ERAS following Gastrectomy for Octo- and Nonagenarians: A Single-Center Retrospective Analysis.

Background: The safety and efficacy of enhanced recovery after surgery (ERAS) following elective gastrectomy for gastric cancer in patients >80 years of age are not well described. The aim of this study was to explore whether an ERAS protocol following gastrectomy in this age group can be safely implemented and reduce postoperative length of stay. Methods: A retrospective, single-center analysis was performed. All patients >80 years of age with gastric cancer undergoing elective subtotal and total gastrectomy between January 2010 and December 2021 were identified. With the implementation of an ERAS protocol in January 2016, patients treated beforehand were allocated to Group A (pre-ERAS) and Group B (ERAS). The length of stay, incidence of postoperative complications and representation/readmission to the hospital were compared between the groups. Results: Of the 221 patients identified, 56 met the inclusion criteria with 22 patients (39.3%) allocated to Group A and 34 patients (60.7%) to Group B. There were no differences with regard to the type of resection and surgical approach. Length of stay was shorter in Group B (5 days, range 2-27 versus 10 days, 3-109, P = .040). A trend toward more discharges by postoperative day 3 was noted among patients in Group B (7/34, 20.6% versus 2/22, 9.1%, P = .253). There were no differences in the incidence of postoperative complications or readmission hospital between the groups. Conclusion: Among patients >80 years of age, ERAS following gastrectomy for cancer is associated with a reduced length of stay and can be safely implemented.

HiChIP-based Epigenomic Footprinting Identifies a Promoter Variant of UXS1 that Confers Genetic Susceptibility to Gastroesophageal Cancer.

Genome-wide association studies (GWAS) have identified more than a hundred single nucleotide variants (SNVs) associated with the risk of gastroesophageal cancer (GEC). The majority of the identified SNVs map to noncoding regions of the genome. Uncovering the causal SNVs and the genes they modulate could help improve GEC prevention and treatment. Here, we used HiChIP against histone 3 lysine 27 acetylation (H3K27ac) to simultaneously annotate active promoters and enhancers, identify the interactions between them, and detect nucleosome free regions (NFRs) harboring potential causal SNVs in a single assay. Application of H3K27Ac HiChIP in GEC relevant models identified 61 potential functional SNVs that reside in NFRs and interact with 49 genes at 17 loci. The approach led to a 67% reduction in the number of SNVs in linkage disequilibrium at these 17 loci, and at seven loci a single putative causal SNV was identified. One SNV, rs147518036, located within the promoter of the UDP-glucuronate decarboxylase 1 (UXS1) gene appeared to underlie the GEC risk association captured by the rs75460256 index SNV. The rs147518036 SNV creates a GABPA DNA recognition motif, resulting in increased promoter activity, and CRISPR-mediated inhibition of the UXS1 promoter reduced viability of GEC cells. These findings provide a framework that simplifies the identification of potentially functional regulatory SNVs and target genes underlying risk-associated loci. In addition, the study implicates increased expression of the enzyme UXS1 and activation of its metabolic pathway as a predisposition to gastric cancer, which highlights potential therapeutic avenues to treat this disease.

Survival in esophageal cancer with nonregional lymphadenopathy: a propensity score-matched analysis.

BACKGROUND: Survival among patients with esophageal cancer with stage IV nonregional lymphadenopathy treated with neoadjuvant therapy and surgical resection is not well described. This study aimed to compare the survival outcomes of patients with nonregional lymphadenopathy with a propensity-matched cohort of patients with locoregional disease. METHODS: This was a retrospective cohort analysis of a prospectively maintained database from a regional upper gastrointestinal cancer network in Quebec, Canada. From January 2010 to December 2022, patients with radiologically suspicious nonregional retroperitoneal or supraclavicular lymphadenopathy were identified. Using 1:1 propensity score matching, a control group without nonregional disease was created. RESULTS: Of the 1235 patients identified, 39 met the inclusion criteria and were allocated to the study group of whom 35 of 39 (89%) had adenocarcinoma. Retroperitoneal and supraclavicular lymphadenopathy occurred in 26 of 39 patients (67%) and 13 of 39 patients (33%). Of the 39 patients, 34 (87%) received neoadjuvant chemotherapy, and 5 (13%) received chemoradiotherapy. After resection, ypN0 of nonregional lymph node stations occurred in 21 of 39 patients (54%). When comparing the study group with a matched non-stage IV control group, the median overall survival was similar in patients with retroperitoneal lymphadenopathy (21.0 months [95% CI, 8.0-21.0] vs 27.0 months [95% CI, 13.0-41.0]; P = .262) but not with supraclavicular disease (13.0 months; 95% CI, 8.0-18.0; P = .039). The median follow-up intervals were 40.1 months (95% CI, 1.0-83.0) for the study group and 70.0 (95% CI, 33.0-106.0) for the control groups. CONCLUSION: Compared with a matched cohort of patients with similar disease burden but not stage IV disease, retroperitoneal lymphadenopathy did not negatively affect survival outcomes. Multimodal curative intent therapy may be appropriate in select cases.

Enhanced recovery after surgery after radical gastrectomy: Improved compliance over time is associated with a shorter postoperative hospital stay.

BACKGROUND: Changing adherence over time to enhanced recovery after surgery (ERAS) protocols following radical gastrectomy and the impact this has on length of stay (LoS) is not well described. This study aimed to explore the changes in adherence to core ERAS elements over time and the relationship between compliance and LoS. METHODS: A retrospective, single center cohort study was performed between 01/2016-12/2021. An ad hoc analysis revealed the point at which a significant difference in the number of patients being discharge on postoperative day (PoD) 3 was noted allowing allocation of patients to Group A (01/2016-12/2019) or B (01/2020-12/2021). Compliance with core ERAS elements was compared and the relationship between compliance and discharge by (PoD) 3 assessed. Variables significant on univariate analysis were assessed using binary multivariate regression. RESULTS: Of the 268 patients identified, 187 met the inclusion criteria (Group A 112 and Group B 75). More patients in Group B mobilized on PoD 1 (60.0 vs. 31.3%, p = <0.001), tolerated postgastrectomy diet by PoD 3 (84.6 vs. 62.5%, p = 0.049), and were discharged by PoD 3 (34.7 vs. 20.5%, p = 0.002). Protocol compliance of >75% was associated with discharge on PoD 3 (area under the curve, 0.726). Active mobilization on PoD 1 (OR 3.5, p = 0.009), compliance ≥75% (OR 3.3, p = 0.036), and preoperative nutritional consult (OR 0.2, p = 0.002) were independently associated with discharge on PoD 3. Discharge on PoD 3 did not increase readmission or representation to hospital. CONCLUSION: Early mobilization, protocol compliance >75%, and preoperative nutritional consult were associated with discharge on PoD 3 after radical gastrectomy.

Ictal Bradycardia and Asystole in Sleep-Related Hypermotor Epilepsy: A Study of 200 Patients.

Background: Ictal bradycardia (IB) and asystole (IA) represent a rare but potentially harmful feature of epileptic seizures. The aim of this study was to study IB/IA in patients with sleep-related hypermotor epilepsy (SHE). Methods: We retrospectively included cases with video-EEG-confirmed SHE who attended our Institute up to January 2021. We reviewed the ictal polysomnography recordings focusing on ECG and identified cases with IB (R-R interval ≥ 2 s or a ≥10% decrease of baseline heart rate) and IA (R-R interval ≥ 4 s). Results: We included 200 patients (123 males, 61.5%), with a mean age of 42 ± 16 years. Twenty patients (20%) had focal cortical dysplasia (FCD) on brain MRI. Eighteen (out of 104 tested, 17.3%) carried pathogenic variants (mTOR pathway, n = 10, nAchR subunits, n = 4, KCNT1, n = 4). We identified IB/IA in four cases (2%): three had IA (mean 10 s) and one had IB. Three patients had FCD (left fronto-insular region, left amygdala, right mid-temporal gyrus) and two had pathogenic variants in DEPDC5; both features were more prevalent in patients with IB/IA than those without (p = 0.003 and p = 0.037, respectively). Conclusions: We identified IB/IA in 2% of patients with SHE and showed that this subgroup more frequently had FCD on brain MRI and pathogenic variants in genes related to the mTOR pathway.

Tuberous sclerosis complex in adulthood: focus on epilepsy prognosis.

OBJECTIVE: Typically diagnosed in early childhood or adolescence, TSC is a chronic, multisystemic disorder with age-dependent manifestations posing a challenge for transition and for specific surveillance throughout the lifetime. Data on the clinical features and severity of TSC in adults and on the prognosis of epilepsy are scarce. We analyzed the clinical and genetic features of a cohort of adult patients with TSC, to identify the prognostic predictors of seizure remission after a long follow-up. METHOD: We conducted a retrospective analysis of patients diagnosed with TSC according to the updated international diagnostic criteria. Pearson's chi-square or Fisher's exact test and Mann Whitney U test were used to compare variables among the Remission (R) and Non-Remission (NR) group. Univariate and multivariate logistic regression analyses were performed. RESULTS: We selected 43 patients with TSC and neurological involvement in terms of epilepsy and/or brain lesions, attending the Epilepsy Center of our Institute: of them, 16 (37.2%) were transitioning from the pediatric care and 6 (13.9%) were referred by other specialists. Multiorgan involvement includes cutaneous (86.0%), nephrological (70.7%), hepatic (40.0%), ocular (34.3%), pneumological (28.6%) and cardiac (26.3%) manifestations. Thirty-nine patients (90.7 %) had epilepsy. The mean age at seizure onset was 4 ± 7.3 years: most patients (29, 76.3 %) presented with focal seizures or spasms by age 3 years; only 2 (5.3 %) had seizure onset in adulthood. Twenty-seven patients (69.2 %) experienced multiple seizure types overtime, 23 (59.0 %) had intellectual disability (ID). At last assessment, 14 (35.9 %) were seizure free (R group) and 25 (64.1 %) had drug-resistant seizures (NR group). At logistic regression univariate analysis, ID (OR 7.9, 95 % CI 1.8--34.7), multiple seizure types lifelong (OR 13.2, 95 % CI 2.6- 67.2), spasms/tonic seizures at presentation (OR 6.5, 95 % CI 1.2--35.2), a higher seizure frequency at onset (OR 5.4, 95 % CI 1.2--24.3), abnormal neurological examination (OR 9.8, 95 % CI 1.1--90.6) and pathogenic variants in TSC2 (OR 5.4, 95 % CI 1.2--24.5) were significantly associated with non-remission. In the multivariate analysis, both ID and multiple seizure types lifelong were confirmed as independent predictors of poor seizure outcome. CONCLUSIONS: In our cohort of adult patients with TSC, epilepsy remains one of the main neurological challenges with only 5.3% of cases manifesting in adulthood. Approximately 64% of these patients failed to achieve seizure remission. ID and multiple seizure types were the main predictors of poor outcome. Nephrological manifestations require continuous specific follow-up in adults.

Influence of Neoadjuvant Immunotherapy-Chemotherapy on Perioperative Outcomes in Locally Advanced Esophageal Adenocarcinoma.

BACKGROUND: This study evaluated the perioperative outcomes for patients who had locally advanced esophageal adenocarcinoma (EAC) treated with neoadjuvant immunotherapy (IO) and chemotherapy versus a matched cohort of patients who received neoadjuvant chemotherapy (NAC) alone. METHODS: A single-center non-randomized phase 2 trial was undertaken with locally advanced (cT3-4 and/or N+) EAC, and 49 patients completed neoadjuvant avelumab + docetaxel, cisplatin, 5FU (DCF) and esophagectomy between February 2018 and February 2020. These patients were matched with contemporary patients (January 2018 to June 2020) who met the inclusion criteria but received neoadjuvant chemotherapy alone (NAC) with a comparable docetaxel-based therapy. The postoperative outcomes then were compared between the two groups. RESULTS: For this study, 99 patients with locally advanced EAC underwent esophagectomy and met the enrolment criteria. Of these patients, 50 received NAC alone and 49 received IO + NAC. Baseline characteristics such as age, gender, and clinical stage were comparable between the two groups. Operative approach and rate of minimally invasive esophagectomy (~ 60%) were similar in the two groups. For the NAC-alone and IO + NAC groups, the respective overall and major complication rates were similar between the two groups (50% vs. 51% [p = 0.91] and 20% vs. 26% [p = 0.44], respectively), with concordant rates for anastomotic leak (6 [12%] vs. 6 [12%]; p = 0.86) and respiratory complications (13 [26%] vs. 11 [22%]; p = 0.68). The two groups did not differ significantly in terms of hospital length of stay or 30- and 90-day mortality rates. CONCLUSION: The addition of immunotherapy to neoadjuvant chemotherapy for locally advanced esophageal adenocarcinoma does not appear to alter perioperative short-term outcomes significantly after esophagectomy.

The Mutographs biorepository: A unique genomic resource to study cancer around the world.

Large-scale biorepositories and databases are essential to generate equitable, effective, and sustainable advances in cancer prevention, early detection, cancer therapy, cancer care, and surveillance. The Mutographs project has created a large genomic dataset and biorepository of over 7,800 cancer cases from 30 countries across five continents with extensive demographic, lifestyle, environmental, and clinical information. Whole-genome sequencing is being finalized for over 4,000 cases, with the primary goal of understanding the causes of cancer at eight anatomic sites. Genomic, exposure, and clinical data will be publicly available through the International Cancer Genome Consortium Accelerating Research in Genomic Oncology platform. The Mutographs sample and metadata biorepository constitutes a legacy resource for new projects and collaborations aiming to increase our current research efforts in cancer genomic epidemiology globally.

Transitioning to Neoadjuvant Therapy for Resectable Non-Small Cell Lung Cancer: Trends and Surgical Outcomes in a Regionalized Pulmonary Oncology Network.

BACKGROUND: Several regulatory agencies have approved the use of the neoadjuvant chemo-immunotherapy for resectable stage II and III of non-small cell lung cancer (NSCLC) and numerous trials investigating novel agents are underway. However, significant concerns exist around the feasibility and safety of offering curative surgery to patients treated within such pathways. The goal in this study was to evaluate the impact of a transition towards a large-scale neoadjuvant therapy program for NSCLC. METHODS: Medical charts of patients with clinical stage II and III NSCLC who underwent resection from January 2015 to December 2020 were reviewed. The primary outcome was perioperative complication rate between neoadjuvant-treated versus upfront surgery patients. Multivariable logistic regression estimated occurrence of postoperative complications and overall survival was assessed as an exploratory secondary outcome by Kaplan-Meier and Cox-regression analyses. RESULTS: Of the 428 patients included, 106 (24.8%) received neoadjuvant therapy and 322 (75.2%) upfront surgery. Frequency of minor and major postoperative complications was similar between groups (P = .22). Occurrence in postoperative complication was similar in both cohort (aOR = 1.31, 95% CI 0.73-2.34). Neoadjuvant therapy administration increased from 10% to 45% with a rise in targeted and immuno-therapies over time, accompanied by a reduced rate of preoperative radiation therapy use. 1-, 2-, and 5-year overall survival was higher in neoadjuvant therapy compared to upfront surgery patients (Log-Rank P = .017). CONCLUSIONS: No significant differences in perioperative outcomes and survival were observed in resectable NSCLC patients treated by neoadjuvant therapy versus upfront surgery. Transition to neoadjuvant therapy among resectable NSCLC patients is safe and feasible from a surgical perspective.

A trans-Canadian positive deviance seminar for paraesophageal hernia surgery: Reporting national postoperative outcomes and consensus recommendations.

BACKGROUND: The incidence of adverse events (AEs) and length of stay (LOS) varies significantly following paraesophageal hernia surgery. We performed a Canadian multicenter positive deviance (PD) seminar to review individual center and national level data and establish holistic perioperative practice recommendations. METHODS: A national virtual PD seminar was performed in October 2021. Recent best evidence focusing on AEs and LOS was presented. Subsequently, anonymized center-level AE and LOS data collected between 01/2017 and 01/2021 from a prospective, web-based database that tracks postoperative outcomes was presented. The top two performing centers with regards to these metrics were chosen and surgeons from these hospitals discussed elements of their treatment pathways that contributed to these outcomes. Consensus recommendations were then identified with participants independently rating their level of agreement. RESULTS: Twenty-eight surgeons form 8 centers took part in the seminar across 5 Canadian provinces. Of the 680 included patients included, Clavien-Dindo grade I and II/III/IV/V complications occurred in 121/39/12/2 patients (17.8%/5.7%/1.8%/0.3%). Respiratory complications were the most common (effusion 12/680, 1.7% and pneumonia 9/680, 1.3%). Esophageal and gastric perforation occurred in 7 and 4/680, (1.0% and 0.6% respectively). Median LOS varied significantly between institutions (1 day, range 1-3 vs. 7 days, 3-8, p < 0.001). A strong level of agreement was achieved for 10/12 of the consensus statements generated. CONCLUSION: PD seminars provide a supportive forum for centers to review best evidence and experience and generate recommendations based on expert opinion. Further research is ongoing to determine if this approach effectively accomplishes this objective.

Clinical outcomes of endoscopic submucosal dissection for superficial esophageal neoplasia in close proximity to esophageal varices: a multicenter international experience.

BACKGROUND : There are limited data on the feasibility of endoscopic submucosal dissection (ESD) for superficial esophageal neoplasia (SEN) located at or adjacent to esophageal varices. We aimed to evaluate the outcomes of ESD in these patients. METHODS: This multicenter retrospective study included cirrhotic patients with a history of esophageal varices with SEN located at or adjacent to the esophageal varices who underwent ESD. RESULTS: 23 patients with SEN (median lesion size 30 mm; 16 squamous cell neoplasia and seven Barrett's esophagus-related neoplasia) were included. The majority were Child-Pugh B (57 %) and had small esophageal varices (87 %). En bloc, R0, and curative resections were achieved in 22 (96 %), 21 (91 %), and 19 (83 %) of patients, respectively. Severe intraprocedural bleeding (n = 1) and delayed bleeding (n = 1) were successfully treated endoscopically. No delayed perforation, hepatic decompensation, or deaths were observed. During a median (interquartile range) follow-up of 36 (22-55) months, one case of local recurrence occurred after noncurative resection. CONCLUSION: ESD is feasible and effective for SEN located at or adjacent to esophageal varices in cirrhotic patients. Albeit, the majority of the esophageal varices in our study were small in size, when expertise is available, ESD should be considered as a viable option for such patients.

Docetaxel-Based Neoadjuvant Chemotherapy Followed by En Bloc Resection for Esophageal Adenocarcinoma: A 15-Year Retrospective Analysis from a Regional Upper Gastrointestinal Cancer Network.

BACKROUND: Real-world, long-term survival outcomes of neoadjuvant, docetaxel-based therapy for esophageal and junctional adenocarcinoma are lacking. This study describes the long-term survival outcomes of patients with esophageal and junctional adenocarcinoma treated with neoadjuvant docetaxel-based chemotherapy and en bloc transthoracic esophagectomy. METHODS: A retrospective cohort analysis of a prospectively maintained database from a regional upper gastrointestinal cancer network in Quebec, Canada, was performed. From January 2007 to December 2021, all patients with locally advanced (cT3 and/or N1) esophageal/Siewert I/II adenocarcinoma treated with neoadjuvant DCFx3 (Docetaxel/Cisplatin/5FU) or FLOTx4 (5FU/Leucovorin/Oxaliplatin/Docetaxel) and transthoracic en bloc esophagectomy were identified. Postoperative, pathological, and survival outcomes were compared. RESULTS: Overall, 236 of 420 patients met the inclusion criteria. Tumor location was esophageal/Siewert I/Siewert II (118/33/85), most were cT3-4 (93.6%) and cN+ (61.0%). DCF and FLOT were used in 127 of 236 (53.8%) and 109 of 236 (46.2%). All neoadjuvant cycles were completed in 87.3% with no difference between the regimens. Operative procedures included Ivor Lewis (81.8%), left thoraco-abdominal esophagectomy (10.6%) and McKeown (7.6%) with an R0 resection in 95.3% and pathological complete response in 9.7% (DCF 12.6%/FLOT 6.4%, p = 0.111). The median lymph node yield was 32 (range 4-79), and 60.6% were ypN+. Median follow-up was longer for the DCF group (74.8 months 95% confidence interval [CI] 4-173 vs. 37.8 months 95% CI 2-119, p <0.001. Overall survival was similar between the groups (FLOT 97.3 months, 78.6-115.8 vs. DCF 92.9, 9.2-106.5, p = 0.420). CONCLUSIONS: Neoadjuvant DCF and FLOT followed by transthoracic en bloc resection are both highly effective regimens for locally advanced esophageal adenocarcinoma with equivalent survival outcomes despite high disease load.

Esophagectomy versus observation following endoscopic submucosal dissection of pT1b esophageal adenocarcinoma.

BACKGROUND: Management following endoscopic submucosal dissection (ESD) of pT1b esophageal adenocarcinoma (EAC) remains controversial. This study compared pathological and survival outcomes of patients after endoscopic resection (ER) of pT1b EAC followed by either en bloc esophagectomy or observation. METHODS: From 1/12 to 12/22, all patients with pT1b EAC treated with ER were identified from a prospectively maintained departmental database. ESD was curative (all of: Submucosal invasion < 500 µm; G1/2, LVI/PNI-; deep margin-) or non-curative (one or more of Submucosal invasion ≥ 500 µm; G3; LVI/PNI+; deep margin+). Patients were allocated to observation (OBS) or esophagectomy (SURG) based on patient factors/preference and pathological variables. RESULTS: 56/171 ERs met the inclusion criteria. ER was curative in 8/56 (14%) and non-curative in 48/56 (86%). OBS was undertaken after 8/27 (30%) curative and 19/27 (70%) non-curative resections. All 29 SURG patients had non-curative ERs and were younger, had lower Charlson comorbidity scores and had more deep margin + lesions than OBS patients. Post-esophagectomy, 15/29 (52%) had no residual disease within the surgical specimen while pT+N-/pT-N+/pT+N+ occurred in 5/3/6 (17%/10%/21%) patients. Of those with residual disease in the surgical specimen, 12/14 (86%) had deep margin + ERs; however, only ESD instead of EMR was independently associated with a lower risk of residual disease (OR 0.431, 95% CI - 0.016 to 1.234, p = 0.045). OBS and SURG patients had equivalent overall survival outcomes and recurrence was low in both groups even following non-curative ER. Follow-up was 28 months (0-102) and 30 months (0-97), respectively. CONCLUSION: In select patients, including some of those with a non-curative ESD resection of pT1B EAC, surveillance alone may be appropriate. Alternatives beyond traditional pathological features is needed to direct patient care more accurately.

A Video-Based Procedure-Specific Competency Assessment Tool for Minimally Invasive Esophagectomy.

Importance: Minimally invasive esophagectomy (MIE) is a complex procedure with substantial learning curves. In other complex minimally invasive procedures, suboptimal surgical performance has convincingly been associated with less favorable patient outcomes as assessed by peer review of the surgical procedure. Objective: To develop and validate a procedure-specific competency assessment tool (CAT) for MIE. Design, Setting, and Participants: In this international quality improvement study, a procedure-specific MIE-CAT was developed and validated. The MIE-CAT contains 8 procedural phases, and 4 quality components per phase are scored with a Likert scale ranging from 1 to 4. For evaluation of the MIE-CAT, intraoperative MIE videos performed by a single surgical team in the Esophageal Center East Netherlands were peer reviewed by 18 independent international MIE experts (with more than 120 MIEs performed). Each video was assessed by 2 or 3 blinded experts to evaluate feasibility, content validity, reliability, and construct validity. MIE-CAT version 2 was composed with refined content aimed at improving interrater reliability. A total of 32 full-length MIE videos from patients who underwent MIE between 2011 and 2020 were analyzed. Data were analyzed from January 2021 to January 2023. Exposure: Performance assessment of transthoracic MIE with an intrathoracic anastomosis. Main Outcomes and Measures: Feasibility, content validity, interrater and intrarater reliability, and construct validity, including correlations with both experience of the surgical team and clinical parameters, of the developed MIE-CAT. Results: Experts found the MIE-CAT easy to understand and easy to use to grade surgical performance. The MIE-CAT demonstrated good intrarater reliability (range of intraclass correlation coefficients [ICCs], 0.807 [95% CI, 0.656 to 0.892] for quality component score to 0.898 [95% CI, 0.846 to 0.932] for phase score). Interrater reliability was moderate (range of ICCs, 0.536 [95% CI, -0.220 to 0.994] for total MIE-CAT score to 0.705 [95% CI, 0.473 to 0.846] for quality component score), and most discrepancies originated in the lymphadenectomy phases. Hypothesis testing for construct validity showed more than 75% of hypotheses correct: MIE-CAT performance scores correlated with experience of the surgical team (r = 0.288 to 0.622), blood loss (r = -0.034 to -0.545), operative time (r = -0.309 to -0.611), intraoperative complications (r = -0.052 to -0.319), and severe postoperative complications (r = -0.207 to -0.395). MIE-CAT version 2 increased usability. Interrater reliability improved but remained moderate (range of ICCs, 0.666 to 0.743), and most discrepancies between raters remained in the lymphadenectomy phases. Conclusions and Relevance: The MIE-CAT was developed and its feasibility, content validity, reliability, and construct validity were demonstrated. By providing insight into surgical performance of MIE, the MIE-CAT might be used for clinical, training, and research purposes.

Multicentre positive deviance seminar to generate best practice recommendations to reduce anastomotic leak and length of stay for patients undergoing oesophagectomy.

BACKGROUND: We describe a novel process using positive deviance (PD) with the Canadian Association of Thoracic Surgeons members, to identify perioperative best practice to minimise anastomotic leak (AL) and length of stay (LOS) following oesophagectomy. To our knowledge, this is the first National combination of level 1 evidence with expert opinion (ie, PD seminar) aimed at reducing AL and LOS in oesophageal surgery. Our primary hypothesis is that a multicentre National PD seminar is feasible, and could lead to the generation of best practices recommendations aimed at reducing AL and LOS in patients with oesophageal cancer. METHODS: Adverse events, LOS and AL incidence/severity following oesophagectomy were prospectively collected from seven Canadian thoracic institutions using Thoracic Morbidity and Mortality classification system (2017-2020). Anonymised display of centre's data were presented, with identification of centres demonstrating PD. Surgeons from PD sites discussed principles of care, culminating in the consensus recommendations, anonymously rated by all (5-point Likert scale). RESULTS: Data from 795 esophagectomies were included, with 25 surgeons participating. Two centres were identified as having the lowest AL rates 44/395 (11.1%) (vs five centres 71/400 (17.8%) (p<0.01)) and shortest LOS 8 days 45 (IQR: 6-14) (vs 10 days (IQR: 8-18) (p<0.001)). Recommendations included preoperative (prehabilitation, smoking cessation, chemotherapy for patients with dysphagia, minimise stents/feeding tubes), intraoperative (narrow gastric conduit, intrathoracic anastomosis, avoid routine jejunostomy, use small diameter closed-suction drains), postoperative day (POD) (early (POD 2-3) enteral feeding initiation, avoid routine barium swallow studies, early removal of tubes/drains (POD 2-3)). All ranked above 80% (4/5) in agreement to implement recommendations into their practice. CONCLUSION: We report the feasibility of a National multicentre PD seminar with the generation of best practice recommendations aimed at reducing AL and LOS following oesophagectomy. Further research is required to demonstrate whether National PD seminars can be an effective quality improvement tool.

Feasibility Study Utilizing NanoString's Digital Spatial Profiling (DSP) Technology for Characterizing the Immune Microenvironment in Barrett's Esophagus Formalin-Fixed Paraffin-Embedded Tissues.

Characterization of the Barrett's esophagus (BE) microenvironment in patients with a known progression status, to determine how it may influence BE progression to esophageal adenocarcinoma (EAC), has been understudied, hindering both the biological understanding of the progression and the development of novel diagnostics and therapies. This study's aim was to determine if a highly multiplex interrogation of the microenvironment can be performed on endoscopic formalin-fixed, paraffin-embedded (FFPE) samples, utilizing the NanoString GeoMx digital spatial profiling (GeoMx DSP) platform and if it can begin to identify the types of immune cells and pathways that may mediate the progression of BE. We performed a spatial proteomic analysis of 49 proteins expressed in the microenvironment and epithelial cells of FFPE endoscopic biopsies from patients with non-dysplastic BE (NDBE) who later progressed to high-grade dysplasia or EAC (n = 7) or from patients who, after at least 5 years follow-up, did not (n = 8). We then performed an RNA analysis of 1812 cancer-related transcripts on three endoscopic mucosal resections containing regions of BE, dysplasia, and EAC. Profiling with GeoMx DSP showed reasonable quality metrics and detected expected differences between epithelium and stroma. Several proteins were found to have an increased expression within NDBE biopsies from progressors compared to non-progressors, suggesting further studies are warranted.

Seizure outcomes and safety profiles of surgical options for epilepsy associated to hypothalamic hamartomas. A systematic review and meta-analysis.

PURPOSE: Several surgical options are available for treating hypothalamic hamartoma-related epilepsy but their respective efficacy and safety profiles are poorly defined. METHODS: A literature search identified English-language articles reporting series of patients (minimum 3 patients with a follow-up ≥12 months) operated on by either microsurgery, endoscopic surgery, radiosurgery, radiofrequency thermocoagulation or laser interstitial thermal therapy for hypothalamic hamartoma-related epilepsy. The unit of analysis was each selected study. Pooled rates of seizure freedom and of neurological and endocrinological complications were analyzed using meta-analysis to calculate both fixed and random effects. The results of meta-analyses were compared. RESULTS: Thirty-nine studies were included. There were 568 and 514 participants for seizure outcome and complication analyses, respectively. The pairwise comparison showed that: i) the proportion of seizure-free cases was significantly lower for radiosurgery as compared to microsurgery, radiofrequency thermocoagulation and laser ablation, and significantly lower for endoscopic surgery as compared to radiofrequency thermocoagulation; ii) the proportion of permanent hypothalamic dysfunction was significantly higher for microsurgery as compared to all other techniques, and significantly lower for endoscopic surgery as compared to radiofrequency thermocoagulation and laser ablation; iii) the incidence of permanent neurological disorders was significantly higher for microsurgery as compared to endoscopic surgery, radiosurgery and radiofrequency thermocoagulation, and significantly lower for radiosurgery as compared to laser ablation. CONCLUSIONS: Minimally invasive surgical techniques, including endoscopic surgery, radiofrequency thermocoagulation and laser ablation, represent an acceptable compromise between efficacy and safety in the treatment of hypothalamic hamartoma-related epilepsy. Microsurgery and radiosurgery should be considered in carefully selected cases.

Transabdominal Management of Epiphrenic Diverticula in the Setting of Achalasia: A Single-center Review.

BACKGROUND: The perioperative and functional outcomes of patients with epiphrenic diverticula (ED) on a background of achalasia managed via a minimally invasive transabdominal approach are under-reported. We describe our center's experience over 10 years of treating such patients. METHODS: A single-center, retrospective chart of a prospectively maintained hospital database was performed. All patients with a diagnosis of ED and manometrically proven achalasia were identified. Demographic, clinical, and surgical data were extracted from the institution's medical records. Patients were stratified by whether they underwent myotomy only or myotomy plus diverticulectomy and compared in a univariate manner. RESULTS: There were 18 patients who met the inclusion criteria. The median age of the cohort was 67.1 years (range 53.1 to 77.8), the maximal size of the diverticula was 3.5 cm (range 2.0 to 7.0), and the distance of the proximal lip of the diverticulum to the incisors was 33.5 cm (range 28.0 to 38.0). In terms of surgical intervention, 14 patients (77.8%) underwent myotomy plus diverticulectomy, and 4 (22.2%) underwent myotomy alone. The duration of surgery was significantly longer in the former (177.5 vs. 75.0 min, P =0.031). In total, 9/18 (50.0%) of patients were discharged on the day of surgery. There was a trend to more major postoperative complications following diverticulectomy plus myotomy, with 2/13 (15.4%) patients suffering staple line leaks. Excellent long-term functional outcomes were achieved, with 81.3% of patients having sustained resolution of their symptoms. CONCLUSIONS: Laparoscopic transabdominal approach for the treatment of ED offers an acceptable risk profile and favorable functional outcomes in patients with underlying achalasia.