Hospital variation and outcomes after repeat hepatic resection for colorectal liver metastases: a nationwide cohort study.

BACKGROUND: Approximately 70% of patients with colorectal liver metastases (CRLM) experiences intrahepatic recurrence after initial liver resection. This study assessed outcomes and hospital variation in repeat liver resections (R-LR). METHODS: This population-based study included all patients who underwent liver resection for CRLM between 2014 and 2022 in the Netherlands. Overall survival (OS) was collected for patients operated on between 2014 and 2018 by linkage to the insurance database. RESULTS: Data of 7479 liver resections (1391 (18.6%) repeat and 6088 (81.4%) primary) were analysed. Major morbidity and mortality were not different. Factors associated with major morbidity included ASA 3+, major liver resection, extrahepatic disease, and open surgery. Five-year OS after repeat versus primary liver resection was 42.3% versus 44.8%, P = 0.37. Factors associated with worse OS included largest CRLM >5 cm (aHR 1.58, 95% CI: 1.07-2.34, P = 0.023), >3 CRLM (aHR 1.33, 95% CI: 1.00-1.75, P = 0.046), extrahepatic disease (aHR 1.60, 95% CI: 1.25-2.04, P = 0.001), positive tumour margins (aHR 1.42, 95% CI: 1.09-1.85, P = 0.009). Significant hospital variation in performance of R-LR was observed, median 18.9% (8.2% to 33.3%). CONCLUSION: Significant hospital variation was observed in performance of R-LR in the Netherlands reflecting different treatment decisions upon recurrence. On a population-based level R-LR leads to satisfactory survival.

Multimodal prehabilitation in elective oncological colorectal surgery enhances preoperative physical fitness: a single center prospective real-world data analysis.

BACKGROUND: Surgery can lead to curation in colorectal cancer (CRC) but is associated with significant morbidity. Prehabilitation plays an important role in increasing preoperative physical fitness to reduce morbidity risk; however, data from real-world practice is scarce. This study aimed to evaluate the change in preoperative physical fitness and to evaluate which patients benefit most from prehabilitation. MATERIALS AND METHODS: In this single-arm prospective cohort study, consecutive patients undergoing elective colorectal oncological surgery were offered a 3- to 4-week multimodal prehabilitation program (supervised physical exercise training, dietary consultation, protein and vitamin supplementation, smoking cessation, and psychological support). The primary outcome was the change in preoperative aerobic fitness (steep ramp test (SRT)). Secondary outcomes were the change in functional walking capacity (6-minute walk test (6MWT)), and muscle strength (one-repetition maximum (1RM) for various muscle groups). To evaluate who benefit most from prehabilitation, participants were divided in quartiles (Q1, Q2, Q3, and Q4) based on baseline performance. RESULTS: In total, 101 patients participated (51.4% male, aged 69.7 ± 12.7 years). The preoperative change in SRT was +28.3 W, +0.36 W/kg, +16.7% (P<0.001). Patients in all quartiles improved at the group level; however, the relative improvement decreased from Q1-Q2, Q2-Q3, and Q3-Q4 (P=0.049). Change in 6MWT was +37.5 m, +7.7% (P<0.001) and 1RM improved with 5.6-33.2 kg, 16.1-32.5% for the various muscle groups (P<0.001). CONCLUSION: Prehabilitation in elective oncological colorectal surgery is associated with enhanced preoperative physical fitness regardless of baseline performance. Improvements were relatively larger in less fit patients.

Multimodal prehabilitation in elective oncological colorectal surgery enhances postoperative functional recovery: A secondary analysis of the PREHAB randomized clinical trial.

INTRODUCTION: Colorectal cancer (CRC) ranks as the second leading cause of cancer-related deaths. The PREHAB trial revealed that prehabilitation in colorectal surgery leads to a reduction of severe complications and enhanced functional capacity. Nevertheless, risk selection for prehabilitation and the potential benefits for patients without postoperative complications remains unclear. This study aims to assess postoperative functional capacity, also in patients without postoperative complications. MATERIALS & METHODS: This study was a secondary analysis of the PREHAB trial. Functional capacity tests, including cardiopulmonary exercise testing (CPET), steep ramp test (SRT), 6-min walking test (6MWT), stair climb test (SCT), 30" sit-to-stand test (STS), timed-up-and-go test (TUG), and muscle strength assessments, were conducted at baseline (T0) and 4 weeks postoperatively (T3). The primary outcome was the relative change in functional capacity from baseline to postoperative (ΔT0-T3) per group (i.e., prehabilitation vs control). Secondary, identical analysis were performed for patients without postoperative complications in each group. RESULTS: Intention-to-treat analysis included 251 patients. For postoperative functional capacity, prehabilitation patients showed improvements in VO2peak (p = 0.024), VO2AT (p = 0.017), SRT (p = 0.001), 6MWT (p = 0.049), SCT (p = 0.012), and STS (p = 0.001) compared to the control group. Regarding muscle strength, prehabilitation patients showed improvements in estimated 1RM lateral pull down (p = 0.016), 1RM chest press (p = 0.001), 1RM leg press (p = 0.001) and HGS (p = 0.005) compared to controls. Additionally, prehabilitation patients more often reached baseline levels at T3 in VO2AT (p = 0.037), SRT (p = 0.008), 6MWT (p = 0.013), STS (p = 0.012), estimated 1RM lateral pull down (p = 0.002), 1RM chest press (p = 0.001) and 1RM leg press (p = 0.001) compared to controls. Moreover, even patients without postoperative complications in the prehabilitation group showed better postoperative functional capacity and more often reached baseline levels at T3, compared to controls. CONCLUSION: Multimodal prehabilitation in CRC surgery is associated with improved postoperative functional capacity, even in patients without postoperative complications.

Treatment interval in curative treatment of colon cancer, does it impact (cancer free) survival? A non-inferiority analysis.

BACKGROUND: In treatment of colon cancer, strict waiting-time targets are enforced, leaving professionals no room to lengthen treatment intervals when advisable, for instance to optimise a patient's health status by means of prehabilitation. Good quality studies supporting these targets are lacking. With this study we aim to establish whether a prolonged treatment interval is associated with a clinically relevant deterioration in overall and cancer free survival. METHODS: This retrospective multicenter non-inferiority study includes all consecutive patients who underwent elective oncological resection of a biopsy-proven primary non-metastatic colon carcinoma between 2010 and 2016 in six hospitals in the Southern Netherlands. Treatment interval was defined as time between diagnosis and surgical treatment. Cut-off points for treatment interval were ≤35 days and ≤49 days. FINDINGS: 3376 patients were included. Cancer recurred in 505 patients (15.0%) For cancer free survival, a treatment interval >35 days and >49 days was non-inferior to a treatment interval ≤35 days. Results for overall survival were inconclusive, but no association was found. CONCLUSION: For cancer free survival, a prolonged treatment interval, even over 49 days, is non-inferior to the currently set waiting-time target of ≤35 days. Therefore, the waiting-time targets set as fundamental objective in current treatment guidelines should become directional instead of strict targets.

Prehabilitation in colorectal cancer surgery improves outcome and reduces hospital costs.

INTRODUCTION: Increasing evidence suggests that multimodal prehabilitation programs reduce postoperative complication rates and length of stay. Nevertheless, prehabilitation is not standard care yet, also as financial consequences of such programs are lacking. Aim of this study was to analyse clinical outcomes and effects on hospital resources if prehabilitation is implemented for patients who are planned for colorectal surgery. MATERIALS AND METHODS: Patients undergoing elective colorectal surgery and who received either prehabilitation or standard care between January 2017 and March 2022 in a regional Dutch hospital were included. Outcome parameters were length of hospital stay, 30-day postoperative complications, 30-day ICU admission, readmission rates and hospital costs. RESULTS: A total of 196 patients completed prehabilitation whereas 390 patients received standard care. Lower overall complication rates (31 % vs 40 %, p = 0.04) and severe complication rates (20 % vs 31 %, p = 0.01) were observed in the prehabilitation group compared to standard care. Length of stay was shorter in the prehabilitation group (mean 5.80 days vs 6.71 days). In hospital cost savings were €1109 per patient, while the calculated investment for prehabilitation was €969. CONCLUSION: Implementation of a multimodal prehabilitation program in colorectal surgery reduces postoperative complication rates, length of stay and hospital costs.

A retrospective analysis of the association of effort-independent cardiopulmonary exercise test variables with postoperative complications in patients who underwent elective colorectal surgery.

PURPOSE: This study aimed to investigate the association of effort-independent variables derived from the preoperative cardiopulmonary exercise test (CPET) with 30-day postoperative complications after elective colorectal surgery. METHODS: A multicenter (n=4) retrospective explorative study was performed using data of patients who completed a preoperative CPET and underwent elective colorectal surgery. The preoperative slope of the relation between minute ventilation and carbon dioxide production (VE/VCO2-slope) and the oxygen uptake efficiency slope (OUES), as well as 30-day postoperative complications, were assessed. Multivariable logistic regression analyses and receiver operating characteristic (ROC) curves were used to investigate the prognostic value of the relationship between these preoperative CPET-derived effort-independent variables and postoperative complications. RESULTS: Data from 102 patients (60.1% males) with a median age of 72.0 (interquartile range 67.8-77.4) years were analyzed. Forty-four patients (43.1%) had one or more postoperative complications (of which 52.3% general and 77.3% surgical complications). Merely 10 (9.8%) patients had a general complication only. In multivariate analysis adjusted for surgical approach (open versus minimally invasive surgery), the VE/VCO2-slope (odds ratio (OR) 1.08, confidence interval (CI) 1.02-1.16) and OUES (OR 0.94, CI 0.89-1.00) were statistically significant associated with the occurrence of 30-day postoperative complications. CONCLUSION: The effort-independent VE/VCO2-slope and OUES might be used to assist in future preoperative risk assessment and could especially be of added value in patients who are unable or unwilling to deliver a maximal cardiorespiratory effort. Future research should reveal the predictive value of these variables individually and/or in combination with other prognostic (CPET-derived) variables for postoperative complications. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT05331196.

Preoperative multimodal prehabilitation before elective colorectal cancer surgery in patients with WHO performance status I or II: randomized clinical trial.

BACKGROUND: Multimodal prehabilitation is a promising adjunct to the current surgical treatment pathway for colorectal cancer patients to further improve postoperative outcomes, especially for high-risk patients with low functional capacity. The aim of the present study was to test the effect of prehabilitation on immediate postoperative recovery. METHOD: The study was designed as a RCT with two arms (intervention and control). The intervention consisted of 4 weeks of multimodal prehabilitation, with supervised physical training, nutritional support and medical optimization. The control group received standard of care. A total of 40 patients with colorectal cancer (WHO performance status I or II) undergoing elective surgery with curative intent were included. The primary outcome was postoperative recovery within the first 3 postoperative days, measured by Quality of Recovery-15, a validated questionnaire with a scoring range between 0 and 150 and a minimal clinically relevant difference of 8. RESULTS: In total, 36 patients were analysed with 16 in the intervention group and 20 in the control group. The mean age of the included patients was 79 years. The overall treatment effect associated with the intervention was a 21.9 (95% c.i. 4.5-39.3) higher quality of recovery-15 score during the first 3 postoperative days compared to control, well above the minimal clinically relevant difference. CONCLUSION: Four weeks of multimodal prehabilitation prior to elective curative intended colorectal cancer surgery in patients with WHO performance status I or II was associated with a clinically relevant improvement in postoperative recovery.Registration number: NCT04167436 (http://www.clinicaltrials.gov).

Multimodal prehabilitation in patients with non-small cell lung cancer undergoing anatomical resection: protocol of a non-randomised feasibility study.

BACKGROUND: The preoperative period can be used to enhance a patient's functional capacity with multimodal prehabilitation and consequently improve and fasten postoperative recovery. Especially, non-small cell lung cancer (NSCLC) surgical patients may benefit from this intervention, since the affected and resected organ is an essential part of the cardiorespiratory fitness. Drafting a prehabilitation programme is challenging, since many disciplines are involved, and time between diagnosis of NSCLC and surgery is limited. We designed a multimodal prehabilitation programme prior to NSCLC surgery and aimed to conduct a study to assess feasibility and indicative evidence of efficacy of this programme. Publication of this protocol may help other healthcare facilities to implement such a programme. METHODS: The multimodal prehabilitation programme consists of an exercise programme, nutritional support, psychological support, smoking cessation, patient empowerment and respiratory optimisation. In two Dutch teaching hospitals, 40 adult patients with proven or suspected NSCLC will be included. In a non-randomised fashion, 20 patients follow the multimodal prehabilitation programme, and 20 will be assessed in the control group, according to patient preference. Assessments will take place at four time points: baseline, the week before surgery, 6 weeks postoperatively and 3 months postoperatively. Feasibility and indicative evidence of efficacy of the prehabilitation programme will be assessed as primary outcomes. DISCUSSION: Since the time between diagnosis of NSCLC and surgery is limited, it is a challenge to implement a prehabilitation programme. This study will assess whether this is feasible, and evidence of efficacy can be found. The non-randomised fashion of the study might result in a selection and confounding bias. However, the control group may help putting the results of the prehabilitation group in perspective. By publishing this protocol, we aim to facilitate others to evaluate and implement a multimodal prehabilitation programme for surgical NSCLC patients. TRIAL REGISTRATION: The current study is registered as NL8080 in the Netherlands Trial Register on the 10th of October 2019, https://www.trialregister.nl/trial/8080 . Secondary identifiers: CCMO (Central Committee on Research Involving Human Subjects) number NL70578.015.19, reference number of the Medical Ethical Review Committee of Máxima MC W19.045.

Fluid management and vasopressor use during colorectal surgery: the search for the optimal balance.

BACKGROUND: Although it is known that excessive intraoperative fluid and vasopressor agents are detrimental for anastomotic healing, optimal anesthesiology protocols for colorectal surgery are currently lacking. OBJECTIVE: To scrutinize the current hemodynamic practice and vasopressor use and their relation to colorectal anastomotic leakage. DESIGN: A secondary analysis of a previously published prospective observational study: the LekCheck study. STUDY SETTING: Adult patients undergoing a colorectal resection with the creation of a primary anastomosis. OUTCOME MEASURES: Colorectal anastomotic leakage (CAL) within 30 days postoperatively, hospital length of stay and 30-day mortality. RESULTS: Of the 1548 patients, 579 (37%) received vasopressor agents during surgery. Of these, 201 were treated with solely noradrenaline, 349 were treated with phenylephrine, and 29 received ephedrine. CAL rate significantly differed between the patients receiving vasopressor agents during surgery compared to patients without (11.8% vs 6.3%, p < 0.001). CAL was significantly higher in the group receiving phenylephrine compared to noradrenaline (14.3% vs 6%, p < 0.001). Vasopressor agents were used more often in patients treated with Goal Directed Therapy (47% vs 34.6%, p < 0.001). There was a higher mortality rate in patients with vasopressors compared to the group without (2.8% vs 0.4%, p = 0.01, OR 3.8). Mortality was higher in the noradrenaline group compared to the phenylephrine and those without vasopressors (5% vs. 0.4% and 1.7%, respectively, p < 0.001). In multivariable analysis, patients with intraoperative vasopressor agents had an increased risk to develop CAL (OR 2.1, CI 1.3-3.2, p = 0.001). CONCLUSION: The present study contributes to the evidence that intraoperative use of vasopressor agents is associated with a higher rate of CAL. This study helps to create awareness on the (necessity to) use of vasopressor agents in colorectal surgery patients in striving for successful anastomotic wound healing. Future research will be required to balance vasopressor agent dosage in view of colorectal anastomotic leakage.

Prehabilitation for patients with colorectal cancer: a snapshot of current daily practice in Dutch hospitals.

BACKGROUND: Multimodal prehabilitation programmes are increasingly being imbedded in colorectal cancer (CRC) pathways to enhance the patient's recovery after surgery. However, there is no (inter)national consensus on the content or design of such a programme. This study aimed to evaluate the current practice and opinion regarding preoperative screening and prehabilitation for patients undergoing surgery for CRC throughout the Netherlands. METHODS: All regular Dutch hospitals offering colorectal cancer surgery were included. An online survey was sent to one representative colorectal surgeon per hospital. Descriptive statistics were used for analyses. RESULTS: Response rate was 100% (n = 69). Routine preoperative screening of patients with CRC for frailty, diminished nutritional status and anaemia was the standard of care in nearly all Dutch hospitals (97%, 93% and 94%, respectively). Some form of prehabilitation was provided in 46 hospitals (67%) of which more than 80% addressed nutritional status, frailty, physical status and anaemia. All but two of the remaining hospitals were willing to adopt prehabilitation. The majority of the hospitals offered prehabilitation to specific subgroups of patients with CRC, such as the elderly (41%), the frail (71%) or high-risk patients (57%). There was high variability in the setting, design and content of the prehabilitation programmes. CONCLUSIONS: Whereas preoperative screening is sufficiently incorporated in Dutch hospitals, standardised enhancement of the patient's condition in the context of multimodal prehabilitation seems to be challenging. This study presents an overview of current clinical practice in the Netherlands. Uniform clinical prehabilitation guidelines are vital to diminish heterogeneity in programmes and to produce useful data to enable a nationwide implementation of an evidence-based prehabilitation programme.

Prehabilitation versus no prehabilitation to improve functional capacity, reduce postoperative complications and improve quality of life in colorectal cancer surgery.

BACKGROUND: Surgery is the cornerstone in curative treatment of colorectal cancer. Unfortunately, surgery itself can adversely affect patient health. 'Enhanced Recovery After Surgery' programmes, which include multimodal interventions, have improved patient outcomes substantially. However, these are mainly applied peri- and postoperatively. Multimodal prehabilitation includes multiple preoperative interventions to prepare patients for surgery with the aim of increasing resilience, thereby improving postoperative outcomes. OBJECTIVES: To determine the effects of multimodal prehabilitation programmes on functional capacity, postoperative complications, and quality of life in adult patients undergoing surgery for colorectal cancer. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and PsycINFO in January 2021. We also searched trial registries up to March 2021. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in adult patients with non-metastatic colorectal cancer, scheduled for surgery, comparing multimodal prehabilitation programmes (defined as comprising at least two preoperative interventions) with no prehabilitation. We focused on the following outcomes: functional capacity (i.e. 6-minute walk test, VO2peak, handgrip strength), postoperative outcomes (i.e. complications, mortality, length of hospital stay, emergency department visits, re-admissions), health-related quality of life, compliance, safety of prehabilitation, and return to normal activities. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies, extracted data, assessed risk of bias and used GRADE to assess the certainty of the evidence. Any disagreements were solved with discussion and consensus. We pooled data to perform meta-analyses, where possible. MAIN RESULTS: We included three RCTs that enrolled 250 participants with non-metastatic colorectal cancer, scheduled for elective (mainly laparoscopic) surgery. Included trials were conducted in tertiary care centres and recruited patients during periods ranging from 17 months to 45 months. A total of 130 participants enrolled in a preoperative four-week trimodal prehabilitation programme consisting of exercise, nutritional intervention, and anxiety reduction techniques. Outcomes of these participants were compared to those of 120 participants who started an identical but postoperative programme. Postoperatively, prehabilitation may improve functional capacity, determined with the 6-minute walk test at four and eight weeks (mean difference (MD) 26.02, 95% confidence interval (CI) -13.81 to 65.85; 2 studies; n = 131; and MD 26.58, 95% CI -8.88 to 62.04; 2 studies; n = 140); however, the certainty of evidence is low and very low, respectively, due to serious risk of bias, imprecision, and inconsistency. After prehabilitation, the functional capacity before surgery improved, with a clinically relevant mean difference of 24.91 metres (95% CI 11.24 to 38.57; 3 studies; n = 225). The certainty of evidence was moderate due to downgrading for serious risk of bias. The effects of prehabilitation on the number of complications (RR 0.95, 95% CI 0.70 to 1.29; 3 studies; n = 250), emergency department visits (RR 0.72, 95% CI 0.39 to 1.32; 3 studies; n = 250) and re-admissions (RR 1.20, 95% CI 0.54 to 2.65; 3 studies; n = 250) were small or even trivial. The certainty of evidence was low due to downgrading for serious risk of bias and imprecision. The effects on VO2peak, handgrip strength, length of hospital stay, mortality rate, health-related quality of life, return to normal activities, safety of the programme, and compliance rate could not be analysed quantitatively due to missing or insufficient data. The included studies did not report a difference between groups for health-related quality of life and length of hospital stay. Data on remaining outcomes were not reported or were reported inadequately in the included studies. AUTHORS' CONCLUSIONS: Prehabilitation may result in an improved functional capacity, determined with the 6-minute walk test both preoperatively and postoperatively. A solid effect on the number of omplications, postoperative emergency department visits and re-admissions could not be established. The certainty of evidence ranges from moderate to very low, due to downgrading for serious risk of bias, imprecision and inconsistency. In addition, only three heterogeneous studies were included in this review. Therefore, the findings of this review should be interpreted with caution. Numerous relevant RCTs are ongoing and will be included in a future update of this review.

A Dutch prediction tool to assess the risk of incidental gallbladder cancers after cholecystectomies for benign gallstone disease.

BACKGROUND: Despite the increasing implementation of selective histopathologic policies for post-cholecystectomy evaluation of gallbladder specimens in low-incidence countries, the fear of missing incidental gallbladder cancer (GBC) persists. This study aimed to develop a diagnostic prediction model for selecting gallbladders that require additional histopathological examination after cholecystectomy. METHODS: A registration-based retrospective cohort study of nine Dutch hospitals was conducted between January 2004 and December 2014. Data were collected using a secure linkage of three patient databases, and potential clinical predictors of gallbladder cancer were selected. The prediction model was validated internally by using bootstrapping. Its discriminative capacity and accuracy were tested by assessing the area under the receiver operating characteristic curve (AUC), Nagelkerke's pseudo-R2, and Brier score. RESULTS: Using a cohort of 22,025 gallbladders, including 75 GBC cases, a prediction model with the following variables was developed: age, sex, urgency, type of surgery, and indication for surgery. After correction for optimism, Nagelkerke's R2 and Brier score were 0.32 and 88%, respectively, indicating a moderate model fit. The AUC was 90.3% (95% confidence interval, 86.2%-94.4%), indicating good discriminative ability. CONCLUSION: We developed a good clinical prediction model for selecting gallbladder specimens for histopathologic examination after cholecystectomy to rule out GBC.

Effect of Multimodal Prehabilitation on Reducing Postoperative Complications and Enhancing Functional Capacity Following Colorectal Cancer Surgery: The PREHAB Randomized Clinical Trial.

Importance: Colorectal surgery is associated with substantial morbidity rates and a lowered functional capacity. Optimization of the patient's condition in the weeks prior to surgery may attenuate these unfavorable sequelae. Objective: To determine whether multimodal prehabilitation before colorectal cancer surgery can reduce postoperative complications and enhance functional recovery. Design, Setting, and Participants: The PREHAB randomized clinical trial was an international, multicenter trial conducted in teaching hospitals with implemented enhanced recovery after surgery programs. Adult patients with nonmetastasized colorectal cancer were assessed for eligibility and randomized to either prehabilitation or standard care. Both arms received standard perioperative care. Patients were enrolled from June 2017 to December 2020, and follow-up was completed in December 2021. However, this trial was prematurely stopped due to the COVID-19 pandemic. Interventions: The 4-week in-hospital supervised multimodal prehabilitation program consisted of a high-intensity exercise program 3 times per week, a nutritional intervention, psychological support, and a smoking cessation program when needed. Main Outcomes and Measures: Comprehensive Complication Index (CCI) score, number of patients with CCI score more than 20, and improved walking capacity expressed as the 6-minute walking distance 4 weeks postoperatively. Results: In the intention-to-treat population of 251 participants (median [IQR] age, 69 [60-76] years; 138 [55%] male), 206 (82%) had tumors located in the colon and 234 (93%) underwent laparoscopic- or robotic-assisted surgery. The number of severe complications (CCI score >20) was significantly lower favoring prehabilitation compared with standard care (21 of 123 [17.1%] vs 38 of 128 [29.7%]; odds ratio, 0.47 [95% CI, 0.26-0.87]; P = .02). Participants in prehabilitation encountered fewer medical complications (eg, respiratory) compared with participants receiving standard care (19 of 123 [15.4%] vs 35 of 128 [27.3%]; odds ratio, 0.48 [95% CI, 0.26-0.89]; P = .02). Four weeks after surgery, 6-minute walking distance did not differ significantly between groups when compared with baseline (mean difference prehabilitation vs standard care 15.6 m [95% CI, -1.4 to 32.6]; P = .07). Secondary parameters of functional capacity in the postoperative period generally favored prehabilitation compared with standard care. Conclusions and Relevance: This PREHAB trial demonstrates the benefit of a multimodal prehabilitation program before colorectal cancer surgery as reflected by fewer severe and medical complications postoperatively and an optimized postoperative recovery compared with standard care. Trial Registration: trialregister.nl Identifier: NTR5947.

Implementation of perioperative music in day care surgery.

BACKGROUND: Perioperative music can have beneficial effects on postoperative pain and perioperative opioid requirement. This study aims to assess the implementation feasibility of music in day care surgery through adherence to implementation, as well as its effects. METHODS: This implementation study employed a prospective single-center study design. Perioperative music was implemented as part of standard surgical care during day care surgery procedures. The music intervention consisted of preselected playlists. Primary outcome was adherence to implementation. Barriers and attitudes towards music of patients and perioperative care providers were evaluated. Furthermore, the effects of music were assessed through a matched cohort analysis. This study was registered with the Netherlands Trial Register (NL8213). RESULTS: From January to April 2020, a total of 109 patients received the music intervention and 97 were analyzed after matching to retrospective controls. Adherence rate to the music intervention was 92% preoperatively, 81% intraoperatively, and 86% postoperatively, with 83% of patients satisfied with the preselected music, and 93% finding music to be beneficial to surgical care. All health care providers believed perioperative music to be beneficial (63%) or were neutral (37%) towards its use. Postoperative pain was not significantly different (mean numeric rating scale 0.74; the music intervention group versus 0.68; control group, p = .363). Although not statistically significant, postoperative opioid requirement in the music group was lower (30% versus 40%, p = .132). CONCLUSION: Perioperative music implementation in day care surgery is feasible with high adherence rates, patient satisfaction levels, and positive attitudes of health care providers towards its use.

Oncological Safety and Potential Cost Savings of Routine vs Selective Histopathological Examination After Appendectomy: Results of the Multicenter, Prospective, Cross-Sectional FANCY Study.

OBJECTIVE: To investigate the oncological safety and potential cost savings of selective histopathological examination after appendectomy. BACKGROUND: The necessity of routine histopathological examination after appendectomy has been questioned, but prospective studies investigating the safety of a selective policy are lacking. METHODS: In this multicenter, prospective, cross-sectional study, inspection and palpation of the (meso)appendix was performed by the surgeon in patients with suspected appendicitis. The surgeon's opinion on additional value of histopathological examination was reported before sending all specimens to the pathologist. Main outcomes were the number of hypothetically missed appendiceal neoplasms with clinical consequences benefiting the patient (upper limit two-sided 95% confidence interval below 3:1000 considered oncologically safe) and potential cost savings after selective histopathological examination. RESULTS: Seven thousand three hundred thirty-nine patients were included. After a selective policy, 4966/7339 (67.7%) specimens would have been refrained from histopathological examination. Appendiceal neoplasms with clinical consequences would have been missed in 22/4966 patients. In 5/22, residual disease was completely resected during additional surgery. Hence, an appendiceal neoplasm with clinical consequences benefiting the patient would have been missed in 1.01:1000 patients (upper limit 95% confidence interval 1.61:1000). In contrast, twice as many patients (10/22) would not have been exposed to potential harm due to re-resections without clear benefit, whereas consequences were neither beneficial nor harmful in the remaining seven. Estimated cost savings established by replacing routine for selective histopathological examination were €725,400 per 10,000 patients. CONCLUSIONS: Selective histopathological examination after appendectomy for suspected appendicitis is oncologically safe and will likely result in a reduction of pathologists' workload, less costs, and fewer re-resections without clear benefit.

Quality of Recovery and Innate Immune Homeostasis in Patients Undergoing Low-pressure Versus Standard-pressure Pneumoperitoneum During Laparoscopic Colorectal Surgery (RECOVER): A Randomized Controlled Trial.

OBJECTIVE: To study the effects of intra-abdominal pressure on the quality of recovery and innate cytokine production capacity after laparoscopic colorectal surgery within the enhanced recovery after surgery program. BACKGROUND: There is increasing evidence for the safety and advantages of low-pressure pneumoperitoneum facilitated by deep neuromuscular blockade (NMB). Nonetheless, there is a weak understanding of the relationship between clinical outcomes, surgical injury, postoperative immune dysfunction, and infectious complications. METHODS: Randomized controlled trial of 178 patients treated at standard-pressure pneumoperitoneum (12 mm Hg) with moderate NMB (train-of-four 1-2) or low pressure (8 mm Hg) facilitated by deep NMB (posttetanic count 1-2). The primary outcome was the quality of recovery (Quality of Recovery 40 questionnaire) on a postoperative day 1 (POD1). The primary outcome of the immune substudy (n=100) was ex vivo tumor necrosis factor α production capacity upon endotoxin stimulation on POD1. RESULTS: Quality of Recovery 40 score on POD1 was significantly higher at 167 versus 159 [mean difference (MD): 8.3 points; 95% confidence interval (CI): 2.5, 14.1; P =0.005] and the decline in cytokine production capacity was significantly less for tumor necrosis factor α and interleukin-6 (MD: -172 pg/mL; 95% CI: -316, -27; P =0.021 and MD: -1282 pg/mL; 95% CI: -2505, -59; P =0.040, respectively) for patients operated at low pressure. Low pressure was associated with reduced surgical site hypoxia and inflammation markers and circulating damage-associated molecular patterns, with a less impaired early postoperative ex vivo cytokine production capacity. At low pressure, patients reported lower acute pain scores and developed significantly less 30-day infectious complications. CONCLUSIONS: Low intra-abdominal pressure during laparoscopic colorectal surgery is safe, improves the postoperative quality of recovery and preserves innate immune homeostasis, and forms a valuable addition to future enhanced recovery after surgery programs.

Prehabilitation versus no prehabilitation to improve functional capacity, reduce postoperative complications and improve quality of life in colorectal cancer surgery.

BACKGROUND: Surgery is the cornerstone in curative treatment of colorectal cancer. Unfortunately, surgery itself can adversely affect patient health. 'Enhanced Recovery After Surgery' programmes, which include multimodal interventions, have improved patient outcomes substantially. However, these are mainly applied peri- and postoperatively. Multimodal prehabilitation includes multiple preoperative interventions to prepare patients for surgery with the aim of increasing resilience, thereby improving postoperative outcomes. OBJECTIVES: To determine the effects of multimodal prehabilitation programmes on functional capacity, postoperative complications, and quality of life in adult patients undergoing surgery for colorectal cancer. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and PsycINFO in January 2021. We also searched trial registries up to March 2021. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in adult patients with non-metastatic colorectal cancer, scheduled for surgery, comparing multimodal prehabilitation programmes (defined as comprising at least two preoperative interventions) with no prehabilitation. We focused on the following outcomes: functional capacity (i.e. 6-minute walk test, VO2peak, handgrip strength), postoperative outcomes (i.e. complications, mortality, length of hospital stay, emergency department visits, re-admissions), health-related quality of life, compliance, safety of prehabilitation, and return to normal activities. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies, extracted data, assessed risk of bias and used GRADE to assess the certainty of the evidence. Any disagreements were solved with discussion and consensus. We pooled data to perform meta-analyses, where possible. MAIN RESULTS: We included three RCTs that enrolled 250 participants with non-metastatic colorectal cancer, scheduled for elective (mainly laparoscopic) surgery. Included trials were conducted in tertiary care centres and recruited patients during periods ranging from 17 months to 45 months. A total of 130 participants enrolled in a preoperative four-week trimodal prehabilitation programme consisting of exercise, nutritional intervention, and anxiety reduction techniques. Outcomes of these participants were compared to those of 120 participants who started an identical but postoperative programme. Postoperatively, prehabilitation may improve functional capacity, determined with the 6-minute walk test at four and eight weeks (mean difference (MD) 26.02, 95% confidence interval (CI) -13.81 to 65.85; 2 studies; n = 131; and MD 26.58, 95% CI -8.88 to 62.04; 2 studies; n = 140); however, the certainty of evidence is low and very low, respectively, due to serious risk of bias, imprecision, and inconsistency. After prehabilitation, the functional capacity before surgery improved, with a clinically relevant mean difference of 24.91 metres (95% CI 11.24 to 38.57; 3 studies; n = 225). The certainty of evidence was moderate due to downgrading for serious risk of bias. Prehabilitation may also result in fewer complications (RR 0.95, 95% CI 0.70 to 1.29; 3 studies; n = 250) and fewer emergency department visits (RR 0.72, 95% CI 0.39 to 1.32; 3 studies; n = 250). The certainty of evidence was low due to downgrading for serious risk of bias and imprecision. On the other hand, prehabilitation may also result in a higher re-admission rate (RR 1.20, 95% CI 0.54 to 2.65; 3 studies; n = 250). The certainty of evidence was again low due to downgrading for risk of bias and imprecision. The effect on VO2peak, handgrip strength, length of hospital stay, mortality rate, health-related quality of life, return to normal activities, safety of the programme, and compliance rate could not be analysed quantitatively due to missing or insufficient data. The included studies did not report a difference between groups for health-related quality of life and length of hospital stay. Data on remaining outcomes were not reported or were reported inadequately in the included studies. AUTHORS' CONCLUSIONS: Prehabilitation may result in an improved functional capacity, determined with the 6-minute walk test both preoperatively and postoperatively. Complication rates and the number of emergency department visits postoperatively may also diminish due to a prehabilitation programme, while the number of re-admissions may be higher in the prehabilitation group. The certainty of evidence ranges from moderate to very low, due to downgrading for serious risk of bias, imprecision and inconsistency. In addition, only three heterogeneous studies were included in this review. Therefore, the findings of this review should be interpreted with caution. Numerous relevant RCTs are ongoing and will be included in a future update of this review.

Safety and economic analysis of selective histopathology following cholecystectomy: multicentre, prospective, cross-sectional FANCY study.

BACKGROUND: There is ongoing debate concerning the necessity of routine histopathological examination following cholecystectomy. In order to reduce the pathology workload and save costs, a selective approach has been suggested, but evidence regarding its oncological safety is lacking. METHODS: In this multicentre, prospective, cross-sectional study, all gallbladders removed for gallstone disease or cholecystitis were systematically examined by the surgeon for macroscopic abnormalities indicative of malignancy. Before sending all specimens to the pathologist, the surgeon judged whether histopathological examination was indicated. The main outcomes were the number of patients with hypothetically missed malignancy with clinical consequences (upper limit two-sided 95 per cent c.i. below 3:1000 considered oncologically safe) and potential cost savings of selective histopathological examination. RESULTS: Twenty-two (2.19:1000) of 10 041 specimens exhibited malignancy with clinical consequences. In case of a selective policy, surgeons would have held back 7846 of 10041 (78.1 per cent) gallbladders from histopathological examination. Malignancy with clinical consequences would have been missed in seven of 7846 patients (0.89:1000, upper limit 95% c.i. 1.40:1000). No patient benefitted from the clinical consequences, while two were harmed (futile additional surgery). Of 15 patients in whom malignancy with clinical consequences would have been diagnosed, one benefitted (residual disease radically removed), two potentially benefitted (palliative systemic therapy), and four experienced harm (futile additional surgery). Estimated cost savings established by replacing routine for selective histopathological examination were €703 500 per 10 000 patients. CONCLUSION: Selective histopathological examination following cholecystectomy is oncologically safe and could reduce pathology workload, costs, and futile re-resections.