Background Open esophagectomy results in significant morbidity and mortality. Minimally invasive esophagectomy (MIE) has become increasingly popular at specialized centers with the aim of improving ...perioperative outcomes. Numerous single-institution studies suggest MIE may offer lower short-term morbidity. The two approaches are compared using a large, multiinstitutional database. Methods The Society of Thoracic Surgeons (STS) National Database (v2.081) was queried for all resections performed for esophageal cancer between 2008 and 2011 (n = 3,780). Minimally invasive approaches included both transhiatal (n = 214) and Ivor Lewis (n = 600), and these were compared directly with open transhiatal (n = 1,065) and Ivor Lewis (n = 1,291) procedures, respectively. Thirty-day outcomes were examined using nonparametric statistical testing. Results Both open and MIE groups were similar in terms of preoperative risk factors. Morbidity and all-cause mortality were equivalent at 62.2% and 3.8%. MIE was associated with longer median procedure times (443.0 versus 312.0 minutes; p < 0.001), but a shorter median length of hospital stay (9.0 versus 10.0 days; p < 0.001). Patients who underwent MIE had higher rates of reoperation (9.9% versus 4.4%; p < 0.001) and empyema (4.1% versus 1.8%; p < 0.001). Open technique led to an increased rate of wound infections (6.3% versus 2.3%; p < 0.001), postoperative transfusion (18.7% versus 14.1%; p = 0.002), and ileus (4.5% versus 2.2%; p = 0.002). Propensity score-matched analysis confirmed these findings. High- and low-volume centers had similar outcomes. Conclusions Early results from the STS National Database indicate that MIE is safe, with comparable rates of morbidity and mortality as open technique. Longer procedure times and a higher rate of reoperation following MIE may reflect a learning curve.
We sought to determine the safety and feasibility of esophagectomy after neoadjuvant immunotherapy and chemoradiotherapy in clinical trial patients with locally advanced esophageal cancer.
We ...retrospectively identified patients who were treated with neoadjuvant immunotherapy and chemoradiotherapy (n = 25) or chemoradiotherapy alone (n = 143) at our institution between 2017 and 2020. The primary end point was risk of 30-day major complications (Clavien-Dindo classification system grade ≥ 3), which was assessed between groups using a multivariable log-binomial regression model to obtain adjusted relative risk ratios. Secondary end points were interval to surgery, 30-day readmission rate, and 30-day mortality.
All included patients successfully completed neoadjuvant therapy and underwent esophagectomy with negative margins. Age, sex, performance status, clinical stage, histologic subtype, procedure type, and operative approach were similar between groups. Neoadjuvant immunotherapy was not associated with a statistically significantly increased risk of developing a major pulmonary (relative risk, 1.43; 95% confidence interval, 0.53-3.84; P = .5), anastomotic (relative risk, 1.34; 95% confidence interval, 0.45-3.94; P = .6), or other complication (relative risk, 1.29; 95% confidence interval, 0.26-6.28; P = .8). Median (interquartile range) interval to surgery was 54 days (47-61 days) in the immune checkpoint inhibitor group versus 53 days (47-66 days) in the control group (P = .6). Minimally invasive approaches were successful in 72% of cases, with only 1 conversion. Thirty-day mortality and readmission rates were 0% and 17%, respectively, in the immune checkpoint inhibitor group and 1.4% and 13%, respectively, in the control group.
On the basis of our preliminary experience, esophagectomy appears to be safe and feasible following combined neoadjuvant immunotherapy and standard chemoradiotherapy for locally advanced esophageal cancer.
On the basis of this preliminary experience, esophagectomy appears to be safe and feasible after combined immunotherapy and chemoradiotherapy for esophageal cancer. ICI, Immune checkpoint inhibitor; PET, positron-emission tomography; CT, computed tomography; SUV, standardized uptake value; fx, fraction; AUC, area under the curve. Display omitted
Surgeons are increasingly asked to operate on patients with residual disease after immunotherapy. The safety and utility of lung resection in this setting are unknown.
We retrospectively reviewed ...patients who underwent lung resection within 6 months of treatment with checkpoint blockade agents for metastatic or unresectable cancer. Survival was estimated from the first resection using the Kaplan-Meier approach.
Database query identified 19 patients who underwent 22 resections for suspected residual disease with therapeutic intent after immunotherapy between 2012 and 2016. Lung cancer was the most common diagnosis (47%), followed by metastatic melanoma (37%). The most frequently used agents were nivolumab (32%), pembrolizumab (32%), and ipilimumab (16%). Patients received a mean of 21 doses (range, 1 to 70 doses). The final dose was administered at an average of 75 days (range, 7 to 183 days) before the operation. Anatomic resection (lobectomy or greater) was performed in 11 patients (50%). Four lobectomies were attempted minimally invasively, and one required conversion to thoracotomy. Of the resected patients, 68% had viable tumor remaining. R0 resection was achieved in 95%. Mean operative time for lobectomy was 227 minutes (range, 150 to 394 minutes). Complications occurred in 32% of patients; all but 1 were minor (grade 1/2). The 2-year overall and disease-free survival were 77% and 42%, respectively.
In patients with previously metastatic or unresectable cancer, lung resection for suspected residual disease after immunotherapy is feasible, with high rates of R0 resection. Operations can be technically challenging, but significant morbidity appears to be rare. Outcomes are encouraging, with reasonable survivals during short-interval follow-up.
Radical esophagectomy with two or three-field lymphadenectomy remains the mainstay of curative treatment for localized esophageal cancer, often in combination with systemic chemotherapy and/or ...radiotherapy. In this article, we describe notable advances in the surgical management of esophageal cancer over the past decade that have led to an improvement in both surgical and oncologic outcomes. In addition, we discuss new approaches to surgical management currently under investigation that have the potential to offer further benefits to appropriately selected patients. These incremental breakthroughs primarily include advances in endoscopic and minimally invasive techniques, perioperative management protocols, as well as the application of local therapies, including surgery, to oligometastatic disease.
The aim of this study was to assess the difference (Δ) in neutrophil to lymphocyte ratio (NLR), before and after chemoradiotherapy, as a predictor of treatment response and a prognostic factor for ...recurrence and disease-free survival in patients with esophageal squamous cell cancer treated with chemoradiotherapy with or without surgery.
Patients with locally advanced esophageal squamous cell cancer treated with chemoradiation with and without surgery who had a complete blood count before and after chemoradiotherapy were included. Pretreatment and posttreatment NLR were calculated by dividing the absolute neutrophil count by the absolute lymphocyte count. The ΔNLR was defined as posttreatment minus pretreatment NLR. Characteristics were evaluated for association with ΔNLR using the Wilcoxon signed rank test or the Kruskal-Wallis test. Risk of recurrence and disease-free survival were evaluated using Gray’s and the log rank tests, respectively.
We included 217 patients. Of them, 133 patients (61.3%) received only chemoradiotherapy and 84 (38.7%) underwent surgery after chemoradiotherapy. Among the surgical patients, 43% with pathologic complete response showed significantly lower median ΔNLR than patients with residual disease (−0.03 versus 1.04, p = 0.004). High ΔNLR was a negative predictor of treatment response (odds ratio 0.77, 95% confidence interval: 0.62 to 0.9, p = 0.004). A significant association between high ΔNLR and increased risk of recurrence was also identified.
The ΔNLR was inversely related to pathologic complete response and associated with risk of recurrence. This simple test, in concert with other clinical tools, can help identify patients with pathologic complete response.
Mitochondria are tailored to meet the metabolic and signaling needs of each cell. To explore its molecular composition, we performed a proteomic survey of mitochondria from mouse brain, heart, ...kidney, and liver and combined the results with existing gene annotations to produce a list of 591 mitochondrial proteins, including 163 proteins not previously associated with this organelle. The protein expression data were largely concordant with large-scale surveys of RNA abundance and both measures indicate tissue-specific differences in organelle composition. RNA expression profiles across tissues revealed networks of mitochondrial genes that share functional and regulatory mechanisms. We also determined a larger “neighborhood” of genes whose expression is closely correlated to the mitochondrial genes. The combined analysis identifies specific genes of biological interest, such as candidates for mtDNA repair enzymes, offers new insights into the biogenesis and ancestry of mammalian mitochondria, and provides a framework for understanding the organelle's contribution to human disease.
Recent studies have shown that genes involved in oxidative phosphorylation (OXPHOS) exhibit reduced expression in skeletal muscle of diabetic and prediabetic humans. Moreover, these changes may be ...mediated by the transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α). By combining PGC-1α-induced genome-wide transcriptional profiles with a computational strategy to detect cis-regulatory motifs, we identified estrogen-related receptor α (Errα) and GA repeat-binding protein α as key transcription factors regulating the OXPHOS pathway. Interestingly, the genes encoding these two transcription factors are themselves PGC-1α-inducible and contain variants of both motifs near their promoters. Cellular assays confirmed that Errα and GA-binding protein a partner with PGC-1α in muscle to form a double-positive-feedback loop that drives the expression of many OXPHOS genes. By using a synthetic inhibitor of Errα, we demonstrated its key role in PGC-1α-mediated effects on gene regulation and cellular respiration. These results illustrate the dissection of gene regulatory networks in a complex mammalian system, elucidate the mechanism of PGC-1α action in the OXPHOS pathway, and suggest that Errα agonists may ameliorate insulin-resistance in individuals with type 2 diabetes mellitus.
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