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.

Tracheobronchomalacia and Excessive Dynamic Airway Collapse: Current Concepts and Future Directions.

Tracheobronchomalacia (TBM) and excessive dynamic airway collapse (EDAC) are airway abnormalities that share a common feature of expiratory narrowing but are distinct pathophysiologic entities. Both entities are collectively referred to as expiratory central airway collapse (ECAC). The malacia or weakness of cartilage that supports the tracheobronchial tree may occur only in the trachea (ie, tracheomalacia), in both the trachea and bronchi (TBM), or only in the bronchi (bronchomalacia). On the other hand, EDAC refers to excessive anterior bowing of the posterior membrane into the airway lumen with intact cartilage. Clinical diagnosis is often confounded by comorbidities including asthma, chronic obstructive pulmonary disease, obesity, hypoventilation syndrome, and gastroesophageal reflux disease. Additional challenges include the underrecognition of ECAC at imaging; the interchangeable use of the terms TBM and EDAC in the literature, which leads to confusion; and the lack of clear guidelines for diagnosis and treatment. The use of CT is growing for evaluation of the morphology of the airway, tracheobronchial collapsibility, and extrinsic disease processes that can narrow the trachea. MRI is an alternative tool, although it is not as widely available and is not used as frequently for this indication as is CT. Together, these tools not only enable diagnosis, but also provide a road map to clinicians and surgeons for planning treatment. In addition, CT datasets can be used for 3D printing of personalized medical devices such as stents and splints. An invited commentary by Brixey is available online. Online supplemental material is available for this article. ©RSNA, 2022.

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.

Isoform alterations in the ubiquitination machinery impacting gastrointestinal malignancies.

The advancement of RNAseq and isoform-specific expression platforms has led to the understanding that isoform changes can alter molecular signaling to promote tumorigenesis. An active area in cancer research is uncovering the roles of ubiquitination on spliceosome assembly contributing to transcript diversity and expression of alternative isoforms. However, the effects of isoform changes on functionality of ubiquitination machineries (E1, E2, E3, E4, and deubiquitinating (DUB) enzymes) influencing onco- and tumor suppressor protein stabilities is currently understudied. Characterizing these changes could be instrumental in improving cancer outcomes via the identification of novel biomarkers and targetable signaling pathways. In this review, we focus on highlighting reported examples of direct, protein-coded isoform variation of ubiquitination enzymes influencing cancer development and progression in gastrointestinal (GI) malignancies. We have used a semi-automated system for identifying relevant literature and applied established systems for isoform categorization and functional classification to help structure literature findings. The results are a comprehensive snapshot of known isoform changes that are significant to GI cancers, and a framework for readers to use to address isoform variation in their own research. One of the key findings is the potential influence that isoforms of the ubiquitination machinery have on oncoprotein stability.

Quality improvement mechanisms to improve lymph node staging for lung cancer: Trends from a statewide database.

OBJECTIVE: Our statewide thoracic quality collaborative has implemented multiple quality improvement initiatives to improve lung cancer nodal staging. We subsequently implemented a value-based reimbursement initiative to further incentivize quality improvement. We compare the impact of these programs to steer future quality improvement initiatives. METHODS: Since 2016, our collaborative focused on improving lymph node staging for lung cancer by leveraging unblinded, hospital-level metrics and collaborative feedback. In 2021, a value-based reimbursement initiative was implemented with statewide yearly benchmark rates for (1) preoperative mediastinal staging for ≥T2N0 lung cancer, and (2) sampling ≥5 lymph node stations. Participating surgeons would receive additional reimbursement if either benchmark was met. We reviewed patients from January 2015 to March 2023 at the 21 participating hospitals to determine the differential effects on quality improvement. RESULTS: We analyzed 6228 patients. In 2015, 212 (39%) patients had ≥5 nodal stations sampled, and 99 (51%) patients had appropriate preoperative mediastinal staging. During 2016 to 2020, this increased to 2253 (62%) patients and 739 (56%) patients, respectively. After 2020, 1602 (77%) patients had ≥5 nodal stations sampled, and 403 (73%) patients had appropriate preoperative mediastinal staging. Interrupted time-series analysis demonstrated significant increases in adequate nodal sampling and mediastinal staging before value-based reimbursement. Afterward, preoperative mediastinal staging rates briefly dropped but significantly increased while nodal sampling did not change. CONCLUSIONS: Collaborative quality improvement made significant progress before value-based reimbursement, which reinforces the effectiveness of leveraging unblinded data to a collaborative group of thoracic surgeons. Value-based reimbursement may still play a role within a quality collaborative to maintain infrastructure and incentivize participation.

ISG15-GRAIL1-CD3 axis influences survival of esophageal adenocarcinoma patients.

Immunosuppression is a common feature of esophageal adenocarcinoma (EAC) and has been linked to poor overall survival (OS). We hypothesized that upstream factors might negatively influence CD3 levels and T-cell activity, thus promoting immunosuppression and worse survival. We used clinical data and patient samples of those who progressed from Barrett's (BE) to dysplasia to EAC, investigated gene (RNAseq), protein (tissue microarray) expression and performed cell biology studies to delineate a pathway impacting CD3 protein stability that might influence EAC outcome. We show that the loss of both CD3-ε expression and CD3+ T-cell number are correlated with worse OS in EAC. The GRAIL (gene related to anergy in lymphocytes) isoform 1 (GRAIL1), which is the prominent isoform in EACs, degrades (ε, γ, δ) CD3s and inactivates T-cells. In contrast, isoform 2 (GRAIL2), which is reduced in EACs, stabilizes CD3s. Further, GRAIL1 mediated CD3 degradation is facilitated by interferon stimulated gene 15 (ISG15), a ubiquitin-like protein. Consequently, either the overexpression of a ligase-dead GRAIL1, ISG15 knockdown, or the overexpression of a conjugation-defective ISG15-LRAA mutant can increase CD3 levels. Together, we identified that an ISG15→GRAIL1→mutant p53 amplification loop negatively influencing CD3 levels and T-cell activity, thus promoting immunosuppression in EAC.

The Role of Lung Cancer Surgical Technique on Lymph Node Sampling and Pathologic Nodal Upstaging.

BACKGROUND: The role of operative approach in surgical lymphadenectomies and pathologic nodal upstaging for lung cancer remains unclear. METHODS: This study retrospectively reviewed patients who underwent lobectomy for non-small cell lung cancer from January 2015 to December 2020 at 16 centers within a statewide quality improvement collaborative in Michigan. Patients were stratified by operative approach, and our primary end points were number of LN recovered, number of LN stations sampled, and rates of nodal upstaging with nodal upstaging defined as a higher final pathologic nodal stage compared with preoperative clinical nodal staging. RESULTS: A total of 3036 patients were included: 608 (20.0%) with open lobectomies, 1362 (41.3%) with video-assisted thoracoscopic surgery (VATS), and 1233 (37.4%) with robot-assisted thoracoscopic surgery (RATS) lobectomies. Using multivariable logistic regression, study investigators found that VATS was associated with lower rates of nodal upstaging (odds ratio [OR], 0.71; 95% CI, 0.54-0.94; P = .015) and harvesting ≥10 LNs (OR, 0.40; 95% CI, 0.31-0.50; P < .001) as compared with open surgery, whereas no significant difference was found between RATS and open techniques. Compared with open surgery, VATS had lower rates of sampling at ≥5 nodal stations (OR, 0.66; 95% CI, 0.53-0.84; P = .001), whereas RATS rates were higher (OR, 2.38; 95% CI, 1.85-3.06; P < .001). CONCLUSIONS: VATS lobectomies were associated with lower rates of harvesting ≥10 LNs, sampling ≥5 LN stations, and pathologic nodal upstaging compared with open and RATS lobectomies. Compared with open procedures, RATS lobectomies were associated with higher rates of sampling ≥5 LN stations, but there was no significant difference between open and RATS approaches in rates of nodal upstaging or harvesting ≥10 LNs.

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.

Adequate lung cancer surgery lymphadenectomy within a statewide quality collaborative: Quality improvement in action.

OBJECTIVES: In January 2016, our statewide quality improvement collaborative focused on 3 metrics of adequate lymph node harvest during lung cancer surgery: (1) rates of pathologic examination of 10 lymph nodes or more; (2) sampling 5 or more lymph node stations or more within the hilum or mediastinum; and (3) pathologic nodal upstaging (pathologic nodal stage higher than clinical nodal stage). Unblinded, hospital-level outcomes were presented at biannual meetings, and opportunities for education or improvement were discussed. We set out to describe this quality improvement initiative and the subsequent impact on surgical lymphadenectomies statewide. METHODS: We retrospectively reviewed patients undergoing lobectomy for stage IA to IIIA non-small-cell lung cancer from July 2015 to December 2020 at the 16 participating centers. RESULTS: The study cohort included 3753 patients. The rates of examining 10 lymph nodes or more statewide increased from 215 lobectomies (44.0%) in 2015 to 522 lobectomies (78.9%) in 2020 (P < .001). Similar trends were noted statewide for 5 lymph node stations or more, which increased from 193 lobectomies (39.6%) to 531 lobectomies (80.3%) in 2020 (P < .001). The overall rate of nodal upstaging was more variable year to year and generally declined over time (P = .004). CONCLUSIONS: Our statewide quality improvement initiative improved rates of appropriate lymph node staging for surgically treated non-small cell lung cancer compared with national rates. This work demonstrates the power that a "community of practice" philosophy can have on surgical treatment of lung cancer. Quality improvement interventions including transparent data-driven discussions and collaboration can help guide future quality improvement initiatives and should be readily transferrable to other clinical domains.

Clinically Occult Diffuse Pleural Mesothelioma in Patients Presenting With Spontaneous Pneumothorax.

OBJECTIVES: To report histologic features of unsuspected diffuse pleural mesothelioma (DPM) in surgical specimens for pneumothorax and demonstrate how ancillary markers support a diagnosis of malignancy in this context. We explored whether pneumothorax may be a clinical manifestation of mesothelioma in situ (MIS). METHODS: A single-institution database search identified patients who underwent surgical resection for spontaneous pneumothorax (n = 229) and/or were diagnosed with DPM (n = 88) from 2000 to 2020. RESULTS: Spontaneous pneumothorax without clinical, radiologic, or intraoperative suspicion of mesothelioma was the initial presentation in 2 (2.3%) of 88 patients diagnosed with DPM. This represented 0.9% (2/229) of all patients undergoing surgical management of pneumothorax but accounted for a larger proportion of older patients (12.5% older than 70 years). Immunohistochemistry for BAP-1 and/or MTAP confirmed the diagnosis of DPM in 2 cases. Mesothelioma in situ was identified retrospectively by immunohistochemistry in 1 case of spontaneous pneumothorax from a 77-year-old man who developed invasive DPM 25 months later. No additional cases of MIS were identified in 19 surgical lung resections for spontaneous pneumothorax. CONCLUSIONS: Histologic examination of bleb resections with ancillary testing for cases with ambiguous features is essential for detection of early DPM. It is uncertain whether spontaneous pneumothorax may represent a clinical manifestation of MIS.

Epidemiology of Postoperative Complications After Esophagectomy: Implications for Management.

BACKGROUND: Despite advances in operative techniques and postoperative care, esophagectomy remains a morbid operation. Leveraging complication epidemiology and the correlation of these complications may improve rescue and refine early recovery pathways. METHODS: This study retrospectively reviewed all esophagectomies performed at a tertiary academic center from 2014 to 2021 and quantified the timing of the most common complications. Daily incidence values for index complications were calculated, and a covariance matrix was created to examine the correlation of the complications with each other. Study investigators performed a Cox proportional hazards analysis to clarify the association between early diagnosis of postoperative atrial fibrillation and pneumonia with subsequent anastomotic leak. RESULTS: The study analyzed 621 esophagectomies, with 580 (93.4%) cervical anastomoses and 474 (76%) patients experiencing complications. A total of 159 (25.6%) patients had postoperative atrial fibrillation, and 155 (25.0%) had an anastomotic leak. The median (interquartile range [IQR]) postoperative day of these complications was day 2 (IQR, days 2-3) and day 8 (IQR, days 7-11), respectively. Our covariance matrix found significant associations in the variance of the most common postoperative complications, including pneumonia, atrial fibrillation, anastomotic leak, and readmissions. Early postoperative atrial fibrillation (hazard ratio, 8.1; 95% CI, 5.65-11.65) and postoperative pneumonia (hazard ratio, 3.8; 95% CI, 1.98-7.38) were associated with anastomotic leak. CONCLUSIONS: Maintaining a high index of suspicion for early postoperative complications is crucial for rescuing patients after esophagectomy. Early postoperative pneumonia and atrial fibrillation may be sentinel complications for an anastomotic leak, and their occurrence may be used to prompt further clinical investigation. Early recovery protocols should consider the development of early complications into postoperative feeding and imaging algorithms.

Factors affecting timing of surgery following neoadjuvant chemoradiation for esophageal cancer.

Background: Neoadjuvant chemoradiation with esophagectomy is standard management for locally advanced esophageal cancer. Studies have shown that surgical timing following chemoradiation is important for minimizing postoperative complications, however in practice timing is often variable and delayed. Although postoperative impact of surgical timing has been studied, less is known about factors associated with delays. Materials and methods: A retrospective review was performed for 96 patients with esophageal cancer who underwent chemoradiation then esophagectomy between 2018 and 2020 at a single institution. Univariable and stepwise multivariable analyses were used to assess association between social (demographics, insurance) and clinical variables (pre-operative weight, comorbidities, prior cardiothoracic surgery, smoking history, disease staging) with time to surgery (≤8 weeks "on-time" vs. >8 weeks "delayed"). Results: Fifty-one patients underwent esophagectomy within 8 weeks of chemoradiation; 45 had a delayed operation. Univariate analysis showed the following characteristics were significantly different between on-time and delayed groups: weight loss within 3 months of surgery (3.9 ± 5.1 kg vs. 1.5 ± 3.6 kg; P = 0.009), prior cardiovascular disease (29% vs. 49%; P = 0.05), prior cardiothoracic surgery (4% vs. 22%; P = 0.01), history of ever smoked (69% vs. 87%; P = 0.04), absent nodal metastasis on pathology (57% vs. 82%; P = 0.008). Multivariate analysis demonstrated that prior cardiothoracic surgery (OR 8.924, 95%CI 1.67-47.60; P = 0.01) and absent nodal metastasis (OR 4.186, 95%CI 1.50-11.72; P = 0.006) were associated with delayed surgery. Conclusions: Delayed esophagectomy following chemoradiotherapy is associated with prior cardiothoracic surgery and absent nodal metastasis. Further investigations should focus on understanding how these factors contribute to delays to guide treatment planning and mitigate sources of outcome disparities.

Evidence-based opioid prescribing guidelines after lung resection: a prospective, multicenter analysis.

Background: Opioid prescribing guidelines have significantly decreased overprescribing and post-discharge use after cardiac surgery; however, limited recommendations exist for general thoracic surgery patients, a similarly high-risk population. We examined opioid prescribing and patient-reported use to develop evidence-based, opioid prescribing guidelines after lung cancer resection. Methods: This prospective, statewide, quality improvement study was conducted between January 2020 to March 2021 and included patients undergoing surgical resection of a primary lung cancer across 11 institutions. Patient-reported outcomes at 1-month follow-up were linked with clinical data and Society of Thoracic Surgery (STS) database records to characterize prescribing patterns and post-discharge use. The primary outcome was quantity of opioid used after discharge; secondary outcomes included quantity of opioid prescribed at discharge and patient-reported pain scores. Opioid quantities are reported in number of 5-mg oxycodone tablets (mean ± standard deviation). Results: Of the 602 patients identified, 429 met inclusion criteria. Questionnaire response rate was 65.0%. At discharge, 83.4% of patients were provided a prescription for opioids of mean size 20.5±13.1 pills, while patients reported using 8.2±13.0 pills after discharge (P<0.001), including 43.7% who used none. Those not taking opioids on the calendar day prior to discharge (32.4%) used fewer pills (4.4±8.1 vs. 11.7±14.9, P<0.001). Refill rate was 21.5% for patients provided a prescription at discharge, while 12.5% of patients not prescribed opioids at discharge required a new prescription before follow-up. Pain scores were 2.4±2.5 for incision site and 3.0±2.8 for overall pain (scale 0-10). Conclusions: Patient-reported post-discharge opioid use, surgical approach, and in-hospital opioid use before discharge should be used to inform prescribing recommendations after lung resection.

Cancer therapy with genetically-modified T cells for the treatment of melanoma.

The aim of this review is to acquaint the reader with the concept of T cell receptor (TCR) gene therapy for metastatic melanoma. We first review antigen choice, followed by gene delivery technology and, finally, we discuss selected clinical applications. To be successful, TCR gene therapy must combine multiple elements and research disciplines. First, there is a need for an understanding of tumor immunology because this is essential in proper antigen choice. Second, gene therapy is a technology-driven field and cutting edge knowledge of protein engineering and gene delivery methods are indispensable. Finally, a dedicated team of physician/scientists and healthcare providers is fundamental to clinical success. TCR gene therapy is now a realistic treatment option for metastatic melanoma. Both tumor regression and on-target/off-tumor toxicities have been observed, which emphasizes the experimental nature of this approach. As with any new medical procedure, future large-scale randomized trials will be necessary to validate this approach, and these are within reason in the next few years. This article is a US Government work and is in the public domain in the USA.

The impact of endovascular procedures on fellowship training in lower extremity revascularization.

OBJECTIVE: The introduction of endovascular aneurysm repair has resulted in a decline in open abdominal aortic aneurysm repairs performed by vascular residents. The purpose of this study was to evaluate if a similar trend has occurred with open lower extremity revascularization procedures, with increased endovascular procedures producing a decrease in the number of open lower extremity revascularizations. Furthermore, this study evaluates the effect of endovascular procedure volume on the frequency of subtypes of open lower extremity procedures performed. METHODS: The total number of vascular procedures, lower extremity bypasses, and endovascular interventions from 2000 to 2010 were analyzed from case logs of vascular residents as reported by the Accreditation Council for Graduate Medical Education. RESULTS: The average number of cases performed by vascular residents has increased by 150% from 463.9 in 2000 to 1168 in 2009, due to the increased number of endovascular procedures. The average number of endovascular revascularizations has increased by 317% from 40.5 performed in 2000 to 168.9 in 2009. Femoral-popliteal bypasses have increased in frequency by 27% whereas the number of infrapopliteal bypass has remained unchanged. The largest difference is seen in femoral endarterectomies with a 234% increase from 3.2 per resident in 2001 to 10.7 per resident in 2010. Comparison of the proportion of femoral-popliteal and tibioperoneal interventions performed by angioplasty or bypass after 2007 revealed that endovascular interventions comprise 50% of procedures in the femoral-popliteal distribution, whereas 65% of infrapopliteal interventions are still performed using open techniques. CONCLUSIONS: The number of procedures performed during vascular residency has dramatically increased over the last decade secondary to the increased number of endovascular procedures. The average vascular surgery resident's open operative experience has been stable over the last 10 years, despite the increasing endovascular case volume. Residents perform femoral endarterectomy with increasing frequency, perhaps representing an increasing volume of hybrid procedures. Gaps in information available for evaluating resident training remain a significant obstacle. Moving forward, revision of the current reporting system to a format that more accurately reflects resident experience would be beneficial.

Higher Long-term Quality of Life Metrics After Video-Assisted Thoracoscopic Surgery Lobectomy Compared With Robotic-Assisted Lobectomy.

BACKGROUND: Robotic-assisted thoracic surgery (RATS) lung lobectomy has emerged as an alternative approach to video-assisted thoracoscopic surgery (VATS). Patient-reported outcomes comparing these approaches have been limited. METHODS: At a single, high-volume academic center, patients undergoing VATS and RATS lobectomies for stage I and II non-small cell lung cancer from 2014 to 2018 were evaluated. The European Organisation for Research and Treatment of Cancer Quality of Life of Cancer Patients Questionnaire (QLQ-C30) and Quality of Life Questionnaire in Lung Cancer (QLQ-LC13), along with the Fear of Recurrence (FoR) survey, were administered preoperatively and at 1, 6, and 12 months postoperatively. Raw scores underwent linear transformation (0-100 scale). Linear mixed-effects models were used for quality of life and FoR score comparisons. RESULTS: The study included 219 patients (139 VATS and 80 RATS). RATS patients had longer (P < .05) operative times and a higher incidence (P < .05) of postoperative myocardial infarction compared to VATS patients. VATS patients reported higher (P < .05) QLQ-C30 summary scores postoperatively and at 12 months, including higher (P < .05) Social Functioning and Cognitive scores, and less (P < .05) appetite loss. VATS patients reported decreased (P < .05) QLQ-LC13 symptom summary scores at 6 months postoperatively, including decreased (P < .05) dyspnea, neuropathy, and pain compared with RATS patients. VATS patients also reported lower (P < .05) FoR summary scores at 6 months postoperatively. CONCLUSIONS: VATS patients report improvement in select quality of life and FoR measures after lobectomy. Further study comparing these 2 approaches is required.

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.

Characterizing isoform switching events in esophageal adenocarcinoma.

Isoform switching events with predicted functional consequences are common in many cancers, but characterization of switching events in esophageal adenocarcinoma (EAC) is lacking. Next-generation sequencing was used to detect levels of RNA transcripts and identify specific isoforms in treatment-naïve esophageal tissues ranging from premalignant Barrett's esophagus (BE), BE with low- or high-grade dysplasia (BE.LGD, BE.HGD), and EAC. Samples were stratified by histopathology and TP53 mutation status, identifying significant isoform switching events with predicted functional consequences. Comparing BE.LGD with BE.HGD, a histopathology linked to cancer progression, isoform switching events were identified in 75 genes including KRAS, RNF128, and WRAP53. Stratification based on TP53 status increased the number of significant isoform switches to 135, suggesting switching events affect cellular functions based on TP53 mutation and tissue histopathology. Analysis of isoforms agnostic, exclusive, and shared with mutant TP53 revealed unique signatures including demethylation, lipid and retinoic acid metabolism, and glucuronidation, respectively. Nearly half of isoform switching events were identified without significant gene-level expression changes. Importantly, two TP53-interacting isoforms, RNF128 and WRAP53, were significantly linked to patient survival. Thus, analysis of isoform switching events may provide new insight for the identification of prognostic markers and inform new potential therapeutic targets for EAC.