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BackgroundIn this single-arm study, the efficacy and safety of neoadjuvant pembrolizumab plus chemotherapy were evaluated in patients with resectable esophageal squamous cell carcinoma (ESCC).MethodsThis study included patients with ESCC of clinical stages II–IVA who underwent surgery within 4 to 6 weeks after completing treatment with pembrolizumab (200 mg) combined with a conventional chemotherapy regimen (3 cycles). The safety and efficacy of this combination treatment were evaluated as primary endpoints of the study.ResultsFrom April 2019 to August 2020, a total of 18 patients (including 14 men) were enrolled, of whom 13 patients progressed to surgery. Postoperative pathology revealed a major pathological response (MPR) in 9 cases (9/13, 69.2%) and a pathological complete response (pCR) in 6 cases (6/13, 46.2%). Five patients (5/18, 27.8%) experienced serious treatment-related adverse events (AEs) of grades 3–4. At the time of data cutoff (Mar 25, 2022), the shortest duration of follow-up was 17.8 months. Programmed death-ligand 1 (PD-L1) expression in pretreatment specimens was not significantly associated with the percentage of residual viable tumor (RVT) (r=−0.55, P=0.08). Changes in counts of CD68+ macrophage between pre- and post-treatment specimens were weakly correlated with RVT (r=0.71; P=0.07), while a positive correlation was observed between postoperative forkhead box P3-positive (Foxp3)+T cells/CD4+Tcells ratios and RVT (r=0.84, P = 0.03).ConclusionsThe combination of neoadjuvant immunotherapy and chemotherapy for ESCC is associated with a high pathological response and immunologic effects in the tumor microenvironment (TME). It has acceptable toxicity and great efficacy, suggesting a strong rationale for its further evaluation in randomized clinical trials (RCTs).Trial RegistrationChiCTR2100048917.

BackgroundThis study aimed to identify the results of the quality assessment and the learning curve of robot-assisted minimally invasive McKeown esophagectomy (RAMIE-MK).MethodsThe study retrospectively reviewed the data of 400 consecutive patients with esophageal cancer who underwent RAMIE-MK by a single surgeon from November 2015 to March 2019. Cumulative summation analysis of the learning curve was performed. The patients were divided into decile cohorts of 40 cases to minimize demographic deviations and to maximize the power of detecting statistically significant changes in performance.ResultsThe 90-day mortality rate for all the patients was 0.5% (2 cases). The authors’ experience was divided into the ascending phase (40 cases), the plateau phase (175 cases), and the descending phase (185 cases). After 40 cases, significant improvements in operative time (328 vs. 251 min; P = 0.019), estimated blood loss (350 vs. 200 ml; P = 0.031), and conversion rates (12.5% vs. 2.5%; P < 0.001) were observed. After 80 cases, a decrease in the rates of anastomotic leakage (22.5% vs. 8.1%; P = 0.001) and vocal cord palsy (31.3% vs. 18.4%; P = 0.024) was observed. The number of harvested lymph nodes increased after 40 cases (13 vs. 23; P < 0.001), especially for lymph nodes along the recurrent laryngeal nerve (3.0 vs. 6.0; P < 0.001).ConclusionsThe learning phase of RAMIE-MK consists of 40 cases, and quality outcomes can be improved after 80 procedures. Several turning points related to the optimization of surgical outcomes can be used as benchmarks for surgeons performing RAMIE-MK.

Robotic lung resection for lung cancer has gained popularity over the last 10 years. As with many surgical techniques, there are improvements in outcomes associated with increased operative volume. We sought to investigate lymph-node harvest and upstaging rates for robotic lobectomies performed at hospitals with varying robotic experience. The National Cancer Data Base was queried for patients with early stage non-small cell lung cancer who received lobectomy between 2010 and 2015. Hospitals were stratified into volume categories based on the number of robotic resections performed, as a proxy for robotic experience: low at  ≤ 12, low–middle 13–26, middle–high 27–52, and high volume at greater than or equal to 53. Lymph-node counts and nodal upstaging were compared among these volume categories. 8360 robotic lobectomies were performed. Mean lymph-node counts were for low, low–middle, middle–high, and high-volume robotic lobectomies were 9.8, 11.4, 12.9, and 12.6, respectively ( P   < 0.001), while nodal-upstaging rates were 10.3%, 10.2%, 12.8%, and 13.4%, respectively ( P  < 0.001). Compared to low-volume hospitals, on multivariable analysis, high-volume robotic centers had increased nodal harvest ( P  < 0.001) and nodal-upstaging rates ( P  < 0.001). Robotic lobectomies performed at high-volume hospitals have greater lymph-node harvest and upstaging than low-volume hospitals.

Fifty percent of lung adenocarcinomas harbor somatic mutations in six genes that encode proteins in the EGFR signaling pathway, i.e., EGFR, HER2/ERBB2, HER4/ERBB4, PIK3CA, BRAF, and KRAS. We performed mutational profiling of a large cohort of lung adenocarcinomas to uncover other potential somatic mutations in genes of this signaling pathway that could contribute to lung tumorigenesis. We analyzed genomic DNA from a total of 261 resected, clinically annotated non-small cell lung cancer (NSCLC) specimens. The coding sequences of 39 genes were screened for somatic mutations via high-throughput dideoxynucleotide sequencing of PCR-amplified gene products. Mutations were considered to be somatic only if they were found in an independent tumor-derived PCR product but not in matched normal tissue. Sequencing of 9MB of tumor sequence identified 239 putative genetic variants. We further examined 22 variants found in RAS family genes and 135 variants localized to exons encoding the kinase domain of respective proteins. We identified a total of 37 non-synonymous somatic mutations; 36 were found collectively in EGFR, KRAS, BRAF, and PIK3CA. One somatic mutation was a previously unreported mutation in the kinase domain (exon 16) of FGFR4 (Glu681Lys), identified in 1 of 158 tumors. The FGFR4 mutation is analogous to a reported tumor-specific somatic mutation in ERBB2 and is located in the same exon as a previously reported kinase domain mutation in FGFR4 (Pro712Thr) in a lung adenocarcinoma cell line. This study is one of the first comprehensive mutational analyses of major genes in a specific signaling pathway in a sizeable cohort of lung adenocarcinomas. Our results suggest the majority of gain-of-function mutations within kinase genes in the EGFR signaling pathway have already been identified. Our findings also implicate FGFR4 in the pathogenesis of a subset of lung adenocarcinomas.

Background Robot-assisted minimally invasive esophagectomy (RAMIE) is increasingly adopted in centers worldwide, with ongoing refinements to enhance results. This study aims to assess the current state of RAMIE worldwide and to identify potential areas for improvement. Methods This descriptive study analyzed prospective data from esophageal cancer patients who underwent transthoracic RAMIE in Upper GI International Robotic Association (UGIRA) centers. Main endpoints included textbook outcome rate, surgical techniques, and perioperative outcomes. Analyses were performed separately for intrathoracic (Ivor–Lewis) and cervical anastomosis (McKeown), divided into three time cohorts (2016–2018, 2019–2020, 2021–2023). A sensitivity analysis was conducted with cases after the learning curve (> 70 cases). Results Across 28 UGIRA centers, 2012 Ivor–Lewis and 1180 McKeown procedures were performed. Over the time cohorts, textbook outcome rates were 39%, 48%, and 49% for Ivor–Lewis, and 49%, 63%, and 61% for McKeown procedures, respectively. Fully robotic procedures accounted for 66%, 51%, and 60% of Ivor–Lewis procedures, and 53%, 81%, and 66% of McKeown procedures. Lymph node yield showed 27, 30, and 30 nodes in Ivor–Lewis procedures, and 26, 26, and 34 nodes in McKeown procedures. Furthermore, high mediastinal lymphadenectomy was performed in 65%, 43%, and 37%, and 70%, 48%, and 64% of Ivor–Lewis and McKeown procedures, respectively. Anastomotic leakage rates were 22%, 22%, and 16% in Ivor–Lewis cases, and 14%, 12%, and 11% in McKeown cases. Hospital stay was 13, 14, and 13 days for Ivor–Lewis procedures, and 12, 9, and 11 days for McKeown procedures. In Ivor–Lewis and McKeown, respectively, the sensitivity analysis revealed textbook outcome rates of 43%, 54%, and 51%, and 47%, 64%, and 64%; anastomotic leakage rates of 28%, 18%, and 15%, and 13%, 11%, and 10%; and hospital stay of 11, 12, and 12 days, and 10, 9, and 9 days. Conclusions This study demonstrates favorable outcomes over time in achieving textbook outcome after RAMIE. Areas for improvement include a reduction of anastomotic leakage and shortening of hospital stay.

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality. Exploration of the tumor microenvironment (TME) has resulted in dramatic advancements in the treatment of NSCLC through the advent of immunotherapy. Indeed, anti-programmed death (PD) ligand 1/PD-1 checkpoint inhibitor therapy has substantially improved survival for advanced, unresectable disease and is now being increasingly utilized in the perioperative setting for early-stage, resectable tumors. This success has generated vigorous interest in exploring other cellular players in the NSCLC TME that could be potentially targeted for therapeutic benefit. In this review, we discuss the current state of therapeutic targets in the NSCLC TME, reflect on the revolution of immunotherapy and future directions for its utilization, and reflect on how the current investigations into TME-specific targets may impact thoracic surgical care.

Introduction Patients undergoing non-elective paraesophageal hernia repair (PEHR) have worse perioperative outcomes. Because they are usually older and sicker, however, these patients may be more prone to adverse events, independent of surgical urgency. Our study aimed to determine whether non-elective PEHR is associated with differential postoperative outcome compared to elective repair, using propensity-score weighting. Methods We abstracted data for patients undergoing PEHR ( n  = 924; non-elective n  = 171 (19 %); 1997–2010). Using boosted regression, we generated a propensity-weighted dataset. Odds of 30-day/in-hospital mortality and major complications after non-elective surgery were determined. Results Patients undergoing non-elective repair were significantly older, had more adverse prognostic factors, and significantly more major complications (38 versus 18 %; p  < 0.001) and death (8 versus 1 %; p  < 0.001). After propensity weighting, median absolute percentage bias across 28 propensity-score variables improved from 19 % (significant imbalance) to 5.6 % (well-balanced). After adjusting propensity-weighted data for age and comorbidity score, odds of major complications were still nearly two times greater (OR 1.67, CI 1.07–2.61) and mortality nearly three times greater (OR 2.74, CI 0.93–8.1) than for elective repair. Conclusions Even after balancing significant differences in baseline characteristics, non-elective PEHR was associated with worse outcomes than elective repair. Symptomatic patients should be referred for elective repair by experienced surgeons.

Primary lung myoepithelial carcinomas are rare neoplasms arising from the salivary glands of the respiratory epithelium. Given the rare occurrences and reports of these tumors, appropriate recommendations for resection are difficult to formulate. Although classified as low-grade neoplasms, these tumors have a significant rate of recurrence and distant metastasis.