Personalised exercise rehabilitation in cancer survivorship: the percs triage and referral system study protocol.

BACKGROUND: To effectively embed exercise rehabilitation in cancer survivorship care, a co-ordinated system of acute and community exercise rehabilitation services, forming a stepped model of care, is recommended. Patients can be directed to the exercise rehabilitation service which best meets their needs through a system of assessment, triage and referral. Triage and referral systems are not yet widely applied in cancer survivorship practice and need to be evaluated in real-world contexts. The PERCS (Personalised Exercise Rehabilitation in Cancer Survivorship) study aims to evaluate the real-world application of an exercise rehabilitation triage and referral system in cancer survivors treated during the COVID-19 pandemic. Secondary aims are to evaluate change in physical and psychosocial outcomes, and to qualitatively evaluate the impact of the system and patient experiences, at three months after application of the triage and referral system. METHODS: This study will assess the implementation of an exercise rehabilitation triage and referral system within the context of a physiotherapy-led cancer rehabilitation clinic for cancer survivors who received cancer treatment during the COVID-19 pandemic. The PERCS triage and referral system supports decision making in exercise rehabilitation referral by recommending one of three pathways: independent exercise; fitness professional referral; or health professional referral. Up to 100 adult cancer survivors treated during the COVID-19 pandemic who have completed treatment and have no signs of active disease will be recruited. We will assess participants' physical and psychosocial wellbeing and evaluate whether medical clearance for exercise is needed. Participants will then be triaged to a referral pathway and an exercise recommendation will be collaboratively decided. Reassessment will be after 12 weeks. Primary outcomes are implementation-related, guided by the RE-AIM framework. Secondary outcomes include physical function, psychosocial wellbeing and exercise levels. Qualitative analysis of semi-structured interviews guided by the Consolidated Framework for Implementation Research (CFIR) will provide insights on implementation and system impact. DISCUSSION: The PERCS study will investigate the real-world application of a cancer rehabilitation triage and referral system. This will provide proof of concept evidence for this triage approach and important insights on the implementation of a triage system in a specialist cancer centre. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov, registration number: NCT05615285, date registered: 21st October 2022.

Analysing the Combined Effects of Radiotherapy and Chemokine Receptor 5 Antagonism: Complementary Approaches to Promote T Cell Function and Migration in Oesophageal Adenocarcinoma.

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.

Valid consent in the acute hospital setting: perspectives of patients and members of the public.

BACKGROUND: People who interact with healthcare services have an ethical and legal right to control their own lives, to make informed decisions, and to consent to what happens to them. For consent to be considered ethically and legally valid, three key criteria must be met: consent must be given voluntarily; people must be sufficiently informed of all options; and people should have capacity to make the decision to give or withhold their consent. AIM: This study set out to explore, through the use of surveys, the perspectives of patients and public in relation to consent. METHOD: Surveys were developed for patients and the public and administered paper based (patients) and through social media (public). RESULTS: One hundred and forty surveys were posted to patients, with a 38% response rate; 104 responses were received from the public. Ninety-six percent of patients were satisfied that the decision they made was informed; 100% felt they had made a voluntary decision; 98% felt the clinician seemed knowledgeable about the procedure. What matters most to the public were being informed about the risks associated with the proposed procedure and being assured that whatever choice they make they will receive the best care possible. CONCLUSIONS: The results highlight interesting similarities and differences in relation to consent between members of the public thinking about a possible treatment, surgery, or procedure and those patients who have actually been through the process in the past 12 months. Recommendations have been developed on the basis of these findings to co-design improvements in consent practices.

'SurgTalk': The Educational Outcomes Associated With Development of a Surgical Podcast for Undergraduate Medical Students.

OBJECTIVE: Educational podcast series are becoming increasingly popular as free open access medical education (FOAMed) resources, however, the educational benefit associated with their use is unclear. The aim of this study was to assess the educational outcomes associated with the implementation of a surgical podcast series for undergraduate medical students. METHODS: Two conversational case-based podcast episodes were recorded covering 2 common surgical presentations. Final-year medical students were recruited prospectively in January 2023 and underwent a baseline multiple choice question (MCQ) test covering the material within the podcast episodes. Participants were then provided with the episode files through encrypted Google Drive links. Two weeks following baseline assessment, students repeated the initial MCQ test and completed a postpodcast reaction survey. Data were analyzed using a paired t-test, multivariable regression analyses, and simple descriptive statistics. RESULTS: Fifty students were enrolled in the study. All participants undertook the baseline assessment. About 98% completed the postpodcast MCQ, while 94% completed the postpodcast reaction survey. All participants who undertook the reaction survey (n = 47) found the podcast helpful in explaining surgical concepts, 92% of participants found the podcast enjoyable to listen to. The most commonly reported activity undertaken while listening was "commuting/driving" (n = 24, 48%). The mean baseline MCQ score was 44.6%. The mean postpodcast MCQ score was 65.51%. There was a mean absolute increase in test score of 20.2% from baseline which was statistically significant (95%CI 14.67-25.6, p < 0.001). CONCLUSION: Implementation of this podcast series was associated with a statistically significant improvement in mean test score from baseline, reflecting knowledge acquisition. There was a positive user reaction and students were able to listen while performing other activities. Further evaluation of the educational outcomes associated with podcast use, particularly the effects on knowledge retention and clinical competence, is required.

Potential of damage associated molecular patterns in synergising radiation and the immune response in oesophageal cancer.

BACKGROUND: There is an intimate crosstalk between cancer formation, dissemination, treatment response and the host immune system, with inducing tumour cell death the ultimate therapeutic goal for most anti-cancer treatments. However, inducing a purposeful synergistic response between conventional therapies and the immune system remains evasive. The release of damage associated molecular patterns (DAMPs) is indicative of immunogenic cell death and propagation of established immune responses. However, there is a gap in the literature regarding the importance of DAMP expression in oesophageal adenocarcinoma (OAC) or by immune cells themselves. AIM: To investigate the effects of conventional therapies on DAMP expression and to determine whether OAC is an immunogenic cancer. METHODS: We investigated the levels of immunogenic cell death-associated DAMPs, calreticulin (CRT) and HMGB1 using an OAC isogenic model of radioresistance. DAMP expression was also assessed directly using ex vivo cancer patient T cells (n = 10) and within tumour biopsies (n = 9) both pre and post-treatment with clinically relevant chemo(radio)therapeutics. RESULTS: Hypoxia in combination with nutrient deprivation significantly reduces DAMP expression by OAC cells in vitro. Significantly increased frequencies of T cell DAMP expression in OAC patients were observed following chemo(radio)therapy, which was significantly higher in tumour tissue compared with peripheral blood. Patients with high expression of HMGB1 had a significantly better tumour regression grade (TRG 1-2) compared to low expressors. CONCLUSION: In conclusion, OAC expresses an immunogenic phenotype with two distinct subgroups of high and low DAMP expressors, which correlated with tumour regression grade and lymphatic invasion. It also identifies DAMPs namely CRT and HMGB1 as potential promising biomarkers in predicting good pathological responses to conventional chemo(radio)therapies currently used in the multimodal management of locally advanced disease.

External validation of a nomogram predicting conditional survival after tri-modality treatment of esophageal cancer.

BACKGROUND: A conditional survival nomogram was developed at a single high-volume center to predict 5-year overall survival for esophageal cancer patients after neoadjuvant chemoradiation and esophagectomy. The aim of this study was to externally validate the nomogram in a cohort of patients with esophageal adeno- or squamous cell carcinoma from another high-volume center. METHODS: Consecutive patients with an esophageal adeno- or squamous cell carcinoma who had undergone esophagectomy after being treated with preoperative chemoradiation between 2004 and 2016 were selected from a prospectively maintained institutional database. The level of discrimination for prediction of 5-year overall survival was quantified by Harrell's C statistic. Calibration of the conditional survival nomogram was visualized by plotting predicted 5-year survival and observed 5-year survival for comparison. RESULTS: Of the 296 patients examined, the probability of 5-year overall survival directly after surgery was 45% and increased to 51%, 68%, 78%, and 89% for each additional year survived. The predicted 5-year overall survival differed from the observed survival, with a calibration slope of 0.54, 0.55, 0.59, 0.73, and 1.09 directly after surgery and 1, 2, 3, and 4 years of survival after surgery, respectively. The nomogram's discrimination level for 5-year survival was moderate, with a C statistic of 0.65 compared to the 0.70 reported in the original study. CONCLUSION: The nomogram model has moderate predictive discrimination and accuracy, supporting its applicability to external cohorts to predict conditional survival. Further validation studies should empirically assess the model for predictive performance.

Management Experiences of Post-Gastrectomy Severe Alkaline Reflux Esophagitis.

Alkaline reflux esophagitis is a recognized complication of procedures that compromise the lower esophageal sphincter (LES), including gastrectomy. Incidence of reflux is dependent on the reconstructive procedure, with Roux-en-Y (RY) esophagojejunostomy commonly accepted as the optimal method. The authors report their experience of 5 patients who underwent remedial intervention for severe alkaline reflux esophagitis following gastric cancer surgery, over a 6-year period (2014-2020). Primary diagnoses encompassed 4 gastric adenocarcinomas and 1 gastric neuroendocrine tumor. Four patients previously underwent total gastrectomy and 1 subtotal gastrectomy with RY reconstruction. Onset of postoperative reflux symptoms ranged from 2 weeks to 3 years. Failing medical management, all patients underwent jejunojejunal anastomosis and Roux limb length revision with surgical jejunostomy. At follow-up, 4 out of 5 patients had some degree of symptom resolution and one with unresolved symptoms. The authors report our experience of managing this complication following gastrectomy with jejunojejunal anastomosis and Roux limb length revision.

PD-1 blockade attenuates surgery-mediated immunosuppression and boosts Th1 immunity perioperatively in oesophagogastric junctional adenocarcinoma.

Introduction: This timely study assesses the immunosuppressive effects of surgery on cytotoxic Th1-like immunity and investigates if immune checkpoint blockade (ICB) can boost Th1-like immunity in the perioperative window in upper gastrointestinal cancer (UGI) patients. Methods: PBMCs were isolated from 11 UGI patients undergoing tumour resection on post-operative days (POD) 0, 1, 7 and 42 and expanded ex vivo using anti-CD3/28 and IL-2 for 5 days in the absence/presence of nivolumab or ipilimumab. T cells were subsequently immunophenotyped via flow cytometry to determine the frequency of T helper (Th)1-like, Th1/17-like, Th17-like and regulatory T cell (Tregs) subsets and their immune checkpoint expression profile. Lymphocyte secretions were also assessed via multiplex ELISA (IFN-γ, granzyme B, IL-17 and IL-10). The 48h cytotoxic ability of vehicle-, nivolumab- and ipilimumab-expanded PBMCs isolated on POD 0, 1, 7 and 42 against radiosensitive and radioresistant oesophageal adenocarcinoma tumour cells (OE33 P and OE33 R) was also examined using a cell counting kit-8 (CCK-8) assay to determine if surgery affected the killing ability of lymphocytes and whether the use of ICB could enhance cytotoxicity. Results: Th1-like immunity was suppressed in expanded PBMCs in the immediate post-operative setting. The frequency of expanded circulating Th1-like cells was significantly decreased post-operatively accompanied by a decrease in IFN-γ production and a concomitant increase in the frequency of expanded regulatory T cells with an increase in circulating levels of IL-10. Interestingly, PD-L1 and CTLA-4 immune checkpoint proteins were also upregulated on expanded Th1-like cells post-operatively. Additionally, the cytotoxic ability of expanded lymphocytes against oesophageal adenocarcinoma tumour cells was abrogated post-surgery. Of note, the addition of nivolumab or ipilimumab attenuated the surgery-mediated suppression of lymphocyte cytotoxicity, demonstrated by a significant increase in tumour cell killing and an increase in the frequency of Th1-like cells and Th1 cytokine production. Conclusion: These findings support the hypothesis of a surgery-mediated suppression in Th1-like cytotoxic immunity and highlights a rationale for the use of ICB within the perioperative setting to abrogate tumour-promoting effects of surgery and ameliorate the risk of recurrence.

MicroRNA dysregulation and therapeutic opportunities in esophageal diseases.

MicroRNAs (miRNAs) are a class of small endogenous RNA molecules between 18 and 25 nucleotides long. The primary function of miRNAs is in the posttranscriptional regulation of mRNA targets through RNA interference culminating in mRNA degradation or translational repression. MiRNAs are fundamental in physiological and pathological processes such as cell proliferation, differentiation, apoptosis, and inflammation. Among this includes the uncovered potential of miRNAs in overall esophageal disease with a focus on the clinicopathologic allergic disease eosinophilic esophagitis (EoE), gastroesophageal reflux disease (GERD), and the tumorigenic continuum from Barrett's esophagus (BE) toward esophageal adenocarcinoma (EAC). Although these pathologies are distinct from one another, they share pathophysiological elements such as an intense inflammatory milieu, esophageal dysfunction, and as presented in this review, an overlap in miRNA expression which contributes to overall esophageal disease. The overlap in the dysregulated miRNA transcriptome of these pathologies highlights the key role miRNAs play in contributing to esophageal disease progression. Owing to this notable dysregulation, there is an attractive utility for miRNAs as diagnostic and prognostic biomarkers in esophageal diseases that already require invasive endoscopies and biopsy retrieval. In this review miRNAs within EoE, GERD, BE, EAC, and esophageal achalasia are discussed, as well as reviewing a core set of miRNAs shared in the disease progression among some of these pathologies, along with the potential utility of targeting miRNAs as therapeutic options in overall esophageal disease.

Energy Metabolism, Metabolite, and Inflammatory Profiles in Human Ex Vivo Adipose Tissue Are Influenced by Obesity Status, Metabolic Dysfunction, and Treatment Regimes in Patients with Oesophageal Adenocarcinoma.

Oesophageal adenocarcinoma (OAC) is a poor prognosis cancer with limited response rates to current treatment modalities and has a strong link to obesity. To better elucidate the role of visceral adiposity in this disease state, a full metabolic profile combined with analysis of secreted pro-inflammatory cytokines, metabolites, and lipid profiles were assessed in human ex vivo adipose tissue explants from obese and non-obese OAC patients. These data were then related to extensive clinical data including obesity status, metabolic dysfunction, previous treatment exposure, and tumour regression grades. Real-time energy metabolism profiles were assessed using the seahorse technology. Adipose explant conditioned media was screened using multiplex ELISA to assess secreted levels of 54 pro-inflammatory mediators. Targeted secreted metabolite and lipid profiles were analysed using Ultra-High-Performance Liquid Chromatography coupled with Mass Spectrometry. Adipose tissue explants and matched clinical data were collected from OAC patients (n = 32). Compared to visceral fat from non-obese patients (n = 16), visceral fat explants from obese OAC patients (n = 16) had significantly elevated oxidative phosphorylation metabolism profiles and an increase in Eotaxin-3, IL-17A, IL-17D, IL-3, MCP-1, and MDC and altered secretions of glutamine associated metabolites. Adipose explants from patients with metabolic dysfunction correlated with increased oxidative phosphorylation metabolism, and increases in IL-5, IL-7, SAA, VEGF-C, triacylglycerides, and metabolites compared with metabolically healthy patients. Adipose explants generated from patients who had previously received neo-adjuvant chemotherapy (n = 14) showed elevated secretions of pro-inflammatory mediators, IL-12p40, IL-1α, IL-22, and TNF-ß and a decreased expression of triacylglycerides. Furthermore, decreased secreted levels of triacylglycerides were also observed in the adipose secretome of patients who received the chemotherapy-only regimen FLOT compared with patients who received no neo-adjuvant treatment or chemo-radiotherapy regimen CROSS. For those patients who showed the poorest response to currently available treatments, their adipose tissue was associated with higher glycolytic metabolism compared to patients who had good treatment responses. This study demonstrates that the adipose secretome in OAC patients is enriched with mediators that could prime the tumour microenvironment to aid tumour progression and attenuate responses to conventional cancer treatments, an effect which appears to be augmented by obesity and metabolic dysfunction and exposure to different treatment regimes.

Translating evidence in a priority setting partnership: knowledge gaps between healthcare providers and oesophageal cancer patients.

INTRODUCTION: Despite the fact that health information is now more accessible than ever, knowledge gaps remain between patients and healthcare providers (HCPs). To date, the patients' need for information following a diagnosis of oesophageal cancer has not been adequately met. PURPOSE: The purpose of this study was to identify why knowledge gaps exist between oesophageal cancer patients and HCPs and how to address them. METHODS: Purposive sampling of a group of people living with and after oesophageal cancer who had participated in a priority-setting partnership where 45% of questions from patients had existing evidence-based answers. A 7-set question series was developed for use in a patient/HCP focus group in addition to 11 individual phone interviews with survivors of oesophageal cancer. Qualitative semistructured interviews were conducted to explore oesophageal cancer patients' access to information. The data was analysed thematically, which involved coding all patient transcripts before identifying and reviewing key themes. RESULTS: The three primary themes that emerged were as follows: opportunity (HCP team factors and relationship development), ability (patient factors) and priority (pacing of information delivery). CONCLUSION: Effective communication between patients and HCPs was identified as an integral component of the enhancement of patient knowledge. HCPs should continue to refine and improve methods of information delivery and encourage conversations regarding information preferences.

What works best in hiatus hernia repair, sutures alone, absorbable mesh or non-absorbable mesh? A systematic review and network meta-analysis of randomized clinical trials.

Laparoscopic hiatal hernia repair (HHR) and fundoplication is a common low risk procedure providing excellent control of gastro-oesophageal reflux disease and restoring of normal anatomy at the hiatus. HHR may fail, however, resulting in hiatus hernia (HH) recurrence, and the use of tension-free mesh-augmented hernioplasty has been proposed to reduce recurrence. Previous research on this topic has been heterogeneous, including study methods, mesh type used and technique performed. A systematic review and network meta-analysis were carried out. An electronic systematic research was carried out using 'PUBMED', 'EMBASE', 'Medline (OVID)' and 'Web of Science', of articles identifying HHR with suture cruroplasty, non-absorbable mesh (NAM) and absorbable mesh (AM) reinforcement. Eight RCTs with 766 patients were evaluated. NAM had significantly (P < 0.05) lower early recurrence rates (OR: 0.225, 95% CI 0.0342, 0.871) compared with suture repair alone; however, no differences in late recurrences were evident. For AM, no difference in early (0.508, 95% CI 0.0605, 4.81) or late (1.07. 95% CI 0.116, 11.4) recurrence rates were evident compared with the suture only group. Major complication rates were similar in all groups. NAM reinforcement significantly reduced early HH recurrence when compared with sutured cruroplasty alone; however, late recurrence rates were similar with all techniques. Given the limited data in comparing AM with NAM, this study was unable to conclude which composition was significant. We emphasize caution when interpreting small sample size RCTs, and recommend more research with larger randomized studies.

Assessing medical students' perception and educational experience during COVID-19 pandemic.

INTRODUCTION: The COVID-19 pandemic has significantly impacted the traditional delivery of medical education. Medical education programmes have had to cope with limitations on face-to-face learning, and accelerate the adoption of digital learning. In addition, the pandemic has potential serious implications on the psychological well-being of medical students. We aim to assess the changes in perceptions and experiences of medical students as a consequence of this pandemic. METHODS: Cross-sectional survey of medical students at Trinity College Dublin (TCD) between March and April 2022 was performed. The survey explored student satisfaction with the current education program, teaching delivery and the impact of COVID-19 on education and student well-being. RESULTS: 175 medical students participated in the survey. Overall, the majority of students were happy/neutral with their medical education. 93 (53.1%) felt tutorials and problem-based learning (PBL) to be the most effective method of teaching, followed by laboratory and clinical placements in 78 participants (44.6%) and hybrid-learning in 85 participants (48.6%). There was a mixed reaction to the changes in the delivery of education brought about by the pandemic. 67 participants (40.6%) felt happy with the changes, another 64 participants (38.8%) felt neutral, whilst only 34 participants (20.6%) were unhappy. However, most participants felt the pandemic negatively impacted their mental health, with 96 participants (55.8%) reporting negative responses. 58% of participants (n = 102/175) reported utilising the student support services at university campus and 49% (n = 50) were satisfied with their services. CONCLUSION: Digital content and delivery confer the benefit of greater flexibility in learning, the ability to learn at one's own pace and in a preferred environment, however lacks the advantage of bedside teaching and hands-on training. Our findings reinforce the potential advantages of online learning.

Acidosis significantly alters immune checkpoint expression profiles of T cells from oesophageal adenocarcinoma patients.

Tumour acidosis contributes to cancer progression by inhibiting anti-tumour immunity. However, the effect of acidosis on anti-tumour T cell phenotypes in oesophageal adenocarcinoma (OAC) is unknown. Therefore, this study investigated the effect of acidosis on anti-tumour T cell profiles and if immune checkpoint blockade (ICB) could enhance anti-tumour T cell immunity under acidosis. Acidic conditions substantially altered immune checkpoint expression profiles of OAC patient-derived T cells, upregulating TIM-3, LAG-3 and CTLA-4. Severe acidosis (pH 5.5) significantly decreased the percentage of central memory CD4+ T cells, an effect that was attenuated by ICB treatment. ICB increased T cell production of IFN-γ under moderate acidosis (pH 6.6) but not severe acidosis (pH 5.5) and decreased IL-10 production by T cells under severe acidic conditions only. A link between lactate and metastasis was also depicted; patients with nodal metastasis had higher serum lactate levels (p = 0.07) which also positively correlated with circulating levels of pro-angiogenic factor Tie-2. Our findings establish that acidosis-induced upregulation of immune checkpoints on T cells may potentially contribute to immune evasion and disease progression in OAC. However, acidic conditions curtailed ICB efficacy, supporting a rationale for utilizing systemic oral buffers to neutralize tumour acidity to improve ICB efficacy. Study schematic-PBMCs were isolated from OAC patients (A) and expanded ex vivo for 7 days using anti-CD3/28 +IL-2 T cell activation protocol (B) and further cultured for 48 h under increasing acidic conditions in the absence or presence of immune checkpoint blockade (nivolumab, ipilimumab or dual nivolumab + ipilimumab) (C). Immunophenotyping was then carried out to assess immune checkpoint expression profiles and anti-tumour T cell phenotypes (D). Serum lactate was assessed in OAC patients (E-F) and levels were correlated with patient demographics (G) and the levels of circulating immune/pro-angiogenic cytokines that were determined by multiplex ELISA (H). Key Findings-severe acidic conditions upregulated multiple immune checkpoints on T cells (I). Efficacy of ICB was curtailed under severe acidic conditions (J). Circulating lactate levels positively correlated with circulating levels of pro-angiogenic factor tie-2 and higher serum lactate levels were found in patients who had nodal metastasis (K).

Vitamin B12 supplementation post-gastrectomy: a service closed-loop audit at St. James's Hospital, Dublin.

BACKGROUND: Vitamin B12 (VB12) deficiency is a well-described complication post-gastrectomy. It is caused by the loss of parietal cell mass leading to megaloblastic anaemia. This closed-loop audit assesses patient understanding of and adherence with VB12 supplementation guidelines post-gastrectomy. METHODS: A closed-loop audit cycle was performed. After the first cycle, an educational intervention was actioned prior to re-audit. One hundred twenty-five patients who underwent gastrectomy between 2010 and 2020 were available for study (86 total gastrectomies (TG), 39 subtotal gastrectomies (STG)). Twenty-nine patients who had not been adherent with VB12 supplementation/surveillance were eligible for re-audit. RESULTS: 91.9% (79/86) of TG patients reported adherence in regular parenteral VB12 supplementation. Adherence was significantly lower for STG for checking (and/or replacing) their VB12, with only 53.8% (21/39) checking their VB12 levels. 67/125 (53.6%) of the patients stated that they knew it was important to supplement B12 post-gastrectomy. 37.8% (43/113) of participants could explain why this was important, and 14.4% (18/125) had any knowledge of the complications of VB12 deficiency. Following re-audit, 5/8 (57.5%) of TG patients who had not been adherent with VB12 supplementation in the first cycle were now adherent with VB12 supplementation following our educational intervention. 7/17 (41.2%) of the STG group had received VB12 or made arrangements to receive supplemental VB12 if it was indicated. CONCLUSION: This study demonstrates good adherence in those undergoing TG. Patient understanding correlates with adherence, suggesting that patient education and knowledge reinforcement may be key to adherence with VB12 supplementation. A simple educational intervention can improve adherence with VB12 supplementation in patients undergoing gastrectomy.

Single-center experience in implementation of endoscopic surveillance protocol after esophagectomy.

Esophageal cancer has a notably high recurrence rate with a paucity of robust evidence in defining the optimal surveillance strategy. The surveillance protocol at our institution comprises of annual esophagogastroduodenoscopy (OGD) from years 1 to 5 postoperatively. This study aims to evaluate the implementation of the endoscopic surveillance at our center and ascertain the value of endoscopy in detecting local recurrence after esophagectomy. A retrospective cohort review of all patients (320 patients) who underwent esophagectomy between 2013 and 2018 was conducted. The local esophageal cancer database and corresponding OGD reports were accessed to obtain data on demographics, operation details, local recurrence, and endoscopy performed. 1086 OGDs were performed between 2014 and 2020, broadly categorized to surveillance and symptomatic OGDs; 555 and 531, respectively. Surveillance OGDs detected four asymptomatic local recurrences, of which only one was treated with curative intent. Symptomatic OGDs resulted in a higher yield for the detection of local recurrence compared with surveillance endoscopy; 5% versus 0.7%, with overall median time-to-recurrence of 11.5 months (95% confidence interval 9-17). Of local recurrences, 85.7% occurred within the first 2 years postoperatively. The proportion of endoscopic findings differed between intensive and ad hoc surveillance cohorts for strictures, esophagitis, Barrett's esophagus, and sloughing. Thirteen patients were diagnosed with histologically confirmed Barrett's with no subsequent local recurrences. Surveillance endoscopy had a low positive yield rate with subsequent minimal survival benefits. Therefore, it is prudent to consider an alternative protocol that focuses on the period with the highest risk of recurrence and symptom presentation.

CROSS Versus FLOT Regimens in Esophageal and Esophagogastric Junction Adenocarcinoma: A Propensity-Matched Comparison.

BACKGROUND: The FLOT protocol and the CROSS trimodality regimen represent current standards in the management of locally advanced esophageal adenocarcinoma. In the absence of published Randomised Controlled Trial data, this propensity-matched comparison evaluated tolerance, toxicity, impact on sarcopenia and pulmonary physiology, operative complications, and oncologic metrics. METHODS: Two hundred and twenty-two patients, 111 in each arm, were included from 2 high-volume centers. Computed tomography-measured sarcopenia, and pulmonary function (forced expiratory volume in first second/forced vital capacity/diffusion capacity for carbon monoxide) were compared pretherapy and posttherapy. Operative complications were defined as per the Esophageal Complications Consensus Group (ECCG) criteria, and severity per Clavien-Dindo. Tumor regression grade and R status were measured, and survival estimated per Kaplan-Meier. RESULTS: A total of 83% were male, cT3/cN+ was 92%/68% for FLOT, and 86%/60% for CROSS. The full prescribed regimen was tolerated in 40% of FLOT patients versus 92% for CROSS. Sarcopenia increased from 16% to 33% for FLOT, and 14% to 30% in CROSS ( P <0.01 between arms). Median decrease in diffusion capacity for carbon monoxide was -8.25% (-34 to 25) for FLOT, compared with -13.8%(-38 to 29), for CROSS ( P =0.01 between arms). Major pathologic response was 27% versus 44% for FLOT and CROSS, respectively ( P =0.03). In-hospital mortality, respectively, was 1% versus 2% ( P =0.9), and Clavien Dindo >III 22% versus 27% ( P =0.59), however, respiratory failure was increased by CROSS, at 13% versus 3% ( P <0.001). Three-year survival was similar at 63% (FLOT) and 60% (CROSS) ( P =0.42). CONCLUSIONS: Both CROSS and FLOT resulted in equivalent survival. Operative outcomes were similar, however, the CROSS regimen increased postoperative respiratory failure and atrial fibrillation. Less than half of patients received the prescribed FLOT regimen, although toxicity rates were acceptable. These data support clinical equipoise, caution, however, may be advised with CROSS in patients with greatest respiratory risk.

The immune response to major gastrointestinal cancer surgery and potential implications for adjuvant immunotherapy.

The perioperative period theoretically is a critical time of opportunity for the progression of pre-existing tumour micrometastasis. Therefore,the timing of introducing cancer therapies including chemotherapy, radiation therapy and immunotherapies in the postoperative period is important. A thorough exploration of the perioperative immune events at a cellular level in combination with an intricate review of available clinical rials was conducted to extrapolate the effects of oncological surgery on the perioperative immune milieu.This is timely in view of the recently published Checkmate-577 trial which demonstrated significant disease-free survival in carcinoma of the gastroesophageal junction with the use of adjuvant anti-programmed cell deathprotein 1(PD-1) immunotherapy.This review focusing in particular on perioperative immunosuppression, identifies potential modifiable factors, the effects of perioperative conditioning and optimisation, the most recent trials in the curative setting for Gastrointestinal malignancies and the new treatment avenues possible in the context of the combination of immunotherapy and major oncological gastrointestinal surgery.

Interventions targeting postoperative pulmonary complications (PPCs) in patients undergoing esophageal cancer surgery: a systematic review of randomized clinical trials and narrative discussion.

Postoperative pulmonary complications (PPCs) represent the most common complications after esophageal cancer surgery. The lack of a uniform reporting nomenclature and a severity classification has hampered consistency of research in this area, including the study of interventions targeting prevention and treatment of PPCs. This systematic review focused on RCTs of clinical interventions used to minimize the impact of PPCs. Searches were conducted up to 08/02/2021 on MEDLINE (OVID), CINAHL, Embase, Web of Science, and the COCHRANE library for RCTs and reported in accordance with PRISMA guidelines. A total of 339 citations, with a pooled dataset of 1,369 patients and 14 RCTs, were included. Heterogeneity of study design and outcomes prevented meta-analysis. PPCs are multi-faceted and not fully understood with respect to etiology. The review highlights the paucity of high-quality evidence for best practice in the management of PPCs. Further research in the area of intraoperative interventions and early postoperative ERAS standards is required. A consistent uniform for definition of pneumonia after esophagectomy and the development of a severity scale appears warranted to inform further RCTs and guidelines.