Clinical management of typical and atypical carcinoids/neuroendocrine tumors in ENETS centres of excellence (CoE): Survey from the ENETS lung NET task force.

Lung carcinoid tumours are neuroendocrine neoplasms originating from the bronchopulmonary tract's neuroendocrine cells, accounting for only 1%-3% of all lung cancers but 30% of all neuroendocrine tumours. The incidence of lung carcinoids, both typical and atypical, has been increasing over the years due to improved diagnostic methods and increased awareness among clinicians and pathologists. The most recent WHO classification includes a subgroup of lung carcinoids with atypical morphology and higher mitotic count and/or Ki67 labelling index. Despite appropriate surgery, the 5-year survival rate for atypical carcinoids barely exceeds 50%-70%. The role of adjuvant therapy in lung carcinoids is not well-defined, and clinical decisions are generally based on the presence of high-risk features. Long-term follow-up is essential to monitor for recurrence, although the optimal follow-up protocol remains unclear. To address the lack of consensus in clinical management decisions, the European Neuroendocrine Tumor Society (ENETS) initiated a survey among 20 expert centres. The survey identified varied opinions on approaches to imaging, surgery, use of adjuvant therapy, and follow-up protocols. Notably, the absence of dedicated multidisciplinary lung neuroendocrine tumour boards in some centres was evident. Experts agreed on the need for a prospective adjuvant trial in high-risk patients, emphasizing the feasibility of such a study. In conclusion, the study highlights the need for a more uniform adoption of existing guidelines in the management of lung carcinoid tumours and emphasizes the importance of international collaboration to advance research and patient care. Close collaboration between healthcare providers and patients is vital for effective long-term surveillance and management of these rare tumours.

Extended pleurectomy decortication and chemotherapy versus chemotherapy alone for pleural mesothelioma (MARS 2): a phase 3 randomised controlled trial.

BACKGROUND: Extended pleurectomy decortication for complete macroscopic resection for pleural mesothelioma has never been evaluated in a randomised trial. The aim of this study was to compare outcomes after extended pleurectomy decortication plus chemotherapy versus chemotherapy alone. METHODS: MARS 2 was a phase 3, national, multicentre, open-label, parallel two-group, pragmatic, superiority randomised controlled trial conducted in the UK. The trial took place across 26 hospitals (21 recruiting only, one surgical only, and four recruiting and surgical). Following two cycles of chemotherapy, eligible participants with pleural mesothelioma were randomly assigned (1:1) to surgery and chemotherapy or chemotherapy alone using a secure web-based system. Individuals aged 16 years or older with resectable pleural mesothelioma and adequate organ and lung function were eligible for inclusion. Participants in the chemotherapy only group received two to four further cycles of chemotherapy, and participants in the surgery and chemotherapy group received pleurectomy decortication or extended pleurectomy decortication, followed by two to four further cycles of chemotherapy. It was not possible to mask allocation because the intervention was a major surgical procedure. The primary outcome was overall survival, defined as time from randomisation to death from any cause. Analyses were done on the intention-to-treat population for all outcomes, unless specified. This study is registered with ClinicalTrials.gov, NCT02040272, and is closed to new participants. FINDINGS: Between June 19, 2015, and Jan 21, 2021, of 1030 assessed for eligibility, 335 participants were randomly assigned (169 to surgery and chemotherapy, and 166 to chemotherapy alone). 291 (87%) participants were men and 44 (13%) women, and 288 (86%) were diagnosed with epithelioid mesothelioma. At a median follow-up of 22·4 months (IQR 11·3-30·8), median survival was shorter in the surgery and chemotherapy group (19·3 months [IQR 10·0-33·7]) than in the chemotherapy alone group (24·8 months [IQR 12·6-37·4]), and the difference in restricted mean survival time at 2 years was -1·9 months (95% CI -3·4 to -0·3, p=0·019). There were 318 serious adverse events (grade ≥3) in the surgery group and 169 in the chemotherapy group (incidence rate ratio 3·6 [95% CI 2·3 to 5·5], p<0·0001), with increased incidence of cardiac (30 vs 12; 3·01 [1·13 to 8·02]) and respiratory (84 vs 34; 2·62 [1·58 to 4·33]) disorders, infection (124 vs 53; 2·13 [1·36 to 3·33]), and additional surgical or medical procedures (15 vs eight; 2·41 [1·04 to 5·57]) in the surgery group. INTERPRETATION: Extended pleurectomy decortication was associated with worse survival to 2 years, and more serious adverse events for individuals with resectable pleural mesothelioma, compared with chemotherapy alone. FUNDING: National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (15/188/31), Cancer Research UK Feasibility Studies Project Grant (A15895).

Strategies to address recruitment to a randomised trial of surgical and non-surgical treatment for cancer: results from a complex recruitment intervention within the Mesothelioma and Radical Surgery 2 (MARS 2) study.

OBJECTIVES: Recruiting to randomised trials is often challenging particularly when the intervention arms are markedly different. The Mesothelioma and Radical Surgery 2 randomised controlled trial (RCT) compared standard chemotherapy with or without (extended) pleurectomy decortication surgery for malignant pleural mesothelioma. Anticipating recruitment difficulties, a QuinteT Recruitment Intervention was embedded in the main trial phase to unearth and address barriers. The trial achieved recruitment to target with a 4-month COVID-19 pandemic-related extension. This paper presents the key recruitment challenges, and the strategies delivered to optimise recruitment and informed consent. DESIGN: A multifaceted, flexible, mixed-method approach to investigate recruitment obstacles drawing on data from staff/patient interviews, audio recorded study recruitment consultations and screening logs. Key findings were translated into strategies targeting identified issues. Data collection, analysis, feedback and strategy implementation continued cyclically throughout the recruitment period. SETTING: Secondary thoracic cancer care. RESULTS: Respiratory physicians, oncologists, surgeons and nursing specialists supported the trial, but recruitment challenges were evident. The study had to fit within a framework of a thoracic cancer service considered overstretched where patients encountered multiple healthcare professionals and treatment views, all of which challenged recruitment. Clinician treatment biases, shaped in part by the wider clinical and research context alongside experience, adversely impacted several aspects of the recruitment process by restricting referrals for study consideration, impacting eligibility decisions, affecting the neutrality in which the study and treatment was presented and shaping patient treatment expectations and preferences. Individual and group recruiter feedback and training raised awareness of key equipoise issues, offered support and shared good practice to safeguard informed consent and optimise recruitment. CONCLUSIONS: With bespoke support to overcome identified issues, recruitment to a challenging RCT of surgery versus no surgery in a thoracic cancer setting with a complex recruitment pathway and multiple health professional involvement is possible. TRIAL REGISTRATION NUMBER: ISRCTN ISRCTN44351742, Clinical Trials.gov NCT02040272.

Segmental arterial mediolysis after fenestrated endovascular abdominal aortic aneurysm repair-A rare complication.

Segmental arterial mediolysis (SAM) is a rare, noninflammatory, nonatherosclerotic condition that occurs commonly in mesenteric vessels. There are no known predisposing risk factors to the development of SAM. We present a case of a 67-year-old woman who presented with abdominal pain 2 days following discharge after an elective endovascular abdominal aortic intervention. Repeat imaging 2 days after readmission showed the presence of multiple new aneurysms involving the mesenteric vasculature. She underwent attempted endovascular embolization of the largest aneurysm. The postmortem and histopathologic examinations confirmed the diagnosis of SAM.

Consumers' Experiences of Comprehensive-Prepared Graduate Nurses and Their Nursing Care in Acute Mental Health Settings.

Pre-registration nursing education has long moved away from preparing nurses with mental health specialisation to nurses with comprehensive knowledge and skills. However, the consumers' experiences of comprehensive-prepared nurses and their nursing care has not been widely explored. This paper reports on a study with consumers to explore their experiences with comprehensive-prepared graduate nurses and the nursing care that they provide in acute mental health settings. An exploratory qualitative study using semi-structured interviews was chosen as the research method. Purposeful sampling recruited 12 consumers and data saturation was achieved. Braun and Clarke's method of thematic analysis was used to analyse the collected data and three themes emerged. The themes are: (i) You got what it takes to be a mental health nurse, (ii) Slow down and spend quality time with us, and (iii) Read in between the lines when we share our negative lived experiences. The findings are useful for identifying strategies to develop evidence-based nursing education for comprehensive-prepared graduate nurses to improve the consumers' experiences of their nursing care.

A 12-year experience in the management of blunt thoracic aortic injury in Otautahi Christchurch.

BACKGROUND: Blunt thoracic aortic injury (BTAI) is associated with a high mortality and is the second most common cause of death from trauma. The approach to major trauma, imaging technology and advancement in endovascular therapy have revolutionised the management of BTAI. Endovascular therapy has now become the gold standard technique replacing surgery with its high mortality and morbidity in unstable patients. We aim to assess the outcomes following management of BTAI. METHOD: This is a retrospective study of all patients with BTAI between 1 January 2010 and 1 January 2022. Data were obtained from electronic health records. The grading of BTAI severity was done based on the Society of Vascular Surgery (SVS) Criteria. RESULTS: Fifty patients were included in the study analysis. The most common cause of BTAI was due to high-speed motor vehicle accidents (MVA) (36 patients, 72%). Grade 1 and grade 3 BTAI injuries were mostly encountered in 40% and 30% of the study cohort, respectively. Twenty-three patients (46%) underwent thoracic endovascular aortic repair (TEVAR). There was no secondary aortic re-intervention, conversion to open surgery or aortic-related deaths at 30 days or at most recent follow-up. CONCLUSION: Management of BTAI in our centre compares well with currently published studies. Long-term studies are warranted to guide clinicians in areas of controversy in BTAI management.

Agreement between observed and predicted postoperative forced expiratory volume in one second, forced vital capacity, and diffusing capacity for carbon monoxide after anatomic lung resection.

Background: Despite its importance in clinical practice, clinical guideline pathway selection and as an outcome in clinical trials, little work has been undertaken to understand the agreement between expected lung function loss and actual observed values. This is particular pertinent in view of the unexpected findings of JCOG 0802 and CALBG 140503 demonstrating no clinically meaningful difference in lung function loss between the sub-lobar resection and lobectomy arm. Methods: We performed a retrospective analysis on preoperative and postoperative forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO) collated from 158 patients who underwent anatomical lung resection between January 2013 to July 2023. Patient's true preoperative and postoperative lung function was obtained via formal lung function testing while predicted postoperative lung function was derived using the 20-segment counting method. Longitudinal postoperative lung function analysis demonstrated sufficient stability over time. A formal testing of agreement between predicted and true postoperative lung function was undertaken using the Bland and Altman method and graphically demonstrated using scatter plots. We defined a deviation of more than 5% as a clinically minimally important difference. Results: Scatter plots for effort-dependent measures suggested the tendency for underprediction (observed values were higher than predicted) for FEV1 and FVC but good agreement for DLCO. Formal agreement confirmed mean difference for FEV1 was -9.84% [95% confidence interval (CI): -39.33% to 19.65%], FVC -11.39% (95% CI: -50.14% to 27.36%) and DLCO -4.83% (95% CI: -25.59% to 15.92%). Conclusions: Our study demonstrated that effort-dependent parameters of lung function including FEV1 and FVC tends to overestimate the amount of lung function loss after anatomic lung resection, clinicians should be cautious in using these measures to determine suitability of surgery based on current established guidelines. However, independent measures such as DLCO demonstrate good agreement suggesting that predicted lung tissue loss is consistent with a 20-segment lung model.

Role of vitamin D supplementation in modifying outcomes after surgery: a systematic review of randomised controlled trials.

BACKGROUND: There is increasing evidence to suggest vitamin D plays a role in immune and vascular function; hence, it may be of biological and clinical relevance for patients undergoing major surgery. With a greater number of randomised studies being conducted evaluating the impact of vitamin D supplementation on surgical patients, it is an opportune time to conduct further analysis of the impact of vitamin D on surgical outcomes. METHODS: MEDLINE, EMBASE and the Cochrane Trials Register were interrogated up to December 2023 to identify randomised controlled trials of vitamin D supplementation in surgery. The risk of bias in the included studies was assessed using the Cochrane Risk of Bias tool. A narrative synthesis was conducted for all studies. The primary outcome assessed was overall postoperative survival. RESULTS: We screened 4883 unique studies, assessed 236 full-text articles and included 14 articles in the qualitative synthesis, comprising 1982 patients. The included studies were highly heterogeneous with respect to patient conditions, ranging from open heart surgery to cancer operations to orthopaedic conditions, and also with respect to the timing and equivalent daily dose of vitamin D supplementation (range: 0.5-7500 mcg; 20-300 000 IU). No studies reported significant differences in overall survival or postoperative mortality with vitamin D supplementation. There was also no clear evidence of benefit with respect to overall or intensive care unit length of stay. DISCUSSION: Numerous studies have reported the benefits of vitamin D supplementation in different surgical settings without any consistency. However, this systematic review found no clear evidence of benefit, which warrants the supposition that a single biological effect of vitamin D supplementation does not exist. The observed improvement in outcomes in low vitamin D groups has not been convincingly proven beyond chance findings. TRIAL REGISTRATION NUMBER: CRD42021232067.

Multimodality local consolidative treatment versus conventional care of advanced lung cancer after first-line systemic anti-cancer treatment: study protocol for the RAMON multicentre randomised controlled trial with an internal pilot.

INTRODUCTION: Lung cancer is the most common cause of cancer death worldwide and most patients present with extensive disease. One-year survival is improving but remains low (37%) despite novel systemic anti-cancer treatments forming the current standard of care. Although new therapies improve survival, most patients have residual disease after treatment, and little is known on how best to manage it. Therefore, residual disease management varies across the UK, with some patients receiving only maintenance systemic anti-cancer treatment while others receive local consolidative treatment (LCT), alongside maintenance systemic anti-cancer treatment. LCT can be a combination of surgery, radiotherapy and/or ablation to remove all remaining cancer within the lung and throughout the body. This is intensive, expensive and impacts quality of life, but we do not know if it results in better survival, nor the extent of impact on quality of life and what the cost might be for healthcare providers. The RAMON study (RAdical Management Of Advanced Non-small cell lung cancer) will evaluate the acceptability, effectiveness and cost-effectiveness of LCT versus no LCT after first-line systemic treatment for advanced lung cancer. METHODS AND ANALYSIS: RAMON is a pragmatic open multicentre, parallel group, superiority randomised controlled trial. We aim to recruit 244 patients aged 18 years and over with advanced non-small-cell lung cancer from 40 UK NHS hospitals. Participants will be randomised in a 1:1 ratio to receive LCT alongside maintenance treatment, or maintenance treatment alone. LCT will be tailored to each patient's specific disease sites. Participants will be followed up for a minimum of 2 years. The primary outcome is overall survival from randomisation. ETHICS AND DISSEMINATION: The West of Scotland Research Ethics Committee (22/WS/0121) gave ethical approval in August 2022 and the Health Research Authority in September 2022. Participants will provide written informed consent before participating in the study. Findings will be presented at international meetings, in peer-reviewed publications, through patient organisations and notifications to patients. TRIAL REGISTRATION NUMBER: ISRCTN11613852.

The International Association for the Study of Lung Cancer Staging Project for Lung Cancer: Proposals for the Revision of the N Descriptors in the Forthcoming Ninth Edition of the TNM Classification for Lung Cancer.

INTRODUCTION: The accurate assessment of nodal (N) status is crucial to the management and prognostication of nonmetastatic NSCLC. We sought to determine whether the current N descriptors should be maintained or revised for the upcoming ninth edition of the international TNM lung cancer staging system. METHODS: Data were assembled by the International Association for the Study of Lung Cancer on patients with NSCLC, detailing both clinical and pathologic N status, with information about anatomical location and individual station-level identification. Survival was calculated by the Kaplan-Meier method and prognostic groups were assessed by a Cox regression analysis. RESULTS: Data for clinical N and pathologic N status were available in 45,032 and 35,009 patients, respectively. The current N0 to N3 descriptors for both clinical N and pathologic N categories reflect prognostically distinct groups. Furthermore, single-station N2 involvement (N2a) exhibited a better prognosis than multistation N2 involvement (N2b) in both clinical and pathologic classifications, and the differences between all neighboring nodal subcategories were highly significant. The prognostic differences between N2a and N2b were robust and consistent across resection status, histologic type, T category, and geographic region. CONCLUSIONS: The current N descriptors should be maintained, with the addition of new subdescriptors to N2 for single-station involvement (N2a) and multiple-station involvement (N2b).

Outcomes of chest drain management using only air leak (without fluid) criteria for removal after general thoracic surgery-a drainology study.

Background: Chest drain management is a variable aspect of postoperative care in thoracic surgery, with different opinion for air and drain volume output. We aim to study if acceptable safety was maintained using air leak criteria alone. Methods: A 9-year retrospective analysis of protocolised chest drain management using digital drain air leak cut off less than 20 mL/min for more than 6 h for drain removal in patients undergoing general thoracic surgery. We excluded patients if a chest drain was not required nor removed during admission or if patients underwent volume reduction or pneumonectomy. Withdrawal criteria were suspected bleeding or chylothorax. Postoperative films were reviewed to document post-drain removal pneumothorax, pleural effusion, and reintervention (drain re-insertion). Results: Between 2012 and 2021, 1,187 patients had thoracic surgery under a single surgeon. Following exclusion and withdrawal criteria, 797 patients were left for analysis. The mean age [standard deviation (SD)] was 61 [16] years and 383 (48%) were male. Median [interquartile range (IQR)] duration of drain insertion was 1 [1-2] day with a median length of hospital stay of 4 [2-6] days. Post-drain removal pneumothorax was observed in 141 (17.7%), post-drain removal pleural effusion was observed in 75 (9.4%) and re-intervention (reinsertion of chest drain) required in 17 (2.1%). Conclusions: Our results demonstrate acceptable levels of safety using digital assessment of air leak as the sole criteria for drain removal in selected patients after general thoracic surgery.

Mechanical aortic valve may no longer be a contraindication to inner branch aortic arch endografts.

OBJECTIVES: The presence of a mechanical aortic valve has been a contraindication to the use of an arch branch aortic endograft due to the risk of damaging the valve, resulting in acute aortic regurgitation, or a trapped endograft. METHODS: We present a 67-year-old woman, with a background of Marfan's syndrome and a previous Bentall's procedure, who presented with a symptomatic enlarging aortic arch and descending thoracic aortic aneurysm, with a type 1A endoleak. RESULTS: Using an inner branch arch endograft (Cook Medical, Bloomington, Indiana), the nose cone of the delivery system was passed laterally through the semi-circular aperture of the mechanical aortic valve to facilitate deployment just distal to the coronary buttons. CONCLUSIONS: With advancement of endovascular technology, techniques and experience, endovascular aortic arch repair in the presence of a mechanical aortic valve is feasible.

Acute aortic syndrome: nationwide study of epidemiology, management, and outcomes.

BACKGROUND: Epidemiological studies on acute aortic syndrome (AAS) have relied largely on unverified administrative coding, leading to wide-ranging estimates of incidence. This study aimed to evaluate the incidence, management, and outcomes of AAS in Aotearoa New Zealand. METHODS: This was a national population-based retrospective study of patients presenting with an index admission of AAS from 2010 to 2020. Cases from the Ministry of Health National Minimum Dataset, National Mortality Collection, and the Australasian Vascular Audit were cross-verified with hospital notes. Poisson regression adjusted for sex and age was used to investigate trends over time. RESULTS: During the study interval, 1295 patients presented to hospital with confirmed AAS, including 790 with type A (61.0 per cent) and 505 with type B (39.0 per cent) AAS. A total of 290 patients died out of hospital between 2010 and 2018. The overall incidence of aortic dissection including out-of-hospital cases was 3.13 (95 per cent c.i. 2.96 to 3.30) per 100 000 person-years, and this increased by an average of 3 (95 per cent c.i. 1 to 6) per cent per year after adjustment for age and sex adjustment on Poisson regression, driven by increasing type A cases. Age-standardized rates of disease were higher in men, and in Maori and Pacific populations. The management strategies used, and 30-day mortality rates among patients with type A (31.9 per cent) and B (9.7 per cent) disease have remained constant over time. CONCLUSION: Mortality after AAS remains high despite advances over the past decade. The disease incidence and burden are likely to continue to increase with an ageing population. There is impetus now for further work on disease prevention and the reduction of ethnic disparities.

Pluripotent stem cell-derived committed cardiac progenitors remuscularize damaged ischemic hearts and improve their function in pigs.

Ischemic heart disease, which is often associated with irreversibly damaged heart muscle, is a major global health burden. Here, we report the potential of stem cell-derived committed cardiac progenitors (CCPs) have in regenerative cardiology. Human pluripotent embryonic stem cells were differentiated to CCPs on a laminin 521 + 221 matrix, characterized with bulk and single-cell RNA sequencing, and transplanted into infarcted pig hearts. CCPs differentiated for eleven days expressed a set of genes showing higher expression than cells differentiated for seven days. Functional heart studies revealed significant improvement in left ventricular ejection fraction at four and twelve weeks following transplantation. We also observed significant improvements in ventricular wall thickness and a reduction in infarction size after CCP transplantation (p-value < 0.05). Immunohistology analyses revealed in vivo maturation of the CCPs into cardiomyocytes (CM). We observed temporary episodes of ventricular tachyarrhythmia (VT) in four pigs and persistent VT in one pig, but the remaining five pigs exhibited normal sinus rhythm. Importantly, all pigs survived without the formation of any tumors or VT-related abnormalities. We conclude that pluripotent stem cell-derived CCPs constitute a promising possibility for myocardial infarction treatment and that they may positively impact regenerative cardiology.

Management of secondary aorto-enteric fistulae: a multi-centre study.

BACKGROUND: Secondary aorto-enteric fistulae (SAEF) are a rare, complex and life-threatening complication following aortic repair. Traditional treatment strategy has been with open aortic repair (OAR), with emergence of endovascular repair (EVAR) as a potentially viable initial treatment option. Controversy exists over optimal immediate and long-term management. METHODS: This was a retrospective, observational, multi-institutional cohort study. Patients who had been treated for SAEF between 2003 and 2020 were identified using a standardized database. Baseline characteristics, presenting features, microbiological, operative, and post-operative variables were recorded. The primary outcomes were short and mid-term mortality. Descriptive statistics, binomial regression, Kaplan-Meier and Cox age-adjusted survival analyses were performed. RESULTS: Across 5 tertiary centres, a total of 47 patients treated for SAEF were included, 7 were female and the median (range) age at presentation was 74 years (48-93). In this cohort, 24 (51%) patients were treated with initially with OAR, 15 (32%) with EVAR-first and 8 (17%) non-operatively. The 30-day and 1-year mortality for all cases that underwent intervention was 21% and 46% respectively. Age-adjusted survival analysis revealed no statistically significant difference in mortality in the EVAR-first group compared to the OAR-first group, HR 0.99 (95% CI 0.94-1.03, P = 0.61). CONCLUSION: In this study there was no difference in all-cause mortality in patients who had OAR or EVAR as first line treatment for SAEF. In the acute setting, alongside broad-spectrum antimicrobial therapy, EVAR can be considered as an initial treatment for patients with SAEF, as a primary treatment or a bridge to definitive OAR.