Lung cancer mortality reduction by LDCT screening: UKLS randomised trial results and international meta-analysis.

BACKGROUND: The NLST reported a significant 20% reduction in lung cancer mortality with three annual low-dose CT (LDCT) screens and the Dutch-Belgian NELSON trial indicates a similar reduction. We present the results of the UKLS trial. METHODS: From October 2011 to February 2013, we randomly allocated 4 055 participants to either a single invitation to screening with LDCT or to no screening (usual care). Eligible participants (aged 50-75) had a risk score (LLPv2) ≥ 4.5% of developing lung cancer over five years. Data were collected on lung cancer cases to 31 December 2019 and deaths to 29 February 2020 through linkage to national registries. The primary outcome was mortality due to lung cancer. We included our results in a random-effects meta-analysis to provide a synthesis of the latest randomised trial evidence. FINDINGS: 1 987 participants in the intervention and 1 981 in the usual care arms were followed for a median of 7.3 years (IQR 7.1-7.6), 86 cancers were diagnosed in the LDCT arm and 75 in the control arm. 30 lung cancer deaths were reported in the screening arm, 46 in the control arm, (relative rate 0.65 [95% CI 0.41-1.02]; p=0.062). The meta-analysis indicated a significant reduction in lung cancer mortality with a pooled overall relative rate of 0.84 (95% CI 0.76-0.92) from nine eligible trials. INTERPRETATION: The UKLS trial of single LDCT indicates a reduction of lung cancer death of similar magnitude to the NELSON and NLST trials and was included in a meta-analysis of nine randomised trials which provides unequivocal support for lung cancer screening in identified risk groups. FUNDING: NIHR Health Technology Assessment programme; NIHR Policy Research programme; Roy Castle Lung Cancer Foundation.

Does neoadjuvant chemoradiotherapy increase survival in patients with resectable oesophageal cancer?

A best evidence topic in cardiothoracic surgery was written according to a structured protocol. The question addressed was whether trimodal therapy [neoadjuvant chemoradiotherapy (nCRT) in addition to surgery] improves survival in patients with resectable oesophageal cancer. Altogether 565 studies were identified using the below-mentioned search. Eleven represented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group, relevant outcomes and weaknesses are tabulated. All 11 studies were randomized controlled trials comparing surgery with trimodal therapy, 5 of which showed a survival advantage with combined treatment. The remaining six randomized controlled trials showed no difference between trimodal therapy and surgery alone. The 3-year survival for trimodal treatment varied between 19.3 and 58% compared with that for surgery alone which varied between 7 and 53%. Five of these studies compared trimodal therapy with surgery in terms of resection margins, three of which showed that trimodal therapy led to increased R0 resection rate. One study focused on the differences between adenocarcinoma and squamous cell tumours, and described equivalent effects of trimodal therapy in terms of survival. One randomized controlled trial showed improved survival in patients with complete regression of their tumour following induction treatment. Two studies suggested that induction treatment may lead to a higher operative mortality; however, an increase in disease-free survival was noted in one of the two studies. We conclude that trimodal therapy for resectable oesophageal cancer offers similar or even improved results compared with surgery alone in terms of survival. Furthermore, it is likely that there is an advantage for those patients who have a complete pathological response following induction treatment.

The UK Lung Cancer Screening Trial: a pilot randomised controlled trial of low-dose computed tomography screening for the early detection of lung cancer.

BACKGROUND: Lung cancer kills more people than any other cancer in the UK (5-year survival < 13%). Early diagnosis can save lives. The USA-based National Lung Cancer Screening Trial reported a 20% relative reduction in lung cancer mortality and 6.7% all-cause mortality in low-dose computed tomography (LDCT)-screened subjects. OBJECTIVES: To (1) analyse LDCT lung cancer screening in a high-risk UK population, determine optimum recruitment, screening, reading and care pathway strategies; and (2) assess the psychological consequences and the health-economic implications of screening. DESIGN: A pilot randomised controlled trial comparing intervention with usual care. A population-based risk questionnaire identified individuals who were at high risk of developing lung cancer (≥ 5% over 5 years). SETTING: Thoracic centres with expertise in lung cancer imaging, respiratory medicine, pathology and surgery: Liverpool Heart & Chest Hospital, Merseyside, and Papworth Hospital, Cambridgeshire. PARTICIPANTS: Individuals aged 50-75 years, at high risk of lung cancer, in the primary care trusts adjacent to the centres. INTERVENTIONS: A thoracic LDCT scan. Follow-up computed tomography (CT) scans as per protocol. Referral to multidisciplinary team clinics was determined by nodule size criteria. MAIN OUTCOME MEASURES: Population-based recruitment based on risk stratification; management of the trial through web-based database; optimal characteristics of CT scan readers (radiologists vs. radiographers); characterisation of CT-detected nodules utilising volumetric analysis; prevalence of lung cancer at baseline; sociodemographic factors affecting participation; psychosocial measures (cancer distress, anxiety, depression, decision satisfaction); and cost-effectiveness modelling. RESULTS: A total of 247,354 individuals were approached to take part in the trial; 30.7% responded positively to the screening invitation. Recruitment of participants resulted in 2028 in the CT arm and 2027 in the control arm. A total of 1994 participants underwent CT scanning: 42 participants (2.1%) were diagnosed with lung cancer; 36 out of 42 (85.7%) of the screen-detected cancers were identified as stage 1 or 2, and 35 (83.3%) underwent surgical resection as their primary treatment. Lung cancer was more common in the lowest socioeconomic group. Short-term adverse psychosocial consequences were observed in participants who were randomised to the intervention arm and in those who had a major lung abnormality detected, but these differences were modest and temporary. Rollout of screening as a service or design of a full trial would need to address issues of outreach. The health-economic analysis suggests that the intervention could be cost-effective but this needs to be confirmed using data on actual lung cancer mortality. CONCLUSIONS: The UK Lung Cancer Screening (UKLS) pilot was successfully undertaken with 4055 randomised individuals. The data from the UKLS provide evidence that adds to existing data to suggest that lung cancer screening in the UK could potentially be implemented in the 60-75 years age group, selected via the Liverpool Lung Project risk model version 2 and using CT volumetry-based management protocols. FUTURE WORK: The UKLS data will be pooled with the NELSON (Nederlands Leuvens Longkanker Screenings Onderzoek: Dutch-Belgian Randomised Lung Cancer Screening Trial) and other European Union trials in 2017 which will provide European mortality and cost-effectiveness data. For now, there is a clear need for mortality results from other trials and further research to identify optimal methods of implementation and delivery. Strategies for increasing uptake and providing support for underserved groups will be key to implementation. TRIAL REGISTRATION: Current Controlled Trials ISRCTN78513845. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 40. See the NIHR Journals Library website for further project information.

Giant pulmonary hamartoma causing acute right heart failure.

Giant pulmonary hamartomas are rare. We describe a case of a 59-year-old female patient with a giant chondroid hamartoma in the lower lobe of the right lung presenting with acute right heart failure. To the best of our knowledge such a unique presentation has not been previously described in the literature.

The impact of positive circumferential margin on survival following oesophagectomy using the new 7th TNM classification.

OBJECTIVES: Previous studies looking at the influence of positive circumferential margin (CRM) on survival after oesophagectomy are conflicting. This may be due to the fact that older versions of the TNM classification were used, which do not predict survival as accurately as the new 7th edition. We examine whether CRM involvement has an impact on survival when the 7th TNM classification is used. METHODS: Over a 10-year period, 199 patients who had undergone potentially curative resection for oesophageal cancer with postoperative histopathological T3 were identified. A total of 151 (75.9%) were found to have CRM involvement (<1 mm), and these were compared with patients in whom the CRM was free of tumour. Cancers were staged according to the International Union against Cancer TNM 7th edition. First, univariate and then multivariate Cox regression analysis were performed to assess the factors influencing survival. Potentially significant predictors (P < 0.1) from the univariate analysis were inserted in the forward-stepwise Cox regression model and was allowed to remain in the final model if a P-value of <0.05 was achieved. A sub-group analysis was also performed for different N-stages (N0-N3). RESULTS: After all analyses were performed, CRM involvement was found to have no effect on survival following oesophagectomy [hazard ratio 1.28 (95% CI: 0.82-2.01) (P = 0.28)]. This was seen for all N-stages. Stage of disease, age at operation, % predicted forced expiratory volume in 1 second and shortness of breath [(according to New York Heart Association classification)] were all significant predictors of survival. CONCLUSIONS: With this study, it became clear that CRM involvement does not affect long-term survival of patients after oesophagectomy. Patients with CRM involvement should not necessarily be considered to have had an incomplete resection.

Phenylephrine infusion improves blood flow to the stomach during oesophagectomy in the presence of a thoracic epidural analgesia.

OBJECTIVES: Gastric tube necrosis is a major cause of mortality after oesophagectomy. The construction of the gastric tube used for oesophageal reconstruction involves a division of several arteries leading to a reduction in the blood supply at the fundus, which is used for the oesophageal anastomosis. This study was undertaken to determine the effect of thoracic epidural anaesthesia and intravenous phenylephrine on haemodynamics and blood flow in the tubularized stomach. METHODS: Ten patients undergoing an oesophagectomy were prospectively studied. Pulmonary artery catheters were used to measure haemodynamic changes, and laser Doppler flow probes were used to measure gastric blood flow. The effects of an intraoperative thoracic epidural and subsequent intravenous phenylephrine infusion were documented. RESULTS: The administration of a thoracic epidural bolus of bupivacaine 0.25% at 0.1 ml kg resulted in a significant reduction in flux at the anastomotic end of the newly formed gastric tube from a median of 57-41 perfusion units (P = 0.003). A subsequent intravenous phenylephrine infusion titrated to restore mean arterial pressure significantly increased the flux at the anastomotic end from a median of 41-66 perfusion units (P = 0.009). CONCLUSIONS: An intravenous phenylephrine infusion can reverse the epidural bolus-induced reduction in blood flow at the anastomotic end of the newly formed gastric tube.

Routine endoscopy to detect anastomotic leakage after esophagectomy.

BACKGROUND: This study evaluated the safety and efficacy of endoscopy in diagnosing anastomotic leaks after esophagectomy. METHODS: One hundred consecutive postesophagectomy patients, all having reconstruction using the stomach, underwent endoscopy in the first week after operation. The anastomosis and gastric mucosa were examined for evidence of ischemia, necrosis, and leak. RESULTS: There was no evidence that the procedure caused damage to the anastomosis or gastric conduit. The results of 79 examinations were normal, 15 showed gastric ischemia, 2 showed a leak, and 4 showed ischemia plus leakage. The 15 patients with ischemia alone were monitored with a repeat endoscopy after a further week: a late leak developed in 1 patient that was diagnosed at the second examination. No further leaks developed subsequently, making endoscopy 100% accurate in the diagnosis of leaks after esophagectomy. CONCLUSIONS: Esophagoscopy within 1 week of esophagectomy is a safe and highly accurate method of diagnosing leaks and provides unique information on the condition of the stomach. We believe it allows a more targeted approach to patient care in the context of anastomotic healing and in the treatment of leaks.

Tumour budding and a low host inflammatory response are associated with a poor prognosis in oesophageal and gastro-oesophageal junction cancers.

AIMS: Tumour budding and host inflammatory response are parameters easily assessed histologically that have prognostic significance in many cancers. There have been few studies examining these parameters in oesophageal or gastro-oesophageal cancers. This study aims to address that deficiency. METHODS AND RESULTS: A two-centre, retrospective study was carried out on 356 patients. Tumour budding and host inflammatory response at the invasive front were assessed histologically. Statistical analysis was performed to determine the prognostic significance of these factors. The median number of tumour buds was four (range 0-50) with 172 of 356 cases having five or more buds at the invasive front. The presence of five or more buds was associated with a poor prognosis on univariate analysis (P = 0.0001), as was a sparse or moderate host inflammatory response (P = 0.001). Tumour budding retained prognostic significance when tumours were separated into adenocarcinomas (n = 287) and squamous cell carcinomas (n = 69), but host inflammatory response was a significant prognostic factor only for adenocarcinomas. On multivariate analysis the presence of five or more buds retained significance (P = 0.002). CONCLUSIONS: Tumour budding and host inflammatory response are important prognostic factors in patients with oesophageal/gastro-oesophageal cancer and can be used to identify high-risk patients who would benefit from closer follow-up and adjuvant therapies.

Splenic injury following diaphragmatic plication: an avoidable life-threatening complication.

We report an unusual complication of left-sided diaphragmatic plication, namely bleeding from the spleen due to tearing of adhesions between the spleen and the abdominal aspect of the diaphragm. We believe that making a small incision in the diaphragm prior to the plication to identify and divide the adhesions could have prevented the complication, and that this manoeuvre should be a standard part of the operation.

Cardiac comorbidity is not a risk factor for mortality and morbidity following surgery for primary non-small cell lung cancer.

OBJECTIVE: We examined the effect of cardiac comorbidity on mortality and postoperative complications following surgery for primary non-small cell lung cancer. METHODS: Between October 2001 to December 2005, 1067 consecutive patients underwent lung resection for primary cancer within a single centre; patient data was collected prospectively. Two hundred and seventy-one patients had a history of cardiac comorbidity, which included 196 angina, 118 myocardial infarction, 36 revascularisation, 10 congestive cardiac failure and 19 rhythm disorders (numbers not mutually exclusive). To account for differences in case-mix we used logistic regression to develop a propensity score for cardiac comorbidity group membership and then performed a propensity-matched analysis. Kaplan-Meier curves were used to assess follow-up mortality. RESULTS: Patients with cardiac comorbidity were more likely to be hypertensive, have severe dyspnoea, diabetes, current or ex-smokers and were older. After performing propensity matching to account for these differences we successfully matched 199 patients with cardiac comorbidity to 398 patients with no cardiac history. There was no difference in in-hospital mortality (2.5% vs 3%, p=0.73), myocardial infarction (0.5% vs 0.3%, p>0.99), arrhythmia (15.6% vs 14.1%, p=0.62), renal failure (2% vs 1.5%, p=0.65), stroke (0.5% vs 0.3%, p>0.99), respiratory insufficiency (4% vs 3.3%, p=0.64), reintubation (1% vs 2.5%, p=0.35), tracheostomy (4% vs 7.8%, p=0.08), intensive care readmission (8.5% vs 6.5%, p=0.37) and length of stay (8 days vs 8 days, p=0.98). Three-year survival was similar (61.4% vs 56.2%, p=0.39). No differences in outcomes existed with different cardiac conditions. CONCLUSION: With careful assessment and patient selection, patients with cardiac comorbidity were not found to be at increased risk of mortality and morbidity following lung resection for primary non-small cell lung cancer in a propensity-matched population.

Spontaneous infection of a stable mediastinal cystic mass: A case report.

Mediastinal cysts have an unpredictable course but can cause complications such as infection or local pressure effects. Persons with mediastinal cysts can be asymptomatic for many years or can develop symptoms as a result of complications of the cyst. There is a lack of consensus on the best approach to managing those patients without symptoms. In this case report, a 56 year old woman with an indolent mediastinal cyst initially managed conservatively suddenly developed symptoms suggestive of an infected mediastinal cyst requiring surgical resection.

The utility of intrapleural instillation of autologous blood for prolonged air leak after lobectomy.

PURPOSE OF REVIEW: Air leak after pulmonary lobectomy is a relatively common problem, which when persistent can be a cause of other postoperative morbidity as well as contributing to extended hospitalization. A number of methods have been proposed to prevent and treat air leakage, but none have proved incontrovertibly effective. This article reviews the practice of using autologous blood as an effective technique to treat postoperative air leaks after lobectomy. RECENT FINDINGS: Five reports have looked specifically at the technique. In all cases, the procedure was safe and efficacious, with proven advantages over other methods of managing persistent air leaks. It allows earlier removal of chest drains and shortens hospitalization times. SUMMARY: Instillation of autologous blood into the pleural drain in the early postoperative period can lead to immediate sealing of the air leak and allow for earlier drain removal and timely patient discharge. It is a safe bed-side procedure and can be done with relative ease and at minimal cost.

The effect of thoracic epidural bupivacaine and an intravenous adrenaline infusion on gastric tube blood flow during esophagectomy.

BACKGROUND: Gastric tube necrosis is a major cause of anastomotic leak after esophagectomy. A correlation has been shown between reduced flux at the anastomotic end of the gastric tube and anastomotic leaks. METHODS: We prospectively studied the effect of intraoperative thoracic epidural bupivacaine and subsequent adrenaline infusion on hemodynamics and flux in the gastric tube. RESULTS: Administering the epidural bolus significantly decreased flux at the anastomotic end of the gastric tube (P < 0.01). Gastric flux was returned to baseline by an adrenaline infusion. CONCLUSIONS: The administration of a thoracic epidural bolus may decrease flux at the anastomotic end of the gastric tube.

Colo-pleural fistula following pneumonectomy.

Following pneumonectomy and diaphragmatic reconstruction for carcinoid tumour, a fistula developed between the pneumonectomy space and the splenic flexure of the colon. The problem was successfully treated by colon resection and thoracoplasty.

Late presentation of congenital Bochdalek hernia: a case report.

A 23-year-old man presented with a long history of dyspnea and wheezing thought to be due to asthma. Abnormal appearance of the left hemithorax was an incidental finding on a chest X-Ray. On further investigations he was found to have congenital Bochdalek hernia which was repaired surgically. All his respiratory symptoms resolved and he was able to discontinue treatment for asthma. We want to emphasise that late presentations can be misleading even to an astute clinician.

Intrapleural instillation of autologous blood in the treatment of prolonged air leak after lobectomy: a prospective randomized controlled trial.

BACKGROUND: The aim of this study was to assess the value of instilling autologous blood into the pleural cavity to seal prolonged air leaks after lobectomy. METHODS: Of 319 lobectomies performed over an 18-month period, 22 patients (6.9%) experienced prolonged air leak (more than 5 days after surgery). Twenty patients consented to be randomly assigned to one of two treatment pathways. The study group received instillation of 120 mL autologous blood into their apical chest drain on the fifth postoperative day, and again if the air leak persisted on days 7 and 9 respectively. No anticoagulation was used for this blood. The control group continued to be treated by tube thoracostomy alone, but if the air leak was still present on the 10th postoperative day they "crossed over" and underwent intrapleural installation of blood as in the study group. RESULTS: After instillation of blood, the air leak was sealed by the next day in 58.6% of treatments. The median length of air leak was 5 days in the study group and 11 days in the control group (p < 0.001). Time to chest drain removal (median 6.5 days versus 12 days) and hospital discharge (median 8 days versus 13.5 days) were both significantly (p < 0.001) shorter in the study group. CONCLUSIONS: This technique is effective in sealing air leaks after lobectomy. It allows earlier chest drain removal and shortens hospital stay.

Aorto-bronchial fistula following aortic and bronchial stenting of a thoracic aneurysm.

A 66-year-old man underwent repair of an abdominal aortic aneurysm and synchronous stenting of a thoracic aneurysm compressing his left main bronchus. This resulted in further bronchial compression which was also stented. An aorto-bronchial fistula resulting in severe haemoptysis occurred a few weeks later. This was successfully treated with repeat endovascular stenting and left pneumonectomy. Open repair should be the treatment of choice for thoracic aneurysms with bronchial compression.