[Immunonutrition, evidence and experiences]. / Inmunonutrición, evidencias y experiencias.

Introduction: Immunonutrition is a science that encompasses aspects related to nutrition, immunity, infection, inflammation and tissue damage. Immunomodulatory formulas have shown benefits in a wide variety of clinical situations. The objective of this work was to review the available evidence in immunonutrition (IN). For this, a bibliographic search has been carried out with the keywords: immunonutrition, arginine, glutamine, nucleotides, omega-3 fatty acids, ERAS, fast-track. Clinical trials, reviews and clinical practice guidelines have been included. IN has been shown to reduce postoperative fistulae in head and neck cancer patients and in gastric and esophageal cancer patients, infectious complications and hospital stay. Other clinical situations that benefit from the use of IN are pancreatic cancer surgery, colorectal cancer surgery and major burns. More controlled, prospective, and randomized studies are necessary to confirm the potential benefits of IN in other clinical situations such as non-esophageal thoracic surgery, bladder cancer, gynecological surgery, hip fracture, liver pathology and COVID-19, among others.

Introducción: La inmunonutrición es una ciencia que engloba aspectos relacionados con la nutrición, la inmunidad, la infección, la inflamación y el daño tisular. Las fórmulas inmunomoduladoras han demostrado beneficios en una amplia variedad de situaciones clínicas. El objetivo de este trabajo es revisar la evidencia disponible en inmunonutrición (IN). Para ello, se ha realizado una búsqueda bibliográfica con las palabras clave: inmunonutrición, arginina, glutamina, nucleótidos, ácidos grasos omega-3, ERAS, fast-track. Se han incluido ensayos clínicos, revisiones y guías de práctica clínica. La IN ha demostrado reducir las fístulas en el postoperatorio en pacientes con cáncer de cabeza y cuello. En pacientes con cáncer gástrico y cáncer de esófago, la IN se asocia a una disminución de las complicaciones infecciosas y la estancia hospitalaria. Otras situaciones clínicas que se benefician del uso de la IN son la cirugía del cáncer de páncreas, la cirugía del cáncer colorrectal y los grandes quemados. Son necesarios más estudios controlados, prospectivos y aleatorizados para confirmar los potenciales beneficios de la IN en otras situaciones clínicas como la cirugía torácica no esofágica, el cáncer vesical, la cirugía ginecológica, la fractura de cadera, la patología hepática y la COVID-19, entre otros.

The COVID-19 Era Is Associated With Delays in Esophageal Cancer Diagnosis and Treatment.

INTRODUCTION: The coronavirus disease-2019 (COVID-19) pandemic has substantially affected the delivery of healthcare globally. The purpose of this study was to evaluate the association of this era with the timeline of care in esophageal cancer patients. METHODS: We performed a retrospective chart-review of patients presenting to a single high-volume tertiary care center with the diagnosis of esophageal cancer. COVID era was defined as March 2020-December 2020 and compared with the year before (3/2019-12/2019). RESULTS: In total, 117 patients presented in the COVID-era versus 190 in pre-COVID. Stage 3 + 4 disease was found in 77.8% of the patients in the COVID-era compared to 68.9% in the pre-COVID era (P = 0.34). Diagnoses through emergency department admission were 35.5% in the COVID versus 26.7% in the pre-COVID group (P = 0.15). In the COVID era it took a median of 78 d to visit primary care provider (versus 52 d, P = 0.12 in pre-COVID), 45 d to endoscopy (versus 18 d, P = 0.004) and 38 d to treatment initiation (versus 36 d, P = 0.48). Thirty-five percent of the patients underwent esophagectomy compared to 26% in the pre-COVID-era. Median days of intensive-care-unit (ICU) (2 versus 3, P = 0.16) and hospital stay (14 versus 15, P = 0.28) were similar in both groups as well as postoperative 30-day morbidities (63 versus 63%, P = 0.48). One-year follow-up showed 83.7% (95% confidence interval [CI]: 73.8%-90.1%) survival in the COVID-group compared to 76.4% (95% CI: 66.9%-83.5%) in the pre-COVID-group (P = 0.58). Only three patients had a positive COVID result. CONCLUSIONS: Our institution treated fewer esophageal cancer patients during COVID-19 accompanied by a delay in endoscopic diagnosis. Postoperative outcomes and 1-year survival remained similar.

Development and validation of a multivariable risk factor questionnaire to detect oesophageal cancer in 2-week wait patients.

INTRODUCTION: Oesophageal cancer is associated with poor health outcomes. Upper GI (UGI) endoscopy is the gold standard for diagnosis but is associated with patient discomfort and low yield for cancer. We used a machine learning approach to create a model which predicted oesophageal cancer based on questionnaire responses. METHODS: We used data from 2 separate prospective cross-sectional studies: the Saliva to Predict rIsk of disease using Transcriptomics and epigenetics (SPIT) study and predicting RIsk of diSease using detailed Questionnaires (RISQ) study. We recruited patients from National Health Service (NHS) suspected cancer pathways as well as patients with known cancer. We identified patient characteristics and questionnaire responses which were most associated with the development of oesophageal cancer. Using the SPIT dataset, we trained seven different machine learning models, selecting the best area under the receiver operator curve (AUC) to create our final model. We further applied a cost function to maximise cancer detection. We then independently validated the model using the RISQ dataset. RESULTS: 807 patients were included in model training and testing, split in a 70:30 ratio. 294 patients were included in model validation. The best model during training was regularised logistic regression using 17 features (median AUC: 0.81, interquartile range (IQR): 0.69-0.85). For testing and validation datasets, the model achieved an AUC of 0.71 (95% CI: 0.61-0.81) and 0.92 (95% CI: 0.88-0.96) respectively. At a set cut off, our model achieved a sensitivity of 97.6% and specificity of 59.1%. We additionally piloted the model in 12 patients with gastric cancer; 9/12 (75%) of patients were correctly classified. CONCLUSIONS: We have developed and validated a risk stratification tool using a questionnaire approach. This could aid prioritising patients at high risk of having oesophageal cancer for endoscopy. Our tool could help address endoscopic backlogs caused by the COVID-19 pandemic.

Hazardous giant pharyngoesophageal liposarcoma.

A man in his early 80s presented to the otorhinolaryngology department with progressively worsening dysphagia to solids and a recent episode of difficulty breathing accompanied by a very brief expulsion of a solid mass from the mouth. Based on the endoscopic appearance of a fatty lesion of an elongated mass with a thick stalk on the posterior pharyngeal wall, a diagnosis of the benign fibrovascular polyp was given after clinical and radiological correlation. The pharyngeal polyp was resected at the base of its pedicle by transoral endoscopy with a thunder beat vessel sealing device. Histopathological examination of the mass revealed a well-differentiated liposarcoma composed of mature adipocytes. Following surgical excision, the patient made a full recovery. This case signifies the integrated role of preoperative biopsy, new surgical technologies and targeted therapies in managing pharyngoesophageal polyps.

Use of a Cytosponge biomarker panel to prioritise endoscopic Barrett's oesophagus surveillance: a cross-sectional study followed by a real-world prospective pilot.

BACKGROUND: Endoscopic surveillance is recommended for patients with Barrett's oesophagus because, although the progression risk is low, endoscopic intervention is highly effective for high-grade dysplasia and cancer. However, repeated endoscopy has associated harms and access has been limited during the COVID-19 pandemic. We aimed to evaluate the role of a non-endoscopic device (Cytosponge) coupled with laboratory biomarkers and clinical factors to prioritise endoscopy for Barrett's oesophagus. METHODS: We first conducted a retrospective, multicentre, cross-sectional study in patients older than 18 years who were having endoscopic surveillance for Barrett's oesophagus (with intestinal metaplasia confirmed by TFF3 and a minimum Barrett's segment length of 1 cm [circumferential or tongues by the Prague C and M criteria]). All patients had received the Cytosponge and confirmatory endoscopy during the BEST2 (ISRCTN12730505) and BEST3 (ISRCTN68382401) clinical trials, from July 7, 2011, to April 1, 2019 (UK Clinical Research Network Study Portfolio 9461). Participants were divided into training (n=557) and validation (n=334) cohorts to identify optimal risk groups. The biomarkers evaluated were overexpression of p53, cellular atypia, and 17 clinical demographic variables. Endoscopic biopsy diagnosis of high-grade dysplasia or cancer was the primary endpoint. Clinical feasibility of a decision tree for Cytosponge triage was evaluated in a real-world prospective cohort from Aug 27, 2020 (DELTA; ISRCTN91655550; n=223), in response to COVID-19 and the need to provide an alternative to endoscopic surveillance. FINDINGS: The prevalence of high-grade dysplasia or cancer determined by the current gold standard of endoscopic biopsy was 17% (92 of 557 patients) in the training cohort and 10% (35 of 344) in the validation cohort. From the new biomarker analysis, three risk groups were identified: high risk, defined as atypia or p53 overexpression or both on Cytosponge; moderate risk, defined by the presence of a clinical risk factor (age, sex, and segment length); and low risk, defined as Cytosponge-negative and no clinical risk factors. The risk of high-grade dysplasia or intramucosal cancer in the high-risk group was 52% (68 of 132 patients) in the training cohort and 41% (31 of 75) in the validation cohort, compared with 2% (five of 210) and 1% (two of 185) in the low-risk group, respectively. In the real-world setting, Cytosponge results prospectively identified 39 (17%) of 223 patients as high risk (atypia or p53 overexpression, or both) requiring endoscopy, among whom the positive predictive value was 31% (12 of 39 patients) for high-grade dysplasia or intramucosal cancer and 44% (17 of 39) for any grade of dysplasia. INTERPRETATION: Cytosponge atypia, p53 overexpression, and clinical risk factors (age, sex, and segment length) could be used to prioritise patients for endoscopy. Further investigation could validate their use in clinical practice and lead to a substantial reduction in endoscopy procedures compared with current surveillance pathways. FUNDING: Medical Research Council, Cancer Research UK, Innovate UK.

The safety of esophageal cancer surgery during COVID-19.

BACKGROUND: The ongoing coronavirus disease 2019 (COVID-19) pandemic has drastically challenged the safety of on esophageal cancer (EC) surgery during COVID-19. The study aimed to evaluate the safety of EC surgery during the COVID-19 pandemic. METHODS: This systematic review was performed in accordance with the PRISMA-P 2015 guidelines and registered in PROSPERO (registration number: CRD42022335164). A systematic search of PubMed, Embase, Cochrane Library, Web of Science, Medline, Chinese National Knowledge Infrastructure database, Chinese Scientific Journal database, and Wan Fang database was conducted to identify potentially relevant publications from January 2020 to May 2022. All data were independently extracted by two researchers. We will apply a fixed-effect model or random effect model basis on the heterogeneity test and employ with RevMan 5.4.1 software for data synthesis. The dichotomous surgical outcomes used risk ratios or risk differences, and for continuous surgical outcomes, mean differences (MD) or standardized MD, both with 95% confidence intervals were used. The primary outcomes were postoperative complications, anastomotic leaks, and mortality. The secondary outcomes were total hospital stay, postoperative stay, preoperative waiting, operation time, blood loss, transfusion, postoperative intensive care unit (ICU) stay, number of patients needing ICU stay, and 30-day readmission. RESULTS: This study will comprehensively summarize the high-quality trials to determine the safety of EC surgery during COVID-19. CONCLUSION: Our systematic review and meta-analysis will present evidence for the safety of EC surgery during COVID-19.

Sleep Problems Prior to Radio-chemotherapy in Patients With Locally Advanced Cancer of the Esophagus or the Esophagogastric Junction.

BACKGROUND/AIM: Many patients with locally advanced cancer of the esophagus or esophagogastric junction receive definitive or neoadjuvant radiochemotherapy. Patient anticipation of this treatment can cause or aggravate distress and sleep disorders. This study aimed to identify the prevalence of sleep disorders and risk factors. PATIENTS AND METHODS: Thirty-eight patients assigned to radio-chemotherapy were retrospectively evaluated for pre-treatment sleep disorders. Investigated characteristics included age; sex; performance score; comorbidity index; previous malignancies; family history; distress score; emotional, physical or practical problems; tumor site; histology and grading; tumor stage; planned treatment; and relation to 2019 Coronavirus pandemic. RESULTS: Sleep problems were reported by 15 patients (39.5%). Significant associations were found for higher distress scores (p=0.016) and greater numbers of emotional problems (p<0.0001). A trend was observed for greater numbers of physical problems (p=0.176). CONCLUSION: The prevalence of sleep problems was high. Risk factors were found that can help identify patients requiring psychological support already prior to radio-chemotherapy.

Early vs Delayed Surgery for Esophageal Cancer During the COVID-19 Pandemic.

BACKGROUND: During the coronavirus disease 2019 pandemic, national guidelines recommended that elective surgery for esophageal cancer be deferred by 3 months when hospital resources are limited. The impact of this delay on patient outcomes is unknown. We sought to evaluate the survival of patients with stage I and II/III esophageal cancer who undergo early vs delayed treatment. STUDY DESIGN: Using the National Cancer Database from 2010 to 2017, multivariable Cox proportional hazards modeling and propensity score-matched analysis were employed to compare survival of patients with stage I esophageal cancer who received early (0 to 4 weeks after diagnosis) vs delayed esophagectomy (12 to 16 weeks) and of patients with stage II/III esophageal cancer who-after receiving timely chemoradiation (0 to 4 weeks after diagnosis)-underwent early (9 to 17 weeks) vs delayed esophagectomy (21 to 29 weeks). RESULTS: For stage I esophageal cancer, 226 (41.7%) patients underwent early esophagectomy, and 316 (58.3%) patients underwent delayed esophagectomy. Propensity score matching created 2 groups of 134 patients with early or delayed esophagectomy, whose 5-year survival was comparable (hazard ratio [HR] 65.0% [95% confidence interval (CI) 55.2% to 73.2%] vs HR 65.1% [95% CI 55.6% to 73.1%], p = 0.50). For stage II/III esophageal cancer, 1,236 (86.1%) patients underwent early esophagectomy, and 200 (13.9%) underwent delayed esophagectomy. Propensity score matching created 2 groups of 130 patients; the early esophagectomy group had improved 5-year survival compared with the delayed esophagectomy group (HR 41.6% [95% CI 32.1% to 50.8%] vs HR 22.9% [95% CI 14.9% to 31.8%], p = 0.006). CONCLUSIONS: Early esophagectomy was associated with similar survival compared with delayed esophagectomy for patients with stage I esophageal cancer. For patients with stage II/III esophageal cancer, early esophagectomy was associated with improved survival relative to delayed esophagectomy.

Dispositional optimism and all-cause mortality after esophageal cancer surgery: a nationwide population-based cohort study.

PURPOSE: To examine the association between dispositional optimism and all-cause mortality after esophageal cancer surgery and whether pathological tumor stage and the COVID-19 pandemic modified this association. METHODS: This nationwide, population-based prospective cohort study included 335 patients undergoing esophageal cancer surgery in Sweden between January 1, 2013, and December 31, 2019. Dispositional optimism was measured 1 year post-surgery using Life Orientation Test-Revised (LOT-R). A higher LOT-R sum score represents higher dispositional optimism. Mortality information was obtained from the Swedish Register of the Total Population. All patients were followed up until death or until December 31, 2020, whichever occurred first. Cox regression with adjustments for confounders was used. RESULTS: The median follow-up was 20.8 months, during which 125 (37.3%) patients died. Among the included 335 patients, 219 (65.4%) patients had tumor pathologically staged Tis-II, and 300 (89.6%) patients entered the cohort before the COVID-19 pandemic. Both tumor stage and the COVID-19 pandemic were effect modifiers. For each unit increase in LOT-R sum score, the risk of all-cause mortality decreased by 11% (HR 0.89, 95% CI 0.81 to 0.98) among patients with tumor staged Tis-II before the COVID-19 pandemic. This association was non-significant in patients with tumor staged III-IV (HR 0.99, 95% CI 0.92 to 1.07) and during the COVID-19 pandemic (HR 1.08, 95% CI 0.94 to 1.25). CONCLUSION: Assessing dispositional optimism may help predict postoperative survival, especially for patients with early and intermediate esophageal cancer. Increasing dispositional optimism might be a potential intervention target to improve survival after esophageal cancer surgery.

Anti-glutathione S-transferase omega 1-1 (GSTO1-1) antibodies are increased during acute and chronic inflammation in humans.

Glutathione S-transferase omega-1 (GSTO1-1) is a cytosolic enzyme involved in the modulation of critical inflammatory pathways as well as in cancer progression. Auto-antibodies against GSTO1-1 were detected in the serum of patients with esophageal squamous cell carcinoma and were proposed as potential biomarkers in the early detection of the disease. Our findings show that anti-GSTO1-1 antibodies can be found in a variety of inflammatory diseases, including autoimmune rheumatoid arthritis, infectious SARS-CoV-2, and trichinellosis. Our findings strongly suggest that anti-GSTO1-1 antibodies may be a marker of tissue damage/inflammation rather than a specific tumor-associated biomarker.

Safe oesophageal stent deployment using a checklist system instead of fluoroscopy.

BACKGROUND: Stenting is the management of choice for many benign and malignant oesophageal conditions and in the interest of safety stent insertion has traditionally been performed under fluoroscopic guidance. But this incurs additional expense, time, radiation risk and for the foreseeable future, an increased risk of Covid infection to patients and healthcare personnel. We describe a protocol that obviates the need for fluoroscopic guidance, relying instead on a systematic checklist to ensure safe positioning of the guidewire and the accurate positioning of the stent. The aim of this retrospective study was to review our experience of stent insertion employing a checklist system and compare our outcomes with outcomes using fluoroscopy in the literature. METHODS: We performed a retrospective review of a prospectively collected dataset of all patients undergoing oesophageal stent insertion between December 2007 and October 2019. The primary end points were patient safety parameters and complications of stent insertion. RESULTS: Total of 163 stents were deployed of which 93 (57%) were in males and the median age was 67.9 years (25-92 years). Partially covered self-expanding metallic stents (SEMS) were used in 80% of procedures (130/163). One hundred nineteen stents (73%) were for malignant strictures and 127 (78%) were deployed for strictures in the lower third of the oesophagus. There was no stent misplacement, injury, perforation or death associated with the procedure. Vomiting was the main post-operative complication (14%). Severe odynophagia necessitated stent removal in 3 patients. Stent migration occurred in 17 (10%) procedures with a mean time to stent migration of 6.4 weeks (range 1-20 weeks). CONCLUSIONS: Oesophageal stent placement without fluoroscopy is safe provided that a strict checklist is adhered to. The outcomes are comparable to the results of fluoroscopic stent placement in the literature, with considerable saving in time, cost, personnel, and risks of radiation and Covid exposure.

Sintilimab versus placebo in combination with chemotherapy as first line treatment for locally advanced or metastatic oesophageal squamous cell carcinoma (ORIENT-15): multicentre, randomised, double blind, phase 3 trial.

OBJECTIVE: To evaluate sintilimab versus placebo in combination with chemotherapy (cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil) as first line treatment of unresectable locally advanced, recurrent, or metastatic oesophageal squamous cell carcinoma. DESIGN: Multicentre, randomised, double blind, phase 3 trial. SETTING: 66 sites in China and 13 sites outside of China between 14 December 2018 and 9 April 2021. PARTICIPANTS: 659 adults (aged ≥18 years) with advanced or metastatic oesophageal squamous cell carcinoma who had not received systemic treatment. INTERVENTION: Participants were randomised 1:1 to receive sintilimab or placebo (3 mg/kg in patients weighing <60 kg or 200 mg in patients weighing ≥60 kg) in combination with cisplatin 75 mg/m2 plus paclitaxel 175 mg/m2 every three weeks. The trial was amended to allow investigators to choose the chemotherapy regimen: cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil (800 mg/m2 continuous infusion on days 1-5). MAIN OUTCOME MEASURES: Overall survival in all patients and in patients with combined positive scores of ≥10 for expression of programmed cell death ligand 1. RESULTS: 659 patients were randomly assigned to sintilimab (n=327) or placebo (n=332) with chemotherapy. 616 of 659 patients (93%) received sintilimab or placebo in combination with cisplatin plus paclitaxel and 43 of 659 patients (7%) received sintilimab or placebo in combination with cisplatin plus 5-fluorouracil. At the interim analysis, sintilimab with chemotherapy showed better overall survival compared with placebo and chemotherapy in all patients (median 16.7 v 12.5 months, hazard ratio 0.63, 95% confidence interval 0.51 to 0.78, P<0.001) and in patients with combined positive scores of ≥10 (17.2 v 13.6 months, 0.64, 0.48 to 0.85, P=0.002). Sintilimab and chemotherapy significantly improved progression free survival compared with placebo and chemotherapy in all patients (7.2 v 5.7 months, 0.56, 0.46 to 0.68, P<0.001) and in patients with combined positive scores of ≥10 (8.3 v 6.4 months, 0.58, 0.45 to 0.75, P<0.001). Adverse events related to treatment occurred in 321 of 327 patients (98%) in the sintilimab-chemotherapy group versus 326 of 332 (98%) patients in the placebo-chemotherapy group. Rates of adverse events related to treatment, grade ≥3, were 60% (196/327) and 55% (181/332) in the sintilimab-chemotherapy and placebo-chemotherapy groups, respectively. CONCLUSIONS: Compared with placebo, sintilimab in combination with cisplatin plus paclitaxel showed significant benefits in overall survival and progression free survival as first line treatment in patients with advanced or metastatic oesophageal squamous cell carcinoma. Similar benefits of sintilimab with cisplatin plus 5-fluorouracil seem promising. TRIAL REGISTRATION: ClinicalTrials.gov NCT03748134.

Risk Prediction Model for Esophageal Cancer Among General Population: A Systematic Review.

Objective: The risk prediction model is an effective tool for risk stratification and is expected to play an important role in the early detection and prevention of esophageal cancer. This study sought to summarize the available evidence of esophageal cancer risk predictions models and provide references for their development, validation, and application. Methods: We searched PubMed, EMBASE, and Cochrane Library databases for original articles published in English up to October 22, 2021. Studies that developed or validated a risk prediction model of esophageal cancer and its precancerous lesions were included. Two reviewers independently extracted study characteristics including predictors, model performance and methodology, and assessed risk of bias and applicability with PROBAST (Prediction model Risk Of Bias Assessment Tool). Results: A total of 20 studies including 30 original models were identified. The median area under the receiver operating characteristic curve of risk prediction models was 0.78, ranging from 0.68 to 0.94. Age, smoking, body mass index, sex, upper gastrointestinal symptoms, and family history were the most commonly included predictors. None of the models were assessed as low risk of bias based on PROBST. The major methodological deficiencies were inappropriate date sources, inconsistent definition of predictors and outcomes, and the insufficient number of participants with the outcome. Conclusions: This study systematically reviewed available evidence on risk prediction models for esophageal cancer in general populations. The findings indicate a high risk of bias due to several methodological pitfalls in model development and validation, which limit their application in practice.

Mapping the cancer imaging research landscape: which cancers are more and which cancers are less frequently investigated?

OBJECTIVE: To investigate the proportion of published imaging studies relative to incidence and mortality rate per cancer type. METHODS: From a random sample of 2500 articles published in 2019 by the top 25 imaging-related journals, we included cancer imaging studies. The publication-to-incidence and publication-to-mortality ratios (defined as the publication rate divided by the proportional incidence and mortality rate, respectively) were calculated per cancer type. Ratios >1 indicate a higher publication rate compared to the relative incidence or mortality rate of a specific cancer. Ratios <1 indicate a lower publication rate compared to the relative incidence or mortality rate of a specific cancer. RESULTS: 620 original cancer imaging studies were included. Female breast cancer (20.2%), prostate cancer (13.0%), liver cancer (12.9%), lung cancer (8.8%), and cancers in the central nervous system (8.1%) comprised the top 5 of cancers investigated. Cancers in the central nervous system and liver had publication-to-incidence ratios >2, whereas nonmelanoma of the skin, leukemia, stomach cancer, and laryngeal cancer had publication-to-incidence ratios <0.2. Cancers in the prostate, central nervous system, female breast, and kidney had publication-to-mortality ratios >2, whereas esophageal cancer, stomach cancer, laryngeal cancer, and leukemia had publication-to-mortality ratios <0.2. CONCLUSION: This overview of published cancer imaging research may be informative and useful to all stakeholders in the field of cancer imaging. The potential causes of disproportionality between the publication rate vs. incidence and mortality rates of some cancer types are multifactorial and need to be further elucidated.

Metastatic gastroesophageal cancer in older patients - is this patient cohort represented in clinical trials?

BACKGROUND: Older patients are underrepresented in the clinical trials that determine the standards of care for oncological treatment. We conducted a review to identify whether there have been age-restrictive inclusion criteria in clinical trials over the last twenty five years, focusing on patients with metastatic gastroesophageal cancer. METHODS: A search strategy was developed encompassing Embase, PubMed and The Cochrane Library databases. Completed phase III randomised controlled trials evaluating systemic anti-cancer therapies in metastatic gastroesophageal malignancies from 1st January 1995 to 18th November 2020 were identified. These were screened for eligibility using reference management software (Covidence; Veritas Health Innovation Ltd). Data including age inclusion/exclusion criteria and median age of participants were recorded. The percentage of patients ≥ 65 enrolled was collected where available. The change over time in the proportion of studies using an upper age exclusion was estimated using a linear probability model. RESULTS: Three hundred sixty-three phase III studies were identified and screened, with 66 trials remaining for final analysis. The majority of trials were Asian (48%; n = 32) and predominantly evaluated gastric malignancies, (86%; n = 56). The median age of participants was 62 (range 18-94). Thirty-two percent (n = 21) of studies specified an upper age limit for inclusion and over half of these were Asian studies. The median age of exclusion was 75 (range 65-80). All studies prior to 2003 used an upper age exclusion (n = 12); whereas only 9 that started in 2003 or later did (17%). Among later studies, there was a very modest downward yearly-trend in the proportion of studies using an upper age exclusion (-0.02 per year; 95%CI -0.05 to 0.01; p = 0.31). Fifty-two percent (n = 34) of studies specified the proportion of their study population who were ≥ 65 years. Older patients represented only 36% of the trial populations in these studies (range 7-60%). CONCLUSIONS: Recent years have seen improvements in clinical trial protocols, with many no longer specifying restrictive age criteria. Reasons for poor representation of older patients are complex and ongoing efforts are needed to broaden eligibility criteria and prioritise the inclusion of older adults in clinical trials.

Minimally Invasive Ivor-Lewis Esophagectomy for Esophageal Cancer After Gastric Bypass.

The increasing prevalence of morbid obesity in the United States has been accompanied by a concomitant rise in bariatric surgery to help combat the epidemic. The relationship between obesity and certain cancers, such as esophageal adenocarcinoma, is well established. The need for minimally invasive techniques to treat esophageal cancer in patients with previous bariatric surgery is growing and can present a unique surgical challenge. This report presents the case of a 55-year-old woman with a previous Roux-en-Y gastric bypass who was shown by endoscopy to have an invasive adenocarcinoma located in the distal thoracic esophagus. This necessitated an excision of the thoracic esophagus and the gastric pouch. A laparoscopic and thoracoscopic Ivor-Lewis esophagogastrectomy was performed for this complex patient with esophageal adenocarcinoma. The remnant stomach was fashioned into a gastric conduit using a 60-mm linear stapler with a staple height of 4.1 mm (Echelon, Ethicon Endosurgery, Blue Ash, OH). The reconstruction was performed using a 25-mm Orvil (Covidien, Minneapolis, MN, USA) and EEA 25-mm DST XL (Covidien) to create a circular stapled thoracic esophagogastric anastomosis. A feeding jejunostomy was placed in the residual 130-cm Roux limb. The study demonstrated that minimally invasive esophagectomy is safe and technically feasible with appropriate oncologic outcomes for patients with previous gastric bypass. This cohort of patients will undoubtedly continue to grow in the coming years.