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Objective: To evaluate outcomes after primary surgery (PS) or neoadjuvant treatment followed by surgery (NAT/S) in cT2 staged adenocarcinomas of the esophagus (EAC) and gastroesophageal junction (GEJ), a multinational high-volume center study was undertaken. Background: The optimal treatment approach with either NAT/S or PS for clinically staged cT2cNany or cT2N0 EAC and GEJ remains unknown due to the lack of randomized controlled trials. Methods: A retrospective analysis of prospectively maintained databases from 10 centers was performed. Between January 2012 and August 2023, 645 patients who fulfilled inclusion criteria of GEJ Siewert type I, II, or EAC with cT2 status at diagnosis underwent PS or NAT/S with curative intent. The primary endpoint was overall survival (OS). Results: In the cT2cNany cohort, 192 patients (29.8%) underwent PS and 453 (70.2%) underwentNAT/S. In all cT2cN0 patients (n = 333),NAT/s remained the more frequent treatment (56.2%). Patients undergoing PS were in both cT2 cohorts older (P < 0.001) and had a higher American Society of Anesthesiologists classification (P < 0.05). R0 resection showed no differences between NAT/S and PS in both cT2 cohorts (P > 0.4).Median OS was 51.0 months in the PS group (95% CI: 31.6--70.4) versus 114.0 months (95% CI: 53.9--174.1) in the NAT/S group (P = 0.003) of cT2cNany patients. For cT2cN0 patients,NAT/S was associated with longer OS (P = 0.002) and disease-free survival (P = 0.001). After propensity score matching of the cT2N0 patients, survival benefit for NAT/S remained (P = 0.004). Histopathology showed that 38.1% of cT2cNany and 34.2% of cT2cN0 patients were understaged. Conclusions: Due to the unreliable identification of cT2N0 disease, all patients should be offered a multimodal therapeutic approach. [ABSTRACT FROM AUTHOR]

Objective: To analyze the impact of centralization on key metrics, outcomes, and patterns of care at the Irish National Center. Background: Overall survival rates for esophageal cancer in the West have doubled in the last 25 years. An international trend towards centralization may be relevant; however, this model remains controversial, with Ireland centralizing esophageal cancer surgery in 2011. Methods: All patients (n=1245) with adenocarcinoma of the esophagus or junction treated with curative intent involving surgery, including endoscopic surgery, were included (n=461 from 2000 2011, and 784 from 2012 to 2022). All data entry was prospectively recorded. Overall survival was measured (1) for the entire cohort, (2) for patients with locally advanced disease (cT2-3N0-3), and (3) for patients undergoing neoadjuvant therapy. All complications were recorded as per Esophageal Complication Consensus Group definitions, and the Clavien-Dindo severity classification. Data were analyzed using GraphPad Prism (v.6.0) for Windows and SPSS (v.23.0) software (SPSS) R Studio (R version 4.2.2). Survival times were calculated using a log-rank test and Cox regression analysis, and Kaplan-Meier curves were generated. Results: Endotherapy for cT1a/intramucosal cancer adenocarcinoma increased from 40 (9% total) to 245 (31% total) procedures between the pre-centralization and post-centralization (post-C) periods. significantly (P < 0.001) higher proportion of patients with cT2-3N0- disease in the post-C period underwent neoadjuvant therapy (66% 53%). Operative mortality was lower (P=0.02) post-C, at 2% versus 4.5%, and ZIIIa Clavien-Dindo major complications decreased from 33% to 25% (P < 0.01). Recurrence rates were lower post- (38% vs 53%, P < 0.01). Median overall survival was 73.83 versus 47.23 months in the 2012 to 2022 and 2000 to 2011 cohorts, respectively (P < 0.001). For those who received neoadjuvant therapy, the median survival was 28.5 months pre-centralization and 42.5 months post-C (P < 0.001). Conclusions: These data highlight improvements in both operative outcomes and survival from the time of centralization, and a major expansion of endoscopic surgery. Although not providing proof, the study suggests a positive impact of formal centralization with governance on key quality metrics and an evolution in patterns of care. [ABSTRACT FROM AUTHOR]

Background A proportion of patients undergoing midline laparotomy will develop surgical site infections after surgery. These complications place considerable financial burden on healthcare economies and have negative implications for patient health and quality of life. The prophylactic application of negative pressure wound therapy devices has been mooted as a pragmatic strategy to reduce surgical site infections. Nevertheless, further availability of multicentre randomized clinical trial data evaluating the prophylactic use of negative pressure wound therapy following midline laparotomy is warranted to definitely provide consensus in relation to these closure methods, while also deciphering potential differences among subgroups. The aim of this study is to determine whether prophylactic negative pressure wound therapy reduces postoperative wound complications in patients undergoing midline laparotomy. Methods PROPEL-2 is a multicentre prospective randomized clinical trial designed to compare standard surgical dressings (control arm) with negative pressure wound therapy dressings (Prevena™ and PICO™ being the most commonly utilized). Patient recruitment will include adult patients aged 18 years or over, who are indicated to undergo emergency or elective laparotomy. To achieve 90% power at the 5% significance level, 1006 patients will be required in each arm, which when allowing for losses to follow-up, 10% will be added to each arm, leaving the total projected sample size to be 2013 patients, who will be recruited across a 36-month enrolment period. Conclusion The PROPEL-2 trial will be the largest independent multicentre randomized clinical trial designed to assess the role of prophylactic negative pressure wound therapy in patients indicated to undergo midline laparotomy. The comparison of standard treatment to two commercially available negative pressure wound therapy devices will help provide consensus on the routine management of laparotomy wounds. Enrolment to PROPEL-2 began in June 2023. Registration number: NCT05977816 (http://www.clinicaltrials.gov). [ABSTRACT FROM AUTHOR]

There is currently no consensus as to how to manage esophageal anastomotic leaks. Intervention with endoscopic vacuum-assisted closure (EVAC), stenting, reoperation, and conservative management have all been mooted as potential options. To conduct a systematic review and network meta-analysis (NMA) to evaluate the optimal management strategy for esophageal anastomotic leaks. A systematic review was performed as per the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines with extension for NMA. NMA was performed using R packages and Shiny. In total, 12 retrospective studies were included, which included 511 patients. Of the 449 patients for whom data regarding sex was available, 371 (82.6%) were male, 78 (17.4%) were female. The average age of patients was 62.6 years (standard deviation 10.2). The stenting cohort included 245 (47.9%) patients. The EVAC cohort included 123 (24.1%) patients. The conservative cohort included 87 (17.0%) patients. The reoperation cohort included 56 (10.9%) patients. EVAC had a significantly decreased complication rate compared to stenting (odds ratio 0.23 95%, confidence interval [CI] 0.09;0.58). EVAC had a significantly lower mortality rate than stenting (odds ratio 0.43, 95% CI 0.21; 0.87). Reoperation was used in significantly larger leaks than stenting (mean difference 14.66, 95% CI 4.61;24.70). The growing use of EVAC as a first-line intervention in esophageal anastomotic leaks should continue given its proven effectiveness and significant reduction in both complication and mortality rates. Surgical management is often necessary for significantly larger leaks and will likely remain an effective option in uncontained leaks with systemic features. [ABSTRACT FROM AUTHOR]

Optimal pain control following esophagectomy remains a topic of contention. The aim was to perform a systematic review and network meta-analysis (NMA) of randomized clinical trials (RCTs) evaluating the analgesia strategies post-esophagectomy. A NMA was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-NMA guidelines. Statistical analysis was performed using Shiny and R. Fourteen RCTs which included 565 patients and assessed nine analgesia techniques were included. Relative to systemic opioids, thoracic epidural analgesia (TEA) significantly reduced static pain scores at 24 hours post-operatively (mean difference (MD): −13.73, 95% Confidence Interval (CI): −27.01–0.45) (n  = 424, 12 RCTs). Intrapleural analgesia (IPA) demonstrated the best efficacy for static (MD: −36.2, 95% CI: −61.44–10.96) (n = 569, 15 RCTs) and dynamic (MD: −42.90, 95% CI: −68.42–17.38) (n  = 444, 11 RCTs) pain scores at 48 hours. TEA also significantly reduced static (MD: −13.05, 95% CI: −22.74–3.36) and dynamic (MD: −18.08, 95% CI: −31.70–4.40) pain scores at 48 hours post-operatively, as well as reducing opioid consumption at 24 hours (MD: −33.20, 95% CI: −60.57–5.83) and 48 hours (MD: −42.66, 95% CI: −59.45–25.88). Moreover, TEA significantly shortened intensive care unit (ICU) stays (MD: −5.00, 95% CI: −6.82–3.18) and time to extubation (MD: −4.40, 95% CI: −5.91–2.89) while increased post-operative forced vital capacity (MD: 9.89, 95% CI: 0.91–18.87) and forced expiratory volume (MD: 13.87, 95% CI: 0.87–26.87). TEA provides optimal pain control and improved post-operative respiratory function in patients post-esophagectomy, reducing ICU stays, one of the benchmarks of improved post-operative recovery. IPA demonstrates promising results for potential implementation in the future following esophagectomy. [ABSTRACT FROM AUTHOR]

The presence of an immunosuppressive tumour microenvironment in oesophageal adenocarcinoma (OAC) is a major contributor to poor responses. Novel treatment strategies are required to supplement current regimens and improve patient survival. This study examined the immunomodulatory effects that radiation therapy and chemokine receptor antagonism impose on T cell phenotypes in OAC with a primary goal of identifying potential therapeutic targets to combine with radiation to improve anti-tumour responses. Compared with healthy controls, anti-tumour T cell function was impaired in OAC patients, demonstrated by lower IFN-γ production by CD4+ T helper cells and lower CD8+ T cell cytotoxic potential. Such diminished T cell effector functions were enhanced following treatment with clinically relevant doses of irradiation. Interestingly, CCR5+ T cells were significantly more abundant in OAC patient blood compared with healthy controls, and CCR5 surface expression by T cells was further enhanced by clinically relevant doses of irradiation. Moreover, irradiation enhanced T cell migration towards OAC patient-derived tumour-conditioned media (TCM). In vitro treatment with the CCR5 antagonist Maraviroc enhanced IFN-γ production by CD4+ T cells and increased the migration of irradiated CD8+ T cells towards irradiated TCM, suggesting its synergistic therapeutic potential in combination with irradiation. Overall, this study highlights the immunostimulatory properties of radiation in promoting anti-tumour T cell responses in OAC and increasing T cell migration towards chemotactic cues in the tumour. Importantly, the CCR5 antagonist Maraviroc holds promise to be repurposed in combination with radiotherapy to promote anti-tumour T cell responses in OAC. [ABSTRACT FROM AUTHOR]