoperative complications. Median hospital stay was 3 days (range, 2-15 days). Median diameter of tumor resected was 3 cm (range, 1-12 cm), and Masaoka stage was stage I in 30 patients (38%) and stage II in 49 patients (62%). At a median follow-up of 40 months, 74 patients were alive and 5 had died (4 patients from nonthymoma-related causes and 1 from a diffuse intrathoracic recurrence), with a 5-year survival rate of 90%. CONCLUSIONS: Our data indicate that robot-enhanced thoracoscopic thymectomy for early-stage thymoma is a technically sound and safe procedure with a low complication rate and a short hospital stay. Oncologic outcome seems good, but a longer follow-up is needed to consider this as a standard approach definitively.

Single-institution experience on robot-assisted thoracoscopic operations for mediastinal diseases.

OBJECTIVE: : After the introduction of video-assisted thoracoscopic surgery 20 years ago, the minimally invasive techniques in thoracic surgery have found a growing application. The recent introduction of robotic technology has increased the potentiality of thoracoscopic technique leading to an expansion of indications and applications, particularly for the management of mediastinal diseases. We reviewed our experience in robot-assisted thoracoscopic resection of benign and malignant mediastinal diseases. METHODS: : Between 2002 and 2010, 108 patients (79 women and 29 men; median age 38 y) underwent robot-assisted thoracoscopy using the "da Vinci" robotic system for several mediastinal diseases. There were 100 thymectomies, 3 resections of paravertebral tumors, 1 thymic cyst, 1 ectopic goitre, 1 ectopic mediastinal parathyroidectomy, 1 thymic carcinoid, and 1 foregut cyst. Ninety-five (87.9%) patients were affected by myasthenia gravis. RESULTS: : All procedures were completed successfully using the da Vinci robot; no open conversions were required, but in three (2.8%) cases, a fourth access was added. There was no surgical mortality; four (3.6%) patients had postoperative complications (two hemothorax, one chylothorax, and one fever) treated conservatively. Median operation time was 120 (range 60-300) minutes and median hospitalization was 3 (range 2-14) days. Global benefit rate for patients with myasthenia gravis reached the value of 93.4% with progressive improvement over years. CONCLUSIONS: : Several mediastinal operations may be feasible by using a robot-aided thoracoscopic approach. The technical innovations offered by robotic instrumentation make all procedures safer and easier when compared with standard thoracoscopic approach, with particular reference for application in mediastinal field.

Multidisciplinary approach for advanced stage thymic tumors: long-term outcome.

BACKGROUND: In advanced stage thymic tumors complete surgical resection is not always achievable. Although surgery remains the cornerstone of therapy, there is growing evidence that multimodality treatment increases resectability and reduces the incidence of local and systemic relapses. METHODS: Between 1980 and 2008, 75 patients with stages III (n = 51), IVA (n = 18) and IVB (n = 6) thymic tumors were treated. Twenty-six patients had A-AB-B1 and 49 B2-B3-C histotype. Thirty-eight (50.6%) patients considered not radically resectable at preoperative workup, received induction chemotherapy; postoperatively 37 (49.3%) had radiotherapy, 25 (33.3%) chemoradiotherapy and 4 (5.3%) chemotherapy. RESULTS: No perioperative mortality was recorded. Sixty-one (81.3%) had complete resection (CR) and 14 (18.7%) incomplete resection (IR). CR was lower in patients who received induction chemotherapy (73.7% vs 89.2%, p = 0.02). In 11 (14.7%) cases a vascular procedure was carried out. Overall 5- and 10-year survivals were 70% and 57%, respectively. Five and 10-year tumor-related survival was 78% and 70%. Ten-year survival was better for CR vs IR resection (62% vs 28%; p = 0.003) and for type A-AB-B1 vs B2-B3-C (60% vs 53%; p = 0.03). No statistical difference was found between stage III and IV (10-year survival: 63% and 43%; p = 0.42) and induction vs no induction chemotherapy (10-year survival: 52% vs 56%; p = 0.54). At multivariate analysis CR (p = 0.001) and type A-AB-B1 (p = 0.04) were independent predictors of better survival. During follow-up, 34.4% of CR developed tumor recurrence. CONCLUSIONS: Multimodality treatment of stages III and IV thymic tumors guarantees good disease control and provides high survival and acceptable recurrence rates.

Pneumonectomy for lung cancer over the age of 75 years: is it worthwhile?

The objective of the study was to evaluate the outcome in elderly patients (>75 years) submitted to pneumonectomy for lung cancer. Records of 40 elderly patients, who underwent pneumonectomy at our Institution from 1990 to 2008, were retrospectively reviewed. This group was compared with 289 younger patients submitted to pneumonectomy in the same period. In the older group median age was 77 years (range 75-84 years), 16 were right-side procedures. In the younger group median age was 62 years (range 24-74 years), 114 were right-sided procedures. The overall mortality rate was 7.5% and 6.2% in the older and younger groups, respectively (P=0.75); morbidity rate was 35.1% and 17.7% (P=0.01) and five-year survival rate was 32% and 30%, respectively (P=0.85). Right-sided procedures (P=0.0006) were associated with higher risk of mortality and age over 75 years (P=0.01) with increased risk of morbidity; pathological stage was the only predictor of five-year survival. Pneumonectomy appears to be justified even in patients older than 75 years, because short- and long-term outcomes can be acceptable and comparable with those of younger patients. Advanced age alone does not justify denying curative resection of lung cancer, but right-sided procedures require a careful pre- and postoperative approach.