Wedge resection, segmentectomy, and lobectomy: oncologic outcomes based on extent of surgical resection for ≤2 cm stage IA non-small cell lung cancer.

Background: Long-standing controversy has existed over whether sublobar resection is an adequate oncological procedure for clinical stage IA non-small cell lung cancer (NSCLC) ≤2 cm, despite the recent randomized trial reports of Japanese Clinical Oncology Group (JCOG) 0802 and Cancer and Leukemia Group B (CALGB) 140503 demonstrating non-inferior outcomes with sublobar resection compared to lobectomy. As practice patterns shift, we sought to compare oncologic outcomes in patients with these early-stage tumors after wedge resection, segmentectomy, or lobectomy in a contemporary, real-world, cohort. Methods: A retrospective review of a prospectively maintained database from a single institution was conducted from 2011 to 2020 to identify all patients with clinically staged IA1 or IA2 NSCLC (tumors ≤2 cm with no nodal involvement). The primary outcomes of interest were overall survival (OS) and disease-free survival (DFS), with secondary outcomes of lung cancer-specific survival (LCSS), recurrence patterns, and perioperative morbidity and mortality. Results: A total of 480 patients were identified; 93 (19.4%) patients underwent wedge resection, 90 (18.7%) received segmentectomy, and 297 (61.9%) underwent lobectomy. Patients who underwent wedge resection had worse Eastern Cooperative Oncology Group (ECOG) performance status (23.7% ECOG 1 or 2 vs. 5.6% among segmentectomy and 5.4% among lobectomy, P<0.05). Both wedge resection and segmentectomy patients had lower preoperative mean percentage of predicted forced expiratory volume in one second (%FEV1) compared to the lobectomy group (81.8% and 82.6% vs. 89.6%, P=0.002), a higher proportion of patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD), and a higher Charlson Comorbidity Index. There were no statistically significant differences in 5-year OS, DFS, or LCSS between groups: 90%, 61%, 78% for wedge resections compared with 85%, 75%, 86% for segmentectomy, and 87%, 77%, 87% for lobectomy, respectively. Recurrence was observed in 17 patients who underwent wedge resection (18.3%, 8 local, 9 distant), 12 patients who received segmentectomy (13.4%, 6 local, 6 distant), and 38 patients who underwent lobectomy (12.8%, 11 local, 27 distant), which was not significantly different (P=0.36). Conclusions: Patients with inferior performance status or lower baseline pulmonary function are more likely to receive wedge resection for clinical stage IA NSCLC ≤2 cm in size. For these small tumors, lobectomy, segmentectomy, and wedge resection provide comparable oncologic outcomes.

Polypyrrole-decorated bentonite magnetic nanocomposite: A green approach for adsorption of anionic methyl orange and cationic crystal violet dyes from contaminated water.

In the presented study, a novel polypyrrole-decorated bentonite magnetic nanocomposite (MBnPPy) was synthesized for efficient removal of both anionic methyl orange (MO) and cationic crystal violet (CV) dyes from contaminated water. The synthesis of this novel adsorbent involved a two-step process: the magnetization of bentonite followed by its modification through in-situ chemical polymerization. The adsorbent was characterized by SEM/EDX, TEM/SAED, BET, TGA/DTA-DTG, FTIR, VSM, and XRD studies. The investigation of the adsorption properties of MBnPPy was focused on optimizing various parameters, such as dye concentration, medium pH, dosage, contact time, and temperature. The optimal conditions were established as follows: dye concentration of Co (CV/MO) at 100 mg/L, MBnPPy dosage at 2.0 g/L, equilibrium time set at 105 min for MO and 120 min for CV, medium pH adjusted to 5.0 for MO dye and 8.0 for CV dye, and a constant temperature of 303.15 K. The different kinetic and isotherm models were applied to fit the experimental results, and it was observed that the Pseudo-2nd-order kinetics and Langmuir adsorption isotherm were the best-fitted models. The maximal monolayer adsorption capacities of the adsorbent were found to be 78.74 mg/g and 98.04 mg/g (at 303.15 K) for CV and MO, respectively. The adsorption process for both dyes was exothermic and spontaneous. Furthermore, a reasonably good regeneration ability of MBnPPy (>83.45%/82.65% for CV/MO) was noted for up to 5 adsorption-desorption cycles with little degradation. The advantages of facile synthesis, cost-effectiveness, non-toxicity, strong adsorption capabilities for both anionic and cationic dyes, and easy separability with an external magnetic field make MBnPPy novel.

Neoadjuvant durvalumab plus radiation versus durvalumab alone in stages I-III non-small cell lung cancer: survival outcomes and molecular correlates of a randomized phase II trial.

We previously reported the results of a randomized phase II trial (NCT02904954) in patients with early-stage non-small cell lung cancer (NSCLC) who were treated with either two preoperative cycles of the anti-PD-L1 antibody durvalumab alone or combined with immunomodulatory doses of stereotactic radiation (DRT). The trial met its primary endpoint of major pathological response, which was significantly higher following DRT with no new safety signals. Here, we report on the prespecified secondary endpoint of disease-free survival (DFS) regardless of treatment assignment and the prespecified exploratory analysis of DFS in each arm of the trial. DFS at 2 and 3 years across patients in both arms of the trial were 73% (95% CI: 62.1-84.5) and 65% (95% CI: 52.5-76.9) respectively. For the exploratory endpoint of DFS in each arm of the trial, three-year DFS was 63% (95% CI: 46.0-80.4) in the durvalumab monotherapy arm compared to 67% (95% CI: 49.6-83.4) in the dual therapy arm. In addition, we report post hoc exploratory analysis of progression-free survival as well as molecular correlates of response and recurrence through high-plex immunophenotyping of sequentially collected peripheral blood and gene expression profiles from resected tumors in both treatment arms. Together, our results contribute to the evolving landscape of neoadjuvant treatment regimens for NSCLC and identify easily measurable potential biomarkers of response and recurrence.

Should sampling of three N2 stations be a quality metric for curative resection of stage I lung cancer?

OBJECTIVE: In 2022, the American College of Surgeons Commission on Cancer issued standard 5.8 quality metric for curative lung cancer resections requiring nodal resection from 3 N2 stations. In this report, we compare oncologic outcomes after resection of 3 N2 stations versus 2 N2 stations in stage I non-small cell lung cancer. METHODS: A retrospective review from a single institution database was conducted from 2011 to 2020 to identify patients with clinical stage I non-small cell lung cancer. Patients with a history of lung cancer, carcinoid tumors, and ground-glass lesions less than 50% solid component were excluded. The primary outcome was overall survival. Secondary outcomes included disease-free survival, recurrence patterns, and nodal upstaging. RESULTS: A total of 581 patients were identified and divided into 2 groups based on the number of N2 stations examined: Group A had 2 N2 stations examined (364 patients), and group B had 3 or more N2 stations examined (217 patients). Baseline demographic and clinical characteristics were similar between groups. In group A, N1 and N2 positive nodal stations were present in 8.2% (30/364) and 5.2% (19/364) of patients versus 7.4% (16/217) and 5.5% (12/217), respectively, in group B. Five-year overall survival and disease-free survival were 89% and 74% in group A versus 88% and 78% in group B, respectively. Recurrence occurred in 56 patients (15.4%) in group A (6.6% local and 8.8% distant) and 29 patients (13.4%) in group B (5.1% local and 8.3% distant; P = .73). CONCLUSIONS: There was no significant difference in oncological outcomes in stage I non-small cell lung cancer resections that included 2 N2 stations compared with at least 3 N2 stations examined.

Surgical resection after neoadjuvant durvalumab and radiation is feasible and safe in non-small cell lung cancer: Results from a randomized trial.

OBJECTIVE: Several trials have recently reported the safety of pulmonary resection after neoadjuvant immunotherapy with encouraging major pathological response rates. We report the detailed adverse events profile from a recently conducted randomized phase II trial in patients with resectable non-small cell lung cancer treated with neoadjuvant durvalumab alone or with sub-ablative radiation. METHODS: We conducted a randomized phase II trial in patients with non-small cell lung cancer clinical stages I to IIIA who were randomly assigned to receive neoadjuvant durvalumab alone or with sub-ablative radiation (8Gyx3). Secondary end points included the safety of 2 cycles of preoperative durvalumab with and without radiation followed by pulmonary resection. Postoperative adverse events within 30 days were recorded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0). RESULTS: Sixty patients were enrolled and randomly assigned, with planned resection performed in 26 patients in each arm. Baseline demographics and clinical variables were balanced between groups. The median operative time was similar between arms: 128 minutes (97-201) versus 146 minutes (109-214) (P = .314). There was no 30- or 90-day mortality. Grade 3/4 adverse events occurred in 10 of 26 patients (38%) after monotherapy and in 10 of 26 patients (38%) after dual therapy. Anemia requiring transfusion and hypotension were the 2 most common adverse events. The median length of stay was similar between arms (5 days vs 4 days, P = .172). CONCLUSIONS: In this randomized trial, the addition of sub-ablative focal radiation to durvalumab in the neoadjuvant setting was not associated with increased mortality or morbidity compared with neoadjuvant durvalumab alone.

Ten-Year Survival and Recurrence Patterns After Three-Field Lymph Node Dissection for Squamous Cell and Adenocarcinoma of the Esophagus.

OBJECTIVE: The aim was to determine the prevalence of metastases to the cervical and recurrent laryngeal cervicothoracic (CT) nodes as well as survival and recurrence patterns after esophagectomy with three-field lymph node dissection (TFD) in patients with predominately adenocarcinoma (AC) of the esophagus. BACKGROUND: Although esophagectomy with TFD is commonly practiced in Japan and Southeast Asia for squamous cell cancer (SCC) of the esophagus, there are only a handful of reports about its' utilization and survival benefit in North American patients. METHODS: This is a retrospective case series of patients who had an esophagectomy with TFD. The primary outcomes of interest were the prevalence of nodal metastases to the CT nodes as well as overall survival (OS) and disease-free survival. Secondary outcomes included time to recurrence, recurrence patterns, operative morbidity as well as 30 and 90-day mortality. RESULTS: Two hundred forty-two patients with esophageal cancer (AC: 67%) underwent esophagectomy with TFD. Metastases to the CT nodes were present in 56 patients (23%: AC 20% and SCC 30%). Positive CT nodes were present in 14% of pT1/T2 tumors and 30% of pT3 tumors. For the 56 patients with CT positive nodes, 5-year OS was 25% (AC:16%; SCC:39%). Fifteen of 56 (26.7%) patients with metastases to the CT nodes were alive and disease-free at a minimum of 5 years postoperatively. Ten-year OS was 43% for all patients with SCC and 28% for patients with AC. CONCLUSIONS: Metastases to the CT nodes are common in both SCC and AC of the esophagus and may be present in at least 14% of early lesions. Five-year survival is encouraging particularly for patients with esophageal SCC cancer.

Safety of lung cancer surgery during COVID-19 in a pandemic epicenter.

BACKGROUND: The influence of SARS-CoV-2 on surgery for non-small cell lung cancer needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. OBJECTIVE: This study reports on the 90-day rate of infection as well as the morbidity and mortality of lung surgery for cancer in a tertiary care hospital located in a pandemic epicenter. METHODS: We conducted a retrospective review of a prospective database to identify consecutive patients who underwent lung cancer resection before (January 1, 2020-March 10, 2020, group 1; 57 patients) and during the COVID-19 pandemic (March 11, 2020-June 10, 2020, group 2; 41 patients). The primary end point was the occurrence of SARS-CoV-2 infection during the first 90-days after surgery. The secondary outcome measure was 90-day perioperative morbidity and mortality. RESULTS: Patient characteristics were not significantly different between the groups. Ninety-day COVID-19 infection rates was 7.3% (3 out of 41) for patients undergoing an operation during the pandemic and 3.5% (2 out of 57) in patients operated on immediately before the pandemic. All patients tested positive 10 to 62 days after the index surgical procedure following hospital discharge. Four COVID-19-positive patients were symptomatic and 4 out of 5 patients required hospitalization, were men, previous or current smokers with hyperlipidemia, and underwent a sublobar resection. Univariate analysis did not identify any differences in postoperative complications before or during the COVID-19 pandemic. Ninety-day mortality was 5% (2 out of 41) for lung cancer surgery performed during the pandemic, with all deaths occurring due to COVID-19, compared with 0% (0 out of 57) mortality in patients who underwent an operation before the pandemic. CONCLUSIONS: During the COVID-19 pandemic, COVID-19 infections occurred in 7.3% of patients who underwent surgery for non-small cell lung cancer. In this series all infections occurred after hospital discharge. Our results suggest that COVID-19 infections occurring within 90 days of surgery portend a 40% mortality, warranting close postoperative surveillance.

Expression of the mono-ADP-ribosyltransferase ART1 by tumor cells mediates immune resistance in non-small cell lung cancer.

Most patients with non-small cell lung cancer (NSCLC) do not achieve durable clinical responses from immune checkpoint inhibitors, suggesting the existence of additional resistance mechanisms. Nicotinamide adenine dinucleotide (NAD)-induced cell death (NICD) of P2X7 receptor (P2X7R)-expressing T cells regulates immune homeostasis in inflamed tissues. This process is mediated by mono-adenosine 5'-diphosphate (ADP)-ribosyltransferases (ARTs). We found an association between membranous expression of ART1 on tumor cells and reduced CD8 T cell infiltration. Specifically, we observed a reduction in the P2X7R+ CD8 T cell subset in human lung adenocarcinomas. In vitro, P2X7R+ CD8 T cells were susceptible to ART1-mediated ADP-ribosylation and NICD, which was exacerbated upon blockade of the NAD+-degrading ADP-ribosyl cyclase CD38. Last, in murine NSCLC and melanoma models, we demonstrate that genetic and antibody-mediated ART1 inhibition slowed tumor growth in a CD8 T cell-dependent manner. This was associated with increased infiltration of activated P2X7R+CD8 T cells into tumors. In conclusion, we describe ART1-mediated NICD as a mechanism of immune resistance in NSCLC and provide preclinical evidence that antibody-mediated targeting of ART1 can improve tumor control, supporting pursuit of this approach in clinical studies.

Extent of Resection Influences Survival in Early-Stage Lung Cancer With Occult Nodal Disease.

BACKGROUND: Minimal literature exists evaluating the impact of the extent of resection on survival in patients with small, early-stage non-small cell lung cancer (NSCLC) found to have occult nodal disease. We hypothesized that sublobar resection has comparable overall survival to patients undergoing lobectomy for clinical stage IA NSCLC that harbors occult nodal disease. METHODS: The National Cancer Database was reviewed for identification of patients with clinical stage IA NSCLC who underwent wedge resection, segmentectomy, or lobectomy and were found to have occult nodal disease. Overall survival was compared between groups, and a multivariate Cox regression model identified factors associated with worse survival. RESULTS: Occult nodal disease occurred in 6.1% of all patients with clinical stage IA disease undergoing resection. Patients undergoing wedge resection and segmentectomy found to have occult nodal disease were older (67.6 ± 9.6 years of age vs 66.1 ± 9.3 years of age vs 65.6 ± 9.5 years of age; P = .004) and had more advanced pathologic stage (pStage III: 68.7% vs 50.5% vs 41.5%; P < .001) than those receiving lobectomy. There was no difference in the median overall survival between segmentectomy and lobectomy (68.5 months vs 57.6 months; P = .200). However, wedge resection was independently associated with worse overall survival when controlling for other preoperative variables (hazard ratio, 1.23; 95% confidence interval, 1.01-1.51; P = .042). CONCLUSIONS: Review of the National Cancer Database suggests that there is no improvement in overall survival in patients undergoing lobectomy vs segmentectomy in carefully selected patients with clinical stage IA NSCLC harboring occult nodal disease. However, those undergoing wedge resection may have worse overall survival than those undergoing both lobectomy and segmentectomy.

Outcomes After Surgical Resection of Early-stage Lung Adenocarcinomas With Epidermal Growth Factor Receptor Mutations.

BACKGROUND: Routine mutation profiling for resected lung cancers is not widespread despite an increasing array of targeted therapies. We report the incidence of epidermal growth factor receptor mutations (EGFRmu+) in resected lung adenocarcinomas and their outcomes at a large North American cancer center to characterize this population now eligible for targeted adjuvant therapy. METHODS: Among 1036 pulmonary resections performed between 2015 and 2019, 647 patients (62%) had adenocarcinomas that underwent molecular profiling by next-generation sequencing. Clinical and pathologic characteristics, along with survival, were analyzed. RESULTS: EGFRmu+ were identified in 238 patients (37%). Patients with EGFRmu+ were more likely to be Asian than those with EGFR wild-type (79/238 [33%] vs 37/409 [9%], respectively; P < .001) and more likely to be never-smokers (115/238 [48%] vs 73/409 [18%], P < .001). However, most patients with EGFRmu+ in our cohort were White (45%) and had a history of smoking (52%). A statistically nonsignificant trend was observed toward improved 3-year overall survival for pathologic stage IB to III cancers with EGFRmu+ (91% vs 77%, P = .09). Patients with pathologic stage IB lung cancers with EGFRmu+ had a 97% rate of 3-year disease-free survival, with only 1 recurrence in the first 3 years of follow-up. EGFR mutation subtype was not associated with survival differences. CONCLUSIONS: Although Asians and never-smokers comprised a disproportionately large group of patients with lung adenocarcinomas with EGFRmu+, most EGFR mutations within our cohort were found in patients who were White or with a smoking history, supporting a routine rather than selective approach to mutation profiling. Patients with surgically resected stage IA and IB lung adenocarcinomas enjoy excellent survival regardless of their mutational status.

CUL4high Lung Adenocarcinomas Are Dependent on the CUL4-p21 Ubiquitin Signaling for Proliferation and Survival.

Cullin (CUL) 4A and 4B ubiquitin ligases are often highly accumulated in human malignant neoplasms and are believed to possess oncogenic properties. However, the underlying mechanisms by which CUL4A and CUL4B promote pulmonary tumorigenesis remain largely elusive. This study reports that CUL4A and CUL4B are highly expressed in patients with non-small cell lung cancer (NSCLC), and their high expression is associated with disease progression, chemotherapy resistance, and poor survival in adenocarcinomas. Depletion of CUL4A (CUL4Ak/d) or CUL4B (CUL4Bk/d) leads to cell cycle arrest at G1 and loss of proliferation and viability of NSCLC cells in culture and in a lung cancer xenograft model, suggesting that CUL4A and 4B are oncoproteins required for tumor maintenance of certain NSCLCs. Mechanistically, increased accumulation of the cell cycle-dependent kinase inhibitor p21/Cip1/WAF1 was observed in lung cancer cells on CUL4 silencing. Knockdown of p21 rescued the G1 arrest of CUL4Ak/d or CUL4Bk/d NSCLC cells, and allowed proliferation to resume. These findings reveal that p21 is the primary downstream effector of lung adenocarcinoma dependence on CUL4, highlight the notion that not all substrates respond equally to abrogation of the CUL4 ubiquitin ligase in NSCLCs, and imply that CUL4Ahigh/CUL4Bhigh may serve as a prognostic marker and therapeutic target for patients with NSCLC.

Facile synthesis of polypyrrole decorated chitosan-based magsorbent: Characterizations, performance, and applications in removing cationic and anionic dyes from aqueous medium.

The adsorption characteristic of polypyrrole decorated chitosan-based magsorbent (MChs/Ppy) for the elimination of cationic crystal violet and anionic methyl orange dye from wastewater were explored. The characteristics of MChs/Ppy were studied by TGA, SEM/EDAX, TEM, BET, FTIR, VSM, and XRD analyses. The performance of MChs/Ppy towards the adsorption of CV and MO was investigated by the batch method. Removal performance was obtained to be 88.11 and 92.89% for CV and MO at the optimum conditions. The adsorption of CV was well described by pseudo 2nd order, while that of MO was best followed by the pseudo 1st order kinetics. The adsorption equilibrium data for both the dyes were fitted well with Langmuir adsorption isotherm with the maximum monolayer sorption capacity of 62.89 and 89.29 mg/g for CV and MO, respectively. The negative values of ΔH and ΔF accompanying with the removal of both dyes specified the adsorption process to be exothermic and spontaneous. Regeneration study showed that MChs/Ppy could be reused efficaciously up to three consecutive ad-/de-sorption cycles. The combined benefits of facile synthesis, non-toxicity, and good adsorption potential towards cationic and anionic dyes along with easy magnetic separability make MChs/Ppy as a novel adsorbent.

Treatment of cT3N1M0/IIIA non-small cell lung cancer and the risk of underuse of surgery.

OBJECTIVE: Surgery may be underused for stage IIIA non-small cell lung cancer. Although an argument can be made for definitive chemoradiation for N2/3 mediastinal nodal disease, the role of a nonsurgical strategy is less clear in patients with cT3N1M0 stage IIIA given a lack of randomized data. We sought to determine the outcomes of patients with cT3N1M0 by treatment type from the National Cancer Database. METHODS: The National Cancer Database (2004-2014) was queried for patients with cT3N1M0 non-small cell lung cancer, known treatment modalities, and sequence. Comparisons between groups were performed using Mann-Whitney and chi-square tests. Cox regression was performed to identify predictors of overall survival. Propensity score matching analysis was performed to compare overall survival in surgery versus definitive chemoradiation. RESULTS: We identified 1937 patients undergoing surgery (1518 up-front and 419 after neoadjuvant treatment) and 1844 patients undergoing definitive chemoradiation. Among patients undergoing surgery without prior treatment, 19% were overstaged and were found to have pN0, whereas 9.6% had pN2/3. Median overall survival was 33.1 months in the surgery group (± adjuvant/neoadjuvant) versus 18 months in definitive chemoradiation. To compare outcomes in balanced groups, we propensity matched 1081 pairs of patients. Median overall survival was 31.1 months in the surgery group compared with 19.1 months in the definitive chemoradiation group (P < .001). By multivariable analysis, surgery (hazard ratio, 0.65; confidence interval, 0.59-0.73), female sex (hazard ratio, 0.88; confidence interval, 0.79-0.98), age (hazard ratio, 1.02; confidence interval, 1.01-1.03), squamous histology (hazard ratio, 1.22; confidence interval, 1.07-1.38), and Charlson score of 2 (hazard ratio, 1.31; confidence interval, 1.11-1.54) were predictors of survival. CONCLUSIONS: In the National Cancer Database, approximately half of patients with clinical T3N1M0 were treated with definitive chemoradiation rather than surgery. This practice should be avoided in operable patients, because surgical resection is associated with better survival.

Staple Line Thickening After Sublobar Resection: Reaction or Recurrence?

BACKGROUND: Stapling across lung parenchyma may lead to tissue granulation, which could be confused radiographically with recurrence. We sought to define the time course and radiographic characteristics of such thickening and to determine their association with recurrence. METHODS: Patients who underwent limited resection for non-small cell lung cancer were included. Surveillance computed tomography scans were reviewed to characterize the morphology and size of staple line granulation tissue. Radiological and clinical findings were analyzed and univariate predictors of recurrence were examined. RESULTS: We characterized 78 patients for tissue granulation a total of 314 times in serial scans. On initial postoperative scans, 3.8% (n = 3) of staple lines showed no thickening and 17.9% (n = 14) showed thickening less than 2 mm, whereas 78.2% (n = 61) showed thickening 2 mm or greater. Of the 75 staple lines with thickening, soft tissue was characterized as linear in 32.0% (n = 24), focal along the pleura, hilum, or parenchyma in 24.0% (n = 18), and nodular in 44.0% (n = 33). Subsequent scans revealed that 25.3% of these areas (n = 19) did not change in shape or size over time, 58.7% (n = 44) showed regressive changes, and 16.0% (n = 12) showed progressive changes, the thickening of which in all 12 of these patients showed an increase in the largest dimension by 2 mm or greater. Among the 78 patients, 7.7% (n = 6) had biopsy-proven recurrence along the staple line. An increase in the largest dimension by 2 mm or greater (83.3% versus 9.7%; P = .001) and radiologic concern for malignancy (66.7% versus 11.1%; P = .001) predicted staple line recurrence. CONCLUSIONS: Staple line thickening is a frequent occurrence after pulmonary limited resection, but rarely indicative of recurrence. The characteristics and initial size of granulation tissue do not predict recurrence. Increases in tissue 2 mm or greater at the staple line over time predict local recurrence, which typically occurs after a prolonged time interval.

Role of wedge resection in bronchial carcinoid (BC) tumors: SEER database analysis.

BACKGROUND: There is a paucity of data regarding the role of wedge resection (WR) in the management of bronchial carcinoid (BC) tumors. In this study, we queried the Surveillance, Epidemiology, and End Results (SEER) database to compare the oncologic outcomes of patients with BC tumors treated with WR or anatomic resection. METHODS: The SEER database was retrospectively reviewed for patients with BC treated with surgical resection between 1973-2013. Patients who underwent WR were compared to those who underwent lobectomy or segmentectomy (Lob/Seg). Patients with multiple primaries and those who underwent pneumonectomy or have an unspecified surgical procedure were excluded. Differences in demographics and clinicopathological data were compared using Chi (χ2) test or Mann Whitney U test. Overall and cancer specific survival (OS, CSS) were estimated using Kaplan-Meier method and differences were compared using log-rank test. Cox-regression multivariable analysis (MVA) was performed to explore factors associated with worse CSS. Propensity-score matching analysis was done to compare survival differences between WR and Lob/Seg. RESULTS: A total of 22,350 patients with BC were identified, of them 4,450 met our inclusion criteria (3,511 Lob/Seg, vs. 939 WR). The median age was 59.0 years [interquartile range (IQR) =49.0-68.0], 67.6% were females and the median tumor size was 2 cm (1.5-3 cm). 4,119 patients had typical carcinoid (TC) and 331 had atypical carcinoid (AC). WR was performed more frequently in elderly patients, females, lower lobe tumors, TC's and in earlier stage disease. For patients with TC, there was no difference in CSS between WR and Lob/Seg in both the entire cohort (P=0.654) and in the propensity matched groups (P=0.900). However, for patients with AC, Lob/Seg was associated with better CSS compared to WR both in the entire cohort (P<0.001) and in the propensity matched groups (P=0.001). On MVA of the entire cohort, elderly patients, males, blacks, AC and advanced stages had worse CSS. While, the type of the procedure (WR vs. Lob/Seg) was not associated with CSS (HR =1.16, 95% CI: 0.85-1.60). CONCLUSIONS: A WR may offer equivalent CSS in well-selected patients with early-stage TC. An anatomic resection appears warranted in AC.

Neoadjuvant Therapy for Locally Advanced Esophageal Cancer Should Be Targeted to Tumor Histology.

BACKGROUND: Controversy exists over the optimal neoadjuvant therapy in patients with locally advanced esophageal cancer (EC). Although most groups favor neoadjuvant chemoradiation (nCRT), some prefer preoperative chemotherapy (nCT) without radiation. The objective of this study was to compare outcomes in EC patients undergoing either regimen, followed by surgery. METHODS: We reviewed a prospectively collected database of EC patients undergoing esophagectomy after nCT or nCRT from 1989 to 2016. Choice of therapy was at the discretion of the multidisciplinary team. Disease-free survival (DFS) and cancer-specific survival (CSS) were compared by the Kaplan-Meier log-rank test. Independent predictors of CSS were estimated by Cox regression analysis. RESULTS: Among 700 EC patients 338 patients were treated with nCRT (n = 112) or nCT (n = 226) followed by surgery. Patients were well matched for age, gender, and clinical stage, although patients with squamous cell carcinoma were more likely to receive nCRT (49% vs 26%, p < 0.001). At surgery 90% and 91% of nCRT and nCT patients, respectively, underwent transthoracic esophagectomy. nCRT, in comparison with nCT, was associated with similar rates of Calvien-Dindo grade III/IV complications (34% vs 33%, p = 0.423) but with a trend toward higher perioperative mortality (5% vs 1%, p = 0.064). Among adenocarcinoma patients (n = 239) the use of nCRT was associated with higher rates of complete clinical response (18% vs 7.4%), pathologically negative lymph nodes (52% vs 30%, p = 0.001), and complete pathologic response (21% vs 5.1%, p < 0.001). However, there was no difference between nCRT and nCT for 5-year DFS (28% vs 31%, p = 0.636) or CSS (51% vs 52%, p = 0.824) among adenocarcinoma patients. For patients with squamous cell carcinoma (n = 98), nCRT and nCT had similar rates of complete clinical response (31% vs 26%, p = 0.205), but the rates of negative nodes (65% vs 46%, p = 0.064) and of complete pathologic response (42% vs 12%, p < 0.05) were higher with nCRT. For these patients nCRT was associated with no statistical difference in 5-year DFS (57% vs 40%, p = 0.595) but with improved 5-year CSS (87% vs 68%, p = 0.019) compared with nCT. On multivariable analysis for CSS, nCRT predicted improved survival for patients with squamous cell carcinoma (hazard ratio, 0.242; 95% confidence interval, 0.071-0.830) but not for those with adenocarcinoma (univariate hazard ratio, 0.940; 95% confidence interval, 0.544-1.623). CONCLUSIONS: For adenocarcinoma patients undergoing surgery for EC, nCRT leads to increased local tumor response compared with nCT alone but with no difference in survival. For squamous carcinoma patients nCRT appears to improve CSS compared with nCT. For patients with locally advanced EC targeted neoadjuvant regimens should be used depending on tumor histology.

Lung cancer patients have the highest malignancy-associated suicide rate in USA: a population-based analysis.

PURPOSE: Previous studies have reported that psychological and social distresses associated with a cancer diagnosis have led to an increase in suicides compared to the general population. We sought to explore lung cancer-associated suicide rates in a large national database compared to the general population, and to the three most prevalent non-skin cancers [breast, prostate and colorectal cancer (CRC)]. METHODS: The Surveillance, Epidemiology and End Results (SEER) database (1973-2013) was retrospectively reviewed to identify cancer-associated suicide deaths in all cancers combined, as well as for each of lung, prostate, breast or CRCs. Suicide incidence and standardised mortality ratio (SMR) were estimated using SEER*Stat-8.3.2 program. Suicidal trends over time and timing from cancer diagnosis to suicide were estimated for each cancer type. RESULTS: Among 3,640,229 cancer patients, 6,661 committed suicide. The cancer-associated suicide rate was 27.5/100,000 person years (SMR = 1.57). The highest suicide risk was observed in patients with lung cancer (SMR = 4.17) followed by CRC (SMR = 1.41), breast cancer (SMR = 1.40) and prostate cancer (SMR = 1.18).Median time to suicide was 7 months in lung cancer, 56 months in prostate cancer, 52 months in breast cancer and 37 months in CRC (p < 0.001).We noticed a decreasing trend in suicide SMR over time, which is most notable for lung cancer compared to the other three cancers. In lung cancer, suicide SMR was higher in elderly patients (70-75 years; SMR = 12), males (SMR = 8.8), Asians (SMR = 13.7), widowed patients (SMR = 11.6), undifferentiated tumours (SMR = 8.6), small-cell lung cancer (SMR = 11.2) or metastatic disease (SMR = 13.9) and in patients who refused surgery (SMR = 13). CONCLUSION: The cancer-associated suicide rate is nearly twice that of the general population of the United States of America. The suicide risk is highest among the patients with lung cancer, particularly elderly, widowed, male patients and patients with unfavourable tumour characteristics. The identification of high-risk patients is of extreme importance to provide proper psychological assessment, support and counselling to reduce these rates.

Consequences of Refusing Surgery for Esophageal Cancer: A National Cancer Database Analysis.

BACKGROUND: Given the potential morbidity of esophagectomy, patients may pursue other treatments. We sought to determine predictors and outcomes of esophageal cancer patients who refused esophagectomy. METHODS: The National Cancer Database (2004 to 2014) was queried for locally advanced esophageal cancer patients. A unique field allows identification of patients recommended to have surgery but who refused. Comparisons between the entire cohort and between propensity matched groups were performed using analysis of variance and χ2 tests. Survival was compared using Kaplan-Meier curves. Logistic regression was performed to identify predictors of refusing surgery. RESULTS: We identified 18,459 patients with esophageal cancer meeting criteria, including 708 (3.8) who were recommended but refused surgery. By multivariate analysis, elderly, female, nonwhite race, squamous histology, early year of diagnosis, absence of insurance, treatment at nonacademic centers, lower income, and clinical stage I/II predicted refusal of surgery. Median survival was worse for patients who refused surgery compared with patients undergoing surgery. Among propensity matched groups (n = 525 each), median survival was better for patients undergoing surgery versus patients who refused (32 versus 21 months, p < 0.001). CONCLUSIONS: Although patients may be reluctant to undergo esophagectomy for esophageal cancer, refusal of surgery when offered comes at the expense of decreased survival. These data allow for a discussion of alternative outcomes with those patients in the context of shared decision making.

Synthesis and characterization of a novel electron conducting biocomposite as biofuel cell anode.

This study is based on the construction of an enzymatic bioanode adopting the exclusively reported layer-by-layer (LBL) assembly of Ppy-Ag-GO/ferritin (Frt)/glucose oxidase (GOx). The glassy carbon (GC) electrode was immobilised with the conducting polypyrrole (Ppy)-silver nanoparticles (Ag)-graphene oxide (GO) based biocomposite as electron transfer elevator, horse spleen ferritin (Frt) protein as electron transfer mediator and glucose oxidase (GOx) enzyme in layer by layer configuration. The fabricated bioanode exhibited good electrochemical performance with a maximum current response of 5.7mAcm-2 accompanied with biocompatibility and environmental stability because of the synergistic effect between outstanding properties of PPy, silver and GO, thereby, showing superior catalytic efficiency for the oxidation of glucose.