Affinity fine-tuning anti-CAIX CAR-T cells mitigate on-target off-tumor side effects.

One of the major hurdles that has hindered the success of chimeric antigen receptor (CAR) T cell therapies against solid tumors is on-target off-tumor (OTOT) toxicity due to sharing of the same epitopes on normal tissues. To elevate the safety profile of CAR-T cells, an affinity/avidity fine-tuned CAR was designed enabling CAR-T cell activation only in the presence of a highly expressed tumor associated antigen (TAA) but not when recognizing the same antigen at a physiological level on healthy cells. Using direct stochastic optical reconstruction microscopy (dSTORM) which provides single-molecule resolution, and flow cytometry, we identified high carbonic anhydrase IX (CAIX) density on clear cell renal cell carcinoma (ccRCC) patient samples and low-density expression on healthy bile duct tissues. A Tet-On doxycycline-inducible CAIX expressing cell line was established to mimic various CAIX densities, providing coverage from CAIX-high skrc-59 tumor cells to CAIX-low MMNK-1 cholangiocytes. Assessing the killing of CAR-T cells, we demonstrated that low-affinity/high-avidity fine-tuned G9 CAR-T has a wider therapeutic window compared to high-affinity/high-avidity G250 that was used in the first anti-CAIX CAR-T clinical trial but displayed serious OTOT effects. To assess the therapeutic effect of G9 on patient samples, we generated ccRCC patient derived organotypic tumor spheroid (PDOTS) ex vivo cultures and demonstrated that G9 CAR-T cells exhibited superior efficacy, migration and cytokine release in these miniature tumors. Moreover, in an RCC orthotopic mouse model, G9 CAR-T cells showed enhanced tumor control compared to G250. In summary, G9 has successfully mitigated OTOT side effects and in doing so has made CAIX a druggable immunotherapeutic target.

Hyperthermic intraoperative chemotherapy (HIOC) for Stage IVa thymic malignancy may improve 5-year disease-free survival.

BACKGROUND AND OBJECTIVES: Stage IVa thymic malignancy has limited treatments. This study evaluated whether hyperthermic intraoperative chemotherapy (HIOC) after radical resection of Stage IVa thymic malignancy improves survival. METHODS: All patients who underwent resection, with or without HIOC, for Stage IVa thymic malignancy at a single center from 1990 to 2021 were reviewed. RESULTS: Thirty-four patients were identified; 22 surgery-only versus 12 surgery and HIOC (60 min cisplatin regimen 175 mg/m2 ). Demographics and comorbidities were similar between groups. Three patients in each group were carcinomas; remainder were thymomas. Thirty-two patients underwent attempted macroscopic complete resection; 22 operations succeeded, 68.8%. Significant complications were similar between groups, 18.2% surgery-only versus 25.0% HIOC, p = 0.68. Median time to recurrence trended longer for HIOC patients (42.9 vs. 32.9 months in surgery-only, p = 0.77). Overall survival, 5-year, was similar (75.8% HIOC vs. 76.2% surgery-only, p = 0.91). On stratified analysis, thymoma patients with macroscopic complete resection and HIOC experienced similar 5-year Overall (80.0% vs. 100.0% surgery-only, p = 0.157) but longer trending 5-year disease-free (85.7% vs. 40.0%, p = 0.18) and 5-year locoregional recurrence-free survival (85.7% vs. 68.6%, p = 0.75). CONCLUSIONS: This retrospective cohort study treating Stage IVa thymic malignancy with radical pleurectomy, with or without HIOC, found addition of HIOC-signaled delayed recurrence and improved disease-free survival.

Esophageal squamous cell carcinoma with basaloid features are genetically and prognostically similar to conventional squamous cell carcinoma.

We compared clinicopathologic and molecular features of esophageal squamous cell carcinoma (SCC) with basaloid features to conventional SCC using surgical resections of treatment naïve esophageal carcinomas and cases available from the TCGA database. Twenty-two cases of SCC with basaloid features were identified in the Mass General Brigham pathology archives, including 9 cases with pure basaloid morphology and 13 cases with mixed other features such as conventional well- or poorly differentiated areas or sarcomatoid areas. Thirty-eight cases of conventional SCC matched by tumor stage were used as controls. HPV infection status was tested by p16 immunohistochemistry and HPV mRNA ISH. Digital slides for 94 cases of esophageal SCC from TCGA found in the Genomic Data Commons (GDC) Data Portal were reviewed. Five cases of SCC with basaloid features were identified. Genomic profiles of SCC with basaloid features were compared to the rest of 89 SCCs without basaloid features. In addition, eight tumor sections from six patients selected from our cohort underwent in-house molecular profiling. Compared to conventional SCC, SCC with basaloid features were more frequently associated with diffuse or multifocal squamous dysplasia (p < 0.001). P16 IHC was positive in 2/13 cases, whereas HPV mRNA ISH was negative in 17/17 cases (including both p16-positive cases). SCC with basaloid features and conventional SCC from TCGA showed similar rates of TP53 mutations, CDKN2A/B deletions, and CCDN1 amplifications. TP53 variants were identified in all in-house samples that had sufficient coverage. Survival analyses between SCC with basaloid features versus conventional SCC (matched for tumor stage) did not reveal any statistically significant differences. In conclusion, esophageal SCC with basaloid features has similar survival and genomic alterations to those of conventional SCC, are more frequently associated with diffuse or multifocal dysplasia, and are not associated with HPV (high-risk strains) infection.

Risk of chyle leak after robotic versus video-assisted thoracoscopic esophagectomy.

BACKGROUND: We investigate the incidence and risk factors for post-operative outcomes including chyle leak following minimally invasive esophagectomy (MIE). METHODS: Patients undergoing MIE from May 2016 until August 2020 were prospectively followed. Outcomes of robotic and video-assisted thoracoscopic surgery (VATS) esophagectomy were analyzed. RESULTS: 347 esophagectomies were performed: 70 cases were done robotically by 2 surgeons and 277 by VATS by 14 surgeons. Patients had similar demographics, surgical technique, length of stay (LOS), and re-operation rates. Overall complication rates between robotic and VATS MIE were statistically similar (61% vs. 50%; p = 0.082). The majority of complications for either VATS (41.5%) or robotic-assisted minimally invasive esophagectomy (RAMIE) (51.4%) were grade II. Nineteen patients developed a chyle leak. Patients with a chyle leak were similar in age, gender, and hospital LOS (all p > 0.05), but were more likely to undergo a three-hole or robotic esophagectomy (both p < 0.05) as well as have higher rehabilitation requirements on discharge (26% vs. 10%; p = 0.05). Among the two surgeons who each performed > 20 robotic esophagectomies (n = 70), nine chyle leaks occurred. Rates varied by surgeon (7 vs. 2; p = 0.003). Lower leak rates occurred in the surgeon with more robotic esophagectomy experience (n = 47 vs. 23). Patients were similar in age, and gender (p > 0.05), but those with a chyle leak were more likely to undergo three-hole esophagectomies, prophylactic thoracic duction ligations, undergo the abdominal portion via laparotomy, and not have a prophylactic omental flap (all p < 0.05). CONCLUSION: Robotic and VATS esophagectomy have similar rates of re-operation, length of stay, discharge needs and complications. Differences in outcomes between VATS and Robotic esophagectomy appears to be related to surgeon experience with the robot but may also be associated with techniques such as anastomotic height, omental flap utilization and performance of laparoscopy.

Verrucous carcinoma of the oesophagus is a genetically distinct subtype of oesophageal squamous cell carcinoma.

AIMS: Oesophageal verrucous carcinoma (VSCC) is a rare and morphologically distinct type of oesophageal squamous cell carcinoma (SCC). Diagnosing VSCC on biopsy material is challenging, given the lack of significant atypia and the presence of keratinising epithelium and exophytic growth. The molecular pathogenesis of VSCC remains unclear. The aim of this study was to characterise the genomic landscape of VSCC in comparison to conventional oesophageal SCC. METHODS AND RESULTS: Three cases of VSCC from the Brigham and Women's Hospital pathology archive were identified. Formalin-fixed, paraffin-embedded (FFPE) tumour tissue was used for p16 immunohistochemistry (IHC), high-risk human papillomavirus (HPV) in-situ mRNA hybridisation (ISH) and DNA isolation. Tumour DNA was sequenced using a targeted massively parallel sequencing assay enriched for cancer-associated genes. Three additional cases of VSCC were identified by image review of The Cancer Genome Atlas (TCGA) oesophageal SCC cohort. VSCC cases were negative for p16 IHC and high-risk HPV ISH. TP53 mutations (P < 0.001) and copy number variants (CNVs) for CDKN2A (P < 0.001), CDKN2B (P < 0.01) and CCND1 (P < 0.01) were absent in VSCC and significantly less frequent in comparison to conventional SCC. Five VSCC cases featured SMARCA4 missense mutations or in-frame deletions compared to only four of 88 conventional SCC cases (P < 0.001). VSCC featured driver mutations in PIK3CA, HRAS and GNAS. Recurrent CNVs were rare in VSCC. CONCLUSIONS: VSCC is not only morphologically but also genetically distinct from conventional oesophageal SCC, featuring frequent SMARCA4 mutations and infrequent TP53 mutations or CDKN2A/B CNVs. Molecular findings may aid in establishing the challenging diagnosis of VSCC.

Preserving NLST mortality benefits and acceptable morbidity for lung cancer surgery in a community hospital.

BACKGROUND AND OBJECTIVES: The aim of this study was to demonstrate whether academic thoracic surgeons could achieve morbidity and mortality rates in community hospitals equivalent to those seen in National Lung Screening Trial (NLST). METHODS: This was a retrospective review of community hospital lung cancer procedures for clinical Stage I-III non-small-cell lung cancers from 2007 through 2014. Variables include age, comorbidities, computed tomography (CT) characterization, and operative techniques. RESULTS: There were 177 patients who had lung cancers removed by a minimally invasive approach (79%), including lobectomy in 127 (72%), segmentectomy in 4 (2%), and wedge-resections in 46 (26%). The median patient age was 71 years (interquartile range [IQR], 63-76). The cohort was primarily female (58%), clinical Stage I (82%), with a median tumor size of 2.3 cm (IQR, 1.5-3.3). The median length of stay was 6 days (range: 1-35). Complications were experienced by 78 (44.1%) patients, most commonly atrial fibrillation in 20 (11.3%) followed by air-leak in 19 (10.7%). There were no in-hospital deaths. Tumor location and extent of resection were associated with complications, while larger tumor size, margin contour, and resection method were associated with air-leak (all p < 0.05). Higher clinical stage and larger tumor size were associated with occult Stage III disease (both p < 0.05). CONCLUSIONS: The low morbidity and mortality rates from the NLST were achievable in a community setting for early-stage lung cancer. Characterization of cancers using CT imaging identified factors most commonly associated with postoperative complications and the presence of occult Stage III disease.

Adjuvant therapy following induction therapy and surgery improves survival in N2-positive non-small cell lung cancer.

BACKGROUND: The purpose of this study was to evaluate treatment strategies and factors influencing overall survival (OS) and disease-free survival (DFS) in resectable, non-small cell lung cancer (NSCLC) with mediastinal (N2) lymph node metastasis. METHODS: All patients undergoing surgery for NSCLC with N2 disease between 2006 and 2016 were included. Treatment approaches included surgery only, neoadjuvant therapy followed by surgery, surgery followed by adjuvant therapy, and neoadjuvant therapy followed by surgery and adjuvant therapy (triple therapy). Patient clinical and pathologic data were retrospectively collected. RESULTS: A total of 281 patients were included in the study. In total, 209 patients had neoadjuvant therapy, 47.4% of which went on to received additional adjuvant therapy. The pathologic complete response rate was 12.9%. The treatment strategy which included triple therapy was isolated as a significant contributor to improved OS and DFS. Nodal downstaging (N0) after induction therapy conferred an OS benefit (38.3% vs. 15.6%, p = .03). Patients with single-station N2 disease experienced higher DFS. Video-assisted thoracic surgery (VATS) lobectomy completion rates were higher at the end of the study period compared to the beginning (p < .001). CONCLUSIONS: Patients who undergo neoadjuvant therapy for N2-positive NSCLC may benefit from additional adjuvant therapy. Single-station N2 disease confers higher DFS. VATS completion rates for lobectomy increase as experience increases.

Risk factors for delirium after esophagectomy.

INTRODUCTION: Postoperative delirium is a common complication after major surgical procedures and affects outcomes and long-term survival. We identified factors associated with postoperative delirium in patients undergoing esophagectomy. METHODS: Retrospective cohort analysis of 378 patients undergoing esophagectomy. We examined the association between postoperative delirium (DSM-V) criteria with respect to baseline variables and postoperative complications. RESULTS: Postoperative delirium was diagnosed in 64 (16.93%) patients and associated with increasing age (P < .05), chronic obstructive pulmonary disease (P = .07), pneumonia (P = .01), transfusion intraoperatively or within 72 hours of surgery (P < .001), and sepsis (P = .001). Unplanned intubation and increased length of stay (median, 14 days) were significant in patients with delirium (P = .001 and P < .001, respectively). In a secondary analysis, surgical technique and operative approach were associated with delirium. Modified McKeown (three-hole) esophagectomy was twice more likely to develop delirium compared with Ivor Lewis (odds ratio [OR], 2.09; 95% confidence interval [CI], 1.03-4.23). The strongest association was found between delirium and open techniques (thoracotomy and laparotomy) as compared with minimally invasive techniques (thoracoscopy and laparoscopy) (OR, 2.66; 95% CI, 1.22-5.76). Survival was similar between both groups. CONCLUSIONS: Postoperative delirium is common and associated with complications following esophagectomy. Identification of predisposing factors such as age and pre-existing pulmonary diseases and proper selection of surgical treatment may reduce delirium and improve surgical outcomes.

Image-guided video assisted thoracoscopic surgery (iVATS) - phase I-II clinical trial.

PURPOSE: To facilitate localization and resection of small lung nodules, we developed a prospective clinical trial (ClinicalTrials.gov number NCT01847209) for a novel surgical approach which combines placement of fiducials using intra-operative C-arm computed tomography (CT) guidance with standard thoracoscopic resection technique using image-guided video-assisted thoracoscopic surgery (iVATS). METHODS: Pretrial training was performed in a porcine model using C-arm CT and needle guidance software. Methodology and workflow for iVATS was developed, and a multi-modality team was trained. A prospective phase I-II clinical trial was initiated with the goal of recruiting eligible patients with small peripheral pulmonary nodules. Intra-operative C-arm CT scan was utilized for guidance of percutaneous marking with two T-bars (Kimberly-Clark, Roswell, GA) followed by VATS resection of the tumor. RESULTS: Twenty-five patients were enrolled; 23 underwent iVATS, one withdrew, and one lesion resolved. Size of lesions were: 0.6-1.8 cm, mean = 1.3 ± 0.38 cm.. All 23 patients underwent complete resection of their lesions. CT imaging of the resected specimens confirmed the removal of the T-bars and the nodule. Average and total procedure radiation dose was in the acceptable low range (median = 1501 µGy*m(2), range 665-16,326). There were no deaths, and all patients were discharged from the hospital (median length of stay = 4 days, range 2-12). Three patients had postoperative complications: one prolonged air-leak, one pneumonia, and one ileus. CONCLUSIONS: A successful and safe step-wise process has been established for iVATS, combining intra-operative C-arm CT scanning and thoracoscopic surgery in a hybrid operating room.

Minimally Invasive Modified McKeown Esophagectomy.

McKeown esophagectomy is a transthoracic esophagectomy with a cervical anastomosis that is an established mainstay for the management of benign and malignant esophageal pathology. It has gone through multiple modifications. The most current version utilizes robotic or minimally invasive ports through both the right chest and abdominal portions. There is decreased pain and hospital length of stay compared to the open technique. However, anastomotic leak and recurrent laryngeal nerve injury continue to occur. Advancements in management of complications has decreased mortality, making this surgical approach a relevant option for esophageal pathologies.

An esophagectomy surgical Apgar score-based nomogram-a risk-based postoperative triage system: a phase II randomised trial.

Background: The esophagectomy surgical Apgar score (eSAS) has been found to be a predictor of postoperative complications in esophagectomy. In our previous study, we built a graphic nomogram based on eSAS and demonstrated that it can effectively predict the risk of major morbidity after esophagectomy. In this study, we aimed to assess the benefits of using an eSAS-based nomogram model as a postoperative risk-based triage system for patients undergoing esophagectomy. Methods: We enrolled 119 patients diagnosed with esophageal carcinoma and randomly assigned them to a nomogram group (NG) or control group (CG) from January 2019 to December 2020. Patients in the NG were assigned to a low-risk group and high-risk group based on the nomogram. Patients in the high-risk group were admitted to the intensive care unit (ICU) after esophagectomy. Risk estimation in the CG patients was based on the surgeon's clinical experience. Thirty-day major complications, postoperative hospital stay, hospital costs, and quality of life (QOL) during the follow-up were compared between the two groups. Results: Baseline clinicopathological characteristics were comparable between the NG (n=58) and CG (n=61). All patients underwent esophagectomy. Postoperative complications were significantly higher in the CG (30, 49.2%) than in the NG (14, 24.1%) (P=0.008), with pneumonia being the most common (CG: 23, 37.7%; NG: 12, 20.7%; P=0.042). There was no significant difference in anastomotic leakage (NG: 1, 1.7%; CG: 6, 9.8%; P=0.12). Postoperative median hospital stay was shorter in the NG (14 days) than in the CG (16 days) (P=0.041). Hospital costs (NG: ¥60,045.1; CG: ¥63,961.5; P=0.21) and postoperative QOL did not differ significantly between groups. Conclusions: An eSAS-based nomogram as a triage system can reduce the overall occurrence of postoperative complications and shorten postoperative hospital stay without increasing hospital costs. Trial Registration: Chinese Clinical Trial Registry ChiCTR1900021636.

Association of conduit dimensions with perioperative outcomes and long-term quality of life after esophagectomy for malignancy.

Objective: The impact of conduit dimensions and location of esophagogastric anastomosis on long-term quality of life after esophagectomy remains unexplored. We investigated the association of these parameters with surgical outcomes and patient-reported quality of life at least 18 months after esophagectomy. Methods: We identified all patients who underwent esophagectomy for cancer from 2018 to 2020 in our institution. We reviewed each patient's initial postoperative computed tomography scan measuring the gastric conduit's greatest width (centimeters), linear staple line length (centimeters), and relative location of esophagogastric anastomosis (vertebra). Quality of life was ascertained using patient-reported outcome measures. Perioperative complications, length of stay, and mortality were collected. Multivariate regressions were performed. Results: Our study revealed that a more proximal anastomosis was linked to an increased risk of pulmonary complications, a lower recurrence rate, and greater long-term insomnia. Increased maximum intrathoracic conduit width was significantly associated with trouble enjoying meals and reflux long term after esophagectomy. A longer conduit stapled line correlated with fewer issues related to insomnia, improved appetite, less dysphagia, and significantly enhanced "social," "role," and "physical'" aspects of the patient's long-term quality of life. Conclusions: The dimensions of the gastric conduit and the height of the anastomosis may be independently associated with outcomes and long-term quality of life after esophagectomy for cancer.

Transcriptionally Active Human Papillomavirus Infection in a Minority of Esophageal Squamous Cell Carcinomas in North America.

The role of Human papillomavirus (HPV) infection in esophageal squamous cell carcinoma (ESCC) is a topic of ongoing debate. This study used two screening approaches to look for evidence of HPV infection in esophageal squamous cell carcinoma. We initially checked for HPV infection in a randomly selected group of 53 ESCC cases. We did not detect any tumors positive for high-risk HPV. However, during clinical practice, we identified an HPV-positive ESCC in the distal esophagus, which tested positive for HPV16. This index case was TP53 wild-type, as determined by next-generation DNA sequencing (NGS). Since TP53 mutations are rare in other HPV-driven cancers, we improved our screening method by limiting our screen to a subset of ESCC cases without TP53 mutations. A second screen of 95 ESCCs (from 93 patients) sequenced by NGS revealed an additional 7 ESCCs with TP53 wild-type status (7.3% of the total). Of the 7 cases, 2 cases were found to be high-risk HPV positive. Both patients also tested positive for circulating cell-free HPV DNA and had a complete response to neoadjuvant chemoradiation. The index patient had microscopic residual tumor following neoadjuvant therapy. The patient underwent adjuvant immunotherapy and remained disease free after 22 months of surveillance. This study affirms the transcriptionally active status of high-risk HPV in a minority of ESCC patients in North America.

Routine Reflux Testing Guides Timely Antireflux Treatment to Reduce Acute and Chronic Rejection After Lung Transplantation.

INTRODUCTION: Gastroesophageal reflux has been associated with poorer lung transplantation outcomes, although no standard approach to evaluation/management has been adopted. We aimed to evaluate the effect of timely antireflux treatment as guided by routine reflux testing on postlung transplant rejection outcomes. METHODS: This was a retrospective cohort study of lung transplant recipients at a tertiary center. All patients underwent pretransplant ambulatory pH monitoring. Timely antireflux treatment was defined as proton pump inhibitor initiation or antireflux surgery within 6 months of transplantation. Patients were separated into 3 groups: normal pH monitoring (-pH), increased reflux (+pH) with timely treatment, and +pH with delayed treatment. Rejection outcomes included acute rejection, bronchiolitis obliterans syndrome, and chronic lung allograft dysfunction per International Society for Heart and Lung Transplantation criteria. Time-to-event analyses using Cox proportional hazard models were applied. Patients not meeting outcomes were censored at death or last clinic visit. RESULTS: One hundred seventy-five patients (59% men/mean 56.3 yr/follow-up: 496 person-years) were included. On multivariable analyses, +pH/delayed treatment patients had higher risks of acute rejection (adjust hazard ratio [aHR]:3.81 [95% confidence interval [CI]: 1.90-7.64], P = 0.0002), bronchiolitis obliterans syndrome (aHR: 2.22 [95% CI: 1.07-4.58], P = 0.03), and chronic lung allograft dysfunction (aHR: 2.97 [95% CI: 1.40-6.32], P = 0.005) than +pH/timely treatment patients. Similarly, rejection risks were increased among +pH/delayed treatment patients vs -pH patients (all P < 0.05). No significant differences in rejection risks were noted between +pH/timely treatment patients and -pH patients. Failure/complications of antireflux treatment were rare and similar among groups. DISCUSSION: Timely antireflux treatment, as directed by pretransplant reflux testing, was associated with reduced allograft rejection risks and demonstrated noninferiority to patients without reflux. A standardized peri-transplant test-and-treat algorithm may guide timely reflux management to improve lung transplant outcomes.

When a segmentectomy is not a segmentectomy: Quality assurance audit and evaluation of required elements for an anatomic segmentectomy.

OBJECTIVE: The advent of lung cancer screening and detection of smaller nodules amplifies the need to clarify the oncological quality of sublobar resections. Furthermore, studies comparing sublobar resections to lobectomies offer conflicting conclusions. We hypothesize that this is driven, in part, by inconsistency in reporting; that is, variable interpretation of what constitutes an operative segment. Without an established standard, 2 very different operations may be reported as segmental resections, leaving the data on sublobar approaches subject to interpretative variability. METHODS: A retrospective audit was performed on all segmental resections from May 2016 to December 2019 at Brigham and Women's Hospital. Pathology and operative reports were reviewed, with particular attention to the dissection of the component artery, vein, and bronchus. Resections with dissection and division of at least 1 major vascular structure (the segmental artery or vein), as well as the segmental bronchus, met operative criteria for anatomic segmentectomy. Surgical quality metrics were compared between the 2 groups. RESULTS: There were 271 segmental resections: 219 (80.8%) were anatomic segmentectomies and 52 (19.2%) were nonanatomic segmentectomies. For the entire cohort, nonanatomic segmentectomies had smaller margins (1.0 vs 1.5 cm; P = .02), fewer lymph nodes (2.0 vs 6.0; P < .001), and fewer mediastinal lymph node stations sampled (1.0 vs 2.0; P < .001). Similarly, there were smaller margins (1.5 vs 1.8 cm; P = .03), fewer lymph nodes (2.0 vs 6.0; P < .001), and fewer mediastinal lymph node stations sampled (1.0 vs 2.0; P < .001) in nonanatomic segmentectomies for non-small cell lung cancer. CONCLUSIONS: Nearly 20% of reported segmentectomies may not meet criteria for true segmental resection. Therefore, prior studies may need further scrutiny to clarify outcomes and results. Establishing a professional standard may help mitigate ambiguity in published data on this subject.

Comparison of Global Evaluative Assessment of Robotic Surgery with objective performance indicators for the assessment of skill during robotic-assisted thoracic surgery.

BACKGROUND: The Global Evaluative Assessment of Robotic Skills is a popular but ultimately subjective assessment tool in robotic-assisted surgery. An alternative approach is to record system or console events or calculate instrument kinematics to derive objective performance indicators. The aim of this study was to compare these 2 approaches and correlate the Global Evaluative Assessment of Robotic Skills with different types of objective performance indicators during robotic-assisted lobectomy. METHODS: Video, system event, and kinematic data were recorded from the robotic surgical system during left upper lobectomy on a standardized perfused and pulsatile ex vivo porcine heart-lung model. Videos were segmented into steps, and the superior vein dissection was graded independently by 2 blinded expert surgeons with Global Evaluative Assessment of Robotic Skills. Objective performance indicators representing categories for energy use, event data, movement, smoothness, time, and wrist articulation were calculated for the same task and compared to Global Evaluative Assessment of Robotic Skills scores. RESULTS: Video and data from 51 cases were analyzed (44 fellows, 7 attendings). Global Evaluative Assessment of Robotic Skills scores were significantly higher for attendings (P < .05), but there was a significant difference in raters' scores of 31.4% (defined as >20% difference in total score). The interclass correlation was 0.44 for 1 rater and 0.61 for 2 raters. Objective performance indicators correlated with Global Evaluative Assessment of Robotic Skills to varying degrees. The most highly correlated Global Evaluative Assessment of Robotic Skills domain was efficiency. Instrument movement and smoothness were highly correlated among objective performance indicator categories. Of individual objective performance indicators, right-hand median jerk, an objective performance indicator of change of acceleration, had the highest correlation coefficient (0.55). CONCLUSION: There was a relatively poor overall correlation between the Global Evaluative Assessment of Robotic Skills and objective performance indicators. However, both appear strongly correlated for certain metrics such as efficiency and smoothness. Objective performance indicators may be a potentially more quantitative and granular approach to assessing skill, given that they can be calculated mathematically and automatically without subjective interpretation.

Predicting outcomes in esophageal adenocarcinoma following neoadjuvant chemoradiation: Interactions between tumor response and survival.

OBJECTIVES: The prognostic value of tumor regression scores (TRS) in patients with esophageal adenocarcinoma (EAC) who underwent neoadjuvant chemoradiation remains unclear. We sought to investigate the prognostic value of pathologic and metabolic treatment response among EAC patients undergoing neoadjuvant chemoradiation. METHODS: Patients who underwent esophagectomy for EAC after neoadjuvant CROSS protocol between 2016 and 2020 were evaluated. TRS was grouped according to the modified Ryan score; metabolic response, according to the PERCIST criteria. Variables from endoscopic ultrasound, endoscopic biopsies, and positron emission tomography (primary and regional lymph node standardized uptake values [SUVs]) were collected. RESULTS: The study population comprised 277 patients. A TRS of 0 (complete response) was identified in 66 patients (23.8%). Seventy-eight patients (28.1%) had TRS 1 (partial response), 97 (35%) had TRS 2 (poor response), and 36 (13%) had TRS 3 (no response). On survival analysis for overall survival (OS), patients with TRS 0 had longer survival compared to those with TRS 1, 2, or 3 (P = .010, P < .001, and P = .005, respectively). On multivariable logistic regression, the presence of signet ring cell features on endoscopic biopsy (odds ratio [OR], 7.54; P = .012) and greater SUV uptake at regional lymph nodes (OR, 1.42; P = .007) were significantly associated with residual tumor at pathology (TRS 1, 2, or 3). On multivariate Cox regression for predictors of OS, higher SUVmax at the most metabolically active nodal station (hazard ratio [HR], 1.08; P = .005) was independently associated with decreased OS, whereas pathologic complete response (HR, 0.61; P = .021) was independently associated with higher OS. CONCLUSIONS: Patients with pathologic complete response had prolonged OS, whereas no difference in survival was detected among other TRS categories. At initial staging, the presence of signet ring cells and greater SUV uptake at regional lymph nodes predicted residual disease at pathology and shorter OS, suggesting the need for new treatment strategies for these patients.

Perioperative Esophagectomy Outcomes in Older Esophageal Cancer Patients in Two Different Time Eras.

To investigate perioperative outcomes of esophagectomies by age groups. Retrospective analysis of esophageal cancer patients undergoing esophagectomy from 2005 to 2020 at a single academic institution. Baseline characteristics and outcomes were analyzed by 3 age groups: <70, 70-79, and ≥80 years-old. Sub-analysis was done for 2 time periods: 2005-2012 and 2013-2020. Of 1135 patients, 789 patients were <70, 294 were 70-79, and 52 were ≥80 years-old. Tumor characteristics, and operative technique were similar, except positive longitudinal margins rates (all <3%) (P = 0.008). Older adults experienced increased complications (53.6% vs 69.7% vs 65.4% respectively; P < 0.001) attributable to grade II complications (41.4% vs 62.2% vs 63.5% respectively; P < 0.001). Hospital length of stay (LOS) and rehabilitation requirements were higher in older adults (both P < 0.05). 30-day readmissions, reoperation, and 30-day mortality rates (all <2%) showed no association with age group. Overall complications, LOS, discharge disposition and re-operative rates improved from 2005 to 2012 to 2013-2020 for all (P < 0.05). Increasing age was an independent risk factor for cardiovascular complications (OR 1.7, 95% CI 1.23-2.46 for ages 70-79 and OR 2.7, 95% CI 1.37-5.10 for ages ≥80 ), inpatient rehabilitation (OR 3.3, 95% CI 2.26-5.05 for ages 70-79 and OR 12.1 95% CI 5.83-25.04 for ages ≥80), and prolonged LOS (OR 1.64 95% CI 1.16-2.31 for ages 70-79 and OR 3.6 95% CI 1.71-7.67 for ≥80. After adjusting for time period, older age remained associated with complications (P < 0.05). Highly selected older adults at a large volume esophagectomy center can undergoesophagectomy with increased minor complication and rehabilitation needs.