Implementation and Effectiveness of Opioid Prescribing Guidelines After Hiatal Hernia Repair.

INTRODUCTION: We defined institutional opioid prescribing patterns, established prescribing guidelines, and evaluated the adherence to and effectiveness of these guidelines in association with opioid prescribing after hiatal hernia repair (HHR). METHODS: A retrospective chart review was completed for patients who underwent transthoracic (open) or laparoscopic HHR between January and December 2016. Patient-reported opioid use after surgery was used to establish prescribing recommendations. Guideline efficacy was then evaluated among patients undergoing HHR after implementation (August 2018 to June 2019). Data are reported in oral morphine equivalents (OMEs). RESULTS: The initial cohort included n = 87 patients (35 open; 52 laparoscopic) with a 68% survey response rate. For open repair, median prescription size was 338 mg OME (interquartile range [IQR] 250-420) with patient-reported use of 215 mg OME (IQR 78-308) (P = 0.002). Similarly, median prescription size was 270 mg OME (IQR 200-319) with patient-reported use of 100 mg OME (IQR 4-239) (P < 0.001) for laparoscopic repair. Opioid prescribing guidelines were defined as the 66th percentile of patient-reported opioid use. Postguideline implementation cohort included n = 108 patients (36 open; 72 laparoscopic). Median prescription amount decreased by 54% for open and 43% laparoscopic repair, with no detectable change in the overall refill rate after guideline implementation. Patient education, opioid storage, and disposal practices were also characterized. CONCLUSIONS: Evidence-based opioid prescribing guidelines can be successfully implemented for open and laparoscopic HHR with a high rate of compliance and without an associated increase in opioid refills.

Quantitative assessment of gastric ischemic preconditioning on conduit perfusion in esophagectomy: propensity score weighting study.

BACKGROUND: Gastric ischemic preconditioning prior to esophagectomy has been studied as a method to improve gastric conduit perfusion and reduce anastomotic complications, without conclusive results. The aim of this study is to evaluate the feasibility and safety of gastric ischemic preconditioning in terms of post-operative outcomes and quantitative gastric conduit perfusion. METHODS: Patients who underwent an esophagectomy with gastric conduit reconstruction between January 2015 and October 2022 at a single high-volume academic center were reviewed. Patient characteristics, surgical approach, post-operative outcomes, and indocyanine green fluorescence angiography data (ingress index for arterial inflow and ingress time for venous outflow, and the distance from the last gastroepiploic branch to the perfusion assessment point) were analyzed. Two propensity score weighting methods were used to investigate whether gastric ischemic preconditioning reduces anastomotic leaks. Multiple linear regression analysis was used to evaluate the conduit perfusion quantitatively. RESULTS: There were 594 esophagectomies with gastric conduit performed, with 41 having a gastric ischemic preconditioning. Among 544 with cervical anastomoses, leaks were seen in 2/30 (6.7%) in the ischemic preconditioning group and 114/514 (22.2%) in the control group (p = 0.041). Gastric ischemic preconditioning significantly reduced anastomotic leaks on both weighting methods (p = 0.037 and 0.047, respectively). Ingress index and time of the gastric conduit with ischemic preconditioning were significantly better than those without preconditioning (p = 0.013 and 0.025, respectively) after removing the effect of the distance from the last gastroepiploic branch to the perfusion assessment point. CONCLUSION: Gastric ischemic preconditioning results in a statistically significant improvement in conduit perfusion and reduction in post-operative anastomotic leaks.

Quantitative perfusion assessment of gastric conduit with indocyanine green dye to predict anastomotic leak after esophagectomy.

Impaired gastric conduit perfusion is a risk factor for anastomotic leak after esophagectomy. The aim of this study is to evaluate the feasibility of intraoperative quantitative assessment of gastric conduit perfusion with indocyanine green fluorescence angiography as a predictor for cervical esophagogastric anastomotic leak after esophagectomy. Indocyanine green fluorescence angiography using the SPY Elite system was performed in patients undergoing a transhiatal or McKeown esophagectomy from July 2015 through December 2020. Ingress (dye uptake) and Egress (dye exit) at two anatomic landmarks (the tip of a conduit and 5 cm from the tip) were assessed. The collected data in the leak group and no leak group were compared by univariate and multivariable analyses. Of 304 patients who were evaluated, 70 patients developed anastomotic leak (23.0%). There was no significant difference in patients' demographic between the groups. Ingress Index, which represents a proportion of blood inflow, at both the tip and 5 cm of the conduit was significantly lower in the leak group (17.9 vs. 25.4% [P = 0.011] and 35.9 vs. 44.6% [P = 0.019], respectively). Ingress Time, which represents an estimated time of blood inflow, at 5 cm of the conduit was significantly higher in the leak group (69.9 vs. 57.1 seconds, P = 0.006). Multivariable analysis suggested that these three variables can be used to predict future leak. Variables of gastric conduit perfusion correlated with the incidence of cervical esophagogastric anastomotic leak. Intraoperative measurement of gastric conduit perfusion can be predictive for anastomotic leak following esophagectomy.

Long-Term Quality of Life Following Endoscopic Therapy Compared to Esophagectomy for Neoplastic Barrett's Esophagus.

INTRODUCTION: Endoscopic therapy (ET) and esophagectomy result in similar survival for Barrett's esophagus (BE) with high-grade dysplasia (HGD) or T1a esophageal adenocarcinoma (EAC), but the long-term quality of life (QOL) has not been compared. AIMS: We aimed to compare long-term QOL between patients who had undergone ET versus esophagectomy. METHODS: Patients were included if they underwent ET or esophagectomy at the University of Michigan since 2000 for the treatment of HGD or T1a EAC. Two validated survey QOL questionnaires were mailed to the patients. We compared QOL between and within groups (ET = 91, esophagectomy = 62), adjusting for covariates. RESULTS: The median time since initial intervention was 6.8 years. Compared to esophagectomy, ET patients tended to be older, had a lower prevalence of EAC, and had a shorter duration since therapy. ET patients had worse adjusted physical and role functioning than esophagectomy patients. However, the adjusted odds ratio (OR) of having symptoms was significantly less with ET for diarrhea (0.287; 95% confidence interval [CI] = 0.114, 0.724), trouble eating (0.207; 0.0766, 0.562), choking (0.325; 0.119, 0.888), coughing (0.291; 0.114, 0.746), and speech difficulty (0.306; 0.0959, 0.978). Amongst the ET patients, we found that the number of therapy sessions and need for dilation were associated with worse outcomes. DISCUSSION: Multiple measures of symptom status were better with ET compared to esophagectomy following treatment of BE with HGD or T1a EAC. We observed worse long-term physical and role functioning in ET patients which could reflect unmeasured baseline functional status rather than a causal effect of ET.

Constitutively Higher Level of GSTT2 in Esophageal Tissues From African Americans Protects Cells Against DNA Damage.

BACKGROUND & AIMS: African American and European American individuals have a similar prevalence of gastroesophageal reflux disease (GERD), yet esophageal adenocarcinoma (EAC) disproportionately affects European American individuals. We investigated whether the esophageal squamous mucosa of African American individuals has features that protect against GERD-induced damage, compared with European American individuals. METHODS: We performed transcriptional profile analysis of esophageal squamous mucosa tissues from 20 African American and 20 European American individuals (24 with no disease and 16 with Barrett's esophagus and/or EAC). We confirmed our findings in a cohort of 56 patients and analyzed DNA samples from patients to identify associated variants. Observations were validated using matched genomic sequence and expression data from lymphoblasts from the 1000 Genomes Project. A panel of esophageal samples from African American and European American subjects was used to confirm allele-related differences in protein levels. The esophageal squamous-derived cell line Het-1A and a rat esophagogastroduodenal anastomosis model for reflux-generated esophageal damage were used to investigate the effects of the DNA-damaging agent cumene-hydroperoxide (cum-OOH) and a chemopreventive cranberry proanthocyanidin (C-PAC) extract, respectively, on levels of protein and messenger RNA (mRNA). RESULTS: We found significantly higher levels of glutathione S-transferase theta 2 (GSTT2) mRNA in squamous mucosa from African American compared with European American individuals and associated these with variants within the GSTT2 locus in African American individuals. We confirmed that 2 previously identified genomic variants at the GSTT2 locus, a 37-kb deletion and a 17-bp promoter duplication, reduce expression of GSTT2 in tissues from European American individuals. The nonduplicated 17-bp promoter was more common in tissue samples from populations of African descendant. GSTT2 protected Het-1A esophageal squamous cells from cum-OOH-induced DNA damage. Addition of C-PAC increased GSTT2 expression in Het-1A cells incubated with cum-OOH and in rats with reflux-induced esophageal damage. C-PAC also reduced levels of DNA damage in reflux-exposed rat esophagi, as observed by reduced levels of phospho-H2A histone family member X. CONCLUSIONS: We found GSTT2 to protect esophageal squamous cells against DNA damage from genotoxic stress and that GSTT2 expression can be induced by C-PAC. Increased levels of GSTT2 in esophageal tissues of African American individuals might protect them from GERD-induced damage and contribute to the low incidence of EAC in this population.

How Many Nodes Need to be Removed to Make Esophagectomy an Adequate Cancer Operation, and Does the Number Change When a Patient has Chemoradiotherapy Before Surgery?

INTRODUCTION AND DESIGN: Node dissection during esophagectomy is an important aspect of esophageal cancer staging. Controversy remains as to how many nodes need to be resected in order to properly stage a patient and whether the removal of more nodes carries a stage-independent survival benefit. A review of the literature performed by a group of experts in the subject may help define a minimum accepted number of lymph nodes to be resected in both primary surgery and post-induction therapy scenarios. RESULTS AND CONCLUSIONS: The existing evidence generally supports the goal of obtaining a minimum of 15 lymph nodes for pathological examination in both primary surgery and post-induction therapy scenarios.

Positron Emission Tomography 18F-Fluorodeoxyglucose Uptake Correlates with KRAS and EMT Gene Signatures in Operable Esophageal Adenocarcinoma.

BACKGROUND: 18F-fluorodeoxyglucose positron emission tomography is an imaging modality critical to the diagnosis and staging of esophageal cancer. Despite this, the genetic abnormalities associated with increased 18F-fluorodeoxyglucose (FDG)-maximum standardized uptake value (SUVmax) have not been previously explored in esophageal adenocarcinoma. MATERIALS AND METHODS: Treatment-naïve patients, for whom frozen tissue and 18F-fluorodeoxyglucose positron emission tomography data were available, undergoing esophagectomy from 2003 to 2012, were identified. Primary tumor FDG-uptake (SUVmax) was quantified as low (<5), moderate, or high (>10). Genome-wide expression analyses (e.g., microarray) were used to examine gene expression differences associated with FDG-uptake. RESULTS: Eighteen patients with stored positron emission tomography data and tissue were reviewed. Overall survival was similar between patients with high (n = 9) and low (n = 6) FDG-uptake tumors (P = 0.71). Differences in gene expression between tumors with high and low FDG-uptake included enriched expression of various matrix metalloproteinases, extracellular-matrix components, oncogenic signaling members, and PD-L1 (fold-change>2.0, P < 0.05) among the high-FDG tumors. Glycolytic gene expression and pathway involvement were similar between the high- and low-FDG tumor subsets (P = 0.126). Gene ontology analysis of the most differentially expressed genes demonstrated significant upregulation of gene sets associated with extracellular matrix organization and vascular development (P < 0.005). Gene set enrichment analysis further demonstrated associations between FDG-uptake intensity and canonical oncogenic processes, including hypoxia, angiogenesis, KRAS signaling, and epithelial-to-mesenchymal transition (P < 0.001). Interestingly, KRAS expression did not predict worse survival in a larger cohort (n = 104) of esophageal adenocarcinomas (P = 0.64). CONCLUSIONS: These results suggest that elevated FDG-uptake is associated with a variety of oncogenic alterations in operable esophageal adenocarcinoma. These pathways present potential therapeutic targets among tumors exhibiting high FDG-uptake.

Gastric Cancer, Version 3.2016, NCCN Clinical Practice Guidelines in Oncology.

Gastric cancer is the fifth most frequently diagnosed cancer and the third leading cause of death from cancer in the world. Several advances have been made in the staging procedures, imaging techniques, and treatment approaches. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Gastric Cancer provide an evidence- and consensus-based treatment approach for the management of patients with gastric cancer. This manuscript discusses the recommendations outlined in the NCCN Guidelines for staging, assessment of HER2 overexpression, systemic therapy for locally advanced or metastatic disease, and best supportive care for the prevention and management of symptoms due to advanced disease.

Esophageal and esophagogastric junction cancers, version 1.2015.

Esophageal cancer is the sixth most common cause of cancer deaths worldwide. Adenocarcinoma is more common in North America and Western European countries, originating mostly in the lower third of the esophagus, which often involves the esophagogastric junction (EGJ). Recent randomized trials have shown that the addition of preoperative chemoradiation or perioperative chemotherapy to surgery significantly improves survival in patients with resectable cancer. Targeted therapies with trastuzumab and ramucirumab have produced encouraging results in the treatment of advanced or metastatic EGJ adenocarcinomas. Multidisciplinary team management is essential for patients with esophageal and EGJ cancers. This portion of the NCCN Guidelines for Esophageal and EGJ Cancers discusses management of locally advanced adenocarcinoma of the esophagus and EGJ.

Activation of GATA binding protein 6 (GATA6) sustains oncogenic lineage-survival in esophageal adenocarcinoma.

Gene amplification is a tumor-specific event during malignant transformation. Recent studies have proposed a lineage-dependency (addiction) model of human cancer whereby amplification of certain lineage transcription factors predisposes a survival mechanism in tumor cells. These tumor cells are derived from tissues where the lineage factors play essential developmental and maintenance roles. Here, we show that recurrent amplification at 18q11.2 occurs in 21% of esophageal adenocarcinomas (EAC). Utilization of an integrative genomic strategy reveals a single gene, the embryonic endoderm transcription factor GATA6, as the selected target of the amplification. Overexpression of GATA6 is found in EACs that contain gene amplification. We find that EAC patients whose tumors carry GATA6 amplification have a poorer survival. We show that ectopic expression of GATA6, together with FGFR2 isoform IIIb, increases anchorage-independent growth in immortalized Barrett's esophageal cells. Conversely, siRNA-mediated silencing of GATA6 significantly reduces both cell proliferation and anchorage-independent growth in EAC cells. We further demonstrate that induction of apoptotic/anoikis pathways is triggered upon silencing of GATA6 in EAC cells but not in esophageal squamous cells. We show that activation of p38α signaling and up-regulation of TNF-related apoptosis-inducing ligand are detected in apoptotic EAC cells upon GATA6 deprivation. We conclude that selective gene amplification of GATA6 during EAC development sustains oncogenic lineage-survival of esophageal adenocarcinoma.

Multi-institutional beta testing of a novel cervical esophagogastric anastomosis simulator.

Objective: A novel simulator developed to offer hands-on practice for the stapled side-to-side cervical esophagogastric anastomosis was tested previously in a single-center study that supported its value in surgical education. This multi-institutional trial was undertaken to evaluate validity evidence from 6 independent thoracic surgery residency programs. Methods: After a virtual session for simulation leaders, learners viewed a narrated video of the procedure and then alternated as surgeon or first assistant. Using an online survey, perceived value was measured across fidelity domains: physical attributes, realism of materials, realism of experience, value, and relevance. Objective assessment included time, number of sutures tearing, bubble test, and direct inspection. Comparison across programs was performed using the Kruskal-Wallis test. Results: Surveys were completed by 63 participants as surgeons (17 junior and 20 senior residents, 18 fellows, and 8 faculty). For 3 of 5 tasks, mean ratings of 4.35 to 4.44 correlated with "somewhat easy" to "very easy" to perform. The interrupted outer layer of the anastomosis rated lowest, suggesting this task was the most difficult. The simulator was rated as a highly valuable training tool. For the objective measurements of performance, "direct inspection" rated highest followed by "time." A total of 90.5% of participants rated the simulator as ready for use with only minor improvements. Conclusions: Results from this multi-institutional study suggest the cervical esophagogastric anastomosis simulator is a useful adjunct for training and assessment. Further research is needed to determine its value in assessing competence for independent operating and associations between improved measured performance and clinical outcomes.

Pre-operative chemoradiation followed by post-operative adjuvant therapy with tetrathiomolybdate, a novel copper chelator, for patients with resectable esophageal cancer.

Introduction This phase II trial investigated chemoradiation followed by surgery and 2 years of adjuvant tetrathiomolybdate (TM) for resectable esophageal cancer. Methods Patients with resectable, locally advanced esophageal cancer received neoadjuvant cisplatin 60 mg/m(2) (days 1 and 22), paclitaxel 60 mg/m(2) (days 1, 8, 15, and 22), and 45 Gy hyperfractionated radiotherapy for 3 weeks followed by transhiatal esophagectomy. TM 20 mg PO QD was started 4 weeks post-op, and continued for 2 years to maintain the ceruloplasmin level between 5 and 15 mg/dl. Results Sixty-nine patients were enrolled (median age, 60 years). Sixty-six patients underwent surgery and 61 patients had a complete resection. Histologic complete response rate was 10 %. Twenty-one patients did not receive TM (metastases noted in the peri-operative period, prolonged post-operative recovery time, or patient refusal). Forty-eight patients started TM; 14 completed 24 months of treatment, 11 completed 10-18 months, 15 completed 2-8 months, and 8 completed ≤1 month. Twenty-seven patients had disease recurrence. With a median follow-up of 55 months, 25 patients were alive without disease, 1 was alive with disease, and 43 have died. Three-year recurrence-free survival was 44 % (95 % CI, 32-55 %) and the three-year overall survival was 45 % (95 % CI 33-56 %). Conclusions TM is an antiangiogenic agent that is well tolerated in the adjuvant setting. Disease-free survival and overall survival are promising when compared to historical controls treated at our institution with a similar regimen that did not include TM. However, the challenges associated with prolonged administration limit further investigation.

Gastric cancer, version 2.2013: featured updates to the NCCN Guidelines.

The NCCN Clinical Practice Guidelines in Oncology for Gastric Cancer provide evidence- and consensus-based recommendations for a multidisciplinary approach for the management of patients with gastric cancer. For patients with resectable locoregional cancer, the guidelines recommend gastrectomy with a D1+ or a modified D2 lymph node dissection (performed by experienced surgeons in high-volume centers). Postoperative chemoradiation is the preferred option after complete gastric resection for patients with T3-T4 tumors and node-positive T1-T2 tumors. Postoperative chemotherapy is included as an option after a modified D2 lymph node dissection for this group of patients. Trastuzumab with chemotherapy is recommended as first-line therapy for patients with HER2-positive advanced or metastatic cancer, confirmed by immunohistochemistry and, if needed, by fluorescence in situ hybridization for IHC 2+.

Characterizing the cancer genome in lung adenocarcinoma.

Somatic alterations in cellular DNA underlie almost all human cancers. The prospect of targeted therapies and the development of high-resolution, genome-wide approaches are now spurring systematic efforts to characterize cancer genomes. Here we report a large-scale project to characterize copy-number alterations in primary lung adenocarcinomas. By analysis of a large collection of tumours (n = 371) using dense single nucleotide polymorphism arrays, we identify a total of 57 significantly recurrent events. We find that 26 of 39 autosomal chromosome arms show consistent large-scale copy-number gain or loss, of which only a handful have been linked to a specific gene. We also identify 31 recurrent focal events, including 24 amplifications and 7 homozygous deletions. Only six of these focal events are currently associated with known mutations in lung carcinomas. The most common event, amplification of chromosome 14q13.3, is found in approximately 12% of samples. On the basis of genomic and functional analyses, we identify NKX2-1 (NK2 homeobox 1, also called TITF1), which lies in the minimal 14q13.3 amplification interval and encodes a lineage-specific transcription factor, as a novel candidate proto-oncogene involved in a significant fraction of lung adenocarcinomas. More generally, our results indicate that many of the genes that are involved in lung adenocarcinoma remain to be discovered.

Wider Gastric Conduit Morphology Is Associated with Improved Blood Flow During Esophagectomy.

BACKGROUND: It remains unclear what is the ideal conduit shape. The aim of this study was to evaluate association between specific gastric conduit morphology, considering width and length, with its perfusion and the incidence of anastomotic leaks after esophagectomy. METHODS: Patients who underwent an esophagectomy with cervical esophagogastric anastomosis between 2015 and 2021 were evaluated. Indocyanine green angiography was performed to evaluate gastric conduit perfusion, and ingress index (arterial inflow) and ingress time (venous outflow) were measured. The conduit width at the middle of the conduit and the short gastric length as the length from the last gastroepiploic branch to the perfusion assessment point were measured. Propensity score matching was performed to compare wide conduits with narrow conduits. Narrow and wide conduits were defined as < 4 and ≥ 5 cm, respectively. RESULTS: Three hundred fifty-eight patients were reviewed. After applying matching, the wide conduits had higher ingress index (48.2 vs 33.3%, p < 0.001) and shorter ingress time (51.2 vs 66.3 s, p = 0.004) compared to the narrow conduits. Including the short gastric length in analysis, creating a wide conduit is a significant factor for better ingress index (p = 0.001), especially when the perfusion assessment point is 5 cm or farther from the last gastroepiploic branch. Anastomotic leaks did not differ between the groups. CONCLUSIONS: Conduit width is a significant factor of gastric conduit perfusion, especially when the estimated anastomotic site was > 5 cm from the last gastroepiploic branch. Wide conduits seem to have better perfusion and creating a wider conduit might reduce anastomotic leaks.

Transhiatal robot-assisted minimally invasive esophagectomy: unclear benefits compared to traditional transhiatal esophagectomy.

Esophagectomy is a high-risk operation, regardless of technique. Minimally invasive transthoracic esophagectomy could reduce length of stay and pulmonary complications compared to traditional open approaches, but the benefits of minimally invasive transhiatal esophagectomy are unclear. We performed a retrospective review of prospectively gathered data for open transhiatal esophagectomies (THEs) and transhiatal robot-assisted minimally invasive esophagectomies (TH-RAMIEs) performed at a high-volume academic center between 2013 and 2017. Multivariate logistic regression was used to calculate adjusted odds ratios (aORs) for outcomes. 465 patients met inclusion criteria (378 THE and 87 TH-RAMIE). THE patients more likely had an ASA score of 3 + (89.1% vs 77.0%, p = 0.012), whereas TH-RAMIE patients more likely had a pathologic staging of 3+ (43.7% vs. 31.2%, p = 0.026). TH-RAMIE patients were less likely to receive epidurals (aOR 0.06, 95% confidence interval [CI] 0.03-0.14, p < 0.001), but epidural use itself was not associated with differences in outcomes. TH-RAMIE patients experienced higher rates of pulmonary complications (adjusted odds ratio [OR] 1.82, 95% CI 1.03-3.22, p = 0.040), particularly pulmonary embolus (aOR 5.20, 95% CI 1.30-20.82, p = 0.020). There were no statistically significant differences in lymph node harvest, unexpected ICU admission, length of stay, in-hospital mortality, or 30-day readmission or mortality rates. The TH-RAMIE approach had higher rates of pulmonary complications. There were no statistically significant advantages to the TH-RAMIE approach. Further investigation is needed to understand the benefits of a minimally invasive approach to the open transhiatal esophagectomy.

Similar Quality of Life After Conventional and Robotic Transhiatal Esophagectomy.

BACKGROUND: Patient-reported outcomes (PROs) for minimally invasive esophagectomy (MIE) have demonstrated benefits compared with open transthoracic or 3-hole esophagectomy. PROs, including quality of life (QoL) and fear of recurrence (FoR), comparing open transhiatal esophagectomy (THE) and transhiatal robotic-assisted MIE (Th-RAMIE) have been limited. METHODS: At a single, high-volume academic center, patients undergoing THE and Th-RAMIE with gastric conduit for clinical stage I to III esophageal cancer from 2013 to 2018 were evaluated. The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30), the EORTC Quality of Life Questionnaire in Esophageal Cancer (QLQ-OES18), and the FoR survey were administered preoperatively and at 1, 6, and 12 months postoperatively. Linear mixed-effects models were used for QoL and FoR score comparisons. Perioperative outcomes were also compared. RESULTS: A total of 309 patients (212 in the group and 97 in the Th-RAMIE group) were included. The Th-RAMIE cohort had a significantly higher number of lymph nodes harvested (14 ± 0.8 vs 11.2 ± 0.4; P = .01), a shorter length of stay (days, 10.0 ± 6.7 vs 12.1 ± 7.0; P = .03), lower rates of postoperative ileus (5% vs 15%; P = .02), and fewer opioids prescribed at discharge (71% vs 85%; P = .03). After adjustment, there were no significant differences in QLQ-C30, QLQ-OES18, and FoR scores between the groups out to 1 year postoperatively. CONCLUSIONS: There were no clear patient-reported benefits of Th-RAMIE over THE for esophageal cancer. However, Th-RAMIE conferred several perioperative benefits.

Gene-expression profiles predict survival of patients with lung adenocarcinoma.

Histopathology is insufficient to predict disease progression and clinical outcome in lung adenocarcinoma. Here we show that gene-expression profiles based on microarray analysis can be used to predict patient survival in early-stage lung adenocarcinomas. Genes most related to survival were identified with univariate Cox analysis. Using either two equivalent but independent training and testing sets, or 'leave-one-out' cross-validation analysis with all tumors, a risk index based on the top 50 genes identified low-risk and high-risk stage I lung adenocarcinomas, which differed significantly with respect to survival. This risk index was then validated using an independent sample of lung adenocarcinomas that predicted high- and low-risk groups. This index included genes not previously associated with survival. The identification of a set of genes that predict survival in early-stage lung adenocarcinoma allows delineation of a high-risk group that may benefit from adjuvant therapy.

A novel cervical esophagogastric anastomosis simulator.

OBJECTIVES: At least partially technically related, a cervical esophagogastric anastomosis has a 12% to 14% leak rate, which is theoretically reducible with simulator practice. Preliminary development and testing of a cervical esophagogastric anastomosis simulator are described. METHODS: A portable, low-cost, scale reproduction of the cervical esophagogastric anastomosis operative site was engineered around a 19 × 11 × 6-cm plastic box. Silicone "esophageal" and "gastric tip" castings permitted construction of a stapled side-to-side cervical esophagogastric anastomosis guided by an illustrated curriculum. In a 2-phase pilot study, the simulator and curriculum were evaluated. Phase 1: Seven faculty evaluated fidelity using a 5-point, 24-item survey of (1) physical attributes, (2) realism of materials, (3) realism of experience, (4) value, and (5) relevance, and (6) ability to perform tasks. Overall impression of the simulator was also measured. Phase 2: Eight thoracic surgical trainees similarly evaluated the simulator and the quality of the curriculum. Faculty and trainee ratings were compared using a Rasch model, and inter-rater agreement was estimated. RESULTS: There were no overall fidelity differences across faculty and resident ratings. Combined observed averages ranged from 4.52 (Realism of Materials) to 5.00 (Relevance). Lifelike feel of esophagus had the lowest ratings (observed average = 4.40). Residents rated interrupted outer layer of anterior closure to be more difficult (observed average = 4.13) than faculty (observed average = 4.86; P = .016, d = 1.99). Global ratings (observed average = 3.33/4.00) indicated participants believed the simulator could be used for cervical esophagogastric anastomosis training now, but could be improved slightly. CONCLUSIONS: Preliminary evidence suggests the novel cervical esophagogastric anastomosis simulator is valuable as a surgical training tool.

Autoantibody profiles reveal ubiquilin 1 as a humoral immune response target in lung adenocarcinoma.

There is considerable evidence that the presence of cancer can elicit a humoral immune response to specific proteins in the host, and these resulting autoantibodies may have potential as noninvasive biomarkers. To characterize the autoantibody repertoire present in the sera of patients with lung adenocarcinoma, we developed a high-density peptide microarray derived from biopanning a lung cancer phage display library. Using a 2,304-element microarray, we interrogated a total of 250 sera from Michigan lung cancer patients and noncancer controls to develop an "autoantibody profile" of lung adenocarcinoma. A set of 22 discriminating peptides derived from a training set of 125 serum samples from lung adenocarcinoma patients and control subjects was found to predict cancer status with 85% sensitivity and 86% specificity in an independent test set of 125 sera. Sequencing of the immunoreactive phage-peptide clones identified candidate humoral immune response targets in lung adenocarcinoma, including ubiquilin 1, a protein that regulates the degradation of several ubiquitin-dependent proteasome substrates. An independent validation set of 122 serum samples from Pittsburgh was examined using two overlapping clones of ubiquilin 1 that showed 0.79 and 0.74 of the area under the receiver operating characteristics curve, respectively. Significantly increased levels of both ubiquilin 1 mRNA and protein, as well as reduced levels of the phosphorylated form of this protein, were detected in lung tumors. Immunofluorescence using anti-ubiquilin 1 antibodies confirmed intracellular expression within tumors cells. These studies indicate that autoantibody profiles, as well as individual candidates, may be useful for the noninvasive detection of lung adenocarcinoma.