Long-Term Outcomes after Robotic-Assisted Ivor-Lewis Esophagectomy

Purpose: Robotic assistance has gained a measure of acceptance in thoracic procedures, including esophagectomy. However, there is a paucity of data regarding long-term outcomes for robotic esophagectomy. We have previously reported our initial series of robot assisted Ivor-Lewis (RAIL) esophagectomy. We report long-term outcomes to assess the efficacy of the procedure.Methods : We performed a retrospective review of 112 consecutive patients who underwent a RAIL at our institution. Patient demographics, diagnosis, pathology, operative characteristics, post-operative complications, and long-term outcomes were documented. Descriptive statistical analysis was performed for all the variables. Primary endpoints were mortality and disease-free survival. Overall survival (OS) and disease-free survival (DFS) were calculated using the Kaplan-Meier method. Results: Of the 112 patients, 106 had a diagnosis of cancer, with adenocarcinoma the dominant histology (87.5%). Of the 106 cancer patients, 81(76.4%) received neo-adjuvant chemoradiation (stage 3A most common). The 30, 60, and 90-day mortality was 1 (0.9%), 3 (2.7%), and 4 (3.6%) respectively. There were 9 anastomotic leaks (8%) and 18 (16.1%) patients had a stricture requiring dilation. All patient OS at 1, 3, and 5 years was 81.4%, 60.5%, and 51.0%, respectively. For cancer patients, the 1, 3, and 5 years OS was 81.3%, 59.2%, and 49.4% respectively and the DFS was 75.3%, 42.3%, and 44.0%. Conclusion: We have shown that long term outcomes after RAIL esophagectomy are similar to other non-robotic esophagectomies. Given the potential advantages of robotic assistance, our results are crucial to demonstrate that RAIL does not result in inferior outcomes.https://scholarlycommons.henryford.com/merf2019clinres/1060/thumbnail.jp

Is Esophagectomy for Benign Conditions Benign?

BACKGROUND: Outcomes data on esophagectomy performed for benign conditions is scarce. Using the National Surgical Quality Improvement Program database, we sought to analyze outcomes of esophagectomy performed for benign conditions. METHODS: The National Surgical Quality Improvement Program database was queried for all esophagectomies performed from 2005 to 2015. Outcomes for benign conditions were analyzed and compared with outcomes for malignant conditions. RESULTS: Esophagectomy was performed in 7,477 patients during the study period. Of those, 6,762 underwent esophagectomy for malignant conditions and 715 for benign conditions. For patients with benign conditions, reconstruction was performed using gastric conduit in 631 and colon/intestine in 84. The anastomosis was intrathoracic in 420 and cervical in 295. Benign esophagectomies were more likely to be emergent (10.1% vs 0.4%, p \u3c 0.001). In addition, these patients had a longer hospital length of stay (17.2 days vs 14.5 days, p \u3c 0.001) and higher occurrence of Clavien-Dindo grade IV complications (25% vs 20%, p = 0.003). Mortality was similar at 4%. In patients with benign conditions, reconstruction with colon/intestine had higher occurrence of Clavien-Dindo Grade IV complications (37% vs 23%, p = 0.006), surgical wound infections (33% vs 16%, p \u3c 0.001), and death (10% vs 4%, p = 0.017) compared with gastric reconstruction. Site of anastomosis did not affect outcomes. CONCLUSIONS: Benign esophagectomies are associated with significant morbidity. Although the site of the anastomosis does not alter outcomes, use of colon/intestine conduit should be pursued with caution

Esophageal Cancer Metabolite Biomarkers Detected by LC-MS and NMR Methods

Background: Esophageal adenocarcinoma (EAC) is a rarely curable disease and is rapidly rising worldwide in incidence. Barret’s esophagus (BE) and high-grade dysplasia (HGD) are considered major risk factors for invasive adenocarcinoma. In the current study, unbiased global metabolic profiling methods were applied to serum samples from patients with EAC, BE and HGD, and healthy individuals, in order to identify metabolite based biomarkers associated with the early stages of EAC with the goal of improving prognostication. Methodology/Principal Findings: Serum metabolite profiles from patients with EAC (n = 67), BE (n = 3), HGD (n = 9) and healthy volunteers (n = 34) were obtained using high performance liquid chromatography-mass spectrometry (LC-MS) methods. Twelve metabolites differed significantly (p,0.05) between EAC patients and healthy controls. A partial leastsquares discriminant analysis (PLS-DA) model had good accuracy with the area under the receiver operative characteristic curve (AUROC) of 0.82. However, when the results of LC-MS were combined with 8 metabolites detected by nuclear magnetic resonance (NMR) in a previous study, the combination of NMR and MS detected metabolites provided a much superior performance, with AUROC = 0.95. Further, mean values of 12 of these metabolites varied consistently from healthy controls to the high-risk individuals (BE and HGD patients) and EAC subjects. Altered metabolic pathways including a number of amino acid pathways and energy metabolism were identified based on altered levels of numerous metabolites

Gastroesophageal junction adenocarcinoma displays abnormalities in homologous recombination and nucleotide excision repair

OBJECTIVE: Esophageal adenocarcinoma (EAC) continues to be a disease associated with high mortality. Among the factors leading to poor outcomes are innate resistance to currently available therapies, advanced stage at diagnosis, and complex biology. Platinum and ionizing radiation form the backbone of treatment for the majority of patients with EAC. Of the multiple processes involved in response to platinum chemotherapy or ionizing radiation, deoxyribonucleic acid (DNA) repair has been a major player in cancer sensitivity to these agents. DNA repair defects have been described in various malignancies. The purpose of this study was to determine whether alterations in DNA repair are present in EAC compared with normal gastroesophageal tissues. METHODS: We analyzed the expression of genes involved in homologous recombination (HR), nonhomologous end-joining, and nucleotide excision repair (NER) pathways in 12 EAC tumor samples with their matched normal counterparts. These pathways were chosen because they are the main pathways involved in the repair of platinum- or ionizing-radiation-induced damage. In addition, abnormalities in these pathways have not been well characterized in EAC. RESULTS: We identified increased expression of at least one HR gene in eight of the EAC tumor samples. Alterations in the expression of EME1, a structure-specific endonuclease involved in HR, were the most prevalent, with messenger (m)RNA overexpression in six of the EAC samples. In addition, all EAC samples revealed decreased expression of at least one of numerous NER genes including XPC, XPA, DDB2, XPF, and XPG. CONCLUSION: Our study identified DNA repair dysregulation in EAC involving two critical pathways, HR and NER, and is the first demonstration of EME1 upregulation in any cancer. These DNA repair abnormalities have the potential to affect a number of processes such as genomic instability and therapy response, and the consequences of these defects deserve further study in EAC

Quantitative Serum Glycomics of Esophageal Adenocarcinoma, and Other Esophageal Disease Onsets

Aberrant glycosylation has been implicated in various types of cancers and changes in glycosylation may be associated with signaling pathways during malignant transformation. Glycomic profiling of blood serum, in which cancer cell proteins or their fragments with altered glycosylation patterns are shed, could reveal the altered glycosylation. We performed glycomic profiling of serum from patients with no known disease (N=18), patients with high grade dysplasia (HGD, N=11) and Barrett’s (N=5), and patients with esophageal adenocarcinoma (EAC, N=50) in an attempt to delineate distinct differences in glycosylation between these groups. The relative intensities of 98 features were significantly different among the disease onsets; 26 of these correspond to known glycan structures. The changes in the relative intensities of three of the known glycan structures predicted esophageal adenocarcinoma with 94% sensitivity and better than 60% specificity as determined by receiver operating characteristic (ROC) analysis. We have demonstrated that comparative glycomic profiling of EAC reveals a subset of glycans that can be selected as candidate biomarkers. These markers can differentiate disease-free from HGD, disease-free from EAC, and HGD from EAC. The clinical utility of these glycan biomarkers requires further validation

Differential gene expression profiling of esophageal adenocarcinoma

BackgroundDifferential gene expression offers an attractive means by which to study genes that may be involved in disease development and/or progression. We performed quantitative gene expression in various stages of esophageal adenocarcinoma, treated exclusively by surgery with complete 2-field lymphadenectomy, in an attempt to discern genes involved in disease progression as well as genes that may predict survival.MethodsGene expression profiling was accomplished by cDNA-mediated annealing, selection, extension, and ligation (DASL) assay. RNA was extracted from 89 archived formalin-fixed, paraffin-embedded esophageal adenocarcinoma tissues. DASL assay was performed with the Sentrix Universal Array (Illumina Corp, San Diego, Calif) of 502 known cancer-related genes. Bioinformatics tools were used to determine significant differential gene expression in T1-2 versus T3-4 tumors and tumors without lymph node involvement (N0) versus tumors with lymph node involvement (N+). Gene expression was also correlated with overall survival.ResultsTwenty-one genes were overexpressed in T1-2 compared with T3-4 tumors (false discovery rate of 0). Underexpression of 1 gene was seen in N+ compared with N0 tumors (false discovery rate of 0). For overall survival, underexpression of 9 genes correlated with long survival.ConclusionsUsing differential gene expression of 502 known cancer genes, we identified genes that may be involved at various stages in the progression of esophageal adenocarcinoma. We also identified genes that may correlate with prolonged survival and, thus, may serve as prognostic markers. These findings may provide further insight into the mechanisms of development and/or progression of esophageal adenocarcinoma. Prospective studies are needed to verify the prognostic value of these genes

Characteristics of a novel treatment system for linear accelerator–based stereotactic radiosurgery

The purpose of this study is to characterize the dosimetric properties and accuracy of a novel treatment platform (Edge radiosurgery system) for localizing and treating patients with frameless, image-guided stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT). Initial measurements of various components of the system, such as a comprehensive assessment of the dosimetric properties of the flattening filter-free (FFF) beams for both high definition (HD120) MLC and conical cone-based treatment, positioning accuracy and beam attenuation of a six degree of freedom (6DoF) couch, treatment head leakage test, and integrated end-to-end accuracy tests, have been performed. The end-to-end test of the system was performed by CT imaging a phantom and registering hidden targets on the treatment couch to determine the localization accuracy of the optical surface monitoring system (OSMS), cone-beam CT (CBCT), and MV imaging systems, as well as the radiation isocenter targeting accuracy. The deviations between the percent depth-dose curves acquired on the new linac-based system (Edge), and the previously published machine with FFF beams (TrueBeam) beyond Dmax were within 1.0% for both energies. The maximum deviation of output factors between the Edge and TrueBeam was 1.6%. The optimized dosimetric leaf gap values, which were fitted using Eclipse dose calculations and measurements based on representative spine radiosurgery plans, were 0.700 mm and 1.000 mm, respectively. For the conical cones, 6X FFF has sharper penumbra ranging from 1.2–1.8 mm (80%-20%) and 1.9–3.8 mm (90%-10%) relative to 10X FFF, which has 1.2–2.2mm and 2.3–5.1mm, respectively. The relative attenuation measurements of the couch for PA, PA (rails-in), oblique, oblique (rails-out), oblique (rails-in) were: -2.0%, -2.5%, -15.6%, -2.5%, -5.0% for 6X FFF and -1.4%, -1.5%, -12.2%, -2.5%, -5.0% for 10X FFF, respectively, with a slight decrease in attenuation versus field size. The systematic deviation between the OSMS and CBCT was -0.4 ± 0.2 mm, 0.1± 0.3mm, and 0.0 ± 0.1 mm in the vertical, longitudinal, and lateral directions. The mean values and standard deviations of the average deviation and maximum deviation of the daily Winston-Lutz tests over three months are 0.20 ± 0.03 mm and 0.66 ± 0.18 mm, respectively. Initial testing of this novel system demonstrates the technology to be highly accurate and suitable for frameless, linac-based SRS and SBRT treatment

The 5 Most Important Recent Publications Regarding Robotic Esophageal Surgery

Robotic-assisted minimally invasive esophagectomy is gaining acceptance as a safe and effective alternative to open esophagectomy