Does prehabilitation before esophagectomy improve postoperative outcomes? A systematic review and meta-analysis.

Esophagectomy for esophageal cancer is associated with high morbidity. It remains unclear whether prehabilitation, a strategy aimed at optimizing patients' physical and mental functioning prior to surgery, improves postoperative outcomes. A systematic review and meta-analysis was conducted to evaluate the effect of prehabilitation on post-operative outcomes after esophagectomy. Data sources included Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, and PEDro, with information from 1 January 2000 to 5 August 2023. The analysis included randomized controlled trials and observational studies that compared prehabilitation interventions to standard care prior to esophagectomy. A random effects model was used to generate a pooled estimate for pairwise meta-analysis, meta-analysis of proportions, and meta-analysis of means. A total of 1803 patients were included with 584 in randomized controlled trials (RCTs) and 1219 in observational studies. In the randomized evidence, there were no significant differences between prehabilitation and control in the odds of postoperative pneumonia (15.0 vs. 18.9%, odds ratio (OR) 1.06 [95% confidence interval (CI): 0.66;1.72]) or pulmonary complications (14 vs. 25.6%, OR 0.68 [95% CI: 0.32;1.45]). In the observational data, there was a reduction in both postoperative pneumonia (22.5 vs. 32.9%, OR 0.48 [95% CI: 0.28;0.83]) and pulmonary complications (26.1 vs. 52.3%, OR 0.35 [95% CI: 0.17;0.75]) with prehabilitation. Hospital and intensive care unit length of stay (days), operative mortality, and severe complications (Clavien-Dindo ≥ 3) did not differ between groups in both the randomized data and observational data. Prehabilitation demonstrated reductions in postoperative pneumonia and pulmonary complications in observational studies, but not RCTs. The overall certainty of these findings is limited by the low quality of the available evidence.

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.

Surgical Treatment at an Academic Medical Center is Associated with Statistically Insignificant Lung Cancer Survival Outcome Differences Related to ZIP Code.

BACKGROUND: Low socioeconomic status is a well-characterized adverse prognostic factor in large lung cancer databases. However, such characterizations may be confounded as patients of lower socioeconomic status are more often treated at low-volume, non-academic centers. We evaluated whether socioeconomic status, as defined by ZIP code median income, was associated with differences in lung cancer resection outcomes within a high-volume academic medical center. METHODS: Consecutive patients undergoing resection for non-small cell lung cancer were identified from a prospectively maintained database (2011-18). Patients were assigned an income value based on the median income of their ZIP code as determined by census-based geographic data. We stratified the population into income quintiles representative of SES and compared demographics (chi-square), surgical outcomes, and survival (Kaplan-Meier). RESULTS: We identified 1,693 patients, representing 516 ZIP codes. Income quintiles were Q1: $24,421-53,151; Q2:$53,152-73,982; Q3:$73,983-99,063; Q4:$99,064-123,842; and Q5:$123,843-250,001. Compared to Q5 patients, Q1 patients were younger (median 69 vs. 73, p < 0.001), more likely male (44 vs. 36%, p = 0.035), and more likely Asian, Black, or self-identified as other than white, Asian, or Black. (67 vs. 11%, p = < 0.001). We found minor differences in surgical outcomes and no significant difference in 5-year survival between Q1 and Q5 patients (5-year: 86 vs. 85%, p = 0.886). CONCLUSIONS: Surgical care patterns at a high-volume academic medical center are similar among patients from varying ZIP codes. Surgical treatment at such a center is associated with no survival differences based upon socioeconomic status as determined by ZIP code. Centralization of lung cancer surgical care to high-volume centers may reduce socioeconomic outcome disparities.

Systematic Review - Neuroprotection of ketosis in acute injury of the mammalian central nervous system: A meta-analysis.

To evaluate the neuroprotection exerted by ketosis against acute damage of the mammalian central nervous system (CNS). Search engines were interrogated to identify experimental studies comparing the mitigating effect of ketosis (intervention) versus non-ketosis (control) on acute CNS damage. Primary endpoint was a reduction in mortality. Secondary endpoints were a reduction in neuronal damage and dysfunction, and an 'aggregated advantage' (composite of all primary and secondary endpoints). Hedges' g was the effect measure. Subgroup analyses evaluated the modulatory effect of age, insult type, and injury site. Meta-regression evaluated timing, type, and magnitude of intervention as predictors of neuroprotection. The selected publications were 49 experimental murine studies (period 1979-2020). The intervention reduced mortality (g 2.45, SE 0.48, p < .01), neuronal damage (g 1.96, SE 0.23, p < .01) and dysfunction (g 0.99, SE 0.10, p < .01). Reduction of mortality was particularly pronounced in the adult subgroup (g 2.71, SE 0.57, p < .01). The aggregated advantage of ketosis was stronger in the pediatric (g 3.98, SE 0.71, p < .01), brain (g 1.96, SE 0.18, p < .01), and ischemic insult (g 2.20, SE 0.23, p < .01) subgroups. Only the magnitude of intervention was a predictor of neuroprotection (g 0.07, SE 0.03, p 0.01 per every mmol/L increase in ketone levels). Ketosis exerts a potent neuroprotection against acute damage to the mammalian CNS in terms of reduction of mortality, of neuronal damage and dysfunction. Hematic levels of ketones are directly proportional to the effect size of neuroprotection.

Percutaneous and Open Tracheostomy in Patients with COVID-19: Comparison and Outcomes of an Institutional Series in New York City.

OBJECTIVE: The aim of this study was to report the safety, efficacy, and early results of tracheostomy in patients with COVID-19 and determine whether differences exist between percutaneous and open methods. SUMMARY BACKGROUND DATA: Prolonged respiratory failure is common in symptomatic patients with COVID-19, the disease process caused by infection with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Tracheostomy, although posing potential risk to the operative team and other healthcare workers, may be beneficial for safe weaning of sedation and ventilator support. However, short- and long-term outcomes remain largely unknown. METHODS: A prospectively collected database of patients with COVID-19 undergoing tracheostomy at a major medical center in New York City between April 4 and April 30, 2020 was reviewed. The primary endpoint was need for continued mechanical ventilation. Secondary outcomes included complication rates, sedation weaning, and need for intensive care unit (ICU) level of care. Patient characteristics, perioperative conditions, and outcomes between percutaneous and open groups were analyzed. RESULTS: During the study period, 67 consecutive patients underwent tracheostomy, including 48 males and 19 females with a median age of 66 years [interquartile range (IQR) 52-72]. Two surgeons alternated techniques, with 35 tracheostomies performed percutaneously and 32 via an open approach. The median time from intubation to tracheostomy was 23 days (IQR 20-26). At a median follow-up of 26 days, 52 patients (78%) no longer required mechanical ventilation and 58 patients (87%) were off continuous sedation. Five patients (7.5%) died of systemic causes. There were 11 total complications (16%) in 10 patients, most of which involved minor bleeding. There were no significant differences in outcomes between percutaneous and open methods. CONCLUSIONS: Tracheostomy under apneic conditions by either percutaneous or open technique can be safely performed in patients with respiratory failure due to COVID-19. Tracheostomy facilitated weaning from continuous intravenous sedation and mechanical ventilation. Continued follow-up of these patients to ascertain long-term outcome data is ongoing.

Tumoral CD10 expression correlates with aggressive histology and prognosis in patients with malignant pleural mesothelioma.

BACKGROUND: Currently, tumor-node-metastasis stage and histologic type are the established prognostic factors for malignant pleural mesothelioma, whereas no prognostic markers have been established for clinical practice. We investigated the prognostic value of CD10, a metalloproteinase that can promote cancer aggressiveness through enzymatic degradation and intracellular signaling crosstalk, in malignant pleural mesothelioma. METHODS: CD10 immunostaining was performed for 176 cases of malignant pleural mesothelioma (epithelioid, 148; biphasic, 14; sarcomatoid, 14), and its expression was dichotomized as negative (no staining) or positive (any staining). Epithelioid tumors were classified as pleomorphic subtype when cytologic pleomorphism was ≥10 % of the tumor. Overall survival (OS) was analyzed by log-rank tests and Cox proportional hazard models. RESULTS: Tumoral CD10 expression was identified in 42 % of epithelioid non-pleomorphic tumors, 57 % of epithelioid pleomorphic tumors, 79 % of biphasic tumors, and 93 % of sarcomatoid tumors (p < 0.001). Positive CD10 expression was correlated with higher mitotic count (p = 0.002). Overall survival for patients with positive CD10 expression was significantly shorter than that for patients with negative CD10 expression in all patients (p = 0.001) and in patients with epithelioid tumor (p = 0.04). On multivariate analysis, CD10 expression was an independent prognostic factor for all patients (hazard ratio 1.48; p = 0.019). CONCLUSIONS: Tumoral CD10 expression correlated with aggressive histologic types and higher mitotic activity and is an independent prognostic factor for patients with malignant pleural mesothelioma.

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.

Survival difference among adult and pediatric mediastinal yolk sac tumors cases: A meta-analysis of case reports.

BACKGROUND: Mediastinal Yolk sac tumors (YST) are rare and highly malignant extragonadal germ cell tumors with rapid growth and early metastases. We sought to conduct a meta-analysis of published case reports/case series to compare differences in survival, demographics, and treatment modalities between adult and pediatric patients with YST. METHODS: Ovid Embase, Cochrane, and Ovid Medline databases were searched for primary mediastinal pure YST cases. The primary outcome was overall survival (OS). Log-rank and Cox regression were used. This study is registered on PROSPERO (CRD42022367586). RESULTS: Among 846 studies, 87 met our inclusion criteria including 130 patients (Adults: 90 and Pediatrics: 40). About 41.5% of the patients were from the United States. The median age was 23.0 (Q1-Q3: 17.0-30.0), 88.5% were males, and (32.3%) were Asian. Stage II represented almost 40%. AFP was elevated in 96.9%. Respiratory distress was the presenting symptom in 65.4%. Chemotherapy, radiotherapy, and surgery were utilized in 84.6, 23.1, and 64.7% respectively. Median OS was 24 months (Adults: 23 months, Pediatrics: 25 months, P = 0.89). 3- and 5-year OS were 34.4% and 22.9% in adults and 41.5% and 41.5% in pediatrics, respectively. On multivariate analysis, anterior location of tumors, receipt of chemotherapy, and undergoing surgery were associated with better OS. CONCLUSION: Primary mediastinal YSTs are rare, but lethal neoplasms. Our meta-analysis showed that mediastinal YSTs mimic other non-seminomatous mediastinal GCTs in terms of clinical characteristics and available treatment options. Early diagnosis, neoadjuvant chemotherapy, and surgical resection are the key points for effective management and improved outcomes.

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.

Tumor-Targeted Nonablative Radiation Promotes Solid Tumor CAR T-cell Therapy Efficacy.

Infiltration of tumor by T cells is a prerequisite for successful immunotherapy of solid tumors. In this study, we investigate the influence of tumor-targeted radiation on chimeric antigen receptor (CAR) T-cell therapy tumor infiltration, accumulation, and efficacy in clinically relevant models of pleural mesothelioma and non-small cell lung cancers. We use a nonablative dose of tumor-targeted radiation prior to systemic administration of mesothelin-targeted CAR T cells to assess infiltration, proliferation, antitumor efficacy, and functional persistence of CAR T cells at primary and distant sites of tumor. A tumor-targeted, nonablative dose of radiation promotes early and high infiltration, proliferation, and functional persistence of CAR T cells. Tumor-targeted radiation promotes tumor-chemokine expression and chemokine-receptor expression in infiltrating T cells and results in a subpopulation of higher-intensity CAR-expressing T cells with high coexpression of chemokine receptors that further infiltrate distant sites of disease, enhancing CAR T-cell antitumor efficacy. Enhanced CAR T-cell efficacy is evident in models of both high-mesothelin-expressing mesothelioma and mixed-mesothelin-expressing lung cancer-two thoracic cancers for which radiotherapy is part of the standard of care. Our results strongly suggest that the use of tumor-targeted radiation prior to systemic administration of CAR T cells may substantially improve CAR T-cell therapy efficacy for solid tumors. Building on our observations, we describe a translational strategy of "sandwich" cell therapy for solid tumors that combines sequential metastatic site-targeted radiation and CAR T cells-a regional solution to overcome barriers to systemic delivery of CAR T cells.

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.

Lung Cancer Stage Shift as a Result of COVID-19 Lockdowns in New York City, a Brief Report.

INTRODUCTION: The COVID-19 pandemic reached New York City in early March 2020 resulting in an 11-week lockdown period to mitigate further spread. It has been well documented that cancer care was drastically affected as a result. Given New York City's early involvement, we attempted to identify any stage shift that may have occurred in the diagnoses of non-small cell lung cancer (NSCLC) at our institution as a result of these lockdowns. PATIENTS AND METHODS: We conducted a retrospective review of a prospective database of lung cancer patients at our institution from July 1, 2019 until March 31, 2021. Patients were grouped by calendar year quarter in which they received care. Basic demographics and clinical staging were compared across quarters. RESULTS: Five hundred and fifty four patients were identified that underwent treatment during the time period of interest. During the lockdown period, there was a 50% reduction in the mean number of patients seen (15 ± 3 vs. 28 ± 7, P = .004). In the quarter following easing of restrictions, there was a significant trend towards earlier stage (cStage I/II) disease. In comparison to quarters preceding the pandemic lockdown, there was a significant increase in the proportion of patients with Stage IV disease in the quarters following phased reopening (P = .026). CONCLUSION: After a transient but significant increase in Stage I/II disease with easing of restrictions there was a significant increase in patients with Stage IV disease. Extended longitudinal studies must be conducted to determine whether COVID-19 lockdowns will lead to further increases in the proportion of patients with advanced NSCLC.

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.

Imaging CAR T-cell kinetics in solid tumors: Translational implications.

Success in solid tumor chimeric antigen receptor (CAR) T-cell therapy requires overcoming several barriers, including lung sequestration, inefficient accumulation within the tumor, and target-antigen heterogeneity. Understanding CAR T-cell kinetics can assist in the interpretation of therapy response and limitations and thereby facilitate developing successful strategies to treat solid tumors. As T-cell therapy response varies across metastatic sites, the assessment of CAR T-cell kinetics by peripheral blood analysis or a single-site tumor biopsy is inadequate for interpretation of therapy response. The use of tumor imaging alone has also proven to be insufficient to interpret response to therapy. To address these limitations, we conducted dual tumor and T-cell imaging by use of a bioluminescent reporter and positron emission tomography in clinically relevant mouse models of pleural mesothelioma and non-small cell lung cancer. We observed that the mode of delivery of T cells (systemic versus regional), T-cell activation status (presence or absence of antigen-expressing tumor), and tumor-antigen expression heterogeneity influence T-cell kinetics. The observations from our study underscore the need to identify and develop a T-cell reporter-in addition to standard parameters of tumor imaging and antitumor efficacy-that can be used for repeat imaging without compromising the efficacy of CAR T cells in vivo.

Tricuspid Stenosis in Pregnancy: A Valve-in-Valve Conundrum.

Redo tricuspid valve replacement has high surgical operative mortality. Transcatheter valve-in-valve provides a viable option for valve replacement. We discuss the decision-making process involved in performing transcatheter tricuspid valve-in-valve replacement in a 23-week pregnant woman with multiple comorbidities and symptomatic severe bioprosthetic stenosis. (Level of Difficulty: Intermediate.).

National trends and perioperative outcomes of robotic resection of thymic tumours in the United States: a propensity matching comparison with open and video-assisted thoracoscopic approaches†.

OBJECTIVES: Despite the recent increased rate of adoption of robotic approaches for the resection of thymic tumours, their use is still limited to large-volume academic centres. To date, a large-scale analysis of the robotic approach has not been performed. We assessed the recent trends and outcomes of robotic thymectomies in the United States compared to those of open and video-assisted thoracoscopic surgical (VATS) approaches. METHODS: The National Cancer Database was queried for patients who underwent resection for thymic tumours (2010-2014). Predictors of using the robotic approach were estimated by logistic regression analysis. Propensity matching analysis (robotic versus open and robotic versus VATS) was done (1:1-caliper 0.05), controlling for age, gender, comorbidity index, induction treatment, tumour size and tumour extension. RESULTS: A total of 2558 thymectomies were performed (robotic = 300, VATS = 280, open = 1978). The use of a robotic approach increased from 6% (2010) to 14% (2014). The number of hospitals performing at least 1 robotic thymectomy increased from 22 (2010) to 52 (2014). Independent predictors influencing the choice of a robotic approach included an academic research/integrated cancer programme [odds ratio (OR) 1.66, confidence interval (CI) 1.22-2.27], later year of diagnosis (2014; OR 2.23, CI 1.31-3.80) and a patient's race (Asian) (OR 1.68, CI 1.05-2.69). A robotic approach was less likely to be utilized in midwestern hospitals (OR 0.65, CI 0.42-0.99), in larger tumours (cm) (OR 0.85, CI 0.80-0.90), with invasion of adjacent organs (OR 0.55, CI 0.37-0.82), thymic carcinoma (OR 0.62, CI 0.40-0.97) and following induction chemotherapy (OR 0.22, CI 0.08-0.61). In a propensity-matched analysis, there were no differences in the incidence of positive margins, nodal dissection, 30-day readmission rates and 30-/90-day mortality rates between the groups. However, a robotic approach was associated with fewer conversions compared to VATS, with a trend towards a shorter length of stay compared to an open approach. There were no differences in the 5-year overall survival rate between the matched groups (robotic 93% vs VATS 94%; P = 0.571; robotic 91% vs open 80%; P = 0.094). CONCLUSIONS: Over a 4-year study period, there was a significant increase in robotic utilization for thymectomies and an increase in the number of hospitals performing the procedure. In a matched analysis, a robotic approach was comparable to a VATS or an open approach. Current trends demonstrate increased robotic utilization for small thymomas with excellent perioperative results.