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.

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.

The anticancer effect of statins in obese esophageal cancer patients undergoing esophagectomy.

BACKGROUND: In addition to treating hyperlipidemia and atherosclerosis, statins have demonstrated anti-inflammatory and antitumor activity in various cancers. We evaluate this effect in esophageal cancer patients undergoing esophagectomy. METHODS: Esophageal cancer patients undergoing esophagectomy at Roswell Park Comprehensive Cancer Center between March 2007 and December 2015 were included. Association between presurgery statin use and relevant variables with overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) was analyzed using Cox hazards. Survival analyses were independently performed for body mass index (BMI)-based subgroups. RESULTS: There was no significant association between statin use and outcomes overall. However, in subgroup analysis, there was significant association between statin use and outcomes in patients with BMI ≥ 30. Multivariable analysis in obese patients demonstrated the association of statins with improved OS (hazard ratio [HR]: 0.46, p = 0.025), DSS (HR: 0.39, p = 0.015), and RFS (HR: 0.38, p = 0.022). The only other variable significantly associated with all three outcome measures was stage. CONCLUSIONS: Statin use is associated with improved OS, DSS, and RFS of obese patients in resected esophageal cancer. BMI could be investigated as a biomarker for adjunctive statin use in future studies.

Robotic versus thoraco-laparoscopic minimally invasive Ivor Lewis esophagectomy, a matched-pair single-center cohort analysis.

Minimally invasive esophagectomy (MIE) is becoming more widespread with a documented improvement in postoperative morbidity based on level I evidence. However, there is a lack of consensus regarding the optimal MIE approach, conventional thoracoscopy/laparoscopy vs robotics as well as the ideal anastomotic technique. All patients who underwent MIE via an Ivor Lewis approach with a side-to-side stapled anastomosis were included. The thoracoscopy-laparoscopy (TL) group was compared to the robotic group with respect to perioperative outcomes using the entire cohorts and after 1:1 propensity score matching. Comparisons were made using the Mann-Whitney U and Fisher's exact tests. Between July 2013 and November 2020, 72 TL and 67 robotic Ivor Lewis MIE were performed. After comparing the two unadjusted cohorts and 51 propensity matched pairs, there was a decrease in Clavien-Dindo Grade 2 or above complications in the robotic vs TL group (59.7% vs 41.8% [P = 0.042], (62.7% vs 39.2% [P = 0.029]), respectively. In both analyses, there was a reduction in hospital length of stay (median of 8 vs 7 days, P < 0.001) and a trend toward less anastomotic leaks in the robotic group (Unadjusted: 12.5 vs 3% [P = 0.057], Propensity-matched analysis: 13.7% vs 3.9% [P = 0.16]), respectively. A clinically significant decrease in overall morbidity, cardiac complications and hospital length of stay was observed in the robotic Ivor Lewis cohort when compared with the TL group at a high volume MIE program. Side-to-side stapled thoracic anastomoses utilizing a robotic platform provides the best outcomes in this single institution experience.

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.

Approach to Resectable N1 Non-Small Cell Lung Cancer: An Analysis of the National Cancer Database.

BACKGROUND: In patients with clinical N1 disease, minimally invasive surgery (MIS) has potentially better perioperative outcome compared to open thoracotomy. Additionally, whether adjuvant or neoadjuvant chemotherapy produces the best long-term survival is still debatable. METHODS: We queried The National Cancer Database for patients with clinical N1 NSCLC who underwent surgical resection between 2010 and 2014. Comparison between patients receiving MIS and patients who underwent open thoracotomy was done using an intention-to-treat analysis. Comparison was also done among neoadjuvant, adjuvant chemotherapy, and only surgery. Proportional hazard models were used to evaluate the effects of surgical approach and timing of chemotherapy on overall survival. RESULTS: A total of 1440 and 3942 patients underwent MIS and open thoracotomy respectively. MIS achieved better surgical margins (90.0% versus 88.6%) and shorter length of stay (6.5 ± 6.5 versus 7.3 ± 6.4 d, P ≤ 0.01) compared to open thoracotomy. There were no differences in 30-day and 90-day mortality, nor readmission rates. Neoadjuvant and adjuvant chemotherapy were administered to 13.5% and 57.2% of patients respectively. There was no significant difference in the 5-year overall survival between MIS and open thoracotomy (46% versus 46% P = 0.08). There was significantly better 5-year overall survival in neoadjuvant and adjuvant chemotherapy versus only surgery, but no difference between neoadjuvant and adjuvant chemotherapy (48% versus 47% versus 44%, P < 0.01). CONCLUSIONS: In clinical N1 NSCLC, MIS does not compromise oncological quality or overall survival when compared to open thoracotomy. Overall survival improved in patients treated with chemotherapy but there is no difference when given as neoadjuvant versus adjuvant chemotherapy.

Effects of Preoperative Breathing Exercise on Postoperative Outcomes for Patients With Lung Cancer Undergoing Curative Intent Lung Resection: A Meta-analysis.

OBJECTIVE: To determine the benefits of preoperative breathing exercises on hospital length of stay (LOS), pneumonia, postoperative pulmonary complications (PPC), 6-minute walk distance (6MWD), forced expiratory volume in 1 second (FEV1), and health-related quality of life (HRQOL) in patients undergoing surgical lung cancer resection. DATA SOURCES: PubMed, EMBASE, Web of Science Core Collection, and Cochrane Central Register of Controlled Trials were comprehensively searched from inception to March 2021. STUDY SELECTION: Only studies including preoperative inspiratory muscle training (IMT) and/or breathing exercises compared with a nontraining control group were included. The meta-analysis was done using Cochrane software for multiple variables including LOS, pneumonia, PPC, 6MWD, FEV1, mortality, and HRQOL. DATA EXTRACTION: Two authors extracted the data of the selected studies. The primary outcomes were LOS and PPC. DATA SYNTHESIS: A total of 10 studies were included in this meta-analysis, 8 of which had both IMT and aerobic exercise. Pooled data for patients who performed preoperative breathing exercises, compared with controls, demonstrated a decrease in LOS with a pooled mean difference of -3.44 days (95% confidence interval [CI], -4.14 to -2.75; P<.01). Subgroup analysis also demonstrated that LOS was further reduced when breathing exercises were combined with aerobic exercise (χ2, 4.85; P=.03). Preoperative breathing exercises reduce pneumonia and PPCs with an odds ratio of 0.37 (95% CI, 0.18-0.75; P<.01) and 0.37 (95% CI, 0.21-0.65; P<.01), respectively. An increase in 6MWD of 20.2 meters was noted in those performing breathing exercises (95% CI, 9.12-31.21; P<.01). No significant differences were noted in FEV1, mortality, or HRQOL. CONCLUSIONS: Preoperative breathing exercises reduced LOS, PPC, and pneumonia and potentially improved 6MWD in patients undergoing surgical lung cancer resection. Breathing exercises in combination with aerobic exercise yielded greater reductions in LOS. Randomized controlled trials are needed to test the feasibility of introducing a preoperative breathing exercise program in this patient population.

Discordance of COVID-19 guidelines for patients with cancer: A systematic review.

This review was aimed to systematically evaluate the available literature on the impact of COVID-19 on cancer care and to critically analyze the diagnostic and therapeutic strategies suggested by various healthcare providers, societies, and institutions. Majority guidelines for various types of cancers favored a delay in treatment or a nonsurgical approach wherever feasible. These guidelines are based on a low level of evidence and have significant discordance for the role and timing of surgery, especially in early tumors.

An Optical Surface Applicator for Intraoperative Photodynamic Therapy.

BACKGROUND AND OBJECTIVES: Intraoperative photodynamic therapy (IO-PDT) is typically administered by a handheld light source. This can result in uncontrolled distribution of light irradiance that impacts tissue and tumor response to photodynamic therapy. The objective of this work was to characterize a novel optical surface applicator (OSA) designed to administer controlled light irradiance in IO-PDT. STUDY DESIGN/MATERIALS AND METHODS: An OSA was constructed from a flexible silicone mesh applicator with multiple cylindrically diffusing optical fibers (CDF) placed into channels of the silicone. Light irradiance distribution, at 665 nm, was evaluated on the OSA surface and after passage through solid tissue-mimicking optical phantoms by measurements from a multi-channel dosimetry system. As a proof of concept, the light administration of the OSA was tested in a pilot study by conducting a feasibility and performance test with 665-nm laser light to activate 2-(1'-hexyloxyethyl) pyropheophorbide-a (HPPH) in the thoracic cavity of adult swine. RESULTS: At the OSA surface, the irradiance distribution was non-uniform, ranging from 128 to 346 mW/cm2 . However, in the tissue-mimicking phantoms, beam uniformity improved markedly, with irradiance ranges of 39-153, 33-87, and 12-28 mW/cm2 measured at phantom thicknesses of 3, 5, and 10 mm, respectively. The OSA safely delivered the prescribed light dose to the thoracic cavities of four swine. CONCLUSIONS: The OSA can provide predictable light irradiances for administering a well-defined and potentially effective therapeutic light in IO-PDT. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Sublethal Radiation Affects Antigen Processing and Presentation Genes to Enhance Immunogenicity of Cancer Cells.

While immunotherapy in cancer is designed to stimulate effector T cell response, tumor-associated antigens have to be presented on malignant cells at a sufficient level for recognition of cancer by T cells. Recent studies suggest that radiotherapy enhances the anti-cancer immune response and also improves the efficacy of immunotherapy. To understand the molecular basis of such observations, we examined the effect of ionizing X-rays on tumor antigens and their presentation in a set of nine human cell lines representing cancers of the esophagus, lung, and head and neck. A single dose of 7.5 or 15 Gy radiation enhanced the New York esophageal squamous cell carcinoma 1 (NY-ESO-1) tumor-antigen-mediated recognition of cancer cells by NY-ESO-1-specific CD8+ T cells. Irradiation led to significant enlargement of live cells after four days, and microscopy and flow cytometry revealed multinucleation and polyploidy in the cells because of dysregulated mitosis, which was also revealed in RNA-sequencing-based transcriptome profiles of cells. Transcriptome analyses also showed that while radiation had no universal effect on genes encoding tumor antigens, it upregulated the expression of numerous genes involved in antigen processing and presentation pathways in all cell lines. This effect may explain the immunostimulatory role of cancer radiotherapy.

AIDS-Related Kaposi Sarcoma, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology.

As treatment of HIV has improved, people living with HIV (PLWH) have experienced a decreased risk of AIDS and AIDS-defining cancers (non-Hodgkin's lymphoma, Kaposi sarcoma, and cervical cancer), but the risk of Kaposi sarcoma in PLWH is still elevated about 500-fold compared with the general population in the United States. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for AIDS-Related Kaposi Sarcoma provide diagnosis, treatment, and surveillance recommendations for PLWH who develop limited cutaneous Kaposi sarcoma and for those with advanced cutaneous, oral, visceral, or nodal disease.

Radiation With Neoadjuvant Chemotherapy Does Not Improve Outcomes in Esophageal Squamous Cell Cancer.

BACKGROUND: Neoadjuvant treatment improves survival for patients undergoing esophagectomy for esophageal cancer. Recent evidence suggests that neoadjuvant chemoradiation offers no advantage over chemotherapy alone before surgical resection for adenocarcinoma histology. We sought to examine if this applies to patients with squamous cell histology. MATERIALS AND METHODS: The National Cancer Database was queried for patients who underwent treatment for squamous cell carcinoma of the esophagus from 2004 to 2012. Patients who underwent neoadjuvant chemotherapy before esophagectomy were compared with those undergoing chemotherapy and radiation before surgical resection. Associations between potential covariates and treatment were analyzed using the Pearson chi-square test for categorical variables and Wilcoxon rank sum test for continuous variables. Univariate and multivariate proportional hazards modeling results were used to assess the effect of treatment on overall survival. Relative prognosis was summarized using estimates and 95% confidence limits for the hazard ratio. Unadjusted differences in overall survival and disease-specific survival between the treatment are shown using Kaplan-Meier methods. RESULTS: A total of 902 patients underwent neoadjuvant therapy before surgical resection during the study period, with 827 receiving chemotherapy and radiation, and 75 receiving chemotherapy alone preoperatively. The 30- and 90-d mortality for patients undergoing neoadjuvant chemotherapy and radiation followed by surgery were 5.4% and 10.4% compared to 5.5% and 11.1% for patients who received chemotherapy alone preoperatively (P = 0.963 and P = 0.856), respectively. Median overall survival for patients receiving chemotherapy and radiation was 36.0 mo versus 40.8 mo for chemotherapy alone. The 5-y survival was 39% for the chemotherapy and radiation group and 43% for the chemotherapy group (logrank P = 0.7212). CONCLUSIONS: For patients undergoing neoadjuvant treatment before planned surgical resection of squamous cell carcinoma of the esophagus, the addition of radiation to neoadjuvant chemotherapy did not improve long-term survival and did not appear to impact short-term outcomes postoperatively. Further study with a randomized phase III trial is needed.

Concomitant Mediastinoscopy Increases the Risk of Postoperative Pneumonia After Pulmonary Lobectomy.

BACKGROUND: Mediastinoscopy is considered the gold standard for preresectional staging of lung cancer. We sought to examine the effect of concomitant mediastinoscopy on postoperative pneumonia (POP) in patients undergoing lobectomy. METHODS: All patients in our institutional database (2008-2015) undergoing lobectomy who did not receive neoadjuvant therapy were included in our study. The relationship between mediastinoscopy and POP was examined using univariate (Chi square) and multivariate analyses (binary logistic regression). In order to validate our institutional findings, lobectomy data in the National Surgical Quality Improvement Program (NSQIP) from 2005 to 2014 were analyzed for these associations. RESULTS: Of 810 patients who underwent a lobectomy at our institution, 741 (91.5%) surgeries were performed by video-assisted thoracic surgery (VATS) and 487 (60.1%) patients underwent concomitant mediastinoscopy. Univariate analysis demonstrated an association between mediastinoscopy and POP in patients undergoing VATS [odds ratio (OR) 1.80; p = 0.003], but not open lobectomy. Multivariate analysis retained mediastinoscopy as a variable, although the relationship showed only a trend (OR 1.64; p = 0.1). In the NSQIP cohort (N = 12,562), concomitant mediastinoscopy was performed in 9.0% of patients, with 44.5% of all the lobectomies performed by VATS. Mediastinoscopy was associated with POP in patients having both open (OR1.69; p < 0.001) and VATS lobectomy (OR 1.72; p = 0.002). This effect remained in multivariate analysis in both the open and VATS lobectomy groups (OR 1.46, p = 0.003; and 1.53, p = 0.02, respectively). CONCLUSIONS: Mediastinoscopy may be associated with an increased risk of POP after pulmonary lobectomy. This observation should be examined in other datasets as it potentially impacts preresectional staging algorithms for patients with lung cancer.

A pilot study of stereotactic body radiation therapy (SBRT) after surgery for stage III non-small cell lung cancer.

BACKGROUND: Standard therapy for stage III non-small cell lung cancer with chemotherapy and conventional radiation has suboptimal outcomes. We hypothesized that a combination of surgery followed by stereotactic body radiation therapy (SBRT) would be a safe alternative. METHODS: Patients with stage IIIA (multistation N2) or IIIB non-small cell lung cancer were enrolled from March 2013 to December 2015. The protocol included transcervical extended mediastinal lymphadenectomy (TEMLA) followed by surgical resection, 10 Gy SBRT directed to the involved mediastinum/hilar stations and/or positive surgical margins, and adjuvant systemic therapy. Patients not suitable for anatomic lung resection were treated with 30 Gy to the primary tumor. The primary efficacy end-point was the proportion of patients with grade 3 or higher adverse events (AE) or toxicities. RESULTS: Of 10 patients, 7 patients underwent neoadjuvant chemotherapy. All patients had TEMLA. Nine of 10 patients underwent surgical resection. The remaining patient had an unresectable tumor and received 30 Gy SBRT to the primary lesion. All patients had post-operative SBRT. Median follow-up was 18 months. There were no perioperative mortalities. Six patients had any grade 3 AEs with no grade 4-5 AEs. Of these, 4 were not attributable to radiation. Pulmonary-related grade 3 AEs were experienced by 2 patients. There were no failures within the 10 Gy volume. Overall survival and progression-free survival rates at 2 years were 68% (90% CI 36-86) and 40% (90% CI 16-63), respectively. CONCLUSIONS: In carefully selected patients with locally advanced non-small cell lung cancer, combining surgery with SBRT was well tolerated with no local failure. TRIAL REGISTRATION: ClinicalTrials.gov identifying number NCT01781741 . Registered February 1, 2013.

Esophago-pulmonary fistula manifesting as recurrent pneumonias and migrating mediastinal calcifications.

A 43-year old man presented with recurrent pneumonias, episodes of hemoptysis and an enlarging right lower lobe mass. A clear diagnosis was not previously established in spite of multiple radiological evaluations and biopsies. Meticulous review of his CT imaging showed that he had subcarinal calcification on his prior CT scans, which had decreased in size and now multiple new small areas of calcifications were seen in the right lower lobe lesion. An esophago-pulmonary fistula due to migration of mediastinal calcifications was suspected which was identified on careful review of the CT chest and confirmed by esophagogastroduodenoscopy. Patient had surgical repair with complete recovery.

Outcomes of endoscopic resection for high-grade dysplasia and esophageal cancer.

BACKGROUND: Endoscopic resection (ER) is an important advance in the management of esophageal tumors. It has been used successfully for superficial esophageal cancer and high-grade dysplasia (HGD) arising out of Barrett epithelium. METHODS: From a single institution within the Department of Surgery, patients who underwent ER for esophageal tumors between December 2001 and January 2012 were evaluated. Demographic, clinical, and pathologic variables were collected and reviewed. RESULTS: We identified 81 patients who underwent ER for esophageal lesions. Median patient age was 69 years, and the median follow-up was 3.25 years. In patients with HGD, at the time of last endoscopy, the complete eradication rate of HGD was 84 % and cancer-specific survival was 100 %. During surveillance, one patient developed an invasive carcinoma that required endoscopic therapy. Patients with T1a and negative deep margins on ER had a recurrence-free and cancer-specific survival of 100 %. There were seven patients with T1b and negative margins on ER. Three patients underwent esophagectomy; final pathology revealed no residual malignancy or lymph node metastasis. Two patients had definitive chemoradiation, and two patients were observed. To date, there has been no cancer recurrence. In all patients who underwent ER, there was one episode of bleeding that required endoscopic treatment and admission for observation. CONCLUSIONS: ER can be performed safely and can adequately stage and often treat patients with HGD and superficial cancers. Patients with HGD and T1a disease with negative margins are cured with ER alone. Observation and surveillance may be an option for select patients with low-risk, early submucosal disease (T1b) and negative margins.

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.