Lobe-specific lymph node sampling is associated with lower risk of cancer recurrence.

Objective: Adequate intraoperative lymph node (LN) assessment is a critical component of early-stage non-small cell lung cancer (NSCLC) resection. The National Comprehensive Cancer Network and the American College of Surgeons Commission on Cancer (CoC) recommend station-based sampling minimums agnostic to tumor location. Other institutions advocate for lobe-specific LN sampling strategies that consider the anatomic likelihood of LN metastases. We examined the relationship between lobe-specific LN assessment and long-term outcomes using a robust, highly curated cohort of stage I NSCLC patients. Methods: We performed a cohort study using a uniquely compiled dataset from the Veterans Health Administration and manually abstracted data from operative and pathology reports for patients with clinical stage I NSCLC (2006-2016). For simplicity in comparison, we included patients who had right upper lobe (RUL) or left upper lobe (LUL) tumors. Based on modified European Society of Thoracic Surgeons guidelines, lobe-specific sampling was defined for RUL tumors (stations 2, 4, 7, and 10 or 11) and LUL tumors (stations 5 or 6, 7, and 10 or 11). Our primary outcome was the risk of cancer recurrence, as assessed by Fine and Gray competing risks modeling. Secondary outcomes included overall survival (OS) and pathologic upstaging. Analyses were adjusted for relevant patient, disease, and treatment variables. Results: Our study included 3534 patients with RUL tumors and 2667 patients with LUL tumors. Of these, 277 patients (7.8%) with RUL tumors and 621 patients (23.2%) with LUL tumors met lobe-specific assessment criteria. Comparatively, 34.7% of patients met the criteria for count-based assessment, and 25.8% met the criteria for station-based sampling (ie, any 3 N2 stations and 1 N1 station). Adherence to lobe-specific assessment was associated with lower cumulative incidence of recurrence (adjusted hazard ratio [aHR], 0.83; 95% confidence interval [CI], 0.70-0.98) and a higher likelihood of pathologic upstaging (aHR, 1.49; 95% CI, 1.20-1.86). Lobe-specific assessment was not associated with OS. Conclusions: Adherence to intraoperative LN sampling guidelines is low. Lobe-specific assessment is associated with superior outcomes in early-stage NSCLC. Quality metrics that assess adherence to intraoperative LN sampling, such as the CoC Operative Standards manual, also should consider lobe-specific criteria.

Exposure to Agent Orange is associated with increased recurrence after surgical treatment of stage I non-small cell lung cancer.

OBJECTIVE: Approximately 3 million Americans served in the armed forces during the Vietnam War. Veterans have a higher incidence rate of lung cancer compared with the general population, which may be related to exposures sustained during service. Agent Orange, one of the tactical herbicides used by the armed forces as a means of destroying crops and clearing vegetation, has been linked to the development of several cancers including non-small cell lung cancer. However, traditional risk models of lung cancer survival and recurrence often do not include such exposures. We aimed to examine the relationship between Agent Orange exposure and overall survival and disease recurrence for surgically treated stage I non-small cell lung cancer. METHODS: We performed a retrospective cohort study using a uniquely compiled dataset of US Veterans with pathologic I non-small cell lung cancer. We included adult patients who served in the Vietnam War and underwent surgical resection between 2010 and 2016. Our 2 comparison groups included those with identified Agent Orange exposure and those who were unexposed. We used multivariable Cox proportional hazards and Fine and Gray competing risk analyses to examine overall survival and disease recurrence for patients with pathologic stage I disease, respectively. RESULTS: A total of 3958 Vietnam Veterans with pathologic stage I disease were identified (994 who had Agent Orange exposure and 2964 who were unexposed). Those who had Agent Orange exposure were more likely to be male, to be White, and to live a further distance from their treatment facility (P < .05). Tumor size distribution, grade, and histology were similar between cohorts. Multivariable Cox proportional hazards modeling identified similar overall survival between cohorts (Agent Orange exposure hazard ratio, 0.97; 95% CI, 0.86-1.09). Patients who had Agent Orange exposure had a 19% increased risk of disease recurrence (hazard ratio, 1.19; 95% CI, 1.02-1.40). CONCLUSIONS: Veterans with known Agent Orange exposure who undergo surgical treatment for stage I non-small cell lung cancer have an approximately 20% increased risk of disease recurrence compared with their nonexposed counterparts. Agent Orange exposure should be taken into consideration when determining treatment and surveillance regimens for Veteran patients.

RNA-sequencing attest increased sperm motility in bovine spermatozoa treated with ethanolic extract of Putranjiva roxburghii.

In the course of time, scientific communities have a growing interest in understanding ethano medicines. The Putranjiva roxburghii, a native plant of the Indian Subcontinent is described as a "Child amulet tree" in Ayurveda. Based on the fact that this herbal medicine has an indispensable component of integrative medicine, the present study was planned to assess the effect of ethanolic dried extract of Putranjiva seeds on the motility of X and Y-bearing bovine spermatozoa. The in-vitro effect of seed extract diluted in S-TALP medium on bull semen has been evaluated by Computer Assisted Semen Analysis (CASA) shows a marked increase in the motility of spermatozoa. Motile and non-motile spermatozoa have been separated by glass wool column from the control as well as treated group. The X and Y-bearing sperm quantification have been carried out by droplet digital polymerase chain reaction (ddPCR). The extract didn't exert any differential effect on the motility and viability of X and Y chromosome-bearing spermatozoa. The transcriptome profiling (RNA-Seq) identified 93 differentially expressed genes between the extract treated and control group. It unveils the up-regulation of CATSPER, AKAP3, SPAG, ADAM1B, ADAM2 and ADAM32 genes that are involved in increasing sperm motility. Transcriptome profile also unveil the expression of ZAR1, CYP17A1, APPL2, HOXB4 and SP9 genes involved with embryonic development processes in Putranjiva extract-treated motile spermatozoa. The results envisaged the medicinal value of Putranjiva herb on increased fertility due to combinatory effect like increased sperm motility and favourableness on embryogenesis. The study ruled out the possibility of herbs having any biased effect on the selection of either male or female-bearing spermatozoa in the bull. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03452-4.

Association Between Surgical Quality Metric Adherence and Overall Survival Among US Veterans With Early-Stage Non-Small Cell Lung Cancer.

Importance: Surgical resection remains the preferred treatment for functionally fit patients diagnosed with early-stage non-small cell lung cancer (NSCLC). Process-based intraoperative quality metrics (QMs) are important for optimizing long-term outcomes following curative-intent resection. Objective: To develop a practical surgical quality score for patients diagnosed with clinical stage I NSCLC who received definitive surgical treatment. Design, Setting, and Participants: This retrospective cohort study used a uniquely compiled data set of US veterans diagnosed with clinical stage I NSCLC who received definitive surgical treatment from October 2006 through September 2016. The data were analyzed from April 1 to September 1, 2022. Based on contemporary treatment guidelines, 5 surgical QMs were defined: timely surgery, minimally invasive approach, anatomic resection, adequate lymph node sampling, and negative surgical margin. The study developed a surgical quality score reflecting the association between these QMs and overall survival (OS), which was further validated in a cohort of patients using data from the National Cancer Database (NCDB). The study also examined the association between the surgical quality score and recurrence-free survival (RFS). Exposures: Surgical treatment of early-stage NSCLC. Main Outcomes and Measures: Overall survival and RFS. Results: The study included 9628 veterans who underwent surgical treatment between 2006 and 2016. The cohort consisted of 1446 patients who had a mean (SD) age of 67.6 (7.9) years and included 9278 males (96.4%) and 350 females (3.6%). Among the cohort, 5627 individuals (58.4%) identified as being smokers at the time of surgical treatment. The QMs were met as follows: timely surgery (6633 [68.9%]), minimally invasive approach (3986 [41.4%]), lobectomy (6843 [71.1%]) or segmentectomy (532 [5.5%]), adequate lymph node sampling (3278 [34.0%]), and negative surgical margin (9312 [96.7%]). The median (IQR) follow-up time was 6.2 (2.5-11.4) years. An integer-based score (termed the Veterans Affairs Lung Cancer Operative quality [VALCAN-O] score) from 0 (no QMs met) to 13 (all QMs met) was constructed, with higher scores reflecting progressively better risk-adjusted OS. The median (IQR) OS differed substantially between the score categories (score of 0-5 points, 2.6 [1.0-5.7] years of OS; 6-8 points, 4.3 [1.7-8.6] years; 9-11 points, 6.3 [2.6-11.4] years; and 12-13 points, 7.0 [3.0-12.5] years; P < .001). In addition, risk-adjusted RFS improved in a stepwise manner between the score categories (6-8 vs 0-5 points, multivariable-adjusted hazard ratio [aHR], 0.62; 95% CI, 0.48-0.79; P < .001; 12-13 vs 0-5 points, aHR, 0.39; 95% CI, 0.31-0.49; P < .001). In the validation cohort, which included 107 674 nonveteran patients, the score remained associated with OS. Conclusions and Relevance: The findings of this study suggest that adherence to intraoperative QMs may be associated with improved OS and RFS. Efforts to improve adherence to surgical QMs may improve patient outcomes following curative-intent resection of early-stage lung cancer.

Understanding of molecular basis of histological graded horn cancer by transcriptome profiling.

Horn cancer is most devastating and prominent cancer in Indian zebu cattle that affects socio-economic condition of small-scale farmers who depends on their cattle for farm work. Development in the field for genomics through next generation sequencing and bioinformatics advancement have helped to identify genes which have a role in horn cancer development. Histopathological examination of cancerous tissues of horn revealed myxomatous changes, well, moderate and poorly differentiated squamous cell carcinoma. Differential gene expression analysis showed 40, 11, 66 and 29 upregulated genes and 10, 14, 08 and 07 down-regulated genes in myxomatous, well, moderate and poorly differentiated squamous cell carcinoma as compared to normal. Significant differentially expressed genes are related to cell development, cell proliferation, cell-cell communication, cell signaling and angiogenesis which are linked to Akt pathway, mTOR pathway and Wnt pathway. Activity of these genes and related pathways have already been established about their role in development of cancer. Among the candidate genes; keratin family, keratin family related gene, chemokine signaling and cytokines signaling associated genes could be a prominent target for the development of stage specific prognosis marker after further detailed study at large sample population level. CSTA, PTN, SPP1 genes have upregulation in all stages of cancer and they have enrolled as biomarkers for horn cancer.

Association between imaging surveillance frequency and outcomes following surgical treatment of early-stage lung cancer.

BACKGROUND: Recent studies have suggested that more frequent postoperative surveillance imaging via computed tomography following lung cancer resection may not improve outcomes. We sought to validate these findings using a uniquely compiled dataset from the Veterans Health Administration, the largest integrated health-care system in the United States. METHODS: We performed a retrospective cohort study of veterans with pathologic stage I non-small cell lung cancer receiving surgery (2006-2016). We assessed the relationship between surveillance frequency (chest computed tomography scans within 2 years after surgery) and recurrence-free survival and overall survival. RESULTS: Among 6171 patients, 3047 (49.4%) and 3124 (50.6%) underwent low-frequency (<2 scans per year; every 6-12 months) and high-frequency (≥2 scans per year; every 3-6 months) surveillance, respectively. Factors associated with high-frequency surveillance included being a former smoker (vs current; adjusted odds ratio [aOR] = 1.18, 95% confidence interval [CI] = 1.05 to 1.33), receiving a wedge resection (vs lobectomy; aOR = 1.21, 95% CI = 1.05 to 1.39), and having follow-up with an oncologist (aOR = 1.58, 95% CI = 1.42 to 1.77), whereas African American race was associated with low-frequency surveillance (vs White race; aOR = 0.64, 95% CI = 0.54 to 0.75). With a median (interquartile range) follow-up of 7.3 (3.4-12.5) years, recurrence was detected in 1360 (22.0%) patients. High-frequency surveillance was not associated with longer recurrence-free survival (adjusted hazard ratio = 0.93, 95% CI = 0.83 to 1.04, P = .22) or overall survival (adjusted hazard ratio = 1.04, 95% CI = 0.96 to 1.12, P = .35). CONCLUSIONS: We found that high-frequency surveillance does not improve outcomes in surgically treated stage I non-small cell lung cancer. Future lung cancer treatment guidelines should consider less frequent surveillance imaging in patients with stage I disease.

Development and Validation of the VA Lung Cancer Mortality (VALCAN-M) Score for 90-Day Mortality Following Surgical Treatment of Clinical Stage I Lung Cancer.

OBJECTIVE: The aim was to develop and validate the Veterans Administration (VA) Lung Cancer Mortality (VALCAN-M) score, a risk prediction model for 90-day mortality following surgical treatment of clinical stage I nonsmall-cell lung cancer (NSCLC). BACKGROUND: While surgery remains the preferred treatment for functionally fit patients with early-stage NSCLC, less invasive, nonsurgical treatments have emerged for high-risk patients. Accurate risk prediction models for postoperative mortality may aid surgeons and other providers in optimizing patient-centered treatment plans. METHODS: We performed a retrospective cohort study using a uniquely compiled VA data set including all Veterans with clinical stage I NSCLC undergoing surgical treatment between 2006 and 2016. Patients were randomly split into derivation and validation cohorts. We derived the VALCAN-M score based on multivariable logistic regression modeling of patient and treatment variables and 90-day mortality. RESULTS: A total of 9749 patients were included (derivation cohort: n=6825, 70.0%; validation cohort: n=2924, 30.0%). The 90-day mortality rate was 4.0% (n=390). The final multivariable model included 11 factors that were associated with 90-day mortality: age, body mass index, history of heart failure, forced expiratory volume (% predicted), history of peripheral vascular disease, functional status, delayed surgery, American Society of Anesthesiology performance status, tumor histology, extent of resection (lobectomy, wedge, segmentectomy, or pneumonectomy), and surgical approach (minimally invasive or open). The c statistic was 0.739 (95% CI=0.708-0.771) in the derivation cohort. CONCLUSIONS: The VALCAN-M score uses readily available treatment-related variables to reliably predict 90-day operative mortality. This score can aid surgeons and other providers in objectively discussing operative risk among high-risk patients with clinical stage I NSCLC considering surgery versus other definitive therapies.

Assessment of Duration of Smoking Cessation Prior to Surgical Treatment of Non-small Cell Lung Cancer.

OBJECTIVE: To define the relationship between the duration of smoking cessation and postoperative complications for patients with lung cancer undergoing surgical treatment. BACKGROUND: Smoking increases the risk of postoperative morbidity and mortality in patients with lung cancer undergoing surgical treatment. Although smoking cessation before surgery can mitigate these risks, the ideal duration of preoperative smoking cessation remains unclear. METHODS: Using a uniquely compiled Veterans Health Administration dataset, we performed a retrospective cohort study of patients with clinical stage I non-small cell lung cancer undergoing surgical treatment between 2006 and 2016. We characterized the relationship between duration of preoperative smoking cessation and risk of postoperative complications or mortality within 30-days using multivariable restricted cubic spline functions. RESULTS: The study included a total of 9509 patients, of whom 6168 (64.9%) were smoking at the time of lung cancer diagnosis. Among them, only 662 (10.7%) patients stopped smoking prior to surgery. Longer duration between smoking cessation and surgery was associated with lower odds of major complication or mortality (adjusted odds ratio [aOR] for every additional week, 0.919; 95% confidence interval [CI], 0.850-0.993; P = 0.03). Compared to nonsmokers, patients who quit at least 3 weeks before surgery had similar odds of death or major complication (aOR, 1.005; 95% CI, 0.702-1.437; P = 0.98) whereas those who quit within 3 weeks of surgery had significantly higher odds of death or major complication (aOR, 1.698; 95% CI, 1.203-2.396; P = 0.003). CONCLUSION: Smoking cessation at least 3 weeks prior to the surgical treatment of lung cancer is associated with reduced morbidity and mortality. Providers should aggressively encourage smoking cessation in the preoperative period, since it can disproportionately impact outcomes in early-stage lung cancer.

Comparison Between Veteran and Non-Veteran Populations With Clinical Stage I Non-small Cell Lung Cancer Undergoing Surgery.

OBJECTIVE: The aim of this study was to compare quality of care and outcomes between Veteran and non-Veteran patients undergoing surgery for clinical stage I non-small cell lung cancer (NSCLC). BACKGROUND: Prior studies and the lay media have questioned the quality of care that Veterans with lung cancer receive through the VHA. We hypothesized Veterans undergoing surgery for early-stage NSCLC receive high quality care and have similar outcomes compared to the general population. METHODS: We performed a retrospective cohort study of patients with clinical stage I NSCLC undergoing resection from 2006 to 2016 using a VHA dataset. Propensity score matching for baseline patient- and tumor-related variables was used to compare operative characteristics and outcomes between the VHA and the National Cancer Database (NCDB). RESULTS: The unmatched cohorts included 9981 VHA and 176,304 NCDB patients. The VHA had more male, non-White patients with lower education levels, higher incomes, and higher Charlson/Deyo scores. VHA patients had inferior unadjusted 30-day mortality (VHA 2.1% vs NCDB 1.7%, P = 0.011) and median overall survival (69.0 vs 88.7 months, P < 0.001). In the propensity matched cohort of 6792 pairs, VHA patients were more likely to have minimally invasive operations (60.0% vs 39.6%, P < 0.001) and only slightly less likely to receive lobectomies (70.1% vs 70.7%, P = 0.023). VHA patients had longer lengths of stay (8.1 vs 7.1 days, P < 0.001) but similar readmission rates (7.7% vs 7.0%, P = 0.132). VHA patients had significantly better 30-day mortality (1.9% vs 2.8%, P < 0.001) and median overall survival (71.4 vs 65.2 months, P < 0.001). CONCLUSIONS: Despite having more comorbidities, Veterans receive exceptional care through the VHA with favorable outcomes, including significantly longer overall survival, compared to the general population.

Inhaled medications for chronic obstructive pulmonary disease predict surgical complications and survival in stage I non-small cell lung cancer.

Background: Lung function is routinely assessed prior to surgical resection for non-small cell lung cancer (NSCLC). Further assessment of chronic obstructive pulmonary disease (COPD) using inhaled COPD medications to determine disease severity, a readily available metric of disease burden, may predict postoperative outcomes and overall survival (OS) in lung cancer patients undergoing surgery. Methods: We retrospectively evaluated clinical stage I NSCLC patients receiving surgical treatment within the Veterans Health Administration from 2006-2016 to determine the relationship between number and type of inhaled COPD medications (short- and long-acting beta2-agonists, muscarinic antagonists, or corticosteroids prescribed within 1 year before surgery) and postoperative outcomes including OS using multivariable models. We also assessed the relationship between inhaled COPD medications, disease severity [measured by forced expiratory volume in 1 second (FEV1)], and diagnosis of COPD. Results: Among 9,741 veterans undergoing surgery for clinical stage I NSCLC, patients with COPD were more likely to be prescribed inhaled medications than those without COPD [odds ratio (OR) =5.367, 95% confidence interval (CI): 4.886-5.896]. Increased severity of COPD was associated with increased number of prescribed inhaled COPD medications (P<0.0001). The number of inhaled COPD medications was associated with prolonged hospital stay [adjusted OR (aOR) =1.119, 95% CI: 1.076-1.165), more major complications (aOR =1.117, 95% CI: 1.074-1.163), increased 90-day mortality (aOR =1.088, 95% CI: 1.013-1.170), and decreased OS [adjusted hazard ratio (aHR) =1.061, 95% CI: 1.042-1.080]. In patients with FEV1 ≥80% predicted, greater number of prescribed inhaled COPD medications was associated with increased 30-day mortality (aOR =1.265, 95% CI: 1.062-1.505), prolonged hospital stay (aOR =1.130, 95% CI: 1.051-1.216), more major complications (aOR =1.147, 95% CI: 1.064-1.235), and decreased OS (aHR =1.058, 95% CI: 1.022-1.095). When adjusting for other drug classes and covariables, short-acting beta2-agonists were associated with increased 90-day mortality (aOR =1.527, 95% CI: 1.120-2.083) and decreased OS (aHR =1.087, 95% CI: 1.005-1.177). Conclusions: In patients with early-stage NSCLC, inhaled COPD medications prescribed prior to surgery were associated with both short- and long-term outcomes, including in patients with FEV1 ≥80% predicted. Routine assessment of COPD medications may be a simple method to quantify operative risk in early-stage NSCLC patients.

Assessment of Updated Commission on Cancer Guidelines for Intraoperative Lymph Node Sampling in Early Stage NSCLC.

INTRODUCTION: The American College of Surgeons Commission on Cancer recently updated its sampling recommendations for early stage NSCLC from at least 10 lymph nodes to at least one N1 (hilar) and three N2 (mediastinal) lymph node stations. Nevertheless, intraoperative lymph node sampling minimums remain subject to debate. We sought to evaluate these guidelines in patients with early stage NSCLC. METHODS: We performed a cohort study using a uniquely compiled data set from the Veterans Health Administration. We manually abstracted data from operative notes and pathology reports of patients with clinical stage I NSCLC receiving surgery (2006-2016). Adequacy of lymph node sampling was defined using count-based (≥10 lymph nodes) and station-based (≥three N2 and one N1 nodal stations) minimums. Our primary outcome was recurrence-free survival. Secondary outcomes were overall survival and pathologic upstaging. RESULTS: The study included 9749 patients. Count-based and station-based sampling guidelines were achieved in 3302 (33.9%) and 2559 patients (26.3%), respectively, with adherence to either sampling guideline increasing over time from 35.6% (2006) to 49.1% (2016). Adherence to station-based sampling was associated with improved recurrence-free survival (multivariable-adjusted hazard ratio = 0.815, 95% confidence interval: 0.667-0.994, p = 0.04), whereas adherence to count-based sampling was not (adjusted hazard ratio = 0.904, 95% confidence interval: 0.757-1.078, p = 0.26). Adherence to either station-based or count-based guidelines was associated with improved overall survival and higher likelihood of pathologic upstaging. CONCLUSIONS: Our study supports station-based sampling minimums (≥three N2 and one N1 nodal stations) for early stage NSCLC; however, the marginal benefit compared with count-based guidelines is minimal. Further efforts to promote widespread adherence to intraoperative lymph node sampling minimums are critical for improving patient outcomes after curative-intent lung cancer resection.

Access to Care Metrics in Stage I Lung Cancer: Improved Access Is Associated With Improved Survival.

BACKGROUND: Equitable access to care is a critical component of comprehensive surgical lung cancer management. Despite this, quality measures (QMs) assessing preoperative access to care are lacking. This study determined several preoperative QMs on the basis of contemporary treatment guidelines and hypothesized that poor access to care was associated with worse outcomes. METHODS: This retrospective cohort study used a specially compiled Veterans Health Administration data set of patients with clinical stage I non-small cell lung cancer (NSCLC) who underwent surgical treatment (2006-2016). The study defined 4 QMs that patients with clinical stage I NSCLC should routinely meet in the preoperative period: timely surgery, positron emission tomography imaging, appropriate smoking management, and pulmonary function testing. The relationship between meeting these QMs and various short- and long-term outcomes was assessed. RESULTS: Among 9749 veterans undergoing surgery for clinical stage I NSCLC, 3371 (34.6%) met all QMs. Factors associated with lower likelihood of meeting all QMs included Black race (adjusted odds ratio [aOR], 0.744; 95% CI, 0.652-0.848), higher area deprivation index score (eg, quartile 5 vs 1; aOR, 0.747; 95% CI, 0.647-0.863), and increased distance to hospital (eg, quartile 5 vs 1; aOR, 0.700; 95% CI, 0.605-0.811). Adherence to all QMs was associated with significantly lower likelihood of postoperative mortality (aOR, 0.623; 95% CI, 0.433-0.896) and improved overall survival (adjusted HR, 0.897; 95% CI, 0.844-0.954). CONCLUSIONS: Inadequate access to preoperative care is associated with worse short- and long-term outcomes in clinical stage I NSCLC. Future Veterans Health Administration policy measures should focus on providing more equitable guideline-concordant care to veterans.

Racial Disparities in the Surgical Treatment of Clinical Stage I Non-Small Cell Lung Cancer Among Veterans.

BACKGROUND: Prior studies in the civilian population have reported racial disparities in lung cancer outcomes following surgical treatment, including inferior quality of care and worse survival. It is unclear if racial disparities exist in the Veterans Health Administration (VHA), the largest integrated health care system in the United States. RESEARCH QUESTION: Do racial disparities affect early-stage non-small cell lung cancer (NSCLC) outcomes following surgical treatment within the VHA? STUDY DESIGN AND METHODS: This retrospective cohort study was conducted in veterans with clinical stage I NSCLC undergoing surgical treatment in the VHA system. Demographic characteristics, access to care, surgical quality measures, and short- and long-term oncologic outcomes between White and Black veterans were evaluated. RESULTS: From 2006 to 2016, a total of 18,800 veterans with clinical stage I NSCLC were included. The rates of definitive surgical treatment were similar between Black (57.3%) and White (58.1%) veterans (P = .42). The final study cohort included 9,842 patients receiving surgical treatment, of whom 8,356 (84.9%) were White and 1,486 (15.1%) were Black. Black patients were younger and more likely to smoke, although comorbidities were similar between the two groups. Black patients were somewhat less likely to receive adequate lymph node sampling (30.6% vs 33.3%; P = .050); however, other access-to-care metrics and surgical quality measures, including rates of anatomic lobectomy (71.9% vs 69.4%; P = .189) and positive margins (3.2% vs 3.1%; P = .955), were similar between the two groups. Although Black veterans were less likely to experience major postoperative complications, there was no difference in 30-day readmission, 30-day mortality, or disease-free survival between the two groups. Black patients had significantly better risk-adjusted overall survival (hazard ratio, 0.802; 95% CI, 0.729-0.883; P < .001). INTERPRETATION: Among veterans with NSCLC undergoing surgical treatment through the VHA, Black patients received comparable care with equivalent if not superior outcomes compared with White patients.

The Impact of Persistent Smoking After Surgery on Long-term Outcomes After Stage I Non-small Cell Lung Cancer Resection.

BACKGROUND: Smoking at the time of surgical treatment for lung cancer increases the risk for perioperative morbidity and mortality. The prevalence of persistent smoking in the postoperative period and its association with long-term oncologic outcomes are poorly described. RESEARCH QUESTION: What is the relationship between persistent smoking and long-term outcomes in early-stage lung cancer after surgical treatment? STUDY DESIGN AND METHODS: We performed a retrospective cohort study using a uniquely compiled Veterans Health Administration dataset of patients with clinical stage I non-small cell lung cancer (NSCLC) undergoing surgical treatment between 2006 and 2016. We defined persistent smoking as individuals who continued smoking 1 year after surgery and characterized the relationship between persistent smoking and disease-free survival and overall survival. RESULTS: This study included 7,489 patients undergoing surgical treatment for clinical stage I NSCLC. Of 4,562 patients (60.9%) who were smoking at the time of surgery, 2,648 patients (58.0%) continued to smoke at 1 year after surgery. Among 2,927 patients (39.1%) who were not smoking at the time of surgical treatment, 573 (19.6%) relapsed and were smoking at 1 year after surgery. Persistent smoking at 1 year after surgery was associated with significantly shorter overall survival (adjusted hazard ration [aHR], 1.291; 95% CI, 1.197-1.392; P < .001). However, persistent smoking was not associated with inferior disease-free survival (aHR, 0.989; 95% CI, 0.884-1.106; P = .84). INTERPRETATION: Persistent smoking after surgery for stage I NSCLC is common and is associated with inferior overall survival. Providers should continue to assess smoking habits in the postoperative period given its disproportionate impact on long-term outcomes after potentially curative treatment for early-stage lung cancer.

Analysis of Delayed Surgical Treatment and Oncologic Outcomes in Clinical Stage I Non-Small Cell Lung Cancer.

Importance: The association between delayed surgical treatment and oncologic outcomes in patients with non-small cell lung cancer (NSCLC) is poorly understood given that prior studies have used imprecise definitions for the date of cancer diagnosis. Objective: To use a uniform method to quantify surgical treatment delay and to examine its association with several oncologic outcomes. Design, Setting, and Participants: This retrospective cohort study was conducted using a novel data set from the Veterans Health Administration (VHA) system. Included patients had clinical stage I NSCLC and were undergoing resection from 2006 to 2016 within the VHA system. Time to surgical treatment (TTS) was defined as the time between preoperative diagnostic computed tomography imaging and surgical treatment. We evaluated the association between TTS and several delay-associated outcomes using restricted cubic spline functions. Data analyses were performed in November 2021. Exposure: Wait time between cancer diagnosis and surgical treatment (ie, TTS). Main Outcomes and Measures: Several delay-associated oncologic outcomes, including pathologic upstaging, resection with positive margins, and recurrence, were assessed. We also assessed overall survival. Results: Among 9904 patients who underwent surgical treatment for clinical stage I NSCLC, 9539 (96.3%) were men, 4972 individuals (50.5%) were currently smoking, and the mean (SD) age was 67.7 (7.9) years. The mean (SD) TTS was 70.1 (38.6) days. TTS was not associated with increased risk of pathologic upstaging or positive margins. Recurrence was detected in 4158 patients (42.0%) with median (interquartile range) follow-up of 6.15 (2.51-11.51) years. Factors associated with increased risk of recurrence included younger age (hazard ratio [HR] for every 1-year increase in age, 0.992; 95% CI, 0.987-0.997; P = .003), higher Charlson Comorbidity Index score (HR for every 1-unit increase in composite score, 1.055; 95% CI, 1.037-1.073; P < .001), segmentectomy (HR vs lobectomy, 1.352; 95% CI, 1.179-1.551; P < .001) or wedge resection (HR vs lobectomy, 1.282; 95% CI, 1.179-1.394; P < .001), larger tumor size (eg, 31-40 mm vs <10 mm; HR, 1.209; 95% CI, 1.051-1.390; P = .008), higher tumor grade (eg, II vs I; HR, 1.210; 95% CI, 1.085-1.349; P < .001), lower number of lymph nodes examined (eg, ≥10 vs <10; HR, 0.866; 95% CI, 0.803-0.933; P < .001), higher pathologic stage (III vs I; HR, 1.571; 95% CI, 1.351-1.837; P < .001), and longer TTS, with increasing risk after 12 weeks. For each week of surgical delay beyond 12 weeks, the hazard for recurrence increased by 0.4% (HR, 1.004; 95% CI, 1.001-1.006; P = .002). Factors associated with delayed surgical treatment included African American race (odds ratio [OR] vs White race, 1.267; 95% CI, 1.112-1.444; P < .001), higher area deprivation index [ADI] score (OR for every 1 unit increase in ADI score, 1.005; 95% CI, 1.002-1.007; P = .002), lower hospital case load (OR for every 1-unit increase in case load, 0.998; 95% CI, 0.998-0.999; P = .001), and year of diagnosis, with less recent procedures more likely to have delay (OR for each additional year, 0.900; 95% CI, 0.884-0.915; P < .001). Patients with surgical treatment within 12 weeks of diagnosis had significantly better overall survival than those with procedures delayed more than 12 weeks (HR, 1.132; 95% CI, 1.064-1.204; P < .001). Conclusions and Relevance: Using a more precise definition for TTS, this study found that surgical procedures delayed more than 12 weeks were associated with increased risk of recurrence and worse survival. These findings suggest that patients with clinical stage I NSCLC should undergo expeditious treatment within that time frame.

Synthesis, Characterization, and Drug Delivery Application of Self-assembling Amphiphilic Cyclodextrin.

The main aim of the research was to synthesize amphiphilic cyclodextrin (AMCD) by substituting C12 alkyl chain to a ß-cyclodextrin (ßCD) in a single step and to study its self-assembly in an aqueous medium. The drug delivery application of the AMCD was also evaluated by encapsulating tamoxifen citrate as a model hydrophobic drug. AMCD was able to self-assemble in aqueous media, forming nanovesicles of size < 200 nm, capable of encapsulating tamoxifen citrate (TMX). Molecular docking and MD simulation studies revealed the interaction between TMX and AMCD which formed a stable complex. TEM and AFM studies showed that nanovesicles were perfectly spherical having a smooth surface and a theoretical AMCD bilayer thickness of ~ 7.2 nm as observed from SANS studies. XRD and DSC studies revealed that TMX was amorphized and molecularly dispersed in AMCD bilayer which was released slowly following Fickian diffusion. AMCD has excellent hemocompatibility as opposed to ßCD and no genotoxicity. IC50 of TMX against MCF-7 cell lines was significantly reduced from 11.43 to 7.96 µg/ml after encapsulation in nanovesicle because of nanovesicles being endocytosed by the MCF-7 cells. AMCD was well tolerated by IV route at a dose of > 2000 mg/kg in rats. Pharmacokinetic profile of TMX after encapsulation was improved giving 3-fold higher AUC; extended mean residence time is improving chances of nanovesicle to extravasate in tumor via EPR effect.

Hyperinflation during lung preservation and increased reperfusion injury.

BACKGROUND: Reperfusion injury after lung transplantation remains a perplexing and unpredictable problem. Most surgeons preserve the lung inflated, but the amount of inflation that should be used is not well documented. Therefore, we studied the effect of high inflation during organ preservation on lung function during reperfusion. Our hypothesis is that donor lung hyperinflation during storage contributes to early allograft dysfunction during reperfusion. METHODS: To test our hypothesis we used an isolated, blood-perfused, ventilated rabbit lung model. Group I lungs (control) underwent immediate reperfusion after harvest. Group II lungs (low-inflation, maintained at 6 mmHg airway pressure) and group III lungs (high-inflation, maintained at 20 mmHg airway pressure) were stored for 4 h in 4 degrees C Euro-Collins solution after harvest. All lungs were then reperfused with whole blood for 1 h, and measurements of arterial oxygenation (PO2, mmHg), pulmonary artery pressure (PAP, mmHg), peak inspiratory pressure (PIP, cm H2O), and wet-to-dry weight ratio (WTD) were obtained. RESULTS: Throughout the 1 h reperfusion period group III lungs had significantly lower oxygenation compared to groups I and II. In addition, throughout reperfusion, group III lungs showed significantly higher PAP and PIP compared to group II. WTD did not differ significantly between groups, however, there was a trend toward increased edema in group III. CONCLUSIONS: These results indicate that high inflation during cold storage results in acute pulmonary dysfunction. Careful monitoring of airway inflation pressure during storage, especially to prevent hyperinflation, should be maintained in the current practice for lung transplantation.

Ventricular reconstruction results in improved left ventricular function and amelioration of mitral insufficiency.

INTRODUCTION: Surgical restoration of the left ventricular wall (Dor procedure) has been advocated as a therapy for left ventricular dysfunction due to ischemic cardiomyopathy. This procedure involves placement of an endoventricular patch through a ventriculotomy. METHODS: We reviewed our series of patients that underwent the Dor procedure within the past 4 years and examined their pre and postoperative ventricular function and mitral valve function. Pre and postoperative ejection fraction and degree of mitral regurgitation were analyzed using the paired Student t-test. We hypothesized that this procedure would result in improved ventricular function and that it would also help improve mitral valve function. RESULTS: Thirty-four patients underwent this procedure, with one death. Of these, 30 patients underwent concomitant coronary artery bypass grafting and 8 patients had mitral intervention (seven had an Alfieri repair of the mitral valve, and one had mitral valve annuloplasty). The average preoperative ejection fraction among these patients was 26.8% (range 10-45%). The postoperative ejection fraction was significantly higher at 35.4% (range 25-52%) (P <.001). We noted an improvement in ejection fraction in 27 patients (82%). We also noted that 21 of 33 patients (64%) had improvement in the degree of mitral regurgitation based on echocardiography data (P <.001). CONCLUSIONS: We conclude that the Dor procedure results in improvement in the left ventricular function. Furthermore, we also note that this procedure ameliorates mitral regurgitation in a majority of these patients even in the absence of associated mitral valve procedures, probably due to reduction in the size of the ventricle and improved orientation of the papillary muscles.