Community-based prehabilitation in older patients and high-risk patients undergoing colorectal cancer surgery.

INTRODUCTION: Prehabilitation before colorectal cancer (CRC) surgery is promising to prevent complications and to enhance recovery, especially in patients aged 70 or older or in patients with an American Society of Anaesthesiologist (ASA) physical classification score 3-4, for whom surgery is associated with higher postoperative complications and long-lasting adverse effects on functional performance. MATERIALS AND METHODS: A cohort study was conducted in a large teaching hospital in Alkmaar, the Netherlands. Fifty CRC patients (≥70 years or ASA 3-4) underwent multimodal prehabilitation between September 2020 and July 2021. The reference group comprised 50 patients (≥70 years or ASA 3-4) from a historical cohort receiving CRC surgery without prehabilitation (March 2020-August 2020). The primary outcome was 90-day postoperative complication rate. Secondary outcomes were length of stay, 90-day readmission and mortality rates and functional outcome in the prehabilitation group. RESULTS: One patient in the prehabilitation group decided not to undergo surgery. Of the remaining 49 patients, 48 (98.0 %) received prehabilitation for at least 3 weeks. Of these patients, 32.7 % developed postoperative complications, compared to 58 % in the reference group (p = 0.015), and none were readmitted, in contrast to 6 reference group patients (12.0 %, p = 0.012). Length of stay and mortality did not differ significantly. Six weeks postoperatively, all functional outcomes in the prehabilitation group were significantly higher than at baseline. CONCLUSIONS: Prehabilitation reduced postoperative complications and improved short-term functional outcomes in older and high-risk patients receiving CRC surgery. Further research should investigate the maintenance of long-term enhanced lifestyle and the effects of tailor-made programs.

Ferric carboxymaltose infusion versus oral iron supplementation for preoperative iron deficiency anaemia in patients with colorectal cancer (FIT): a multicentre, open-label, randomised, controlled trial.

BACKGROUND: A third of patients with colorectal cancer who are eligible for surgery in high-income countries have concomitant anaemia associated with adverse outcomes. We aimed to compare the efficacy of preoperative intravenous and oral iron supplementation in patients with colorectal cancer and iron deficiency anaemia. METHODS: In the FIT multicentre, open-label, randomised, controlled trial, adult patients (aged 18 years or older) with M0 stage colorectal cancer scheduled for elective curative resection and iron deficiency anaemia (defined as haemoglobin level of less than 7·5 mmol/L (12 g/dL) for women and less than 8 mmol/L (13 g/dL) for men, and a transferrin saturation of less than 20%) were randomly assigned to either 1-2 g of ferric carboxymaltose intravenously or three tablets of 200 mg of oral ferrous fumarate daily. The primary endpoint was the proportion of patients with normalised haemoglobin levels before surgery (≥12 g/dL for women and ≥13 g/dL for men). An intention-to-treat analysis was done for the primary analysis. Safety was analysed in all patients who received treatment. The trial was registered at ClincalTrials.gov, NCT02243735, and has completed recruitment. FINDINGS: Between Oct 31, 2014, and Feb 23, 2021, 202 patients were included and assigned to intravenous (n=96) or oral (n=106) iron treatment. Treatment began a median of 14 days (IQR 11-22) before surgery for intravenous iron and 19 days (IQR 13-27) for oral iron. Normalisation of haemoglobin at day of admission was reached in 14 (17%) of 84 patients treated intravenously and 15 (16%) of 97 patients treated orally (relative risk [RR] 1·08 [95% CI 0·55-2·10]; p=0·83), but the proportion of patients with normalised haemoglobin significantly increased for the intravenous treatment group at later timepoints (49 [60%] of 82 vs 18 [21%] of 88 at 30 days; RR 2·92 [95% CI 1·87-4·58]; p<0·0001). The most prevalent treatment-related adverse event was discoloured faeces (grade 1) after oral iron treatment (14 [13%] of 105), and no treatment-related serious adverse events or deaths were observed in either group. No differences in other safety outcomes were seen, and the most common serious adverse events were anastomotic leakage (11 [5%] of 202), aspiration pneumonia (5 [2%] of 202), and intra-abdominal abscess (5 [2%] 202). INTERPRETATION: Normalisation of haemoglobin before surgery was infrequent with both treatment regimens, but significantly improved at all other timepoints following intravenous iron treatment. Restoration of iron stores was feasible only with intravenous iron. In selected patients, surgery might be delayed to augment the effect of intravenous iron on haemoglobin normalisation. FUNDING: Vifor Pharma.

Machine learning models in clinical practice for the prediction of postoperative complications after major abdominal surgery.

Complications after surgery have a major impact on short- and long-term outcomes, and decades of technological advancement have not yet led to the eradication of their risk. The accurate prediction of complications, recently enhanced by the development of machine learning algorithms, has the potential to completely reshape surgical patient management. In this paper, we reflect on multiple issues facing the implementation of machine learning, from the development to the actual implementation of machine learning models in daily clinical practice, providing suggestions on the use of machine learning models for predicting postoperative complications after major abdominal surgery.

Feasibility and safety of the 30-second sit-to-stand test delivered via telehealth: An observational study.

INTRODUCTION: Exercise testing is essential to determine the safety and efficacy of prescribing exercise. Limited evidence exists to support remotely supervised exercise testing in oncology literature. OBJECTIVE: To determine the feasibility, safety, and convergent validity of the 30-second sit-to-stand test (30STS) delivered via telehealth in an oncology population. Exploratory analyses informed remote test feasibility according to participant and treatment characteristics. DESIGN: Cross-sectional, observational study. SETTING: Telehealth outpatient clinic, tertiary metropolitan oncology hospital. PARTICIPANTS: Thirty-two consecutive outpatients attending telehealth exercise appointments were screened for inclusion. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: A pre-test safety screening questionnaire included the Australia-modified Karnofsky Performance Status (AKPS) and Clinical Frailty Scale (CFS). Following one practice, one 30STS test was completed using a standardized protocol modified for telehealth assessment. Secondary measures: International Physical Activity Questionnaire-Short Form (IPAQ-SF) and pre/post-test Borg Rating of Perceived Exertion (RPE). RESULTS: Thirty participants were deemed as being safe using the screening questionnaire and completed the remote 30STS. Participants were a median (interquartile range [IQR]) 62.5 (51.8 to 66.5) years old, 59% male, 72% undergoing cancer treatment, 34% with metastatic disease, and 56% met current exercise guidelines. Moderate correlation was found between 30STS and IPAQ-SF (rho = 0.49, p = .006), providing evidence of convergent validity. Correlations between 30STS and AKPS (rho = 0.26, p = .161), and CFS (rho = -0.23, p = .214), were fair. Chair-height standardization was poor (range 43 to 60 cm). The clinician could visualize the participant's whole body in 2 of 30 tests. No significant difference in test performance was found for participants with metastatic disease, higher age, or body mass index. No adverse events occurred. CONCLUSION: With screening, the 30STS, performed by telehealth, is a safe and feasible measure of function and lower limb strength. Telehealth exercise testing presents challenges in standardizing the environment and ensuring participant safety. Minimal space and equipment requirements and moderate convergent validity with physical activity provide good clinical utility in this setting.

The prediction of surgical complications using artificial intelligence in patients undergoing major abdominal surgery: A systematic review.

BACKGROUND: Conventional statistics are based on a simple cause-and-effect principle. Postoperative complications, however, have a multifactorial and interrelated etiology. The application of artificial intelligence might be more accurate to predict postoperative outcomes. The objective of this study was to determine the current quality of studies describing the use of artificial intelligence in predicting complications in patients undergoing major abdominal surgery. METHODS: A literature search was performed in PubMed, Embase, and Web of Science. Inclusion criteria were (1) empirical studies including patients undergoing (2) any type of gastrointestinal surgery, including hepatopancreaticobiliary surgery, whose (3) complications or mortality were predicted with the use of (4) any artificial intelligence system. Studies were screened for description of method of validation and testing in methodology. Outcome measurements were sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve. RESULTS: From a total of 1,537 identified articles, 15 were included for the review. Among a large variety of algorithms used by the included studies, sensitivity was between 0.06 and 0.96, specificity was between 0.61 and 0.98, accuracy was between 0.78 and 0.95, and area under the receiver operating characteristic curve varied between 0.50 and 0.96. CONCLUSION: Artificial intelligence algorithms have the ability to accurately predict postoperative complications. Nevertheless, algorithms should be properly tested and validated, both internally and externally. Furthermore, a complete database and the absence of unsampled imbalanced data are absolute prerequisites for algorithms to predict accurately.

From registration to publication: A study on Dutch academic randomized controlled trials.

INTRODUCTION: Registration of clinical trials has been initiated in order to assess adherence of the reported results to the original trial protocol. This study aimed to investigate the publication rates, timely dissemination of results, and the prevalence of consistency in hypothesis, sample size, and primary endpoint of Dutch investigator-initiated randomized controlled clinical trials (RCTs). METHODS: All Dutch investigator-initiated RCTs with a completion date between December 31, 2010, and January 1, 2012, and registered in the Trial Register of The Netherlands database were included. PubMed was searched for the publication of these RCT results until September 2016, and the time to the publication date was calculated. Consistency in hypothesis, sample size, and primary endpoint compared with the registry data were assessed. RESULTS: The search resulted in a total of 168 Dutch investigator-initiated RCTs. In September 2016, the results of 129 (77%) trials had been published, of which 50 (39%) within 2 years after completion of accrual. Consistency in hypothesis with the original protocol was observed in 108 (84%) RCTs; in 71 trials (55%), the planned sample size was reached; and 103 trials (80%) presented the original primary endpoint. Consistency in all three parameters was observed in 50 studies (39%). CONCLUSION: This study shows that approximately one out of four Dutch investigator-initiated RCTs remains unpublished 5 years after initiation. The observed low overall consistency with the initial study outline is a matter of concern and warrants improvements in trial design and assessment of trial feasibility.

The Association of Preoperative Anemia and the Postoperative Course and Oncological Outcome in Patients Undergoing Rectal Cancer Surgery: A Multicenter Snapshot Study.

BACKGROUND: There is still controversy about the relationship between preoperative anemia and outcomes after rectal cancer surgery. OBJECTIVE: The aim of this study was to analyze the association between preoperative anemia and postoperative complications and the survival of patients undergoing surgery for rectal cancer in the era of laparoscopic surgery and modern perioperative care. DESIGN: This was a cohort study. SETTINGS: Data were gathered from 71 hospitals in The Netherlands. PATIENTS: Patients who underwent resection for rectal cancer in 2011, for whom preoperative hemoglobin level was registered, were included. INTERVENTIONS(S): There were no interventions. MAIN OUTCOME MEASURES: Short-term outcome parameters were any postoperative complication or mortality within 30 days postoperatively, and pelvic infectious complications defined as anastomotic leakage and presacral abscess. Long-term outcomes were chronic sinus diagnosed at any time during 3-year follow-up, 3-year local and distant recurrence rates, and 3-year overall survival. RESULTS: Of 2095 patients, 1857 had a registered preoperative hemoglobin level; 576 (31%) of these patients anemic and 1281 (69%) were nonanemic. Preoperative anemia was not independently associated with postoperative complications (HR, 1.1; 95% CI, 0.9-1.4; p = 0·24) or 30-day mortality (HR, 1.4, 95% CI, 0.7-2.8; p = 0·29). Preoperative anemia was associated with 3-year overall survival (HR, 2.1; 95% CI, 1.7-2.5; p < 0.0001), after multivariable analysis (HR, 1.4; 95% CI, 1.1-1.8; p = 0·008), and with local recurrence rate (HR, 1.6; 95% CI, 1.1-2.4; p = 0.026), but not with distant recurrence rate (HR, 1.2; 95% CI, 1.0-1.5; p = 0.054). LIMITATIONS: Preoperative anemia appeared to have only limited association with postoperative and disease-specific outcome after rectal cancer surgery in contrast to published meta-analysis of small historical series. CONCLUSIONS: Anemia is associated with overall survival. It might be considered as one of the warning signs in identifying high-risk patients. See Video Abstract at http://links.lww.com/DCR/A913.

Improving Outcomes in Oncological Colorectal Surgery by Prehabilitation.

INTRODUCTION: The cornerstone in the treatment of colorectal cancer is surgery. A surgical event poses a significant risk of decreased functional decline and impaired health-related quality of life. Prehabilitation is defined as the multimodal preoperative enhancement of a patient's condition. It may serve as a strategy to improve postoperative outcomes. Prehabilitation requires a multidisciplinary effort of medical health care professionals and a behavioral change of the patient. METHODS: The goal of prehabilitation is threefold: (1) to reduce postoperative complications, (2) to enhance and accelerate the recovery of the patient, and (3) to improve overall quality of life. In this article, we introduce the FIT model illustrating a possible framework toward the implementation of both evidence-based and tailor-made prehabilitation for patients undergoing surgery for colorectal cancer. RESULTS: The model is composed of three pillars: "facts" (how to screen patients and evidence on what content to prescribe), "integration" (data of own questionnaires assessing motivation of patients and specialists), and finally "tools" (which outcome measurements to use). DISCUSSION: Developing implementable methods and defining standardized outcome instruments will help establish a solid base for patient-centered prehabilitation programs. Any party introducing prehabilitation requiring multidisciplinary teamwork and behavioral change can potentially use this framework.

Fit4SurgeryTV At-home Prehabilitation for Frail Older Patients Planned for Colorectal Cancer Surgery: A Pilot Study.

OBJECTIVE: The preoperative phase is a potential window of opportunity. Although frail elderly patients are known to be more prone to postoperative complications, they are often not considered capable of accomplishing a full prehabilitation program. The aim of this study was to assess the feasibility of Fit4SurgeryTV, an at-home prehabilitation program specifically designed for frail older patients with colorectal cancer. DESIGN: The Fit4SurgeryTV program consisted of a daily elderly adapted computer-supported strength training workout and two protein-rich meals. Frail patients 70 yrs or older with colorectal cancer were included. The program was considered feasible if 80% of the patients would be able to complete 70% of the program. RESULTS: Fourteen patients (median age, 79 yrs; 5 males) participated. At baseline, 86% patients were physically impaired and 64% were at risk for malnourishment. The median duration of the program was 26 days. The program was feasible as patients followed the exercises for 6 (86%) of 7 days and prepared the recipes 5 (71%) of 7 d/wk. Patients specifically appreciated at-home exercises. CONCLUSIONS: This study showed that at-home prehabilitation in frail older patients with colorectal cancer is feasible. As a result, patients might be fitter for surgery and might recover faster. The perioperative period could serve as a pivotal time point in reverting complications of immobility.

Oral Nutrition as a Form of Pre-Operative Enhancement in Patients Undergoing Surgery for Colorectal Cancer: A Systematic Review.

BACKGROUND: Nutritional status has major impacts on the outcome of surgery, in particular in patients with cancer. The aim of this review was to assess the merit of oral pre-operative nutritional support as a part of prehabilitation in patients undergoing surgery for colorectal cancer. METHODS: A systematic literature search and meta-analysis was performed according to the Preferred Reporting of Systematic Reviews and Meta-Analyses (PRISMA) recommendations in order to review all trials investigating the effect of oral pre-operative nutritional support in patients undergoing colorectal surgery. The primary outcome was overall complication rate. Secondary outcomes were incision infection rate, anastomotic leakage rate, and length of hospital stay. RESULTS: Five randomized controlled trials and one controlled trial were included. The studies contained a total of 583 patients with an average age of 63 y (range 23-88 y), of whom 87% had colorectal cancer. Malnourishment rates ranged from 8%-68%. All investigators provided an oral protein supplement. Overall patient compliance rates ranged from 72%-100%. There was no significant reduction in the overall complication rate in the interventional groups (odds ratio 0.82; 95% confidence interval 0.52 - 1.25). CONCLUSION: Current studies are too heterogeneous to conclude that pre-operative oral nutritional support could enhance the condition of patients undergoing colorectal surgery. Patients at risk have a relatively lean body mass deficit (sarcopenia) rather than an absolute malnourished status. Compliance is an important element of prehabilitation. Targeting patients at risk, combining protein supplements with strength training, and defining standardized patient-related outcomes will be essential to obtain satisfactory results.

Short-term effect of preoperative intravenous iron therapy in colorectal cancer patients with anemia: results of a cohort study.

BACKGROUND: In the treatment of preoperative anemia, which is associated with increased postoperative morbidity, iron supplementation can replace blood transfusion and erythropoiesis-stimulating agents. The aim of this study was to assess the efficacy of preoperative intravenous (IV) iron infusion in optimizing hemoglobin (Hb) levels in anemic colorectal cancer patients. STUDY DESIGN AND METHODS: A retrospective cohort study was performed on patients who underwent surgery for colorectal cancer between 2010 and 2016 in a single teaching hospital. The primary outcome measure, the change in Hb level, was assessed by comparing anemic patients receiving usual care (UC; i.e. no iron therapy and no blood transfusion) with anemic patients receiving IV iron therapy (no blood transfusion). RESULTS: A total of 758 patients with colorectal cancer were eligible, of whom 318 (41.9%) had anemia. The IV and the UC groups included 52 and 153 patients with mean Hb levels at diagnosis of 6.3 and 6.9 mmol/L, respectively. In the IV group, preoperative Hb level was significantly increased compared to the UC group (0.65 mmol/L vs. 0.10 mmol/L, p < 0.001). High increase in Hb level after iron infusion was associated with initial higher transferrin and lower ferritin levels (high vs. poor responders: median transferrin 2.9 g/L vs. 2.7 g/L, median ferritin 12 µg/L vs. 27 µg/L). CONCLUSION: Implementation of IV iron therapy in anemic colorectal cancer patients leads to a distinct increase of preoperative Hb level. IV iron therapy is most effective in patients presenting with more severe anemia, and with higher transferrin and lower ferritin levels, markers for an absolute iron deficiency (ID), compared to functional ID.

Epigenetic changes in leukocytes after 8 weeks of resistance exercise training.

PURPOSE: Regular engagement in resistance exercise training elicits many health benefits including improvement to muscular strength, hypertrophy and insulin sensitivity, though the underpinning molecular mechanisms are poorly understood. The purpose of this study was to determine the influence 8 weeks of resistance exercise training has on leukocyte genome-wide DNA methylation and gene expression in healthy young men. METHODS: Eight young (21.1 ± 2.2 years) men completed one repetition maximum (1RM) testing before completing 8 weeks of supervised, thrice-weekly resistance exercise training comprising three sets of 8-12 repetitions with a load equivalent to 80 % of 1RM. Blood samples were collected at rest before and after the 8-week training intervention. Genome-wide DNA methylation and gene expression were assessed on isolated leukocyte DNA and RNA using the 450K BeadChip and HumanHT-12 v4 Expression BeadChip (Illumina), respectively. RESULTS: Resistance exercise training significantly improved upper and lower body strength concurrently with diverse genome-wide DNA methylation and gene expression changes (p ≤ 0. 01). DNA methylation changes occurred at multiple regions throughout the genome in context with genes and CpG islands, and in genes relating to axon guidance, diabetes and immune pathways. There were multiple genes with increased expression that were enriched for RNA processing and developmental proteins. Growth factor genes-GHRH and FGF1-showed differential methylation and mRNA expression changes after resistance training. CONCLUSIONS: Our findings indicate that resistance exercise training improves muscular strength and is associated with reprogramming of the leukocyte DNA methylome and transcriptome.