Correlation of Bronchoscopy and CT in Characterizing Malignant Central Airway Obstruction.

BACKGROUND: Malignant Central Airway Obstruction (MCAO) presents a significant challenge in lung cancer management, with notable morbidity and mortality implications. While bronchoscopy is the established diagnostic standard for confirming MCAO and assessing obstruction subtype (intrinsic, extrinsic, mixed) and severity, Computed Tomography (CT) serves as an initial screening tool. However, the extent of agreement between CT and bronchoscopy findings for MCAO remains unclear. METHODS: To assess the correlation between bronchoscopy and CT, we conducted a retrospective review of 108 patients at Roswell Park Comprehensive Cancer Center, analyzing CT and bronchoscopy results to document MCAO presence, severity, and subtype. RESULTS: CT correctly identified MCAO in 99% of cases (107/108). Agreement regarding obstruction subtype (80.8%, Cohen's κ = 0.683, p < 0.001), and severity (65%, Quadratic κ = 0.657, p < 0.001) was moderate. CT tended to equally overestimate (7/19) and underestimate (7/19) the degree of obstruction. CT was also poor in identifying mucosal involvement in mixed MCAO. CONCLUSIONS: CT demonstrates reasonable agreement with bronchoscopy in detecting obstruction. Nevertheless, when CT indicates a positive finding for MCAO, it is advisable to conduct bronchoscopy. This is because CT lacks reliability in determining the severity of obstruction and identifying the mucosal component of mixed disease.

Survivin in lung cancer: a potential target for therapy and prevention-a narrative review.

Background and Objective: A versatile biomarker, survivin, is highly expressed in proliferating cells of multiple cancers in humans and animals. It is an apoptosis-regulating protein, engaging in a cascade of reactions that involve several other genes and protein interactions. Currently, researchers are investigating its therapeutic potential due to the evidence linking its overexpression to advanced-stage lung cancer. This review is centered around examining survivin-related molecular mechanisms and its therapeutic role specifically in lung cancer. Our objective is to discuss the role of survivin in prognosis and treatment response, shedding light on immune-targeted therapies, as well as outlining future directions for survivin-based vaccines in lung cancer. Methods: The PubMed database and the United States National Library of Medicine search engine at the National Institutes of Health were searched on 24 August 2023 to identify published research studies. Searching "((((((airway [Title/Abstract]) OR (lung [Title/Abstract])) OR (pulm[Title/Abstract])) OR (bronch[Title/Abstract])) OR (nslc[Title/Abstract])) AND (((cancer[Title/Abstract]) OR (carcino[Title/Abstract])) OR (oncol[Title/Abstract]))) AND (survivin[Title/Abstract])" gave 728 results. After screening the title and abstracts and excluding the review articles 168 titles were shortlisted and full text studied. The discussions are added to relevant sections. Key Content and Findings: Survivin is a cell cycle-dependent, inhibitor of apoptosis protein that contributes to carcinogenesis, tumor vascularization, metastasis, and treatment resistance. Several treatments that impact survivin either directly or indirectly have been reported as effective in treating lung cancer. Immunity-based therapy, a novel approach known for its targeted nature and minimal side effects, is currently under investigation for lung cancer treatment. Emerging survivin-centered vaccines exhibit promising attributes in terms of safety, effectiveness, and ability to stimulate an immune response. These factors point towards a significant potential for advancing the future of lung cancer prevention and enhancing overall survival rates. Conclusions: Nuclear survivin is a potential biomarker for advanced non-small cell lung cancer. It plays a role in determining drug responsiveness and is found to be significantly elevated in cases of resistance to chemotherapy. Multiple compounds and immunization strategies have been identified to impact lung cancer cells; however, they are currently in the early stages of phase I or phase II clinical trials. The substantial promise of survivin-based immunogenicity-focused treatments warrants in-depth investigation and exploration.

Lung cancer in females-sex-based differences from males in epidemiology, biology, and outcomes: a narrative review.

Background and Objective: The role of biological sex is seldom considered in characterizing lung cancer, the deadliest cancer in both the United States and the world. Lung cancer has traditionally been regarded as a male disease; as such, research in female-specific phenomena is frequently conflicting or absent. Currently, disparities in lung cancer incidence are primarily driven by females, especially non-smokers and those of younger age. This narrative review provides insight into sex-specific characteristics of lung cancer, highlighting risk factors, diagnosis patterns, carcinogenesis, and treatment outcomes in females. Methods: The PubMed database was searched on July 26, 2023 to identify research published between 2013 and 2023 in English. Sixty-three articles were considered relevant, and their full texts and citations were studied to compile information for this narrative review. Key Content and Findings: Exposure-related risk factors, including personal tobacco use, are thought to impact female lung cancer risk more profoundly. However, studies on occupational exposures are underpowered to conclude risk in females. Data characterizing the effect of endogenous and exogenous hormonal exposures on female lung cancer risk remain two-sided. Screening guidelines are tailored to white males, exacerbating sex and race disparities. The effect of biological sex on carcinogenesis and the immune system response to cancer is not fully understood, though the female immune system clearly reacts more aggressively to lung cancer. In early-stage disease, females have greater survival in the perioperative setting and during follow-up of several years, attributed to favorable histopathology and healthier baseline status. Sex-specific response to systemic treatment continues to be optimized as lack of standardization in randomized trials makes interpreting results difficult when aggregated. Conclusions: Biological sex plays a critical role in non-small cell lung cancer (NSCLC), though further study is needed to depict the complex web of factors that affect lung cancer risk, development, and outcomes. Female underrepresentation in studies has contributed to this lack of understanding. As these disparities are eliminated, we can move towards more effective treatment for both sexes in this pervasive yet deadly disease.

Rothia in Nonsmall Cell Lung Cancer is Associated With Worse Survival.

INTRODUCTION: The microbiome is known to play a significant role in cancer biology; however, few studies have elucidated its relationship with Nonsmall Cell Lung Cancer (NSCLC) patient outcomes. We hypothesized that there are specific microorganisms that are closely related with NSCLC patient survival. METHODS: Total of 647 NSCLC (Adenocarcinoma and Squamous Cell Carcinoma combined) patients in The Cancer Genome Atlas (TCGA) were analyzed using the R software. RESULTS: A Volcano Plot was analyzed with the patients divided into Short and Long Survivors by overall survival of 0.9 years, and we found that a bacterium Rothia was significantly abundant in Short Survivors, and Blastococcus, Leptospira, and Haematobacter in Long Survivors, but presence of Rothia alone was associated with overall survival. The age, race, subtype, and sex were not significantly different by the presence of Rothia in NSCLC. Unexpectedly, Rothia-positive NSCLC was associated with less cell proliferation by gene set enrichment analysis, Mki67 expression, proliferation score, with less fraction altered and homologous recombination deficiency, and with high infiltration of stromal cells, indicating favorable oncological characteristics. Further, Rothia-positive tumors were associated with significantly higher infiltration of CD8 T cells, CD4 T cells, Monocytes, and NK cells, and high interferon-gamma response, T-cell receptor richness, cytolytic activity, indicating favorable tumor immune microenvironment. CONCLUSIONS: NSCLC with Rothia was associated with worse survival but also with favorable oncological characteristics such as less cell proliferation and favorable tumor immune microenvironment. We cannot help but speculate that Rothia in NSCLC is associated with mortality unrelated to oncological characteristics.

Neoadjuvant therapy in non-small cell lung cancer: basis, promise, and challenges.

Introduction: Survival rates for early-stage non-small cell lung cancer (NSCLC) remain poor despite the decade-long established standard of surgical resection and systemic adjuvant therapy. Realizing this, researchers are exploring novel therapeutic targets and deploying neoadjuvant therapies to predict and improve clinical and pathological outcomes in lung cancer patients. Neoadjuvant therapy is also increasingly being used to downstage disease to allow for resection with a curative intent. In this review, we aim to summarize the current and developing landscape of using neoadjuvant therapy in the management of NSCLC. Methods: The PubMed.gov and the ClinicalTrials.gov databases were searched on 15 January 2023, to identify published research studies and trials relevant to this review. One hundred and seven published articles and seventeen ongoing clinical trials were selected, and relevant findings and information was reviewed. Results & Discussion: Neoadjuvant therapy, proven through clinical trials and meta-analyses, exhibits safety and efficacy comparable to or sometimes surpassing adjuvant therapy. By attacking micro-metastases early and reducing tumor burden, it allows for effective downstaging of disease, allowing for curative surgical resection attempts. Research into neoadjuvant therapy has necessitated the development of surrogate endpoints such as major pathologic response (MPR) and pathologic complete response (pCR) allowing for shorter duration clinical trials. Novel chemotherapy, immunotherapy, and targeted therapy agents are being tested at a furious rate, paving the way for a future of personalized systemic therapy in NSCLC. However, challenges remain that prevent further mainstream adoption of preoperative (Neoadjuvant) therapy. These include the risk of delaying curative surgical resection in scenarios of adverse events or treatment resistance. Also, the predictive value of surrogate markers of disease cure still needs robust verification. Finally, the body of published data is still limited compared to adjuvant therapy. Addressing these concerns with more large scale randomized controlled trials is needed.

Skeletal muscle index is associated with long term outcomes after lobectomy for non-small cell lung cancer.

BACKGROUND: Skeletal muscle indices have been associated with improved peri-operative outcomes after surgical resection of non-small-cell lung cancer (NSCLC). However, it is unclear if these indices can predict long term cancer specific outcomes. METHODS: NSCLC patients undergoing lobectomy at our institute between 2009-2015 were included in this analysis (N = 492). Preoperative CT scans were used to quantify skeletal muscle index (SMI) at L4 using sliceOmatic software. Cox proportional modelling was performed for overall (OS) and recurrence free survival (RFS). RESULTS: For all patients, median SMI was 45.7 cm2/m2 (IQR, 40-53.8). SMI was negatively associated with age (R = -0.2; p < 0.05) and positively associated with BMI (R = 0.46; P < 0.05). No association with either OS or RFS was seen with univariate cox modelling. However, multivariable modelling for SMI with patient age, gender, race, smoking status, DLCO and FEV1 (% predicted), American Society of Anesthesiology (ASA) score, tumor histology and stage, and postoperative neoadjuvant therapy showed improved OS (HR = 0.97; P = 0.0005) and RFS (HR = 0.97; P = 0.01) with SMI. Using sex specific median SMI as cutoff, a lower SMI was associated with poor OS (HR = 1.65, P = 0.001) and RFS (HR = 1.47, P = 0.03). CONCLUSIONS: SMI is associated with improved outcomes after resection of NSCLC. Further studies are needed to understand the biological basis of this observation. This study provides additional rationale for designing and implementation of rehabilitation trials after surgical resection, to gain durable oncologic benefit.

Metabolic Dysregulation Explains the Diverse Impacts of Obesity in Males and Females with Gastrointestinal Cancers.

The prevalence of obesity, defined as the body mass index (BMI) ≥ 30 kg/m2, has reached epidemic levels. Obesity is associated with an increased risk of various cancers, including gastrointestinal ones. Recent evidence has suggested that obesity disproportionately impacts males and females with cancer, resulting in varied transcriptional and metabolic dysregulation. This study aimed to elucidate the differences in the metabolic milieu of adenocarcinomas of the gastrointestinal (GI) tract both related and unrelated to sex in obesity. To demonstrate these obesity and sex-related effects, we utilized three primary data sources: serum metabolomics from obese and non-obese patients assessed via the Biocrates MxP Quant 500 mass spectrometry-based kit, the ORIEN tumor RNA-sequencing data for all adenocarcinoma cases to assess the impacts of obesity, and publicly available TCGA transcriptional analysis to assess GI cancers and sex-related differences in GI cancers specifically. We applied and integrated our unique transcriptional metabolic pipeline in combination with our metabolomics data to reveal how obesity and sex can dictate differential metabolism in patients. Differentially expressed genes (DEG) analysis of ORIEN obese adenocarcinoma as compared to normal-weight adenocarcinoma patients resulted in large-scale transcriptional reprogramming (4029 DEGs, adj. p < 0.05 and |logFC| > 0.58). Gene Set Enrichment and metabolic pipeline analysis showed genes enriched for pathways relating to immunity (inflammation, and CD40 signaling, among others) and metabolism. Specifically, we found alterations to steroid metabolism and tryptophan/kynurenine metabolism in obese patients, both of which are highly associated with disease severity and immune cell dysfunction. These findings were further confirmed using the TCGA colorectal adenocarcinoma (CRC) and esophageal adenocarcinoma (ESCA) data, which showed similar patterns of increased tryptophan catabolism for kynurenine production in obese patients. These patients further showed disparate alterations between males and females when comparing obese to non-obese patient populations. Alterations to immune and metabolic pathways were validated in six patients (two obese and four normal weight) via CD8+/CD4+ peripheral blood mononuclear cell RNA-sequencing and paired serum metabolomics, which showed differential kynurenine and lipid metabolism, which corresponded with altered T-cell transcriptome in obese populations. Overall, obesity is associated with differential transcriptional and metabolic programs in various disease sites. Further, these alterations, such as kynurenine and tryptophan metabolism, which impact both metabolism and immune phenotype, vary with sex and obesity together. This study warrants further in-depth investigation into obesity and sex-related alterations in cancers that may better define biomarkers of response to immunotherapy.

Obesity and lung cancer-a narrative review.

Background and Objective: A highly nuanced relationship exists between obesity and lung cancer. The association between obesity and lung cancer risk/prognosis varies depending on age, gender, race, and the metric used to quantify adiposity. Increased body mass index (BMI) is counterintuitively associated with decreased lung cancer incidence and mortality, giving rise to the term 'obesity paradox'. Potential explanations for this paradox are BMI being a poor measure of obesity, confounding by smoking and reverse causation. A literature search of this topic yields conflicting conclusions from various authors. We aim to clarify the relationship between various measures of obesity, lung cancer risk, and lung cancer prognosis. Methods: The PubMed database was searched on 10 August 2022 to identify published research studies. Literature published in English between 2018 and 2022 were included. Sixty-nine publications were considered relevant, and their full text studied to collate information for this review. Key Content and Findings: Lower lung cancer incidence and better prognosis was associated with increased BMI even after accounting for smoking and pre-clinical weight loss. Individuals with high BMI also responded better to treatment modalities such as immunotherapy compared to individuals with a normal BMI. However, these associations varied highly depending on age, gender, and race. Inability of BMI to measure body habitus is the main driver behind this variability. The use of anthropometric indicators and image-based techniques to quantify central obesity easily and accurately is on the rise. Increase in central adiposity is associated with increased incidence and poorer prognosis of lung cancer, contrasting BMI. Conclusions: The obesity paradox may arise due to the improper use of BMI as a measure of body composition. Measures of central obesity better portray the deleterious effects of obesity and are more appropriate to be discussed when talking about lung cancer. The use of obesity metrics based on anthropometric measurements and imaging modalities has been shown to be feasible and practical. However, a lack of standardization makes it difficult to interpret the results of studies using these metrics. Further research must be done to understand the association between these obesity metrics and lung cancer.

Analyzing the impact of minimally invasive surgical approaches on post-operative outcomes of pneumonectomy and sleeve lobectomy patients.

Background: Some patients with non-small cell lung cancer (NSCLC) have superior short- and long-term outcomes with sleeve lobectomy rather than pneumonectomy. Originally sleeve lobectomy was reserved for patients with limited pulmonary function, however, the reported superior results allowed sleeve lobectomy to be performed in expanded patient populations. In a further attempt to improve post-operative outcomes surgeons have adopted minimally invasive techniques Minimally invasive approaches have potential benefits to patients such as decreased morbidity and mortality while maintaining the same caliber of oncologic outcomes. Methods: We identified patients at our institution who underwent sleeve lobectomy or pneumonectomy to treat NSCLC from 2007 to 2017. We analyzed these groups in respect to 30- and 90-day mortality, complications, local recurrence, and median survival. We included multivariate analysis to determine the impact of a minimally invasive approach, sex, extent of resection, and histology. Differences in mortality were analyzed using the Kaplan-Meier method using the log-rank test to compare the groups. A two-tailed Z test for difference in proportions was done to analyze complications, local recurrence, 30-day and 90-day mortality. Results: A total of 108 patients underwent sleeve lobectomy (n=34) or pneumonectomy (n=74) for treatment of NSCLC with 18 undergoing open pneumonectomy, 56 undergoing video-assisted thoracoscopic surgery (VATS) pneumonectomy, 29 undergoing open sleeve lobectomy, and 5 undergoing VATS sleeve lobectomy. There was no significant difference in 30-day mortality (P=0.064) but there was a difference in 90-day (P=0.007). There was no difference in complication rates (P=0.234) or local recurrence rates (P=0.779). The pneumonectomy patients had a median survival of 23.6 months (95% CI: 3.8-43.4 months). The sleeve lobectomy group had a median survival of 60.7 months (95% CI: 43.3-78.2 months) (P=0.008). On multivariate analysis extent of resection (P<0.001) and tumor stage (P=0.036) were associated with survival. There was no significant difference between the VATS approach and the open surgical approach (P=0.053). Conclusions: When considering patients undergoing surgery for NSCLC sleeve lobectomy resulted in lower 90-day mortality and better 3-year survival compared to patients undergoing PN. Having a sleeve lobectomy rather than a pneumonectomy and having earlier-stage disease lead to significantly improved survival on multivariate analysis. Having a VATS operation leads to a non-inferior post-operative outcome compared to open surgery.

Survival Benefit of Perioperative Systemic Chemotherapy for Patients With N0 to N1 NSCLC Having Synchronous Brain Metastasis.

Introduction: In stage IV NSCLC with solitary or oligometastatic brain metastasis, surgical resection of the primary and definitive management of the brain metastasis is an accepted standard. However, the effect of systemic chemotherapy after surgical resection on overall survival is not well-established. Methods: We used the National Cancer Database to retrospectively identify individuals with NSCLC as the primary tumor along with synchronous brain metastases who underwent thoracic resection with or without adjuvant chemotherapy. Chi-square and Wilcoxon rank sum tests were performed to compare categorical and continuous variables, respectively, across the treatment groups. Kaplan-Meier and Cox proportional modeling were done to determine the survival benefit. Results: A total of 310 (71.9%) of the cohort received perioperative chemotherapy, most of whom (79.4%) received it in the adjuvant setting. Patients receiving chemotherapy were likely to be younger (p = 0.002), privately insured (p = 0.01), and receive radiation (p < 0.001). Perioperative chemotherapy was significantly associated with survival on both univariate (hazard ratio = 0.71[0.52 - 0.99]) and multivariable (hazard ratio = 0.66 [0.47 - 0.92]) in addition to age (p = 0.03), Charlson-Deyo score (p = 0.02), pathologic N stage (p = 0.02), and adenocarcinoma histology (p = 0.02). Kaplan-Meier analysis confirmed this result with a significantly better survival with perioperative chemotherapy (p = 0.02). Further subgroup analysis using pathologic N stage revealed similar effect in pN1 (p = 0.001), but not pN0 (p = 0.2) patients. Conclusions: Perioperative chemotherapy for pN0-1 NSCLC with synchronous brain metastasis is associated with improved OS in this analysis.

Immunoprofiling bronchoalveolar lavage cells reveals multifaceted smoking-associated immune dysfunction.

Background: Bronchoalveolar lavage (BAL) is an underutilised tool in the search for pulmonary disease biomarkers. While leukocytes with effector and suppressor function play important roles in airway immunity and tumours, it remains unclear if frequencies and phenotypes of BAL leukocytes can be useful parameters in lung cancer studies and clinical trials. We therefore explored the utility of BAL leukocytes as a source of biomarkers interrogating the impact of smoking, a major lung cancer risk determinant, on pulmonary immunity. Methods: In this "test case" observational study, BAL samples from 119 donors undergoing lung cancer screening and biopsy procedures were evaluated by conventional and spectral flow cytometry to exemplify the comprehensive immune analyses possible with this biospecimen. Proportions of major leukocyte populations and phenotypic markers levels were found. Multivariate linear rank sum analysis considering age, sex, cancer diagnosis and smoking status was performed. Results: Significantly increased frequencies of myeloid-derived suppressor cells and PD-L1-expressing macrophages were found in current and former smokers compared to never-smokers. While cytotoxic CD8 T-cells and conventional CD4 helper T-cell frequencies were significantly reduced in current and former smokers, expression of immune checkpoints PD-1 and LAG-3 as well as Tregs proportions were increased. Lastly, the cellularity, viability and stability of several immune readouts under cryostorage suggested BAL samples are useful for correlative end-points in clinical trials. Conclusions: Smoking is associated with heightened markers of immune dysfunction, readily assayable in BAL, that may reflect a permissive environment for cancer development and progression in the airway.

Association between visceral obesity, metformin use, and recurrence risk in early-stage colorectal cancer.

We sought to investigate the association between visceral obesity with disease recurrence and survival in early-stage colorectal cancer (CRC) patients. We also wanted to examine if such an association, if exists, is influenced by metformin use. Stage I/II CRC adenocarcinoma patients treated surgically were identified. L3 level CT VFI (visceral fat index) was used as a metric of visceral obesity and was calculated as the proportion of total fat area composed of visceral fat. N = 492. 53% were males, 90% were Caucasians, 35% had stage I disease, and 14% used metformin. 20.3% patients developed a recurrence over a median follow-up of 56 months. VFI was associated with both RFS and OS in a multivariate model, but not BMI. The final multivariate model for RFS included an interaction term for VFI and metformin (p = 0.04). Confirming this result, subgroup analysis showed an increasing VFI was associated with a poor RFS (p = 0.002), and OS (p < 0.001) in metformin non-users only and metformin use was associated with a better RFS only in the top VFI tertile (p = 0.01). Visceral obesity, but not BMI, is associated with recurrence risk and poorer survival in stage I/II CRC. Interestingly, this association is influenced by metformin use.

Geographical Disparities in Esophageal Cancer Incidence and Mortality in the United States.

BACKGROUND: Our previous research on neuroendocrine and gastric cancers has shown that patients living in rural areas have worse outcomes than urban patients. This study aimed to investigate the geographic and sociodemographic disparities in esophageal cancer patients. METHODS: We conducted a retrospective study on esophageal cancer patients between 1975 and 2016 using the Surveillance, Epidemiology, and End Results database. Both univariate and multivariable analyses were performed to evaluate overall survival (OS) and disease-specific survival (DSS) between patients residing in rural (RA) and urban (MA) areas. Further, we used the National Cancer Database to understand differences in various quality of care metrics based on residence. RESULTS: N = 49,421 (RA [12%]; MA [88%]). The incidence and mortality rates were consistently higher during the study period in RA. Patients living in RA were more commonly males (p < 0.001), Caucasian (p < 0.001), and had adenocarcinoma (p < 0.001). Multivariable analysis showed that RA had worse OS (HR = 1.08; p < 0.01) and DSS (HR = 1.07; p < 0.01). Quality of care was similar, except RA patients were more likely to be treated at a community hospital (p < 0.001). CONCLUSIONS: Our study identified geographic disparities in esophageal cancer incidence and outcomes despite the similar quality of care. Future research is needed to understand and attenuate such disparities.

Postoperative Restrictive Opioid Protocols and Durable Changes in Opioid Prescribing and Chronic Opioid Use.

Importance: Changes in postsurgical opioid prescribing practices may help reduce chronic opioid use in surgical patients. Objective: To investigate whether postsurgical acute pain across different surgical subspecialties can be managed effectively after hospital discharge with an opioid supply of 3 or fewer days and whether this reduction in prescribed opioids is associated with reduced new, persistent opioid use. Design, Setting, and Participants: In this prospective cohort study with a case-control design, a restrictive opioid prescription protocol (ROPP) specifying an opioid supply of 3 or fewer days after discharge from surgery along with standardized patient education was implemented across all surgical services at a tertiary-care comprehensive cancer center. Participants were all patients who underwent surgery from August 1, 2018, to July 31, 2019. Main Outcomes and Measures: Main outcomes were the rate of compliance with the ROPP in each surgical service, the mean number of prescription days and refill requests, type of opioid prescribed, and rate of conversion to chronic opioid use determined via a state-run opioid prescription program. Postsurgical complications were also measured. Results: A total of 4068 patients (mean [SD] age, 61.0 [13.8] years; 2528 women [62.1%]) were included, with 2017 in the pre-ROPP group (August 1, 2018, to January 31, 2019) and 2051 in the post-ROPP group (February 1, 2019, to July 31, 2019). The rate of compliance with the protocol was 95%. After implementation of the ROPP, mean opioid prescription days decreased from a mean (SD) of 3.9 (4.5) days in the pre-ROPP group to 1.9 (3.6) days in the post-ROPP group (P < .001). The ROPP implementation led to a 45% decrease in prescribed opioids after surgery (mean [SD], 157.22 [338.06] mean morphine milligram equivalents [MME] before ROPP vs 83.54 [395.70] MME after ROPP; P < .001). Patients in the post-ROPP cohort requested fewer refills (367 of 2051 [17.9%] vs 422 of 2017 [20.9%] in the pre-ROPP cohort; P = .02). There was no statistically significant difference in surgical complications. The conversion rate to chronic opioid use decreased following ROPP implementation among both opioid-naive patients with cancer (11.3% [143 of 1267] to 4.5% [118 of 2645]; P < .001) and those without cancer (6.1% [19 of 310] to 2.7% [16 of 600]; P = .02). Conclusions and Relevance: In this cohort study, prescribing an opioid supply of 3 or fewer days to surgical patients after hospital discharge was feasible for most patients, led to a significant decrease in the number of opioids prescribed after surgery, and was associated with a significantly decreased conversion to long-term opioid use without concomitant increases in refill requests or significant compromises in surgical recovery.

Quality of Life After Stereotactic Body Radiation Therapy or Surgery for Early-Stage NSCLC: A Systematic Review.

Quality of life (QOL) is a key consideration for patients with early-stage NSCLC choosing between treatment options. Currently, it is not well established whether stereotactic body radiation therapy (SBRT) or surgery offers superior QOL in early-stage NSCLC. The objective of this systematic review is to summarize the prospective literature on QOL in patients with early-stage NSCLC after treatment with SBRT or surgery. A comprehensive literature review using PubMed and EMBASE was performed in April 2022. Prospective studies evaluating QOL data across multiple time points in patients with early-stage NSCLC after SBRT or surgery were included. A total of 25 studies involving 1597 SBRT patients and 1652 surgery patients met the inclusion criteria. Across most studies, QOL remained stable after treatment with SBRT. After surgery, QOL initially decreased; however, it often returned to baseline in the next 6 to 12 months. Utilization of video-assisted thoracoscopic surgery and sublobar resection reduced the magnitude of the initial decrease in QOL after surgery and led to faster recovery to baseline. Owing to the heterogeneity of patient populations between studies evaluating SBRT versus surgery, direct comparisons between the two treatments remain difficult to make. Clinicians should appropriately counsel patients with this information to help guide patient-centered discussions on choosing the optimal treatment modality.

Altered acetyl-CoA metabolism presents a new potential immunotherapy target in the obese lung microenvironment.

Contrary to the "obesity paradox," which arises from retrospective studies relying on body mass index to define obesity, epidemiologic evidence suggests central or visceral obesity is associated with a higher risk for the development of lung cancer. About 60% of individuals at high risk for developing lung cancer or those already with early-stage disease are either overweight or obese. Findings from resected patient tumors and mouse lung tumor models show obesity dampens immune activity in the tumor microenvironment (TME) encouraging disease progression. In line with this, we have observed a marked, obesity-specific enhancement in the presence and phenotype of immunosuppressive regulatory T (Treg) cells in murine tumors as well as the airways of both humans and mice. Leveraging direct metabolomic measurements and robust inferred analyses from RNA-sequencing data, we here demonstrate for the first time that visceral adiposity alters the lung microenvironment via dysregulated acetyl-CoA metabolism in a direction that facilitates immune suppression and lung carcinogenesis.

Visceral Obesity in Non-Small Cell Lung Cancer.

While obesity measured by body mass index (BMI) has been paradoxically associated with reduced risk and better outcome for lung cancer, recent studies suggest that the harm of obesity becomes apparent when measured as visceral adiposity. However, the prevalence of visceral obesity and its associations with demographic and tumor features are not established. We therefore conducted an observational study of visceral obesity in 994 non-small cell lung cancer (NSCLC) patients treated during 2008-2020 at our institution. Routine computerized tomography (CT) images of the patients, obtained within a year of tumor resection or biopsy, were used to measure cross-sectional abdominal fat areas. Important aspects of the measurement approach such as inter-observer variability and time stability were examined. Visceral obesity was semi-quantified as visceral fat index (VFI), the fraction of fat area that was visceral. VFI was found to be higher in males compared to females, and in former compared to current or never smokers. There was no association of VFI with tumor histology or stage. A gene expression-based measure of tumor immunogenicity was negatively associated with VFI but had no bearing with BMI. Visceral obesity is appraisable in routine CT and can be an important correlate in lung cancer studies.

Acute gastric conduit dilation after minimally invasive esophagectomy: a 10-year experience.

Despite decreasing overall morbidity with minimally invasive esophagectomy (MIE), conduit functional outcomes related to delayed emptying remain challenging, especially in the immediate postoperative setting. Yet, this problem has not been described well in the literature. Utilizing a single institutional prospective database, 254 patients who underwent MIEs between 2012 and 2020 were identified. Gastric conduit dilation was defined as a conduit occupying >40% of the hemithorax on the postoperative chest X-ray. Sixty-seven patients (26.4%) demonstrated acute conduit dilation. There was a higher incidence of conduit dilation in the patients who underwent Ivor Lewis esophagectomy compared to those with a neck anastomosis (67.2% vs. 47.1%; P = 0.03). Patients with dilated conduits required more esophagogastroduodenoscopies (EGD) (P < 0.001), conduit-related reoperations within 180 days (P < 0.001), and 90-day readmissions (P = 0.01). Furthermore, in 37 patients (25.5%) undergoing Ivor Lewis esophagectomy, we returned to the abdomen after intrathoracic anastomosis to reduce redundant conduit and pexy the conduit to the crura. While conduit dilation rates were similar, those who had intraabdominal gastropexy required EGD significantly less and trended toward a lower incidence of conduit-related reoperations (5.6% vs. 2.7%). Multivariable analysis also demonstrated that conduit dilation was an independent predictor for delayed gastric conduit emptying symptoms, EGD within 90 days, conduit-related reoperation within 180 days, and 30-day as well as 90-day readmission. Patients undergoing MIE with acute gastric conduit dilation require more endoscopic interventions and reoperations.