Esofaguectomía «tubeless»: menos es más / “Tubeless” esophagectomy: Less is more

La cirugía del cáncer de esófago es un procedimiento complejo con tasas de morbimortalidad elevadas, por lo que para obtener resultados adecuados se precisa de centros experimentados, un completo soporte multidisciplinar y vías clínicas adecuadas. Se describe la experiencia inicial y la técnica de la esofaguectomía «tubeless» en la que tras realizar una resección esofágica y linfadenectomía mediastínica extendida, al final del procedimiento no son colocados drenajes ni sondas de ningún tipo, con el fin de disminuir la agresividad del mismo, mejorar el bienestar postoperatorio y acelerar la recuperación funcional del paciente. (AU)

The esophageal cancer surgery is a complex procedure with elevated rates of both morbidity and mortality, which is why, in order to achieve adequate results, it should be performed in high volume centers, where complete multidisciplinary support is available and recent clinical guidelines are applied. We describe the initial experience and the technique of “tubeless” esophagectomy where esophageal resection and mediastinal lymphadenectomy are performed and no drains nor tubes of any kind are placed, with the aim to decrease the level of surgical aggression, enhance the postoperative comfort and accelerate the patient́s recovery. (AU)

Identifying outcomes reported in exercise interventions in oesophagogastric cancer survivors: a systematic review.

BACKGROUND: Research investigating exercise interventions in oesophagogastric cancer survivors is sparse, and the outcomes are varied. The aim of this systematic review is to identify the domains and outcomes reported in exercise interventions in oesophagogastric cancer survivors to be included in a Delphi study, with a view to informing the development of a core outcome set (COS). METHODS: EMBASE, PubMed, CINHAL, Cochrane Library, SCOPUS, and PEDro were searched up to March 2020 using a predefined search strategy. The outcomes identified during data extraction were categorised using the core areas outlined in the OMERACT Filter 2.0. RESULTS: Fourteen domains and 63 outcomes were identified. The most frequently reported outcomes were in the domains of quality of life using the EORTC-QLQ-C30 questionnaire and the relevant disease-specific modules (100%), exercise capacity/fitness/physical function (100%), anthropometrics (83.33%), physical activity (66.67%), and biomarker analysis (50%). CONCLUSION: This systematic review quantifies and describes the domains and outcomes examined in exercise interventions in oesophagogastric cancer survivors. Some inconsistency exists within the domains and outcomes used, and little attention was given to nutritional or economic endpoints. In order to develop a COS, a Delphi consensus process with key stakeholders is needed to identify the relevant domains and outcomes for inclusion.

Supervised exercise after oesophageal cancer surgery: the PERFECT multicentre randomized clinical trial.

BACKGROUND: This study investigated whether a supervised exercise programme improves quality of life (QoL), fatigue and cardiorespiratory fitness in patients in the first year after oesophagectomy. METHODS: The multicentre PERFECT trial randomly assigned patients to an exercise intervention (EX) or usual care (UC) group. EX patients participated in a 12-week moderate- to high-intensity aerobic and resistance exercise programme supervised by a physiotherapist. Primary (global QoL, QoL summary score) and secondary (QoL subscales, fatigue and cardiorespiratory fitness) outcomes were assessed at baseline, 12 and 24 weeks and analysed as between-group differences using either linear mixed effects models or ANCOVA. RESULTS: A total of 120 patients (mean(s.d.) age 64(8) years) were included and randomized to EX (61 patients) or UC (59 patients). Patients in the EX group participated in 96 per cent (i.q.r. 92-100 per cent) of the exercise sessions and the relative exercise dose intensity was high (92 per cent). At 12 weeks, beneficial EX effects were found for QoL summary score (3.5, 95 per cent c.i. 0.2 to 6.8) and QoL role functioning (9.4, 95 per cent c.i. 1.3 to 17.5). Global QoL was not statistically significant different between groups (3.0, 95 per cent c.i. -2.2 to 8.2). Physical fatigue was lower in the EX group (-1.2, 95 per cent c.i. -2.6 to 0.1), albeit not significantly. There was statistically significant improvement in cardiorespiratory fitness following EX compared with UC (peak oxygen uptake (1.8 ml/min/kg, 95 per cent c.i. 0.6 to 3.0)). After 24 weeks, all EX effects were attenuated. CONCLUSIONS: A supervised exercise programme improved cardiorespiratory fitness and aspects of QoL. TRIAL REGISTRATION: Dutch Trial Register NTR 5045 (www.trialregister.nl/trial/4942).

Physiotherapy With Telerehabilitation in Patients With Complicated Postoperative Recovery After Esophageal Cancer Surgery: Feasibility Study.

BACKGROUND: Improvement of functional status with physiotherapy is an important goal for patients with postoperative complications and an increased length of hospital stay (LoS) after esophagectomy. Supervised physiotherapy with telerehabilitation instead of conventional face-to-face care could be an alternative to treat these patients in their home environment after hospital discharge (T0), but its feasibility has not yet been investigated in detail. OBJECTIVE: The aim of this study was to investigate the feasibility of a 12-week supervised postoperative physiotherapy intervention with telerehabilitation for patients with esophageal cancer who underwent esophagectomy and had postoperative complications or who had an increased LoS. The secondary objective was to investigate the preliminary effectiveness of telerehabilitation on functional recovery compared with usual care. METHODS: A prospective feasibility study with a matched historical comparison group was performed. Feasibility outcomes included willingness and adherence to participate, refusal rate, treatment duration, occurrence of adverse events, and patient satisfaction. Secondary outcome measures were measurements of musculoskeletal and cardiovascular functions and activities according to the domains of the International Classification of Functioning, Disability and Health. RESULTS: A total of 22 patients with esophageal cancer who underwent esophagectomy and had postoperative complications or an increased LoS were included. The mean age at surgery was 64.55 (SD 6.72) years, and 77% (17/22) of patients were male. Moreover, 15 patients completed the intervention. Patient adherence was 99.8% in the first 6 weeks and dropped to 75.6% in the following 6 weeks, with a mean difference of -24.3% (95% CI 1.3 to 47.2; P=.04). At 3 months post operation, no differences in functional status were found between the intervention group and the matched historical comparison group. CONCLUSIONS: This study showed that a postoperative physiotherapeutic intervention with telerehabilitation is feasible for patients with postoperative complications or an increased LoS after esophageal cancer surgery up to 6 weeks after T0.

Rehabilitation strategies following oesophagogastric and Hepatopancreaticobiliary cancer (ReStOre II): a protocol for a randomized controlled trial.

BACKGROUND: Curative treatment for upper gastrointestinal (UGI) and hepatopancreaticobiliary (HPB) cancers, involves complex surgical resection often in combination with neoadjuvant/adjuvant chemo/chemoradiotherapy. With advancing survival rates, there is an emergent cohort of UGI and HPB cancer survivors with physical and nutritional deficits, resultant from both the cancer and its treatments. Therefore, rehabilitation to counteract these impairments is required to maximise health related quality of life (HRQOL) in survivorship. The initial feasibility of a multidisciplinary rehabilitation programme for UGI survivors was established in the Rehabilitation Strategies following Oesophago-gastric Cancer (ReStOre) feasibility study and pilot randomised controlled trial (RCT). ReStOre II will now further investigate the efficacy of that programme as it applies to a wider cohort of UGI and HPB cancer survivors, namely survivors of cancer of the oesophagus, stomach, pancreas, and liver. METHODS: The ReStOre II RCT will compare a 12-week multidisciplinary rehabilitation programme of supervised and self-managed exercise, dietary counselling, and education to standard survivorship care in a cohort of UGI and HPB cancer survivors who are > 3-months post-oesophagectomy/ gastrectomy/ pancreaticoduodenectomy, or major liver resection. One hundred twenty participants (60 per study arm) will be recruited to establish a mean increase in the primary outcome (cardiorespiratory fitness) of 3.5 ml/min/kg with 90% power, 5% significance allowing for 20% drop out. Study outcomes of physical function, body composition, nutritional status, HRQOL, and fatigue will be measured at baseline (T0), post-intervention (T1), and 3-months follow-up (T2). At 1-year follow-up (T3), HRQOL alone will be measured. The impact of ReStOre II on well-being will be examined qualitatively with focus groups/interviews (T1, T2). Bio-samples will be collected from T0-T2 to establish a national UGI and HPB cancer survivorship biobank. The cost effectiveness of ReStOre II will also be analysed. DISCUSSION: This RCT will investigate the efficacy of a 12-week multidisciplinary rehabilitation programme for survivors of UGI and HPB cancer compared to standard survivorship care. If effective, ReStOre II will provide an exemplar model of rehabilitation for UGI and HPB cancer survivors. TRIAL REGISTRATION: The study is registered with ClinicalTrials.gov, registration number: NCT03958019, date registered: 21/05/2019.

Preoperative exercise to improve fitness in patients undergoing complex surgery for cancer of the lung or oesophagus (PRE-HIIT): protocol for a randomized controlled trial.

BACKGROUND: Patients with cancer of the lung or oesophagus, undergoing curative treatment, usually require a thoracotomy and a complex oncological resection. These surgeries carry a risk of major morbidity and mortality, and risk assessment, preoperative optimisation, and enhanced recovery after surgery (ERAS) pathways are modern approaches to optimise outcomes. Pre-operative fitness is an established predictor of postoperative outcome, accordingly, targeting pre-operative fitness through exercise prehabilitation has logical appeal. Exercise prehabilitation is challenging to implement however due to the short opportunity for intervention between diagnosis and surgery. Therefore, individually prescribed, intensive exercise training protocols which convey clinically meaningful improvements in cardiopulmonary fitness over a short period need to be investigated. This project will examine the influence of exercise prehabilitation on physiological outcomes and postoperative recovery and, through evaluation of health economics, the impact of the programme on hospital costs. METHODS: The PRE-HIIT Randomised Controlled Trial (RCT) will compare a 2-week high intensity interval training (HIIT) programme to standard preoperative care in a cohort of thoracic and oesophageal patients who are > 2-weeks pre-surgery. A total of 78 participants will be recruited (39 per study arm). The primary outcome is cardiorespiratory fitness. Secondary outcomes include, measures of pulmonary and physical and quality of life. Outcomes will be measured at baseline (T0), and post-intervention (T1). Post-operative morbidity will also be captured. The impact of PRE-HIIT on well-being will be examined qualitatively with focus groups/interviews post-intervention (T1). Participant's experience of preparation for surgery on the PRE-HIIT trial will also be explored. The healthcare costs associated with the PRE-HITT programme, in particular acute hospital costs, will also be examined. DISCUSSION: The overall aim of this RCT is to examine the effect of tailored, individually prescribed high intensity interval training aerobic exercise on pre-operative fitness and postoperative recovery for patients undergoing complex surgical resections, and the impact on use of health services. TRIAL REGISTRATION: The study is registered with Clinical Trials.Gov (NCT03978325). Registered on 7th June 2019.

Early enteral feeding on esophageal cancer patients after esophageal resection and reconstruction.

BACKGROUND: In patients under esophagectomy, early postoperative oral feeding has traditionally been contraindicated to minimize the risk of anastomotic leaks. Because early oral feeding preserves the integrity and function of gut mucosa, the aim of this study was to investigate the impact of postoperative early oral feeding on esophagectomy. METHODS: Between Oct 2013 and Jan 2016, 41 consecutive patients with esophageal carcinoma (stages I- III), who had undergone minimally invasive Ivor-Lewis surgery, were enrolled in this study. The patients were randomly arranged into the early oral feeding (EOF) group (21 cases) and the simple tube feeding (STF) group (20 cases). The nutritional goal for both groups was 25 kcal/(kg·day). The patients in the EOF group were tube-fed with enteral nutrition and orally fed with 5% glucose in normal saline during the first 4 postoperative days, after that the patients were placed on a liquid diet. The patients in the STF group were postoperatively tube-fed with enteral nutrition for 7 days before being switched to liquid diet. The length of the postoperative hospital stay, rate of perioperative complications, and overall mortality were recorded. Preoperative and postoperative levels of serum albumin (ALB), prealbumin (PA), transferrin (TP), and C reactive protein (CRP) were also monitored. RESULTS: There were no significant differences of the incidence of postoperative complications and overall mortality between the EOF group and the STF group, but the duration of hospital stay, interval until the first liquid food, and time of ambulation in the EOF group were lower than those of the STF group (P<0.05). EOF patients also showed significantly lower CRP levels compared with the STF group (P<0.05). CONCLUSIONS: EOF might reduce the duration of hospital stays and CRP levels in esophageal cancer patients who underwent esophagectomy while the mortality and complications were not affected.

The enhanced recovery after surgery (ERAS) protocol to promote recovery following esophageal cancer resection.

Esophageal cancer surgery, comprising esophagectomy with radical lymphadenectomy, is a complex procedure associated with considerable morbidity and mortality. The enhanced recovery after surgery (ERAS) protocol which aims to improve perioperative care, minimize complications, and accelerate recovery is showing promise for achieving better perioperative outcomes. ERAS is a multimodal approach that has been reported to shorten the length of hospital stay, reduce surgical stress response, decrease morbidity, and expedite recovery. While ERAS components straddle preoperative, intraoperative, and postoperative periods, they need to be seen in continuum and not as isolated elements. In this review, we elaborate on the components of an ERAS protocol after esophagectomy including preoperative nutrition, prehabilitation, counselling, smoking and alcohol cessation, cardiopulmonary evaluation, surgical technique, anaesthetic management, intra- and postoperative fluid management and pain relief, mobilization and physiotherapy, enteral and oral feeding, removal of drains, and several other components. We also share our own institutional protocol for ERAS following esophageal resections.

Synergy Between Licensed Rehabilitation Professionals and Clinical Exercise Physiologists: Optimizing Patient Care for Cancer Rehabilitation.

OBJECTIVES: To differentiate between rehabilitation and exercise training and propose how rehabilitation professionals and exercise physiologists can collaborate to optimize cancer survivor care. DATA SOURCE: Professional organizations and peer-reviewed manuscripts. CONCLUSION: Both professions offer complementary skillsets that, when integrated, optimize the ability of the cancer care team to implement more effective survivorship care plans. Future models of care must incorporate efficient communications between the cancer rehabilitation program and oncology team, include various reimbursement/payment/funding options, and continuously assess program efficacy. IMPLICATIONS FOR NURSING PRACTICE: Nurses must be cognizant of physical needs (ie, functional and conditioning status) and cancer-related comorbidities when referring cancer survivors for exercise reconditioning.

The Who, What, Why, When, Where, and How of Team-Based Interdisciplinary Cancer Rehabilitation.

OBJECTIVE: To review the key components necessary for successful application of rehabilitation principles to oncology survivors. DATA SOURCES: Validated databases, including PubMed, MEDLINE, and Scopus. CONCLUSION: Rehabilitation is an essential component of cancer care that addresses functional needs for oncology survivors and is best accomplished via an interdisciplinary team. Interdisciplinary care, provided by nursing, physiatry, rehabilitation therapy, and exercise physiology, are critical components for comprehensive intervention. Challenges exist in implementing services, but opportunity also exists within the post-acute care sector. IMPLICATIONS FOR NURSING PRACTICE: Nurses play an important role in the screening, assessment, and treatment of cancer-related functional impairments.

Direct Oral Feeding Following Minimally Invasive Esophagectomy (NUTRIENT II trial): An International, Multicenter, Open-label Randomized Controlled Trial.

OBJECTIVE: Patients undergoing an esophagectomy are often kept nil-by-mouth postoperatively out of fear for increasing anastomotic leakage and pulmonary complications. This study investigates the effect of direct start of oral feeding following minimally invasive esophagectomy (MIE) compared with standard of care. BACKGROUND: Elements of enhanced recovery after surgery (ERAS) protocols have been successfully introduced in patients undergoing an esophagectomy. However, start of oral intake, which is an essential part of the ERAS protocols, remains a matter of debate. METHODS: Patients in this multicenter, international randomized controlled trial were randomized to directly start oral feeding (intervention) after a MIE with intrathoracic anastomosis or to receive nil-by-mouth and tube feeding for 5 days postoperative (control group). Primary outcome was time to functional recovery. Secondary outcome parameters included anastomotic leakage, pneumonia rate, and other surgical complications scored by predefined definitions. RESULTS: Baseline characteristics were similar in the intervention (n = 65) and control (n = 67) group. Functional recovery was 7 days for patients receiving direct oral feeding compared with 8 days in the control group (P = 0.436). Anastomotic leakage rate did not differ in the intervention (18.5%) and control group (16.4%, P = 0.757). Pneumonia rates were comparable between the intervention (24.6%) and control group (34.3%, P = 0.221). Other morbidity rates were similar, except for chyle leakage, which was more prevalent in the standard of care group (P = 0.032). CONCLUSION: Direct oral feeding after an esophagectomy does not affect functional recovery and did not increase incidence or severity of postoperative complications.

The pre- and postoperative course of functional status in patients undergoing esophageal cancer surgery.

INTRODUCTION: To optimally target physiotherapy treatment, knowledge of the pre- and postoperative course of functional status in patients undergoing esophagectomy is required. The aim of this prospective longitudinal study was to investigate the course of functional status in patients with esophageal cancer before and after esophagectomy. MATERIALS AND METHODS: Functional status outcome measures of patients with esophageal cancer who underwent surgery between March 2012 and June 2016 were prospectively measured at 3 months and at 1 day before surgery and at 1 week and at 3 months after surgery. Analysis of repeated measurements with the mixed model approach was used to study changes over time. RESULTS: Hundred fifty-five patients were measured at 3 months and at 1 day before surgery, of which 109 (70.3%) at 1 week and 60 (38.7%) at 3 months after surgery. Mean (SD) age at surgery was 63.5 years (9.3), and 122 patients (78.7%) were male. The incidence of postoperative complications was 83 (53.5%). Three months postoperatively, functional status measures returned to baseline levels, except from handgrip strength (beta [95% CI] -6.2 [-11.3 to -1.1]; P = 0.02) and fatigue (4.7 [0.7to 8.7]; P = 0.02). No differences were observed in the course of functional status between patients with and without postoperative complications. CONCLUSION: Functional status of patients undergoing esophagectomy returned to baseline values three months after surgery, despite the high incidence of postoperative complications. This requires rethinking the concept of prehabilitation, where clearly not all patients benefit from high functional status to prevent postoperative complications.

Perioperative prehabilitation and rehabilitation in esophagogastric malignancies: a systematic review.

Cancers of the esophagus and stomach are challenging to treat. With the advent of neoadjuvant therapies, patients frequently have a preoperative window with potential to optimize their status before major resectional surgery. It is unclear as to whether a prehabilitation or optimization program can affect surgical outcomes. This systematic review appraises the current evidence for prehabilitation and rehabilitation in esophagogastric malignancy. A literature search was performed according to PRISMA guidelines using PubMed, EMBASE, Cochrane Library, Google Scholar, and Scopus. Studies including patients undergoing esophagectomy or gastrectomy were included. Studies reporting on at least one of aerobic capacity, muscle strength, quality of life, morbidity, and mortality were included. Twelve studies were identified for inclusion, comprising a total of 937 patients. There was significant heterogeneity between studies, with a variety of interventions, timelines, and outcome measures reported. Inspiratory muscle training (IMT) consistently showed improvements in functional status preoperatively, with three studies showing improvements in respiratory complications with IMT. Postoperative rehabilitation was associated with improved clinical outcomes. There may be a role for prehabilitation among patients undergoing major resectional surgery in esophagogastric malignancy. A large randomized controlled trial is warranted to investigate this further.

Pilot Prehabilitation Program for Patients With Esophageal Cancer During Neoadjuvant Therapy and Surgery.

BACKGROUND: Locally advanced esophageal cancer is often treated with neoadjuvant therapy followed by surgery. Many patients present with or experience clinical deconditioning during neoadjuvant therapy. Prehabilitation programs in other areas of surgery have demonstrated improved postoperative outcomes. The aims of this study were to evaluate the feasibility of a pilot prehabilitation program and determine preliminary effects on surgical and cancer-related outcomes. METHODS: A retrospective review of patients treated at a single institution with resectable esophageal cancer was performed (n = 22). Patients in the prehabilitation group received protocol-structured intervention in several clinical domains including nutrition, psychosocial support, and physical exercise. RESULTS: Clinical stage and comorbidities were well matched between groups. The structured prehabilitation program was feasible and well received by participants. Fewer patients required admission during neoadjuvant therapy in the prehabilitation group (27.3% versus 54.5%). Percentage weight loss during treatment was 3.0% in the prehabilitation group versus 4.3% in the control group. Compared with the control group, the prehabilitation group demonstrated 0.0% versus 18.2% 30-d postoperative readmission rate and 18.2% versus 27.3% 90-d postoperative readmission rate. There were no statistically significant differences between groups in regard to complications or mortality. CONCLUSIONS: The pilot prehabilitation program demonstrated feasibility of implementing a structured program for patients receiving neoadjuvant therapy for esophageal cancer. Although the small population limits evaluation of statistical significance, trends in the data suggest a potential benefit of the prehabilitation program on neoadjuvant hospital admission rates, postsurgical readmission rates, and nutritional status.

The role of rehabilitation in patients undergoing oesophagectomy for cancer and pre-malignant disease: A qualitative exploration of the views of patients, carers and healthcare providers.

OBJECTIVE: Oesophagectomy for cancer is associated with significant morbidity and mortality, and reduced quality of life. Structured rehabilitation potentially offers improved physical and psychological outcomes. We aimed to explore patient, carer and healthcare provider attitudes and preferences towards the role of rehabilitation. METHODS: We interviewed 15 patients who had undergone an oesophagectomy, 10 carers and 13 healthcare providers about perceived impacts of treatment; preferred components of a rehabilitation program; barriers/enablers of support provision; and participation in rehabilitation programs. Data were analysed using framework analysis. RESULTS: The overarching theme was "Getting back to normal." Diagnosis of disease signified a disruption to the normal trajectory of patients' lives and the post-treatment period was characterised as striving to return to normal. Patients and carers focused on rehabilitation needs post-treatment including dietary support, physiotherapy and healthcare provider support. Healthcare providers described rehabilitation as potentially beneficial from the pre-treatment phase and, along with carers, highlighted the importance of psychological support. Barriers included access to services, cost of service provision and appointment burden. CONCLUSION: A need for rehabilitation services was identified by healthcare providers from the point of diagnosis, rather than only after surgery. Implications include improved service provision by healthcare institutions for patients undergoing oesophagectomy.

Impact of an Early Oral Feeding Protocol on Inflammatory Cytokine Changes After Esophagectomy.

BACKGROUND: The aim of the current study was to investigate the impact of early oral feeding (EOF) on inflammatory cytokine levels after McKeown minimally invasive esophagectomy (MIE) for cancer. METHODS: This study was based on a randomized controlled trial (NCT01998230). Patients with esophageal cancer who received McKeown MIE were randomly allocated into a group that started oral feeding on postoperative day (POD) 1 (EOF group) or a second group that received nil by mouth until 7 days after operation (late oral feeding [LOF] group). We chose 86 patients, 46 patients in the EOF group and 40 patients in the LOF group, in which to analyze inflammatory cytokine levels (interleukin [IL]-6, IL-8, tumor necrosis factor-a [TNF-α], and monocyte chemotactic protein-1 [MCP-1]). RESULTS: The EOF and LOF groups exhibited similar preoperative IL-6, IL-8 TNF-α, and MCP-1 levels. The levels of the four inflammatory cytokines at PODs 1 and 3 were significantly higher than the preoperative levels (all p < 0.001). At POD 5 the levels of all four inflammatory cytokines were decreased compared with those at PODs 1 and 3. At PODs 3 and 5 the levels of IL-6, IL-8, and TNF-α were significantly lower in the EOF group than in the LOF group (all p < 0.05). At POD 3 the MCP-1 levels in the EOF group were significantly lower than those in the LOF group (all p < 0.05). CONCLUSIONS: Compared with conventional rehabilitation programs the EOF protocol may decrease stress response after McKeown MIE.

Induction Radiation Therapy for Esophageal Cancer: Does Dose Affect Outcomes?

BACKGROUND: Wide variation is seen in the dosage of preoperative induction radiation therapy for esophageal cancer. We investigated associations between outcomes after esophagectomy and dosage of induction radiation therapy. METHODS: Patients undergoing induction radiation therapy (30 to 70 Gy), followed by esophagectomy, were identified from the National Cancer Database and classified as low (<40 Gy), standard (40 to 50.4 Gy), and high dose (>50.4 Gy). Perioperative outcomes and overall survival were compared. Subgroup analysis compared two common dosages: 45 Gy and 50.4 Gy. RESULTS: From 2004 to 2014, 10,738 patients (84.7%) received standard-dose radiation, increasing from 69.7% in 2004 to 93.6% in 2014 (p < 0.001), 1,329 (10.5%) received low-dose radiation, and 608 (4.8%) received high-dose radiation. Higher rates of pathologic complete response (pCR; low: 11.7%, standard: 16.2%, high: 21.0%; p < 0.001) and downstaging (low: 52.0%, standard: 56.4%, high: 63.1%, p = 0.001) were observed as the dosage increased. On multivariable analysis, compared with standard-dose, high-dose radiation was associated with higher 30-day mortality (odds ratio [OR], 2.11; p < 0.001) without a higher likelihood of downstaging or pCR. Low-dose radiation was associated with lower likelihood of downstaging (OR, 0.85; p = 0.04) and pCR (OR, 0.67; p < 0.001) without lowering the risk of 30-day mortality. The dose of 50.4 Gy was associated with higher likelihood of pCR (OR, 1.12; p = 0.04), without affecting 30-day mortality, compared with 45 Gy. CONCLUSIONS: High-dose induction radiation (>50.4 Gy) is associated with increased perioperative death after esophagectomy, without a significant improvement in tumor response. Low-dose radiation (<30 Gy) is associated with worse tumor response without a lower risk of perioperative death. Within standard dosages, 50.4 Gy is associated with higher likelihood of pCR without adversely affecting perioperative mortality compared with 45 Gy.

A randomised controlled trial to assess whether prehabilitation improves fitness in patients undergoing neoadjuvant treatment prior to oesophagogastric cancer surgery: study protocol.

INTRODUCTION: Neoadjuvant therapy prior to oesophagogastric resection is the gold standard of care for patients with T2 and/or nodal disease. Despite this, studies have taught us that chemotherapy decreases patients' functional capacity as assessed by cardiopulmonary exercise (CPX) testing. We aim to show that a multimodal prehabilitation programme, comprising supervised exercise, psychological coaching and nutritional support, will physically, psychologically and metabolically optimise these patients prior to oesophagogastric cancer surgery so they may better withstand the immense physical and metabolic stress placed on them by radical curative major surgery. METHODS AND ANALYSIS: This will be a prospective, randomised, controlled, parallel, single-centre superiority trial comparing a multimodal 'prehabilitation' intervention with 'standard care' in patients with oesophagogastric malignancy who are treated with neoadjuvant therapy prior to surgical resection. The primary aim is to demonstrate an improvement in baseline cardiopulmonary function as assessed by anaerobic threshold during CPX testing in an interventional (prehab) group following a 15-week preoperative exercise programme, throughout and following neoadjuvant treatment, when compared with those that undergo standard care (control group). Secondary objectives include changes in peak oxygen uptake and work rate (total watts achieved) at CPX testing, insulin resistance, quality of life, chemotherapy-related toxicity and completion, nutritional assessment, postoperative complication rate, length of stay and overall mortality. ETHICS AND DISSEMINATION: This study has been approved by the London-Bromley Research Ethics Committee and registered on ClinicalTrials.gov. The results will be disseminated in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT02950324; Pre-results.

Effect of Exercise and Nutrition Prehabilitation on Functional Capacity in Esophagogastric Cancer Surgery: A Randomized Clinical Trial.

Importance: Preserving functional capacity is a key element in the care continuum for patients with esophagogastric cancer. Prehabilitation, a preoperative conditioning intervention aiming to optimize physical status, has not been tested in upper gastrointestinal surgery to date. Objective: To investigate whether prehabilitation is effective in improving functional status in patients undergoing esophagogastric cancer resection. Design, Setting, and Participants: A randomized clinical trial (available-case analysis based on completed assessments) was conducted at McGill University Health Centre (Montreal, Quebec, Canada) comparing prehabilitation with a control group. Intervention consisted of preoperative exercise and nutrition optimization. Participants were adults awaiting elective esophagogastric resection for cancer. The study dates were February 13, 2013, to February 10, 2017. Main Outcomes and Measures: The primary outcome was change in functional capacity, measured with absolute change in 6-minute walk distance (6MWD). Preoperative (end of the prehabilitation period) and postoperative (from 4 to 8 weeks after surgery) data were compared between groups. Results: Sixty-eight patients were randomized, and 51 were included in the primary analysis. The control group were a mean (SD) age, 68.0 (11.6) years and 20 (80%) men. Patients in the prehabilitation group were a mean (SD) age, 67.3 (7.4) years and 18 (69%) men. Compared with the control group, the prehabilitation group had improved functional capacity both before surgery (mean [SD] 6MWD change, 36.9 [51.4] vs -22.8 [52.5] m; P < .001) and after surgery (mean [SD] 6MWD change, 15.4 [65.6] vs -81.8 [87.0] m; P < .001). Conclusions and Relevance: Prehabilitation improves perioperative functional capacity in esophagogastric surgery. Keeping patients from physical and nutritional status decline could have a significant effect on the cancer care continuum. Trial Registration: ClinicalTrials.gov Identifier: NCT01666158.

The RESTORE Randomized Controlled Trial: Impact of a Multidisciplinary Rehabilitative Program on Cardiorespiratory Fitness in Esophagogastric cancer Survivorship.

OBJECTIVE: The Rehabilitation Strategies in Esophagogastric cancer (RESTORE) randomized controlled trial evaluated the efficacy of a 12-week multidisciplinary program to increase the cardiorespiratory fitness and health-related quality of life (HRQOL) of esophagogastric cancer survivors. BACKGROUND: Patients following treatment for esophagogastric cancer are at risk of physical deconditioning, nutritional compromise, and sarcopenia. Accordingly, compelling rationale exists to target these impairments in recovery. METHODS: Disease-free patients treated for esophagogastric cancer were randomized to either usual care or the 12-week RESTORE program (exercise training, dietary counseling, and multidisciplinary education). The primary outcome was cardiopulmonary exercise testing (VO2peak). Secondary outcomes included body composition (bioimpedance analysis), and HRQOL (EORTC-QLQ-C30). Outcomes were assessed at baseline (T0), postintervention (T1), and at 3-month follow-up (T2). RESULTS: Twenty-two participants were randomized to the control group [mean (standard deviation) age 64.14 (10.46) yr, body mass index 25.67 (4.83) kg/m, time postsurgery 33.68 (19.56) mo], and 21 to the intervention group [age 67.19(7.49) yr, body mass index 25.69(4.02) kg/m, time postsurgery 23.52(15.23) mo]. Mean adherence to prescribed exercise sessions were 94(12)% (supervised) and 78(27)% (unsupervised). Correcting for baseline VO2peak, the intervention arm had significantly higher VO2peak at both T1, 22.20 (4.35) versus 21.41 (4.49) mL ·â€Šmin ·â€Škg, P < 0.001, and T2, 21.75 (4.27) versus 20.74 (4.65) mL ·â€Šmin ·â€Škg, P = 0.001, compared with the control group. Correcting for baseline values, no changes in body composition or HRQOL were observed. CONCLUSIONS: The RESTORE program significantly improved cardiorespiratory fitness of disease-free patients after esophagogastric cancer surgery, without compromise to body composition. This randomized controlled trial provides proof of principle for rehabilitation programs in esophagogastric cancer. CLINICAL TRIAL REGISTRATION NUMBER: NCT03314311.