Population-based study on practice variation regarding preoperative systemic chemotherapy in patients with colorectal liver metastases and impact on short-term outcomes

Introduction: Definitions regarding resectability and hence indications for preoperative chemotherapy vary. Use of preoperative chemotherapy may influence postoperative outcomes. This study aimed to assess the variation in use of preoperative chemotherapy for CRLM and related postoperative outcomes in the Netherlands. Materials and methods: All patients who underwent liver resection for CRLM in the Netherlands between 2014 and 2018 were included from a national database. Case-mix factors contributing to the use of preoperative chemotherapy, hospital variation and postoperative outcomes were assessed using multivariable logistic regression. Postoperative outcomes were postoperative complicated course (PCC), 30-day morbidity and 30-day mortality. Results: In total, 4469 patients were included of whom 1314 patients received preoperative chemotherapy and 3155 patients did not. Patients receiving chemotherapy were significantly younger (mean age (+SD) 66.3 (10.4) versus 63.2 (10.2) p < 0.001) and had less comorbidity (Charlson scores 2+ (24% versus 29%, p = 0.010). Unadjusted hospital variation concerning administration of preoperative chemotherapy ranged between 2% and 55%. After adjusting for case-mix factors, three hospitals administered significantly more preoperative chemotherapy than expected and six administered significantly less preoperative chemotherapy than expected. PCC was 12.1%, 30-day morbidity was 8.8% and 30-day mortality was 1.5%. No association between preoperative chemotherapy and PCC (OR 1.24, 0.98–1.55, p = 0.065), 30-day morbidity (OR 1.05, 0.81–1.39, p = 0.703) or with 30-day mortality (OR 1.22, 0.75–2.09, p = 0.467) was found. Conclusion: Significant hospital variation in the use of preoperative chemotherapy for CRLM was present in the Netherlands. No association between postoperative outcomes and use of preoperative chemotherapy was found

Hospital variation and outcomes of simultaneous resection of primary colorectal tumour and liver metastases:a population-based study

BACKGROUND: The optimal treatment sequence for patients with synchronous colorectal liver metastases (CRLM) remains uncertain. This study aimed to assess factors associated with the use of simultaneous resections and impact on hospital variation. METHOD: This population-based study included all patients who underwent liver surgery for synchronous colorectal liver metastases between 2014 and 2019 in the Netherlands. Factors associated with simultaneous resection were identified. Short-term surgical outcomes of simultaneous resections and factors associated with 30-day major morbidity were evaluated. RESULTS: Of 2146 patients included, 589 (27%) underwent simultaneous resection in 28 hospitals. Simultaneous resection was associated with age, sex, BMI, number, size and bilobar distribution of CRLM, and administration of preoperative chemotherapy. More minimally invasive and minor resections were performed in the simultaneous group. Hospital variation was present (range 2.4%-83.3%) with several hospitals performing simultaneous procedures more and less frequently than expected. Simultaneous resection resulted in 13% 30-day major morbidity, and 1% mortality. ASA classification ≥3 was independently associated with higher 30-day major morbidity after simultaneous resection (aOR 1.97, CI 1.10-3.42, p = 0.018). CONCLUSION: Distinctive patient and tumour characteristics influence the choice for simultaneous resection. Remarkable hospital variation is present in the Netherlands

Case-mix adjustment to compare nationwide hospital performances after resection of colorectal liver metastases

Background: Differences in patient demographics and disease burden can influence comparison of hospital performances. This study aimed to provide a case-mix model to compare short-term postoperative outcomes for patients undergoing liver resection for colorectal liver metastases (CRLM). Methods: This retrospective, population-based study included all patients who underwent liver resection for CRLM between 2014 and 2018 in the Netherlands. Variation in case-mix variables between hospitals and influence on postoperative outcomes was assessed using multivariable logistic regression. Primary outcomes were 30-day major morbidity and 30-day mortality. Validation of results was performed on the data from 2019. Results: In total, 4639 patients were included in 28 hospitals. Major morbidity was 6.2% and mortality was 1.4%. Uncorrected major morbidity ranged from 3.3% to 13.7% and mortality ranged from 0.0% to 5.0%. between hospitals. Significant differences between hospitals were observed for age higher than 80 (0.0%-17.1%, p <0.001), ASA 3 or higher (3.3%-36.3%, p <0.001), histopathological parenchymal liver disease (0.0%-47.1%, p <0.001), history of liver resection (8.1%-36.3%, p <0.001), major liver resection (6.7%-38.0%, p <0.001) and synchronous metastases (35.5%-62.1%, p <0.001). Expected 30-day major morbidity between hospitals ranged from 6.4% to 11.9% and expected 30-day mortality ranged from 0.6% to 2.9%. After case-mix correction no significant outliers concerning major morbidity and mortality remained. Validation on patients who underwent liver resection for CRLM in 2019 affirmed these outcomes. Conclusion: Case-mix adjustment is a prerequisite to allow for institutional comparison of short-term postoperative outcomes after liver resection for CRLM. (C) 2020 University Medical Center Groningen. Published by Elsevier Ltd

A randomized controlled trial of eplerenone in asymptomatic phospholamban p.Arg14del carriers

INTRODUCTION Phospholamban (PLN; p.Arg14del) cardiomyopathy is an inherited disease caused by the pathogenic p.Arg14del variant in the PLN gene. Clinically, it is characterized by malignant ventricular arrhythmias and progressive heart failure.1,2 Cardiac fibrotic tissue remodelling occurs early on in PLN p.Arg14del carriers.3,4 Eplerenone was deemed a treatment candidate because of its beneficial effects on ventricular remodelling and antifibrotic properties.5,6 We conducted the multicentre randomized trial ‘intervention in PHOspholamban RElated CArdiomyopathy STudy’ (i-PHORECAST) to assess whether treatment with eplerenone of asymptomatic PLN p.Arg14del carriers attenuates disease onset and progression

Nationwide oncological networks for resection of colorectal liver metastases in the Netherlands:Differences and postoperative outcomes

INTRODUCTION: Widespread differences in patient demographics and disease burden between hospitals for resection of colorectal liver metastases (CRLM) have been described. In the Netherlands, networks consisting of at least one tertiary referral centre and several regional hospitals have been established to optimize treatment and outcomes. The aim of this study was to assess variation in case-mix, and outcomes between these networks. METHODS: This was a population-based study including all patients who underwent CRLM resection in the Netherlands between 2014 and 2019. Variation in case-mix and outcomes between seven networks covering the whole country was evaluated. Differences in case-mix, expected 30-day major morbidity (Clavien-Dindo ≥3a) and 30-day mortality between networks were assessed. RESULTS: In total 5383 patients were included. Thirty-day major morbidity was 5.7% and 30-day mortality was 1.5%. Significant differences between networks were observed for Charlson Comorbidity Index, ASA 3+, previous liver resection, liver disease, preoperative MRI, preoperative chemotherapy, ≥3 CRLM, diameter of largest CRLM ≥55 mm, major resection, combined resection and ablation, rectal primary tumour, bilobar and extrahepatic disease. Uncorrected 30-day major morbidity ranged between 3.3% and 13.1% for hospitals, 30-day mortality ranged between 0.0% and 4.5%. Uncorrected 30-day major morbidity ranged between 4.4% and 6.0% for networks, 30-day mortality ranged between 0.0% and 2.5%. No negative outliers were observed after case-mix correction. CONCLUSION: Variation in case-mix and outcomes are considerably smaller on a network level as compared to a hospital level. Therefore, auditing is more meaningful at a network level and collaboration of hospitals within networks should be pursued

A randomized controlled trial of eplerenone in asymptomatic phospholamban p.Arg14del carriers

Phospholamban (PLN; p.Arg14del) cardiomyopathy is an inherited disease caused by the pathogenic p.Arg14del variant in the PLN gene. Clinically, it is characterized by malignant ventricular arrhythmias and progressive heart failure.1,2 Cardiac fibrotic tissue remodelling occurs early on in PLN p.Arg14del carriers.3,4 Eplerenone was deemed a treatment candidate because of its beneficial effects on ventricular remodelling and antifibrotic properties.5,6 We conducted the multicentre randomized trial ‘intervention in PHOspholamban RElated CArdiomyopathy STudy’ (i-PHORECAST) to assess whether treatment with eplerenone of asymptomatic PLN p.Arg14del carriers attenuates disease onset and progression

Evaluation of the 2021 ESC recommendations for family screening in hereditary transthyretin cardiac amyloidosis

AIMS: The 2021 European Society of Cardiology (ESC) screening recommendations for individuals carrying a pathogenic transthyretin amyloidosis variant (ATTRv) are based on expert opinion. We aimed to (i) determine the penetrance of ATTRv cardiomyopathy (ATTRv-CM) at baseline; (ii) examine the value of serial evaluation; and (iii) establish the yield of first-line diagnostic tests (i.e. electrocardiogram, echocardiogram, and laboratory tests) as per 2021 ESC position statement.METHODS AND RESULTS: We included 159 relatives (median age 55.6 [43.2-65.9] years, 52% male) at risk for ATTRv-CM from 10 centres. The primary endpoint, ATTRv-CM diagnosis, was defined as the presence of (i) cardiac tracer uptake in bone scintigraphy; or (ii) transthyretin-positive cardiac biopsy. The secondary endpoint was a composite of heart failure (New York Heart Association class ≥II) and pacemaker-requiring conduction disorders. At baseline, 40/159 (25%) relatives were diagnosed with ATTRv-CM. Of those, 20 (50%) met the secondary endpoint. Indication to screen (≤10 years prior to predicted disease onset and absence of extracardiac amyloidosis) had an excellent negative predictive value (97%). Other pre-screening predictors for ATTRv-CM were infrequently identified variants and male sex. Importantly, 13% of relatives with ATTRv-CM did not show any signs of cardiac involvement on first-line diagnostic tests. The yield of serial evaluation (n = 41 relatives; follow-up 3.1 [2.2-5.2] years) at 3-year interval was 9.4%.CONCLUSIONS: Screening according to the 2021 ESC position statement performs well in daily clinical practice. Clinicians should adhere to repeating bone scintigraphy after 3 years, as progressing to ATTRv-CM without signs of ATTRv-CM on first-line diagnostic tests or symptoms is common.</p

A nationwide assessment of hepatocellular adenoma resection:Indications and pathological discordance

Hepatocellular adenomas (HCAs) are benign liver tumors associated with bleeding or malignant transformation. Data on the indication for surgery are scarce. We analyzed indications and outcome of patients operated for HCAs 50 mm (52%), suspicion of (pre)malignancy (28%), and (previous) bleeding (5.1%). No difference was observed in HCA-subtype distribution between small and large tumors. Ninety-six (43%) patients had a postoperative change in diagnosis. Independent risk factors for change in diagnosis were tumor size <50 mm (adjusted odds ratio [aOR], 3.4; p < 0.01), male sex (aOR, 3.7; p = 0.03), and lack of hepatobiliary contrast-enhanced magnetic resonance imaging (CE-MRI) (aOR, 1.8; p = 0.04). Resection for small (suspected) HCAs was mainly indicated by suspicion of (pre)malignancy, whereas for large (suspected) HCAs, tumor size was the most prevalent indication. Male sex, tumor size <50 mm, and lack of hepatobiliary CE-MRI were independent risk factors for postoperative change in tumor diagnosis

Rebanding for slippage after gastric banding: should we do it?

Laparoscopic adjustable gastric banding (LAGB) is a commonly performed bariatric procedure. LAGB is frequently complicated by slippage. Possible treatment for slippage is rebanding, but long-term effects are unknown. The aim of this study was to investigate whether rebanding after gastric band slippage is associated with weight loss failure. This was a post hoc analysis of a prospectively collected database of 627 consecutive LAGB patients. Rebanding for slippage was performed in 81 patients. The effect of rebanding on weight loss was evaluated by three analyses: (1) in 81 rebanded patients, weight loss was compared before and after rebanding, separately for patients in whom primary LAGB was successful or unsuccessful; (2) 81 rebanded patients were matched to 81 patients without slippage for prognostic variables and compared for weight loss after rebanding; (3) multivariate logistic regression was performed whether rebanding was independently associated with weight loss failure. The chance of a fair result of rebanding for patients following primary successful (n = 34) and unsuccessful LAGB (n = 22) was 62 and 27 % after median follow-up of 113 and 97 months, respectively. There was no difference in weight loss failure between 81 rebanded patients and 81 matched patients: 54 vs 59 % (P = 0.43). In multivariate analysis, rebanding was not significantly associated with weight loss failure: adjusted odds ratio 1.42; 95 % confidence interval 0.85-2.38; P = 0.18. In general, rebanding after LAGB has no negative effect on weight loss. However, patients in whom LAGB was unsuccessful prior to rebanding have poor long-term weight loss result

Parenchymal transection in robotic liver resection: results of 70 resections using the Vessel Sealer

Aim: There is no standard technique for transection of the hepatic parenchyma during robotic liver resection. The aim of this study was to describe the outcomes of robotic liver resections using the Vessel Sealer for parenchymal transection.Methods: This is a post hoc analysis of a prospective database. All consecutive patients who underwent robotic liver resection in the Regional Academic Cancer Centre, Utrecht, Netherlands, between August 2015 and January 2019 were included.Results: A total of 70 robotic liver resections were performed, including 60 minor resections (86%) and ten hemihepatectomies (14%). Five procedures (7%) were converted. Mean parenchymal transection time was 43 ± 26 min. Median blood loss was 150 mL (interquartile range 40-300). Ten patients (14%) suffered from a major complication, and three patients (4%) had bile leakage postoperatively. One patient died from post-hepatectomy liver failure.Conclusion: Based on the results of this series, consisting of 60 minor liver resections and 10 hemihepatectomies, we conclude that the use of the Vessel Sealer during the parenchymal transection in liver resection is feasible and safe