Risk Factor Targeted Perioperative Care Reduces Anastomotic Leakage after Colorectal Surgery: The DoubleCheck study.

OBJECTIVE: The DoubleCheck study aimed to introduce pre- and perioperative interventions minimizing exposure to modifiable risk factors and determine its effect on CAL. SUMMARY BACKGROUND DATA: Colorectal anastomotic leakage (CAL) is a severe complication. In order to predict and prevent its occurrence, the LekCheck study identified intraoperative modifiable risk factors for CAL: anemia, hyperglycemia, hypothermia, incorrect timing of antibiotic prophylaxis, administration of vasopressors and epidural analgesia. METHODS: This international open-labelled interventional study was performed between September 2021 and December 2023. An enhanced care bundle consisting of anemia correction, glucose measurement, attaining normothermia, antibiotics administration within 60 to 15 minutes preoperatively, refraining from vasopressors and epidural analgesia was introduced. Primary outcome was the occurrence of intraoperative risk factors just prior to the anastomosis creation. Secondary outcomes were CAL and mortality. Univariate and multivariate regression analysis were performed to establish the relationship between the enhanced care bundle, exposure to the six factors and CAL. RESULTS: The historical LekCheck group consisted of 1572 patients versus 902 in the DoubleCheck. The LekCheck group had a mean of 1.84 risk factors versus 1.63 in DoubleCheck ( P <0.001). In the DoubleCheck significantly less patients had ≥3 risk factors ( P <0.001). CAL was significantly lower in the DoubleCheck group (8.6% vs. 6.2%, P =0.039). The reduction of CAL was associated with the enhanced care bundle in multivariate regression analysis (OR 1.521, 95% CI 1.01-2.29, P =0.045). The mortality rate did not differ significantly (1.3%, vs. 0.8%, P =0.237). CONCLUSIONS: The DoubleCheck study showed that optimization of modifiable risk factors reduced CAL in colorectal surgery.

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.

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.

Improved survival prediction and comparison of prognostic models for patients with hepatocellular carcinoma treated with sorafenib.

BACKGROUND: The 'Prediction Of Survival in Advanced Sorafenib-treated HCC' (PROSASH) model addressed the heterogeneous survival of patients with hepatocellular carcinoma (HCC) treated with sorafenib in clinical trials but requires validation in daily clinical practice. This study aimed to validate, compare and optimize this model for survival prediction. METHODS: Patients treated with sorafenib for HCC at five tertiary European centres were retrospectively staged according to the PROSASH model. In addition, the optimized PROSASH-II model was developed using the data of four centres (training set) and tested in an independent dataset. These models for overall survival (OS) were then compared with existing prognostic models. RESULTS: The PROSASH model was validated in 445 patients, showing clear differences between the four risk groups (OS 16.9-4.6 months). A total of 920 patients (n = 615 in training set, n = 305 in validation set) were available to develop PROSASH-II. This optimized model incorporated fewer and less subjective parameters: the serum albumin, bilirubin and alpha-foetoprotein, and macrovascular invasion, extrahepatic spread and largest tumour size on imaging. Both PROSASH and PROSASH-II showed improved discrimination (C-index 0.62 and 0.63, respectively) compared with existing prognostic scores (C-index ≤0.59). CONCLUSIONS: In HCC patients treated with sorafenib, individualized prediction of survival and risk group stratification using baseline prognostic and predictive parameters with the PROSASH model was validated. The refined PROSASH-II model performed at least as good with fewer and more objective parameters. PROSASH-II can be used as a tool for tailored treatment of HCC in daily practice and to define pre-planned subgroups for future studies.

The impact of imaging on the surgical management of biliary cystadenomas and cystadenocarcinomas; a systematic review.

BACKGROUND: Biliary Cystadenomas (BCA) are considered to be benign but may transform to Biliary Cystadenocarcinomas (BCAC). The aim of this systematic review was to assess the diagnostic work-up and necessity of complete surgical resection. METHOD: A systematic literature search was performed in Embase.com, Medline (Ovid), Cochrane Central, Web-of-Science and Google Scholar. Articles reporting on diagnostic work-up or outcome of various treatment strategies were included. RESULTS: Fifty-one articles with 1218 patients were included: 971 with BCA and 247 with BCAC. Patients with BCA were more often female (91% vs 63.8%, p < 0.001). On radiologic imaging BCAC more often had calcifications (p = 0.008), mural nodules (p < 0.001) and wall enhancement (p < 0.001). Reported treatment strategies were resection, enucleation, or fenestration/marsupialization. Recurrence was reported in 5.4% after resection for BCA and 4.8% after resection for BCAC. Recurrence after fenestration/marsupialization varied from 81.6% to 100% for both BCA as BCAC. Mortality rate was 0 in patients with BCA and 24% in BCAC. CONCLUSION: Due to the difficulty in accurately diagnosing these biliary cystic lesions and the availability of different surgical approaches, patients with suspected BCA or BCAC should be treated in a center specialized in liver surgery with state-of-the-art imaging and all surgical techniques to prevent mismanagement of this rare disease.

Are we SHARP enough? The importance of adequate patient selection in sorafenib treatment for hepatocellular carcinoma.

BACKGROUND: Upon FDA/EMEA registration for hepatocellular carcinoma (HCC), sorafenib received a broader therapeutic indication than the eligibility criteria of the landmark SHARP trial. This allowed treatment of SHARP non-eligible patients in daily clinical practice. AIM: To assess sorafenib efficacy and safety in SHARP eligible and non-eligible patients, and determine the validity of the current therapeutic indication as described by the FDA/EMEA. PATIENTS AND METHODS: Consecutive patients treated with sorafenib for advanced HCC at two Dutch tertiary referral centers between 2007 and 2016 were analyzed retrospectively. Primary outcome was overall survival (OS). Secondary outcomes were time to progression (TTP), response rate, adverse events and reasons for discontinuation. Outcomes were compared between SHARP eligible and non-eligible patients. RESULTS: One hundred and ninety-three of 257 (75%) patients were SHARP eligible. SHARP eligible patients (9.5 months, 95% CI 7.7-11.3) had a longer median OS than non-eligible patients (5.4 months, 95% CI 3.6-7.1) (log-rank p < .001). SHARP non-eligible patients were more often Child-Pugh B, had higher AST and ALT levels and developed more grade 3-4 liver dysfunction (44 versus 23%, p < .001) during treatment. SHARP ineligibility remained the strongest predictor of OS (HR 1.78, 95% CI 1.32-2.41) and an independent predictor of TTP (HR 1.45, 95% CI 1.05-2.00) in multivariable analysis. CONCLUSIONS: Landmark trial outcomes of sorafenib for HCC are reproducible in daily practice, provided that the SHARP eligibility criteria are respected. Based on the findings of this and previous studies, sorafenib usage should be restricted to Child-Pugh A patients.

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.

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.

Multimodal prehabilitation in patients with non-small cell lung cancer: a feasibility study.

Background: Anatomic pulmonary resection is the preferred curative treatment in operable non-small cell lung cancer (NSCLC) but is associated with postoperative complications and inevitable compromise in functional capacity. Preoperative enhancement of functional capacity can be achieved with prehabilitation, yet the window of opportunity in NSCLC patients is small because patients are required to undergo surgery within 3 weeks from diagnosis. The goal of this study was to assess the feasibility of a prehabilitation programme in NSCLC within a 3-week timeframe and its effect on functional capacity-although the study was not powered to confirm improvements in functional capacity. Methods: Prehabilitation consisted of six interventions: exercise programme, nutritional support, mental support, smoking cessation, patient empowerment, and optimisation of respiratory status and was executed in two large teaching hospitals in the Netherlands. Assessments were scheduled at baseline (T0), end of program preoperatively (T1), and 6 weeks postoperatively (T2). Feasibility was defined as ≥80% of participants completing ≥80% of the programme. Functional capacity [6-minute walk test (6MWT), steep ramp test (SRT), one repetition maximum (1RM), maximal inspiratory pressure (MIP), and hand grip strength (HGS)] was evaluated on T1 and T2 compared to T0 using mixed model analyses. Results: In total, 24 patients were included. In 95.8% of patients, the program proved feasible and preoperative functional capacity significantly improved in all pre-specified tests on T1. 1RM sustained improved at T2. Conclusions: Multimodal prehabilitation for lung surgery is feasible within a timeframe of 3 weeks. Even though this study was not powered to confirm it, prehabilitation may improve preoperative functional capacity.

Are we on the right track in DBS surgery for dystonic head tremor? Polymyography is a promising answer.

The clinical benefit of Deep Brain Stimulation (DBS) is associated with electrode positioning accuracy. Intraoperative assessment of clinical effect is therefore key. Evaluating this clinical effect in patients with dystonic head tremor, as opposed to limb tremor, is challenging because the head is fixed in a stereotactic frame. To clinically assess head tremor during surgery, surface electromyography (EMG) electrodes were bilaterally applied to the sternocleidomastoid and cervical paraspinal muscles. This case shows that intraoperative polymyography is an easy and useful tool to assess the clinical effect of DBS electrode positioning.

Body Composition Is an Independent Predictor of Outcome in Patients with Hepatocellular Carcinoma Treated with Sorafenib.

BACKGROUND: Previous studies have suggested body composition as a predictor of sorafenib toxicity and outcome in patients with advanced hepatocellular carcinoma (HCC). Large studies on the impact of body composition parameters in European HCC patients are lacking. Our aim was to validate the prognostic value of body composition parameters in Dutch patients with HCC treated with sorafenib. PATIENTS AND METHODS: A retrospective analysis was performed in a cohort of HCC patients treated with sorafenib at two Dutch tertiary referral centers between 2007 and 2016. Body composition (adipose and skeletal muscle tissue) was measured at baseline by computed tomography (CT). Low skeletal muscle mass (SMM) and density were defined using published cut-offs. Body composition parameters were correlated with overall survival (OS), time to progression, response rate, and toxicity. RESULTS: A total of 278 patients were included, mostly Child-Pugh class A (85%) and Barcelona Clinic Liver Cancer (BCLC) stage C (73%), with a median OS of 9.5 months (95% CI 8.1-11.0). Patients with combined low SMM and low total adipose tissue index (TATI) (n = 68, 25%) had a poor median OS (5.8, 95% CI 4.8-6.8) compared with other patients (11.7, 95% CI 9.4-14.0). Combined low SMM and low TATI remained an independent predictor of OS (HR 1.56, 95% CI 1.15-2.11, p = 0.004) after adjusting for known prognostic factors. There was no association between body composition and sorafenib toxicity. CONCLUSIONS: In Dutch HCC patients treated with sorafenib, the combined presence of low SMM and low TATI was associated with impaired survival, independent of known prognostic factors. CT assessment of body composition may provide additional prognostic information prior to sorafenib treatment.

Survival after Resection of Multiple Tumor Foci of Intrahepatic Cholangiocarcinoma.

BACKGROUND: Multiple tumor foci of intrahepatic cholangiocarcinoma (ICC) are often considered a contra-indication for resection. We sought to define long-term outcomes after resection of ICC in patients with multiple foci. METHODS: Patients who underwent resection for ICC between 1990 and 2017 were identified from 12 major HPB centers. Outcomes of patients with solitary lesions, multiple lesions (ML), and oligometastases (OM) were compared. OM were defined as extrahepatic metastases spread to a single organ. RESULTS: One thousand thirteen patients underwent resection of ICC. On final pathology, 185 patients (18.4%) had ML and 27 (2.7%) had OM. Median survival of patients with a solitary tumor was 43.2 months, while the median survival of patients with 2 tumors was 21.2 months; the median survival of patients with 3 or more tumors was 15.3 months (p < 0.001). Five-year survival was 43.3%, 28.0%, and 8.6%, respectively. The median survival of patients without OM was 37.8 months versus 14.9 months among patients with OM (p < 0.001); estimated 5-year survival was 39.3% and 10.6%, respectively. In multivariable analysis, the presence of two lesions was not an independent poor prognostic factor for OS (HR 1.19; 95%CI 0.90-1.57; p = 0.229). However, the presence of three or more tumors was an independent poor prognostic factor for OS (HR 1.97; 95%CI 1.48-2.64; p < 0.001). CONCLUSION: Resection of multiple liver tumors for patients with ICC did not preclude 5-year survival: in particular, estimated 5-year OS for resection of two tumors was 28.0%.