Outcomes of single- versus multi-port video-assisted thoracoscopic surgery: Data from a multicenter randomized controlled trial of video-assisted thoracoscopic surgery versus thoracotomy for lung cancer.

Objectives: Surgery through a single port may be less painful because access is supplied by 1 intercostal nerve or more painful because multiple instruments are used in 1 port. We analyzed data collected from the video-assisted thoracoscopic surgery group of a randomized controlled trial to compare differences in pain up to 1 year. Methods: Groups were compared in a prespecified exploratory analysis using direct (regression) and indirect comparison (difference with respect to thoracotomy). In-hospital visual analogue scale pain scores were used, and analgesic ratios were calculated. After discharge, pain was evaluated using European Organization for Research and Treatment of Cancer Quality of Life Questionnaires-Core 30 scores up to 1 year. Results: From July 2015 to February 2019, we randomized 503 participants. After excluding 50 participants who did not receive lobectomy, surgery was performed using a single port in 42 participants (predominately by a single surgeon), multiple ports in 166 participants, and thoracotomy in 245 participants. No differences were observed in-hospital between single- and multiple-port video-assisted thoracoscopic surgery when modeled using a direct comparison, mean difference of -0.24 (95% CI, -1.06 to 0.58) or indirect comparison, mean difference of -0.33 (-1.16 to 0.51). Mean analgesic ratio (single/multiple port) was 0.75 (0.64 to 0.87) for direct comparison and 0.90 (0.64 to 1.25) for indirect comparison. After discharge, pain for single-port video-assisted thoracoscopic surgery was lower than for multiple-port video-assisted thoracoscopic surgery (first 3 months), and corresponding physical function was higher up to 12 months. Conclusions: There were no consistent differences for in-hospital pain when lobectomy was undertaken using 1 or multiple ports. However, better pain scores and physical function were observed for single-port surgery after discharge.

Study protocol for VIdeo assisted thoracoscopic lobectomy versus conventional Open LobEcTomy for lung cancer, a UK multicentre randomised controlled trial with an internal pilot (the VIOLET study).

INTRODUCTION: Lung cancer is a leading cause of cancer deaths worldwide and surgery remains the main treatment for early stage disease. Prior to the introduction of video-assisted thoracoscopic surgery (VATS), lung resection for cancer was undertaken through an open thoracotomy. To date, the evidence base supporting the different surgical approaches is based on non-randomised studies, small randomised trials and is focused mainly on short-term in-hospital outcomes. METHODS AND ANALYSIS: The VIdeo assisted thoracoscopic lobectomy versus conventional Open LobEcTomy for lung cancer study is a UK multicentre parallel group randomised controlled trial (RCT) with blinding of outcome assessors and participants (to hospital discharge) comparing the effectiveness, cost-effectiveness and acceptability of VATS lobectomy versus open lobectomy for treatment of lung cancer. We will test the hypothesis that VATS lobectomy is superior to open lobectomy with respect to self-reported physical function 5 weeks after randomisation (approximately 1 month after surgery). Secondary outcomes include assessment of efficacy (hospital stay, pain, proportion and time to uptake of chemotherapy), measures of safety (adverse health events), oncological outcomes (proportion of patients upstaged to pathologic N2 (pN2) disease and disease-free survival), overall survival and health related quality of life to 1 year. The QuinteT Recruitment Intervention is integrated into the trial to optimise recruitment. ETHICS AND DISSEMINATION: This trial has been approved by the UK (Dulwich) National Research Ethics Service Committee London. Findings will be written-up as methodology papers for conference presentation, and publication in peer-reviewed journals. Many aspects of the feasibility work will inform surgical RCTs in general and these will be reported at methodology meetings. We will also link with lung cancer clinical studies groups. The patient and public involvement group that works with the Respiratory Biomedical Research Unit at the Brompton Hospital will help identify how we can best publicise the findings. TRIAL REGISTRATION NUMBER: ISRCTN13472721.

Single-Port Thoracoscopic Pericardial Window Under Local Anesthesia.

There are numerous surgical approaches for the treatment of pericardial effusions but no clear consensus of best management. We present a 44-year-old woman with metastatic breast cancer presenting with a new 2-cm pericardial effusion on ultrasound. In light of the patient's palliative condition and the urgent need for chemotherapy, careful consideration was made for her surgical drainage of the pericardial effusion. Because of the patient's medical comorbidities, a general anesthetic was deemed not to be in the patient's best interest. Furthermore, the invasive subxiphoid or thoracotomy approach for a pericardial window would have risked delaying her much needed chemotherapy. A single-port thoracoscopic pericardial window was performed under light sedation, ventilating spontaneously on supplementary oxygen through nasal cannula only. The patient was positioned in a supine position, and a single 8-mm port was inserted into the left hemithorax at the 5th intercostal space, midaxillary line under local anesthetic, and a pericardial window made. This minimally invasive approach, without the need for intubation or ventilation, allowed for rapid relief of symptoms and discharge for the patient to begin her chemotherapy in a timely manner. By undergoing the procedure awake and through a single port, the patient was discharged after a short inpatient stay. This novel approach can be advocated for patients where a general anesthetic or invasive surgical procedure is not suitable in the treatment of their pericardial effusion.

Increasing frequency of non-smoking lung cancer: Presentation of patients with early disease to a tertiary institution in the UK.

BACKGROUND: Never-smokers with lung cancer often present late as there are no established aetiological risk factors. The aim of the study is to define the frequency over time and characterise clinical features of never-smokers presenting sufficiently early to determine if it is possible to identify patients at risk. METHODS: We retrospectively analysed data from a prospectively collected database of patients who underwent surgery. The frequency was defined as number of never-smokers versus current and ex-smokers by year. Clinical features at presentation were collated as frequency. RESULTS: A total of 2170 patients underwent resection for lung cancer from March 2008 to November 2014. The annual frequency of developing lung cancer in never-smokers increased from 13% to 28%, attributable to an absolute increase in numbers and not simply a change in the ratio of never-smokers to current and ex-smokers. A total of 436 (20%) patients were never-smokers. The mean age was 60 (16 SD) years and 67% were female. Presenting features were non-specific consisting of cough in 34%, chest infections in 18% and haemoptysis in 11%. A total of 14% were detected on incidental chest film, 30% on computed tomography, 7% on positron-emission tomography/computed tomography and 1% on MRI. CONCLUSIONS: We observed more than a double of the annual frequency of never-smokers in the last 7 years. Patients present with non-specific symptoms and majority were detected on incidental imaging, a modality that is likely to play an increasingly important role for early detection in this cohort that does not have any observable clinical risk factors.

Detection of Circulating Tumour Cells and Survival of Patients with Non-small Cell Lung Cancer.

BACKGROUND: Detection of circulating tumour cells (CTCs) in the peripheral blood of lung cancer patients may predict survival. Various platforms exist that allow capture of these cells for further analysis; little work however, has been done with the ScreenCell device, an antibody-independent CTC platform. The aim of our study was to evaluate the ScreenCell device for detection of CTCs in lung cancer patients and to establish correlations of these findings with survival. MATERIALS AND METHODS: Twenty-three patients, nine males, and fourteen females, underwent surgical treatment from February to May 2014 for non-small cell lung cancer. Thirteen patients had adenocarcinoma and ten squamous cell carcinoma, while eight were at an early stage (I-II) and five at a later stage (III-IV). Blood samples were obtained prior to surgery and following filtration through the ScreenCell device, were independently reviewed by 2 consultant pathologists. RESULTS: The pathologists were able to independently identify CTCs in 78.3% (N=18) and 73.9% (N=17) of the cases examined, with overall 80.6% in early stages compared to 60.0% in late stages. The median survival times of positive vs. negative for CTC patients were 1011 and 711 days respectively, with a survival percentage rate of 77.8% and 60% in positive and negative CTC cohorts respectively. CONCLUSION: The results of this study suggest that the presence of CTCs analyzed by ScreenCell did not necessarily lead to a poorer prognosis in patients with lung cancer after curative surgery.

Selection for adjuvant chemotherapy in completely resected stage I non-small cell lung cancer: external validation of a Chinese prognostic risk model.

BACKGROUND: The ability to sub-stratify survival within stage I is an important consideration as it is assumed that survival is heterogeneous within this sub-group. Liang et al. recently published a nomogram to predict post-operative survival in patients undergoing lung cancer surgery. The aim of our study is external validation of their published nomogram in a British cohort focusing on stages IA and IB to determine applicability in selection of adjuvant chemotherapy within stage I. METHODS: Patient variables were extracted and the score individually calculated. Receiver operative characteristics curve (ROC) was calculated and compared with the original derivation cohort and the discriminatory ability was further quantified using survival plots by splitting our (external) validation cohort into three tertiles and Kaplan Meier plots were constructed and individual curves tested using Cox regression analysis on Stata 13 and R 3.1.2 respectively. RESULTS: A total of 1,238 patients were included for analysis. For all patients from stage IA to IIB the mean (SD) score was 9.95 (4.2). The ROC score comparing patients who died versus those that remained alive was 0.62 (95% CI: 0.58 to 0.67). When divided into prognostic score tertiles, survival discrimination remained evident for the entire cohort, as well as those for stage IA and IB alone. The P value comparing survival between the middle and highest score with baseline (low score) was P=0.031 and P=0.034 respectively. CONCLUSIONS: Our results of external validation suggested lower survival discrimination than reported by the original group; however discrimination between survival remained evident for stage I.

The mediastinal staging accuracy of 18F-Fluorodeoxyglycose positron emission tomography/computed tomography in non-small cell lung cancer with variable time intervals to surgery.

BACKGROUND: PET/CT scanning can determine suitability for curative therapy and inform decision making when considering radical therapy in patients with non-small cell lung cancer (NSCLC). Metastases to central mediastinal lymph nodes (N2) may alter such management decisions. We report a 2 year retrospective series assessing N2 lymph node staging accuracy with PET/CT compared to pathological analysis at surgery. METHODS: Patients with NSCLC attending our centre (excluding those who had induction chemotherapy) who had staging PET/CT scans and pathological nodal sampling between June 2006 and June 2008 were analysed. For each lymph node assessed pathologically, the corresponding PET/CT status was determined. 64 patients with 200 N2 lymph nodes were analysed. RESULTS: Sensitivity of PET/CT scans for indentifying involved N2 lymph nodes was 39%, specificity 96% and overall accuracy 90%. For individual lymph node analysis, logistic regression demonstrated a significant linear association between PET/CT sensitivity and time from scanning to surgery (p=0.031) but not for specificity and accuracy. Those scanned <9 weeks before pathological sampling were significantly more sensitive (64% >9 weeks, 0% ≥ 9 weeks, p=0.013) and more accurate (94% <9 weeks, 81% ≥ 9 weeks, p=0.007). Differences in specificity were not seen (97% <9 weeks, 91% ≥ 9 weeks, p=0.228). No significant difference in specificity was found at any time point. CONCLUSIONS: We recommend that if a PET/CT scan is older than 9 weeks, and management would be altered by the presence of N2 nodes, re-staging of the mediastinum should be undertaken.

Concomitant mitral valve surgery with aortic valve replacement: a 21-year experience with a single mechanical prosthesis.

BACKGROUND: Long-term survival for combined aortic and mitral valve replacement appears to be determined by the mitral valve prosthesis from our previous studies. This 21-year retrospective study assess long-term outcome and durability of aortic valve replacement (AVR) with either concomitant mitral valve replacement (MVR) or mitral valve repair (MVrep). We consider only a single mechanical prosthesis. METHODS: Three hundred and sixteen patients underwent double valve replacement (DVR) (n = 273) or AVR+MVrep (n = 43), in the period 1977 to 1997. Follow up of 100% was achieved via telephone questionnaire and review of patients' medical records. Actuarial analysis of long-term survival was determined by Kaplan-Meier method. The Cox regression model was used to evaluate potential predictors of mortality. RESULTS: There were seventeen cases (5.4%) of early mortality and ninety-six cases of late mortality. Fifteen-year survival was similar in both groups at 44% and 57% for DVR and AVR+MVrep respectively. There were no significant differences in valve related deaths, anticoagulation related complications, or prosthetic valve endocarditis between the groups. There were 6 cases of periprosthetic leak in the DVR group. Sex, pre-operative mitral and aortic valve pathology or previous cardiac surgery did not significantly affect outcome. CONCLUSION: The mitral valve appears to be the determinant of survival following double valve surgery and survival is not significantly influenced by mitral valve repair.

Plasma fibrinogen and serum C-reactive protein are associated with non-small cell lung cancer.

OBJECTIVES: There is an association between coagulation and lung cancer. Therefore, pre-operative plasma fibrinogen and serum C-reactive protein (CRP) concentration were assessed to determine their association with tumour characteristics and to ascertain any role in patient selection for curative resection. METHODS: These parameters were compared with tumour size, pTNM stage, and possibility of complete resection in 93 patients with non-small cell lung cancer who underwent surgical resection. RESULTS: Plasma fibrinogen concentration (r(s)=0.34, P=0.001) and serum CRP concentration (r(s)=0.34, P=0.001) were positively correlated with maximum pathological tumour size. A higher plasma fibrinogen concentration was associated with squamous cell carcinoma versus adenocarcinoma (4.5+/-0.13 g/L versus 3.6+/-0.28 g/L; P=0.008), with a trend towards a similar association for CRP (P=0.06). Pathological T stage was also associated with mean plasma fibrinogen and serum CRP concentration (P=0.01 and 0.04, respectively), but pN stage was not associated with either parameter. Incomplete resection occurred in 23% of patients with plasma fibrinogen > 5 g/L or serum CRP > 40 mg/L (versus only 8% when fibrinogen < or = 5 g/L and CRP < or = 40 mg/L; P=0.09). CONCLUSIONS: Plasma fibrinogen and serum CRP are associated with tumour characteristics. High values were associated with inability to achieve complete resection which may refine patient selection for thoracotomy when used with other staging modalities. Attempted resection may be justified in a patient of borderline fitness who has favourable plasma fibrinogen and serum CRP concentration, where a high resection rate is possible. As the relationship was with T stage rather than N stage it may be complimentary to PET scanning, which has only marginally better accuracy for T stage than CT scanning.