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.

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.

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.

A review: Evolution of enzymatic biofuel cells.

Ever-growing demands for energy, the unsustainability of fossil fuel due to its scarcity and massive impact on global economies and the environment, have encouraged the research on alternative power sources to work upon for the governments, companies, and scientists across the world. Enzymatic biofuel cells (eBFCs) is one category of fuel cell that can harvest energy from biological moieties and has the future to be used as an alternative source of energy. The aim of this review is to summarize the background and state-of-the-art in the field of eBFCs. This review article will be very beneficial for a wide audience including students and new researchers in the field. A part of the paper summarized the challenges in the preparation of anode and cathode and the involvement of nanomaterials and conducting polymers to construct the effective bioelectrodes. It will provide an insight for the researchers working in this challenging field. Furthermore, various applications of eBFCs in implantable power devices, tiny electronic gadgets, and self powered biosensors are reported. This review article explains the development in the area of eBFCs for several years from its origin to growth systematically. It reveals the strategies that have been taken for the improvements required for the better electrochemical performance and operational stability of eBFCs. It also mentions the challenges in this field that will require proper attention so that the eBFCs can be utilized commercially in the future. The review article is written and structurized in a way so that it can provide a decent background of eBFCs to its reader. It will definitely help in enhancing the interest of reader in eBFCs.

National Analysis of Short-Term Outcomes and Volume-Outcome Relationships for Transcatheter Aortic Valve Replacement in the Era of Commercialization.

OBJECTIVES: We queried the 2012 National Inpatient Sample in order to (1) further describe the short-term outcomes for transcatheter aortic valve replacement (TAVR) and (2) characterize possible volume-outcome relationships and other prognostic factors for this procedure. METHODS: Demographics and inhospital outcomes were tabulated for all patients, as were hospital characteristics and procedural-volume data for all centers at which patients underwent TAVR. Logistic regression analyses were performed to identify independent risk factors for mortality or morbidity. RESULTS: 7,635 patients aged ≥ 18 years received TAVR during the study period; 84.5% (n = 6,450) underwent transfemoral TAVR and the rest were treated transapically. The median age was 83 years (IQR 77-88 years) and cardiovascular comorbidities were widespread. Overall inhospital mortality was 5.0% (n = 380), and 1.4% (n = 105) of the patients experienced a stroke. All-cause procedure-related morbidity was 24.7% (n = 1,885). Annual hospital TAVR volume did not predict inhospital mortality or morbidity (OR 1.00, 95% CI 0.99-1.00, p = 0.111 and OR 1.00, 95% CI 0.99-1.00, p = 0.947, respectively). CONCLUSIONS: Our analysis helps to confirm the short-term safety profile of TAVR and further demonstrates that inhospital outcomes have remained acceptable as this procedure has become commercialized.

Predictors of Disease-free Survival and Recurrence in Patients with Resected Bronchial Carcinoid Tumors.

BACKGROUND: Bronchial carcinoids are characterized by neuroendocrine differentiation and have distinct biological behavior, recurrence patterns, and prognosis compared with adenocarcinomas or squamous cell carcinomas. Because of their often indolent nature, it has been suggested that routine postoperative imaging surveillance may not be warranted in the majority of patients. This study aims to define the factors that predict disease-free survival (DFS) and recurrence after resection of these tumors, with the goal of identifying high-risk patients for whom image surveillance may be warranted. METHODS: We conducted a retrospective review of a prospective database to identify patients with completely resected bronchial carcinoid tumors. Surgical procedure, histology, pathological stage, follow-up, tumor recurrence, and survival were assessed. RESULTS: One hundred and forty-two patients were identified. Median age was 62 years and the majority was women (106). Surgical procedures included 20 wedge resections, 10 segmentectomies, 99 lobectomies, 3 bilobectomies, 2 pneumonectomies, 6 sleeve resections, and 2 bronchectomies. Pathologic stages included I (81%), II (10%), III (8%), and IV (1%). With a median follow-up of 31 months, there were seven recurrences. The 5- and 10-year overall survival rates were 92% and 75% and DFS rates were 88% and 72%, respectively. There were 34 patients with atypical carcinoids, and 6 (18%) developed recurrence, compared with 1 recurrence (1%) in the group of 108 patients with typical carcinoids (p = 0.0008). For atypical carcinoid tumors, the 5- and 10-year DFS rates were 72% and 32% versus 92% and 85% in typical carcinoid tumors (p = 0.001). Patients with more advanced tumor stage pT2-4 and pathologic N1/N2 nodal metastases had a significantly decreased 5- and 10-year DFS compared with those with early pT1 stage (p = 0.029) or those without nodal disease (p = 0.043). Multivariate Cox regression analyses showed advancing age (p = 0.001), atypical histology (p = 0.021), and advanced tumor stage (p = 0.047) were significant negative predictors for DFS. CONCLUSION: Long-term survival after resection of bronchial carcinoids is common, especially for patients with typical carcinoid tumors. DFS can be negatively influenced by atypical histology, advanced tumor, and nodal statuses. Efforts at postoperative image surveillance should target those patients with such high-risk factors.

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.

Management and outcomes of patients on preoperative plavix (clopidogrel) undergoing general thoracic surgery.

OBJECTIVES: Plavix (clopidogrel) is a potent antiplatelet agent used to prevent thrombosis in a variety of clinical settings. The perioperative management of thoracic surgery patients who are on clopidogrel at the time of surgery is not well defined. We conducted this review to examine the perioperative management and outcomes of patients undergoing general thoracic surgical procedures. METHODS: From January 2005 to January 2010, 165 patients on clopidogrel underwent 182 operative procedures. Three management strategies were identified: Group I: clopidogrel continued through surgery (n = 17), Group II: clopidogrel discontinued with a bridging agent (n = 44) and Group III clopidogrel discontinued without a bridging agent (n = 121). Propensity score matched cohorts (17 clopidogrel continued; 34 clopidogrel discontinued) were constructed based on age, clopidogrel indication, American Society of Anesthesiology status, and procedure and used to compare the impact of clopidogrel management on postoperative bleeding and cardiovascular morbidity. RESULTS: Unmatched analysis revealed a significantly higher rate of transfusion in the group of patients who continued on clopidogrel throughout the perioperative period, compared with patients who had clopidogrel discontinued. Although there were more cardiovascular events in Groups II and III, there were no significant differences between groups in postoperative mortality, myocardial infarction, stroke, or reoperation for bleeding. In propensity matched patients only the rate of postoperative transfusions was significantly higher in patients continued on clopidogrel compared with patients whose clopidogrel was discontinued (35.3 vs. 2.9%), p < 0.004. CONCLUSIONS: In selected patients, some thoracic surgical procedures can be performed safely on clopidogrel but are associated with higher rates of postoperative transfusion.

Electrodiagnostic profile of conduction slowing in amyotrophic lateral sclerosis.

Objective: Since motor nerve conduction slowing can occur due to loss of large axons, we investigate the conduction slowing profile in amyotrophic lateral sclerosis (ALS) and identify the limits beyond which the diagnosis of exclusive axonal loss is unlikely. Methods: First, using linear regression analysis, we established the range of motor conduction slowing in 76 chronic inflammatory demyelinating polyneuropathy (CIDP) patients. Demyelinating range confidence intervals were defined by assessing conduction velocity (CV), distal latency (DML), and F-wave latency (F) in relation to distal compound muscle action potential (CMAP) amplitude of median, ulnar, fibular, and tibial nerves. Results were subsequently validated in 38 additional CIDP patients. Then, the newly established demyelination confidence intervals were used to investigate the profile of conduction slowing in 95 ALS patients. Results: CV slowing, prolonged DML, and abnormal F were observed in 22.2%, 19.6%, and 47.1% of the studied nerves respectively in ALS patients. When slowing occurred, it affected more than one segment of the motor nerve, suggesting that CMAP amplitude dependent conduction slowing caused by an exclusive loss of large axons is the main mechanism of slowing. No ALS patient had more than 2 nerves with CV slowing in the confidence interval defined by the regression equations or the American Academy of Neurology (AAN) research criteria for CIDP diagnosis. Conclusions: The presence of more than two motor nerves with CV slowing in the demyelinating range defined by the regression analysis or AAN criteria in ALS patients suggests the contribution of acquired demyelination or other additional mechanisms exist in the electrodiagnostic profile of ALS.

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.

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.

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.

Trends in outcome and hospitalization charges of adult patients admitted with botulism in the United States.

BACKGROUND: To assess the impact of new therapeutic strategies on outcomes and hospitalization charges among adult patients with botulism in the United States. METHODS: We determined in-hospital outcomes and charges for patients with botulism hospitalized in 1993-1994 and compared them with those observed among patients hospitalized in 2006-2007. Mortality, length of stay, and hospitalization charges were calculated. Age, sex, race, ethnicity, and discharge status were also reported. RESULTS: There were 66 and 132 admissions of adult patients with botulism in 1993-1994 and 2006-2007, respectively. Men predominance was observed in 2006-2007 compared to women predominance during the 1993-1994 time period. There was no significant difference in the average length of stay and in-hospital mortality rate between the two groups studied. However, in the 2006-2007 group, there was a significant increase in the mean hospitalization charges (USD 126,092 ± 120,535 vs. USD 83,623 ± 82,084; p = 0.0107) and in the proportion of patients requiring mechanical ventilation when compared to 1993-1994 (34 vs. 13.6%; p < 0.0001). CONCLUSION: Botulism continues to be an infrequent cause of hospitalization, with a significant increase in the average hospitalization charges in 2006-2007 when compared to 1993-1994, despite a nonsignificant change in the mortality rate and average length of hospitalization.

Plasma soluble vascular adhesion molecule-1 levels are persistently elevated during the first month after colorectal cancer resection.

INTRODUCTION: Plasma from the second and third weeks after minimally invasive colorectal resection (MICR) has high levels of the proangiogenic proteins VEGF and angiopoietin 2 and also stimulates, in vitro, endothelial cell (EC) proliferation and migration, which are critical to wound and tumor angiogenesis. Soluble vascular cell adhesion molecule-1 (sVCAM-1) stimulates EC chemotaxis and angiogenesis. The impact of MICR on blood levels of sVCAM-1 is unknown. This study's purpose was to determine plasma sVCAM-1 levels after MICR in colorectal cancer (CRC) patients. METHODS: Blood samples from 90 patients (26% rectal, 74% colon) were obtained preoperatively, on postoperative days (POD) 1 and 3, and at other points during the next 2 months. The late samples were bundled into 7-day time blocks. sVCAM-1 levels were determined in duplicate via ELISA and reported as ng/ml. Student's t test was used for data analysis (significance, P < 0.008 after Bonferroni correction). RESULTS: The mean incision length was 7.3 ± 3.1 cm, and the conversion rate was 3%. Compared with preoperative (PreOp) levels (811.3 ± 233.2), the mean plasma sVCAM-1 level was significantly higher on POD 1 (905.7 ± 292.4, P < 0.001) and POD 3 (977.7 ± 271.8, P < 0.001). Levels remained significantly elevated for the POD 7-13, POD 14-20, POD 21-27, and POD 28-67 time blocks. CONCLUSIONS: MICR for CRC is associated with a persistent increase in plasma sVCAM-1 levels during the first month. This sustained increase may promote angiogenesis and stimulate the growth of residual tumor cells early after surgery.

Perioperative polyphenon E, a green tea extract, does not affect the wound complication rate in mice after sham laparotomy yet has an inhibitory effect on wound healing.

INTRODUCTION: Major surgery is associated with physiologic alterations that may promote tumor growth, and catechins in green tea may inhibit tumor growth. This study's aim was to assess the impact of a green tea extract on laparotomy wound healing in mice. METHODS: Mice were randomized to daily oral catechins solution (n = 25) or placebo (n = 20), underwent sham laparotomy after 10 days, and were sacrificed on postoperative day 7 or 21. The peak force and total energy required to rupture the abdominal wall wound, wound collagen content, and histology were assessed. RESULTS: There were no wound complications in either group, and mean peak wound rupture forces and collagen concentration were similar. Mean energy was lower and more fibroblast proliferation was found in the treatment group on postoperative day 21. CONCLUSIONS: These results suggest that catechins has only mild clinically significant adverse effect on wound healing, and its perioperative use warrants further study.

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.

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.

Plasma levels of angiostatin and endostatin remain unchanged for the first 3 weeks after colorectal cancer surgery.

INTRODUCTION: Angiostatin and endostatin are endogenous inhibitors of angiogenesis with anticancer effects. After minimally invasive colorectal resection (MICR), blood levels of the proangiogenic factors vascular endothelial growth factor (VEGF) and angiopoetin 2 (Ang-2) are elevated for 2-4 weeks. Also, postoperative human plasma from weeks 2 and 3 after MICR has been shown to stimulate endothelial cell proliferation and migration, which are critical to angiogenesis. This proangiogenic state may stimulate tumor growth early after MICR. Surgery's impact on angiostatin and endostatin is unknown. This study's purpose is to determine perioperative plasma levels of these two proteins in colorectal cancer (CRC) patients undergoing MICR. METHODS: Endostatin levels were assessed in 34 CRC patients and angiostatin levels in 30 CRC patients. Blood samples were taken preoperatively and on postoperative day (POD) 1 and 3 in all patients; in a subset, samples were taken between POD 7 and 20. The late samples were bundled into 7-day blocks (POD 7-13, POD 14-20) and considered as single time points. Angiostatin and endostatin plasma levels were determined via enzyme-linked immunosorbent assay (ELISA) in duplicate. Wilcoxon signed-rank test and Student's t test were used to analyze endostatin and angiostatin data, respectively. Significance was set at P<0.0125 (after Bonferroni correction). RESULTS: There was a significant decrease in median plasma endostatin levels on POD 1, which returned to the preoperative level by POD 3. There was no significant difference between pre- and postoperative plasma angiostatin levels. CONCLUSIONS: MICR has a very transient impact on plasma levels of endostatin and no impact on angiostatin during the first 21 days following surgery. Thus, angiostatin and endostatin do not likely contribute to or inhibit the persistent proangiogenic changes noted after MICR.