Minimally invasive surgery for clinical T4 non-small-cell lung cancer: national trends and outcomes.

OBJECTIVES: Recent randomized data support the perioperative benefits of minimally invasive surgery (MIS) for non-small-cell lung cancer (NSCLC). Its utility for cT4 tumours remains understudied. We, therefore, sought to analyse national trends and outcomes of minimally invasive resections for cT4 cancers. METHODS: Using the 2010-2019 National Cancer Database, we identified patients with cT4N0-1 NSCLC. Patients were stratified by surgical approach. Multivariable logistic analysis was used to identify factors associated with use of a minimally invasive approach. Groups were matched using propensity score analysis to evaluate perioperative and survival end points. RESULTS: The study identified 3715 patients, among whom 64.1% (n = 2381) underwent open resection and 35.9% (n = 1334) minimally invasive resection [robotic-assisted in 31.5% (n = 420); and video-assisted in 68.5% (n = 914)]. Increased MIS use was noted among patients with higher income [≥$40 227, odds ratio (OR) 1.24; 95% confidence interval (CI) 1.01-1.51] and those treated at academic hospitals (OR 1.25; 95% CI 1.07-1.45). Clinically node-positive patients (OR 0.68; 95% CI 0.55-0.83) and those who underwent neoadjuvant therapy (OR 0.78; 95% CI 0.65-0.93) were less likely to have minimally invasive resection. In matched groups, patients undergoing MIS had a shorter median length of stay (5 vs 6 days, P < 0.001) and no significant differences between 30-day readmissions or 30/90-day mortality. MIS did not compromise overall survival (log-rank P = 0.487). CONCLUSIONS: Nationally, the use of minimally invasive approaches for patients with cT4N0-1M0 NSCLC has increased substantially. In these patients, MIS is safe and does not compromise perioperative outcomes or survival.

Association of socioeconomic factors with the receipt of neoadjuvant therapy for patients with non-small cell lung cancer.

BACKGROUND: Neoadjuvant therapy (NT) will be increasingly used for patients with non-small cell lung cancer (NSCLC), particularly given the recent approval of neoadjuvant chemoimmunotherapy. Several barriers may prevent the uptake of NT and should be identified and addressed. We queried the National Cancer Database (NCDB) to determine predictors of the use of NT. METHODS: Using the NCDB (2006-2019), we identified 80,707 patients who underwent surgery for clinical stage II and III NSCLC. Sociodemographic and clinical factors were reviewed, and univariable and multivariable analyses were performed to identify associations with the uptake of NT. In propensity score-matched groups, survival was determined using the Kaplan-Meier method. RESULTS: Among 80,707 eligible patients, 17,262 (21.4%) received NT. Clinical stage and node positivity were associated with receipt of NT. On multivariable analysis, factors associated with lower rates of NT included black race (odds ratio [OR], 0.78; 95% confidence interval [CI], 0.67-0.90), Charlson Comorbidity Index ≥2 (OR, 0.75; 95% CI, 0.67-0.85), Medicaid/Medicare insurance (OR, 0.82; 95% CI, 0.75-0.90), lower income level (OR, 0.79; 95% CI, 0.71-0.87), and treatment at a community center (OR, 0.81; 95% CI, 0.67-0.96). In an exploratory analysis, those patients who received NT had longer 5-year overall survival compared with those who did not (48.3% vs 46.0%; P < .001). CONCLUSIONS: Rates of NT are relatively low for patients with clinical stage II/III NSCLC treated prior to recent chemoimmunotherapy trials. Socioeconomic barriers to the uptake of NT include race, insurance status, income, and area of residence. As NT becomes more widely offered, accessibility for vulnerable populations must be assured.

The Effect of Neoadjuvant Therapy on Esophagectomy for cT2N0M0 Esophageal Adenocarcinoma.

BACKGROUND: For cT2N0M0 esophageal adenocarcinomas, the effects of neoadjuvant chemoradiotherapy (NT) on surgical outcomes and the oncological benefits to the patients are debatable. In this study, we investigated the optimal management for cT2N0M0 adenocarcinoma (1) assessing the perioperative impact of NT on esophagectomy and (2) evaluating the oncologic effect of NT in a homogeneous group of patients with clinical stage IIA. We hypothesized that NT does not negatively affect perioperative outcomes and provides an oncologic benefit to selected patients with cT2N0M0 disease. METHODS: The National Cancer Database was queried (2010-2019) for patients with cT2N0M0 esophageal adenocarcinoma undergoing esophagectomy. After propensity-matching to adjust for differences in patient and tumor characteristics, we compared postoperative outcomes (logistic regression) and survival (Kaplan-Meier and Cox regression) among those who underwent NT vs upfront surgery (S). RESULTS: This study included 3413 patients, of whom 2359 (69%) received NT, and 1054 (31%) S. In contrast to those who underwent S, in the matched cohort, patients treated with NT had comparable conversion rates (8% vs11.1%, p = 0.06), length of stay (9 vs 10 days, p = 0.078), unplanned readmission (5.4% vs 8.8%, p = 0.109), and 30- (3.9% vs 3.7%, p = 0.90) and 90-day mortality (5.7% vs 4.7%, p = 0.599). In addition, NT associated with improved survival in patients with cT2N0M0 tumors > 5 cm (HR 0.30, 95% CI 0.17-0.36). CONCLUSIONS: NT does not appear to increase technical complexity or to adversely affect postoperative outcomes after esophagectomy. Furthermore, minimally invasive esophagectomy is feasible following NT, with comparable conversion rates to those who had upfront surgery. Lastly, NT was selectively associated with improved survival in patients with cT2N0M0 esophageal cancer.

Underutilization of Systemic Therapy in Patients With NSCLC Undergoing Pneumonectomy: A Missed Opportunity for Survival.

Introduction: Recent trials have reported promising results with the addition of immunotherapy to chemotherapy for patients with locally advanced NSCLC, but in practice, the proportion of patients who receive systemic therapy (ST) has historically been low. Underutilization of ST may be particularly apparent in patients undergoing pneumonectomy, in whom the physiologic insult and surgical complications may preclude adjuvant therapy (ADJ). We, therefore, evaluated the use of ST for patients with NSCLC undergoing pneumonectomy. Methods: We queried the National Cancer Database, including all patients with NSCLC who underwent pneumonectomy between 2006 and 2018. Logistic regression was used to identify associations with ST and neo-ADJ (NEO). Overall survival was compared after propensity score matching (1:1) patients undergoing ST to those undergoing surgery alone using Kaplan-Meier and Cox regression methods. Results: A total of 2619 patients were identified. Among these, 12% received NEO, 43% received ADJ, and 45% surgery alone. Age younger than 65 years (adjusted odds ratio [aOR] = 1.53, 95% confidence interval; [CI]: 1.10-2.11), Asian ethnicity (aOR = 2.68, 95% CI: 1.37-5.23), treatment at a high-volume center (aOR = 1.39, 95% CI: 1.06-1.81), and private insurance (aOR = 1.42, 95% CI: 1.05-1.94) were associated with NEO, whereas age younger than 65 years (aOR = 1.95, 95% CI: 1.61-2.38), comorbidity index less than or equal to 1 (aOR = 1.66, 95% CI: 1.29-2.16), and private insurance (aOR = 1.47, 95% CI: 1.20-1.80) were associated with any ST. In the matched cohort, ST was associated with better survival than surgery (adjusted hazard ratio = 0.67, 95% CI: 0.58-0.78). Conclusions: A high proportion of patients who undergo pneumonectomy do not receive ST. Patient and socioeconomic factors are associated with the receipt of ST. Given its survival benefit, emphasis should be placed on multimodal treatment strategies, perhaps with greater consideration given to neoadjuvant approaches.

Human Breast Milk-Derived Extracellular Vesicles in the Protection Against Experimental Necrotizing Enterocolitis.

PURPOSE: Necrotizing enterocolitis (NEC) is a leading cause of death in premature infants. Breast feeding decreases the incidence of NEC but, even with aggressive promotion of nursing in Neonatal Intensive Care Units, morbidity and mortality remain high. Previous studies from our laboratory have demonstrated that extracellular vesicles (EVs) purified from mouse and rat stem cells can protect the intestines from NEC. The aim of this study was to determine whether human breast milk (BM)-derived EVs could prevent NEC. METHODS: EVs were purified from human donor breast milk. NEC was induced in premature rat pups by exposure to asphyxia/hypothermia/hypercaloric feeds. Pups were randomized to: (1) breast fed, no injury, (2) NEC, (3) NEC + BM-derived EVs once intraperitoneally (IP), (4) NEC + BM-derived EVs enterally (PO) with each feed. Intestinal tracts were examined for histologic damage. Additionally, the effect of BM-derived EVs on intestinal epithelial cells (IEC) subjected to hypoxia/reoxygenation injury in vitro was examined. RESULTS: NEC incidence was 0% in breast-fed pups and 62% in pups subjected to NEC. IP administration of BM-derived EVs decreased NEC incidence to 29% and enteral administration further decreased NEC incidence to 11.9%. (p < 0.05). BM-derived EVs significantly increased cell proliferation and decreased apoptosis in IEC in vitro. CONCLUSION: Breast milk-derived EVs delivered either IP or enterally significantly decrease the incidence and severity of experimental NEC, protect IEC from injury in vitro, and may represent an innovative therapeutic option for NEC in the future. TYPE OF STUDY: Basic science study. LEVEL OF EVIDENCE: N/A.

Successful implantation of an engineered tubular neuromuscular tissue composed of human cells and chitosan scaffold.

BACKGROUND: There is an urgent need for gut lengthening secondary to massive resections of the gastrointestinal tract. In this study, we propose to evaluate the remodeling, vascularization, and functionality of a chitosan-based, tubular neuromuscular tissue on subcutaneous implantation in the back of athymic rats. METHODS: Aligned innervated smooth muscle sheets were bioengineered with the use of human smooth muscle and neural progenitor cells. The innervated sheets were wrapped around tubular chitosan scaffolds. The engineered tubular neuromuscular tissue was implanted subcutaneously in the back of athymic rats. The implant was harvested after 14 days and assessed for morphology, vascularization, and functionality. RESULTS: Gross examination of the implants showed healthy color with no signs of inflammation. The implanted tissue became vascularized as demonstrated by gross and histologic analysis. Chitosan supported the luminal patency of the tissue. The innervated muscle remodeled around the tubular chitosan scaffold. Smooth muscle maintained its circumferential alignment and contractile phenotype. The functionality of the implant was characterized further by the use of real-time force generation. A cholinergic response was demonstrated by robust contraction in response to acetylcholine. Vasoactive intestinal peptide-, and electrical field stimulation-caused relaxation. In the presence of neurotoxin tetrodotoxin, the magnitude of acetylcholine-induced contraction and vasoactive intestinal peptide-induced relaxation was attenuated whereas electrical field stimulation-induced relaxation was completely abolished, indicating neuronal contribution to the response. CONCLUSION: Our results indicated the successful subcutaneous implantation of engineered tubular neuromuscular tissues. The tissues became vascularized and maintained their myogenic and neurogenic phenotype and function, which provides potential therapeutic prospects for providing implantable replacement GI segments for treating GI motility disorders.