The IASLC Mesothelioma Staging Project: Proposals for the 'N' descriptors in the forthcoming 9th edition of the TNM classification for Pleural Mesothelioma.

INTRODUCTION: The International Association for the Study of Lung Cancer developed an international database to inform potential revisions in the 9th edition of the Tumor, Node, Metastasis classification of diffuse pleural mesothelioma (PM). This study analyzed the clinical and pathological N categories to determine whether revisions were indicated relative to the 8th edition staging system. METHODS: Of 7,338 PM cases diagnosed 2013 to 2022, 3,598 met all inclusion criteria for planned analyses. Data on 2,836 patients without metastases were included in this study. Overall survival (OS) was measured from date of diagnosis. Patients were included regardless of whether they received neoadjuvant treatment. For the pathological N analysis, patients who underwent resection (extrapleural pneumonectomy or pleurectomy/decortication) were included. N subgroups were analyzed and overall survival (OS) assessed by the Kaplan Meier method. RESULTS: The existing 8th edition N categories performed adequately in the 9th edition dataset. A median OS advantage was noted for clinical and pathological N0 versus N1 patients: 23.2 versus 18.5 and 33.8 vs. 25.0 months, respectively. Patients with resected pN0 had a 3-year OS of 48%. No difference in OS was noted for single versus multiple station nodal metastases. The number of nodal stations sampled at the time of resection was not associated with a difference in OS. CONCLUSIONS: Data regarding clinical and pathological N categories corroborate those used in the 8th edition. No changes in the N categories are recommended in the 9th edition of PM staging system.

The IASLC Pleural Mesothelioma Staging Project: Proposal for Revision of the TNM Stage Groupings in the Forthcoming (Ninth) Edition of the TNM Classification for Pleural Mesothelioma.

INTRODUCTION: The eighth edition of the tumor, node and metastases (TNM) classification of pleural mesothelioma (PM) saw substantial changes in T and N components and stage groupings. The International Association for the Study of Lung Cancer collected data into a multinational database in order to further refine this classification. This 9th edition proposal incorporates changes proposed in the clinical (c)T component, but not the pathologic (p)T component, to include size criteria, and further refines TNM stage groupings for PM. METHODS: Data were submitted via electronic data capture (EDC) or batch transfer from institutional databases. Survival was measured from diagnosis date. Candidate stage groups were developed using a recursive partitioning and amalgamation (RPA) algorithm applied to all cM0 cases for clinical stage and subsequently for pathological stage. Cox models were developed to estimate survival for each stage group. RESULTS: Of 3598 submitted cases, 2192 were analyzable for overall cStage and 445 for overall pStage. RPA generated survival tree on OS outcomes restricted to cM0 with newly proposed (9th edition) cT and cN component-derived optimal stage groupings of: stage I (T1N0), II (T1N1; T2N0), IIIA (T1N2; T2N1/2; any T3), IIIB (any T4), and IV (any M1). Although cT and pT descriptors are different in the 9th edition, aligning pStage groupings with cStage produced better discrimination than retaining 8th edition pStage groupings. CONCLUSIONS: This revision of the clinical TNM classification for PM is the first to incorporate the measurement-based proposed changes in clinical T category. The pathological TNM aligns with clinical TNM.

The physical and psychosocial benefits of a family judo program for parents of children with Autism Spectrum Disorder: A pilot study.

BACKGROUND: Parents of children with Autism Spectrum Disorder (ASD) tend to have high levels of stress and poor health habits. There is a lack of interventions that focus on improving health outcomes in parents of children with ASD. OBJECTIVE: To examine the physical and psychosocial effects of a family-based judo program on parents of children diagnosed with ASD. METHODS: This study utilized a pre-post single group design. Eighteen parent-child dyads participated in a 14-week judo program for families of children with ASD. Judo sessions were held once a week for 45 min. Parents wore wrist accelerometers to assess physical activity/sleep quality, and completed surveys regarding self-reported stress levels pre- and post-judo. Parents also completed open-ended questions regarding their experience in the program. Paired sample t-tests were conducted to examine changes in stress, physical activity, and sleep quality from pre-to post-program. RESULTS: Both a decrease in parental stress (47.77 vs. 41.61, p < 0.01) and an increase in minutes per day of physical activity (35.49 vs 45.94, p = 0.002) were observed from baseline to post-program. Fourteen of the 18 parents (78 %) reported at least one psychosocial benefit (e.g. increased self-confidence) or physical health benefit (e.g. increased physical activity) from participation in the program. CONCLUSIONS: A family judo program may provide health benefits, such as reducing stress levels and increasing physical activity in parents of children with ASD. Further research involving larger sample sizes is necessary to better determine the effects of judo on both parents and their children with ASD.

Early Interventional Treatment of High Output Chyle Leak following Esophagectomy is Associated with Improved Survival.

OBJECTIVES: Our objective was to investigate overall survival (OS) and length of stay (LOS) associated with differing management for high output (>1 liter over 24 h) leaks (HOCL) following cancer related esophagectomy. SUMMARY BACKGROUND: Although infrequent, chyle leak following esophagectomy is an event that can lead to significant perioperative sequelae. Low volume leaks appear to respond to non-operative measures, while HOCL often require invasive therapeutic interventions. METHODS: From a prospective single-institution database, we retrospectively reviewed patients treated from 2001-2021 who underwent esophagectomy for esophageal cancer. Within that cohort, we focused on a subgroup of patients who manifested a HOCL postoperatively. Clinicopathologic and operative characteristics were collected, including hospital length of stay and survival data. RESULTS: A total of 53/2299 patients manifested a HOCL. These were mostly males (77%), with a mean age of 62 years. Of this group, 15 patients received non-operative management, 15 patients received prompt (<72 h from diagnosis) interventional management, and 23 received late interventional management. Patients in the late intervention group had longer length of stay compared to early intervention (Slope=9.849, 95% Confidence Interval [CI] 3.431 to 16.267). Late intervention (Hazard Ratio (HR) 4.772, CI: 1.384 to 16.460) and non-operative management (HR 4.731, CI: 1.294 to 17.305) were associated with increased mortality compared to early intervention. Patients with early intervention for HOCL had an overall survival similar to patients without chyle leaks in survival analysis. CONCLUSIONS: Patients with HOCL should receive early intervention in order to possibly reverse the prognostic implications of this potentially detrimental complication.

The International Association for the Study of Lung Cancer Mesothelioma Staging Project: Proposals for Revisions of the "T" Descriptors in the Forthcoming Ninth Edition of the TNM Classification for Pleural Mesothelioma.

INTRODUCTION: The primary tumor (T) component in the eighth edition of pleural mesothelioma (PM) staging system is based on pleural involvement and extent of invasion. Quantitative assessment of pleural tumor has been found to be prognostic. We explored quantitative and qualitative metrics to develop recommendations for T descriptors in the upcoming ninth edition of the PM staging system. METHODS: The International Association for the Study of Lung Cancer prospectively collected data on patients with PM. Sum of maximum pleural thickness (Psum) was recorded. Optimal combinations of Psum and eighth edition cT descriptors were assessed using recursive binary splitting algorithm, with bootstrap resampling to correct for the adaptive nature of the splitting algorithm, and validated in the eighth edition data. Overall survival (OS) was calculated by the Kaplan-Meier method and differences in OS assessed by the log-rank test. RESULTS: Of 7338 patients submitted, 3598 were eligible for cT analysis and 1790 had Psum measurements. Recursive partitioning identified optimal cutpoints of Psum at 12 and 30 mm, which, in combination with extent of invasion, yielded four prognostic groups for OS. Fmax greater than 5 mm indicated poor prognosis. cT4 category (based on invasion) revealed similar performance to eighth edition. Three eighth edition descriptors were eliminated based on low predictive accuracy. Eighth edition pT descriptors remained valid in ninth edition analyses. CONCLUSION: Given reproducible prognostication by Psum, size criteria will be incorporated into cT1 to T3 categories in the ninth edition. Current cT4 category and all pT descriptors will be maintained, with reclassification of fissural invasion as pT2.

Effects of a family judo program on sleep quality in youth with Autism Spectrum Disorder.

OBJECTIVE: The purpose of this study was to examine the effects of a family-based judo program on sleep quality in youth diagnosed with Autism Spectrum Disorder (ASD). METHODS: Eighteen youth (13.17 years ± 3.76, 78% male) diagnosed with ASD participated in a 14-week family judo program. Sleep quality was assessed using the Actigraph GT9X accelerometer pre- and post-judo intervention. Non-parametric paired t-tests were conducted to examine changes in sleep quality variables. RESULTS: There was a significant increase in sleep efficiency (p = .05), and a significant decrease in both sleep latency (p = .001) and wake after sleep onset (p = .02) following participation in the judo program. There were no changes in sleep duration observed in this sample (p = .83). CONCLUSION: Participation in a family judo program may improve sleep quality in youth with ASD. More research is necessary to understand the mechanisms by which judo may improve sleep quality in youth with ASD.

Endobronchial ultrasound: A novel screening test for pulmonary hypertension prior to major pulmonary surgery.

Objectives: Pulmonary hypertension (PH) is an important physiologic variable in the assessment of patients undergoing major thoracic operations but all too often neglected because of the need for right heart catheterization (RHC) due to the inaccuracy of transthoracic echocardiography. Patients with lung cancer often require endobronchial ultrasound (EBUS) as part of the staging of the cancer. We sought to investigate whether EBUS can be used to screen these patients for PH. Methods: Patients undergoing a major thoracic operation requiring EBUS for staging were included prospectively in the study. All patients had also a RHC (gold standard). We aimed to compare the pulmonary artery pressure measurements by EBUS with the RHC values. Results: A total of 20 patients were enrolled in the study. The prevalence of abnormal pulmonary artery pressure was 65% based on RHC. All patients underwent measurement of the pulmonary vascular acceleration time (PVAT) by EBUS with no adverse events. Linear regression analysis comparing PVAT and RHC showed a correlation (r = -0.059, -0.010 to -0.018, P = .007). A receiver operator characteristic curve (area under the curve = 0.736) was used to find the optimal PVAT threshold (140 milliseconds) to predict PH; this was used to calculate a positive and negative likelihood ratio following a positive diagnosis of 2.154 and 0.538, respectively. Conclusions: EBUS interrogation of pulmonary artery hemodynamic is safe and feasible. EBUS may be used as a screening test for PH in high-risk individuals.

Octreotide's role in the management of post-esophagectomy chylothorax.

The use of octreotide in managing intrathoracic chyle leak following esophagectomy has gained popularity in the adult population. While the benefits of octreotide have been confirmed in the pediatric population, there remains limited evidence to support its use in the adults post-esophagectomy. Thus, we performed a single-institution cohort study to characterize its efficacy. The study was performed using a prospective, single-center database, from which clinicopathologic characteristics were extracted of patients who had post-esophagectomy chyle leaks. Kaplan-Meier and multivariable Cox regression analyses were performed to investigate the effect of octreotide use on chest tube duration (CTD), hospital length of stay (LOS), and overall survival (OS). In our cohort, 74 patients met inclusion criteria, among whom 27 (36.5%) received octreotide. Kaplan-Meier revealed no significant effect of octreotide on CTD (P = 0.890), LOS (P = 0.740), or OS (P = 0.570). Multivariable Cox regression analyses further corroborated that octreotide had no effect on CTD (HR = 0.62, 95% confidence interval [CI]: 0.32-1.20, P = 0.155), LOS (HR = 0.64, CI: 0.34-1.21, P = 0.168), or OS (1.08, CI: 0.53-2.19, P = 0.833). Octreotide use in adult patients with chyle leak following esophagectomy lacks evidence of association with meaningful clinical outcomes. Level 1 evidence is needed prior to further consideration in this population.

The International Association for the Study of Lung Cancer Pleural Mesothelioma Staging Project: Expanded Database to Inform Revisions in the Ninth Edition of the TNM Classification of Pleural Mesothelioma.

The International Association for the Study of Lung Cancer collaborated with the International Mesothelioma Interest Group to propose the first TNM stage classification system for diffuse pleural mesothelioma in 1995, accepted by the Union for International Cancer Control and the American Joint Committee on Cancer for the sixth and seventh edition stage classification manuals. The International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee Mesothelioma Domain developed and analyzed an international registry of patients with pleural mesothelioma and updated TNM descriptors for the eighth edition of the stage classification system. To inform revisions for the forthcoming ninth edition of the TNM stage classification system, data submission was solicited for patients diagnosed between 2013 and 2022 with expanded data elements on the basis of the first project's exploratory analyses, including pleural thickness measurements, updated surgical nomenclature, and molecular markers. The resulting database consisted of a total of 3598 analyzable cases from Europe, Australia, Asia, North America, and South America, with a median age of 71 years (range: 18-99 y), 2775 (77.1%) of whom were men. With only 1310 patients (36.4%) undergoing curative-intent operations, this iteration of the database includes far more patients treated nonsurgically compared with prior. Four separate manuscripts on T, N, M, and stage groupings submitted to this journal will summarize analyses of these data and will serve collectively as the primary source of the proposed changes to the upcoming ninth edition of the pleural mesothelioma stage classification system.

Does cycle commuting reduce the risk of mental ill-health? An instrumental variable analysis using distance to nearest cycle path.

BACKGROUND: Previous studies have linked cycling with improved mental wellbeing but these studies tend to use cross-sectional survey data that have small sample sizes and self-reported health measures, and are potentially susceptible to omitted-variable bias and reverse causation. We use an instrumental variable approach and an objective measure of mental ill-health taken from linked administrative data to ask: 'Does cycle commuting reduce the risk of mental ill-health?' METHODS: Our study links data on commuting in Edinburgh and Glasgow from the Scottish population census with mental health prescriptions from the National Health Service Prescribing Information System records. We use road distance from home to nearest cycle path as an instrumental variable for cycle commuting. RESULTS: In total, 378 253 people aged 16-74 years living and working in the City of Edinburgh and Glasgow City council areas at the 2011 census were included in our study; 1.85% of commuters in Glasgow and 4.8% of commuters in Edinburgh cycled to work. Amongst cyclists, 9% had a prescription for mental health compared with 14% amongst non-cyclists. Using a bivariate probit model, we estimate a mean average reduction in prescriptions for antidepressants and/or anxiolytics in the 5 years following the census of -15.1% (95% CI: -15.3% to -15.0%) amongst cycle commuters compared with those who use any other mode to commute. CONCLUSIONS: This work suggests that cycle commuting is causally related to reduced mental ill-health and provides further evidence in support of the promotion of active travel to encourage commuters travelling shorter distances to shift to cycle commutes.

Exercise therapy for knee osteoarthritis pain: how does it work? A study protocol for a randomised controlled trial.

INTRODUCTION: Muscle strengthening training (MST) and behavioural graded activity (BGA) show comparable effects on knee osteoarthritic (KOA) pain, but the mechanisms of action remain unclear. Both exercise-induced anti-inflammation and central sensitisation are promising pathways for pain relief in response to exercise therapy in patients with KOA: MST has the potential to decrease inflammation and BGA has the potential to decrease central sensitisation. Hence, this study aims to examine inflammation and central sensitisation as mediators for the effect of MST and/or BGA on pain in patients with KOA. METHODS AND ANALYSIS: The Knee OsteoArthritis PAIN trial started on 10 January 2020 (anticipated end: April 2024). The three-arm clinical trial aims to recruit 90 KOA patients who will be randomly allocated to 12 weeks of (1) MST, (2) BGA or (3) care as usual. Assessments will be performed at baseline, 13 and 52 weeks after finishing the intervention. Outcomes, including pain (Knee injury and Osteoarthritis Outcome Score), were chosen in line with the OARSI recommendations for clinical trials of rehabilitation interventions for OA and the IMMPACT/OMERACT recommendations for the assessment of physical function in chronic pain clinical trials. Inflammation as well as features of central sensitisation (including conditioned pain modulation, offset analgesia, temporal summation of pain and event-related potentials following electrical stimulation), will be considered as treatment mediators. A multiple mediators model will be estimated with a path-analysis using structural equation models. In July 2023, all 90 KOA patients have been included and 42 participants already finished the study. ETHICS AND DISSEMINATION: This study obtained ethics approval (B.U.N. 143201941843). Unravelling the mechanisms of action of exercise therapy in KOA will not only be extremely valuable for researchers, but also for exercise immunology and pain scientists and clinicians. TRIAL REGISTRATION NUMBER: NCT04362618.

Gastric Extent of Tumor Predicts Peritoneal Metastasis in Siewert II Adenocarcinoma.

BACKGROUND: Whereas current guidelines recommend staging laparoscopy for most patients with potentially resectable gastric cancer, such a recommendation for patients with adenocarcinoma of the gastroesophageal junction (AEG) is lacking. This study sought to identify baseline clinicopathologic characteristics associated with peritoneal metastasis (PM) among patients with Siewert II AEG. METHODS: Trimodality therapy-eligible patients with Siewert II AEG (2000-2015, single institution) were retrospectively identified. A composite PM outcome was defined as follows: (1) PM at staging laparoscopy; (2) PM diagnosed during neoadjuvant chemoradiation; or (3) PM ≤6 months postoperatively. Logistic regression was used to identify features associated with PM; bootstrapped analysis (Youden J) identified the distal tumor extension that best discriminated the composite outcome. RESULTS: Of 188 patients, a composite PM outcome was observed in 26 of 188 (13.8%); 12 of 26 had positive staging laparoscopy, 10 of 26 experienced PM during chemoradiation, and 4 of 26 had PM ≤6 months postoperatively. Tumor extension below the GEJ was greater in patients with PM (median, 4.0 cm [interquartile range, 3.0-5.0] vs 3.0 cm [interquartile range, 2.0-3.0]; P < .001). All patients with PM had cT3 to cT4 tumors. Among patients with cT3 to cT4 tumors (n = 168 of 188; 89.4%), distal tumor extent (odds ratio, 1.67/cm; 95% CI, 1.23-2.28; P = .001) was independently associated with increased odds of PM. Gastric tumor extension ≥4 cm remained independently associated with PM (OR, 5.14; 95% CI, 2.11-12.53; P < .001) after adjustment for signet ring cell status. CONCLUSIONS: Distal tumor extent beyond the GEJ is independently associated with increased odds of PM in patients with Siewert II AEG. Patients with extensive gastric involvement should therefore be considered for staging laparoscopy before trimodality therapy.

Surgical outcomes after chemotherapy plus nivolumab and chemotherapy plus nivolumab and ipilimumab in patients with non-small cell lung cancer.

OBJECTIVE: Chemotherapy plus nivolumab is the standard of care neoadjuvant treatment for patients with resectable stage IB to IIIA non-small cell lung cancer. The influence of dual checkpoint blockade with chemotherapy on surgical outcomes remains unknown. We aimed to determine operative complexity and perioperative outcomes associated with neoadjuvant chemotherapy and nivolumab with or without ipilimumab. METHODS: A total of 44 patients with stage IB (≥4 cm) to IIIA non-small cell lung cancer were treated on sequential platform arms of the NEOSTAR trial. A total of 22 patients were treated with nivolumab + chemotherapy, and 22 patients were treated with ipilimumab + nivolumab + chemotherapy. The safety of surgical resection after neoadjuvant therapy was estimated using 30-day complication rates. Operative reports and surgeons' narratives were evaluated to determine procedural complexity and operative conduct. RESULTS: All 22 of 22 patients (100%) treated with nivolumab + chemotherapy underwent surgical resection: 20 R0 (90.9%), 17 (77.3%) lobectomies, 1 wedge resection, 2 segmentectomies, and 2 pneumonectomies. The majority, 21 of 22 (95%), were performed by thoracotomy. A total of 13 of 22 (59.1%) were rated as challenging resections. A total of 4 of 22 patients (18.2%) experienced grade 3 or greater Clavien-Dindo complication. A total of 20 of 22 patients (90.9%) treated with ipilimumab + nivolumab + chemotherapy underwent surgical resection: 19 R0 (95%), 18 (90%) lobectomies, 1 pneumonectomy, and 1 segmentectomy. A total of 16 of 20 (80%) resections were performed via thoracotomy, 3 of 20 (15%) via robotics, and 1 of 20 (5%) via thoracoscopy. A total of 9 of 20 (45%) resections were considered challenging. A total of 4 of 20 patients (20%) experienced grade 3 or greater Clavien-Dindo complication. CONCLUSIONS: Surgical resections are feasible and safe, with high rates of R0 after neoadjuvant chemotherapy and nivolumab with or without ipilimumab. Overall, approximately half of cases (22/42, 52.3%) were considered to be more challenging than a standard lobectomy.

Perspectives, risk factors, and coping mechanisms in patients with self-reported financial burden following lung cancer surgery.

OBJECTIVE: We evaluated self-reported financial burden (FB) after lung cancer surgery and sought to assess patient perspectives, risk factors, and coping mechanisms within this population. METHODS: Patients with lung cancer resected at our institution between January 1, 2016, and December 31, 2021, were surveyed. Descriptive and multivariable analyses were performed to evaluate the association between clinical and financial characteristics with patient-reported major ("significant" or "catastrophic") FB. RESULTS: Of 1477 patients contacted, 31.3% (n = 463) completed the survey. Major FB was reported by 62 (13.4%) patients. multivariable analyses demonstrated increasing age (odds ratio [OR], 0.92; 95% CI, 0.88-0.96), credit score >740 (OR, 0.29; 95% CI, 0.14-0.60), and employer-based insurance (OR, 0.24; 95% CI, 0.07-0.80) were protective factors. In contrast, an out of pocket cost greater than expected (OR, 3.63; 95% CI, 1.67-7.88), decrease in work hours (OR, 4.42; 95% CI, 1.59-12.25), or cessation of work (OR, 5.13; 95% CI, 2.06-12.78), chronic obstructive pulmonary disease diagnosis (OR, 5.39, 95% CI, 1.87-15.50), and hospital readmission (OR, 4.87; 95% CI, 1.11-21.42) were risk factors for FB. To pay for care, some patients reported "often" or "always" decreasing food (n = 102 [23.4%]) or leisure spending (n = 179 [40.7%]). Additionally, use of savings (n = 246 [62.9%]), borrowing funds (n = 72 [16.6%]), and skipping clinic visits (n = 36 [8.3%]) at least once were also reported. Coping mechanisms occurred more often in patients with major FB compared with those without (P < .001). CONCLUSIONS: Patients with resected lung cancer may experience major FB related to treatment with several identifiable risk factors. Targeted interventions are needed to limit the adoption of detrimental coping mechanisms and potentially affect survivorship.

Lung surveillance following colorectal cancer pulmonary metastasectomy: Utilization of clinicopathologic risk factors to guide strategy.

BACKGROUND: Appropriately selected patients clearly benefit from resection of colorectal cancer (CRC) pulmonary metastases (PMs). However, there remains equipoise surrounding optimal chest surveillance strategies following pulmonary metastasectomy. We aimed to identify risk factors that may inform chest surveillance in this population. METHODS: Patients who underwent CRC pulmonary metastasectomy were identified from a single institution's prospectively maintained surgical database. Clinicopathologic and genomic characteristics were collected. Patients were stratified by diagnosis of subsequent PM within 6 months of the index lung resection. Multivariate modeling was used to evaluate risk factors. RESULTS: A total of 197 patients met the study's inclusion criteria, of whom 52.3% (n = 103) developed subsequent PM, at a median of 9.51 months following the index metastasectomy. Patients with KRAS alterations (odds ratio [OR], 3.073; 95% confidence interval [CI], 1.363-6.926; P = .007), TP53 alterations (OR, 3.109; 95% CI, 1.318-7.341; P = .010) were found to be at risk of PM diagnosis within 6 months of the index metastasectomy, while those with an APC alteration (OR, .218; 95% CI, 0.080-0.598; P = .003) were protected. Moreover, patients who received systemic therapy within 3 months of the initial PM diagnosis also were more likely to develop early lung recurrence (OR, 2.105; 95% CI, 0.971-4.563; P = .059). CONCLUSIONS: Patients with KRAS alterations, TP53 alterations, and no APC alterations developed early recurrence in the lung following pulmonary metastasectomy, as did those who received chemotherapy after their initial PM diagnosis. As such, these groups benefit from early lung imaging after metastasectomy, as chest surveillance protocols should be based on patient-centered clinicopathologic and genomic risk factors.