Introduction: Textbook outcome (TO) is a composite outcome measure covering the surgical care process in a single outcome measure. TO has an advantage over single outcome parameters with low event... Show moreIntroduction: Textbook outcome (TO) is a composite outcome measure covering the surgical care process in a single outcome measure. TO has an advantage over single outcome parameters with low event rates, which have less discriminating impact to detect differences between hospitals. This study aimed to assess factors associated with TO, and evaluate hospital and network variation after case-mix correction in TO rates for liver surgery. Methods: This was a population-based retrospective study of all patients who underwent liver resection for malignancy in the Netherlands in 2019 and 2020. TO was defined as absence of severe postoperative complications, mortality, prolonged length of hospital stay, and readmission, and obtaining adequate resection margins. Multivariable logistic regression was used for case-mix adjustment. Results: 2376 patients were included. TO was accomplished in 1380 (80%) patients with colorectal liver metastases, in 192 (76%) patients with other liver metastases, in 183 (74%) patients with hepatocellular carcinoma and 86 (51%) patients with biliary cancers. Factors associated with lower TO rates for CRLM included ASA score >= 3 (aOR 0.70, CI 0.51-0.95 p = 0.02), extrahepatic disease (aOR 0.64, CI 0.44-0.95, p = 0.02), tumour size >55 mm on preoperative imaging (aOR 0.56, CI 0.34-0.94, p = 0.02), Charlson Comorbidity Index >= 2 (aOR 0.73, CI 0.54-0.98, p = 0.04), and major liver resection (aOR 0.50, CI 0.36-0.69, p < 0.001). After case-mix correction, no significant hospital or oncological network variation was observed. Conclusion: TO differs between indications for liver resection and can be used to assess between hospital and network differences. (c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
Bootsma, B.T.; Plat, V.D.; Brug, T. van de; Huisman, D.E.; Botti, M.; Boezem, P.B. van den; ... ; Dutch Pancreatic Canc Grp 2022
Background: Somatostatin analogues (SA) are currently used to prevent postoperative pancreatic fistula (POPF) development. However, its use is controversial. This study investigated the effect of... Show moreBackground: Somatostatin analogues (SA) are currently used to prevent postoperative pancreatic fistula (POPF) development. However, its use is controversial. This study investigated the effect of different SA protocols on the incidence of POPF after pancreatoduodenectomy in a nationwide population.Methods: All patients undergoing elective open pancreatoduodenectomy were included from the Dutch Pancreatic Cancer Audit (2014-2017). Patients were divided into six groups: no SA, octreotide, lanreotide, pasireotide, octreotide only in high-risk (HR) patients and lanreotide only in HR patients. Primary endpoint was POPF grade B/C. The updated alternative Fistula Risk Score was used to compare POPF rates across various risk scenarios.Results: 1992 patients were included. Overall POPF rate was 13.1%. Lanreotide (10.0%), octreotide-HR (9.4%) and no protocol (12.7%) POPF rates were lower compared to the other protocols (varying from 15.1 to 19.1%, p = 0.001) in crude analysis. Sub-analysis in patients with HR of POPF showed a significantly lower rate of POPF when treated with lanreotide (10.0%) compared to no protocol, octreotide and pasireotide protocol (21.6-26.9%, p = 0.006). Octreotide-HR and lanreotide-HR protocol POPF rates were comparable to lanreotide protocol, however not significantly different from the other protocols. Multi-variable regression analysis demonstrated lanreotide protocol to be positively associated with a low odds-ratio (OR) for POPF (OR 0.387, 95% CI 0.180-0.834, p = 0.015). In-hospital mortality rates were not affected.Conclusion: Use of lanreotide in all patients undergoing pancreatoduodenectomy has a potential protective effect on POPF development. Protocols for HR patients only might be favorable too. However, future studies are warranted to confirm these findings. (C) 2022 The Authors. Published by Elsevier B.V. on behalf of IAP and EPC. Show less
BACKGROUNDInfected necrotizing pancreatitis is a potentially lethal disease that is treated with the use of a step-up approach, with catheter drainage often delayed until the infected necrosis is... Show moreBACKGROUNDInfected necrotizing pancreatitis is a potentially lethal disease that is treated with the use of a step-up approach, with catheter drainage often delayed until the infected necrosis is encapsulated. Whether outcomes could be improved by earlier catheter drainage is unknown.METHODSWe conducted a multicenter, randomized superiority trial involving patients with infected necrotizing pancreatitis, in which we compared immediate drainage within 24 hours after randomization once infected necrosis was diagnosed with drainage that was postponed until the stage of walled-off necrosis was reached. The primary end point was the score on the Comprehensive Complication Index, which incorporates all complications over the course of 6 months of follow-up.RESULTSA total of 104 patients were randomly assigned to immediate drainage (55 patients) or postponed drainage (49 patients). The mean score on the Comprehensive Complication Index (scores range from 0 to 100, with higher scores indicating more severe complications) was 57 in the immediate-drainage group and 58 in the postponed-drainage group (mean difference, -1; 95% confidence interval [CI], -12 to 10; P=0.90). Mortality was 13% in the immediate-drainage group and 10% in the postponed-drainage group (relative risk, 1.25; 95% CI, 0.42 to 3.68). The mean number of interventions (catheter drainage and necrosectomy) was 4.4 in the immediate-drainage group and 2.6 in the postponed-drainage group (mean difference, 1.8; 95% CI, 0.6 to 3.0). In the postponed-drainage group, 19 patients (39%) were treated conservatively with antibiotics and did not require drainage; 17 of these patients survived. The incidence of adverse events was similar in the two groups.CONCLUSIONSThis trial did not show the superiority of immediate drainage over postponed drainage with regard to complications in patients with infected necrotizing pancreatitis. Patients randomly assigned to the postponed-drainage strategy received fewer invasive interventions. Show less
Background: Based on excellent outcomes from high-volume centres, laparoscopic liver resection is increasingly being adopted into nationwide practice which typically includes low-medium volume... Show moreBackground: Based on excellent outcomes from high-volume centres, laparoscopic liver resection is increasingly being adopted into nationwide practice which typically includes low-medium volume centres. It is unknown how the use and outcome of laparoscopic liver resection compare between high-volume centres and low-medium volume centres. This study aimed to compare use and outcome of laparoscopic liver resection in three leading European high-volume centres and nationwide practice in the Netherlands.Method: An international, retrospective multicentre cohort study including data from three European high-volume centres (Oslo, Southampton and Milan) and all 20 centres in the Netherlands performing laparoscopic liver resection (low-medium volume practice) from January 2011 to December 2016. A high-volume centre is defined as a centre performing >50 laparoscopic liver resections per year. Patients were retrospectively stratified into low, moderate- and high-risk Southampton difficulty score groups.Results: A total of 2425 patients were included (1540 high-volume; 885 low-medium volume). The median annual proportion of laparoscopic liver resection was 42.9 per cent in high-volume centres and 7.2 per cent in low-medium volume centres. Patients in the high-volume centres had a lower conversion rate (7.4 versus 13.1 per cent; P<0.001) with less intraoperative incidents (9.3 versus 14.6 per cent; P=0.002) as compared to low-medium volume centres. Whereas postoperative morbidity and mortality rates were similar in the two groups, a lower reintervention rate (5.1 versus 7.2 per cent; P=0.034) and a shorter postoperative hospital stay (3 versus 5 days; P<0.001) were observed in the high-volume centres as compared to the low-medium volume centres. In each Southampton difficulty score group, the conversion rate was lower and hospital stay shorter in high-volume centres. The rate of intraoperative incidents did not differ in the low-risk group, whilst in the moderate-risk and high-risk groups this rate was lower in high-volume centres (absolute difference 6.7 and 14.2 per cent; all P<0.004).Conclusion: High-volume expert centres had a sixfold higher use of laparoscopic liver resection, less conversions, and shorter hospital stay, as compared to a nationwide low-medium volume practice. Stratification into Southampton difficulty score risk groups identified some differences but largely outcomes appeared better for high-volume centres in each risk group. Show less
Background & Aims Hepatocellular adenomas (HCA) rarely occur in males, and if so, are frequently associated with malignant transformation. Guidelines are based on small numbers of patients and... Show moreBackground & Aims Hepatocellular adenomas (HCA) rarely occur in males, and if so, are frequently associated with malignant transformation. Guidelines are based on small numbers of patients and advise resection of HCA in male patients, irrespective of size or subtype. This nationwide retrospective cohort study is the largest series of HCA in men correlating (immuno)histopathological and molecular findings with the clinical course. Methods Dutch male patients with available histological slides with a (differential) diagnosis of HCA between 2000 and 2017 were identified through the Dutch Pathology Registry (PALGA). Histopathology and immunohistochemistry according to international guidelines were revised by two expert hepatopathologists. Next generation sequencing (NGS) was performed to confirm hepatocellular carcinoma (HCC) and/or subtype HCA. Final pathological diagnosis was correlated with recurrence, metastasis and death. Results A total of 66 patients from 26 centres fulfilling the inclusion criteria with a mean (+/- SD) age of 45.0 +/- 21.6 years were included. The diagnosis was changed after expert revision and NGS in 33 of the 66 patients (50%). After a median follow-up of 9.6 years, tumour-related mortality of patients with accessible clinical data was 1/18 (5.6%) in HCA, 5/14 (35.7%) in uncertain HCA/HCC and 4/9 (44.4%) in the HCC groups (P = .031). Four B-catenin mutated HCA were identified using NGS, which were not yet identified by immunohistochemistry and expert revision. Conclusions Expert revision with relevant immunohistochemistry may help the challenging but prognostically relevant distinction between HCA and well-differentiated HCC in male patients. NGS may be more important to subtype HCA than indicated in present guidelines. Show less
Background: Pancreatic neuroendocrine tumors (pNETs) have a high prevalence in patients with multiple endocrine neoplasia type 1 (MEN1) and are the leading cause of death. Tumor size is still... Show moreBackground: Pancreatic neuroendocrine tumors (pNETs) have a high prevalence in patients with multiple endocrine neoplasia type 1 (MEN1) and are the leading cause of death. Tumor size is still regarded as the main prognostic factor and therefore used for surgical decision-making. We assessed reliability and agreement of radiological and pathological tumor size in a population-based cohort of patients with MEN1-related pNETs. Methods: Patients were selected from the Dutch MEN1 database if they had undergone a resection for a pNET between 2003 and 2018. Radiological (MRI, CT, and endoscopic ultrasonography [EUS]) and pathological tumor size were collected from patient records. Measures of agreement (Bland-Altman plots with limits of agreement [LoA] and absolute agreement) and reliability (intraclass correlation coefficients [ICC] and unweighted kappa) were calculated for continuous and categorized (< or >= 2 cm) pNET size. Results: In 73 included patients, the median radiological and pathological tumor sizes measured were 22 (3-160) and 21 (4-200) mm, respectively. Mean bias between radiological and pathological tumor size was -0.2 mm and LoA ranged from -12.9 to 12.6 mm. For the subgroups of MRI, CT, and EUS, LoA of radiological and pathological tumor size ranged from -9.6 to 10.9, -15.9 to 15.8, and -13.9 to 11.0, respectively. ICCs for the overall cohort, MRI, CT, and EUS were 0.80, 0.86, 0.75, and 0.76, respectively. Based on the 2 cm criterion, agreement was 81.5%; hence, 12 patients (18.5%) were classified differently between imaging and pathology. Absolute agreement and kappa values of MRI, CT, and EUS were 88.6, 85.7, and 75.0%, and 0.77, 0.71, and 0.50, respectively. Conclusion: Within a population-based cohort, MEN1-related pNET size was not systematically over- or underestimated on preoperative imaging. Based on agreement and reliability measures, MRI is the preferred imaging modality. Show less
Background Little is known about complications after major duodenopancreatic surgery for duodenopancreatic neuroendocrine tumors (dpNETs) in multiple endocrine neoplasia type 1 (MEN1). Therefore,... Show moreBackground Little is known about complications after major duodenopancreatic surgery for duodenopancreatic neuroendocrine tumors (dpNETs) in multiple endocrine neoplasia type 1 (MEN1). Therefore, the incidence and severity of complications after major surgery for MEN1-related dpNETs were assessed. Methods Patients were selected from the population-based Dutch MEN1 database if they had undergone a Whipple procedure or total pancreatectomy from 2003 to 2017. Complications were graded according to the Clavien-Dindo classification (grade III or higher complications were considered a severe complication) and definitions from the International Study Group of Pancreatic Surgery. The Cumulative Complication Index (CCI(R)) was calculated as the sum of all complications weighted for their severity. Univariable logistic regression was performed to assess potential associations between predictor candidates and a severe complication. Results Twenty-seven patients (median age 43 years) underwent a major duodenopancreatic resection, including 14 Whipple procedures and 13 total pancreatectomies. Morbidity and mortality were 100% (27/27) and 4% (1/27), respectively. A severe complication occurred in 17/27 (63%) patients. The median CCI(R) was 47.8 [range 8.7-100]. Grade B/C pancreatic fistulas, delayed gastric emptying, bile leakage, hemorrhage, and chyle leakage occurred in 7/14 (50%), 10/27 (37%), 1/27 (4%), 7/27 (26%), 3/27 (11%) patients, respectively. Patients with a severe complication had longer operative time and higher blood loss. After Whipple, new-onset endocrine and exocrine insufficiency occurred in 1/13 and 9/14 patients, respectively. Conclusions Major duodenopancreatic surgery in MEN1 is associated with a very high risk of severe complications and cumulative burden of complications and should therefore be reserved for a select subgroup of patients with MEN1-related dpNETs. Show less
Background and Aims Patients with a choledochal malformation, formerly described as cysts, are at increased risk of developing a cholangiocarcinoma and resection is recommended. Given the low... Show moreBackground and Aims Patients with a choledochal malformation, formerly described as cysts, are at increased risk of developing a cholangiocarcinoma and resection is recommended. Given the low incidence of choledochal malformation (CM) in Western countries, the incidence in these countries is unclear. Our aim was to assess the incidence of malignancy in CM patients and to assess postoperative outcome. Methods In a nationwide, retrospective study, all adult patients who underwent surgery for CM between 1990 and 2016 were included. Patients were identified through the Dutch Pathology Registry and local patient records and were analysed to determine the incidence of malignancy, as well as postoperative mortality and morbidity. Results A total of 123 patients with a CM were included in the study (Todani Type I, n = 71; Type II, n = 10; Type III, n = 3; Type IV, n = 27; unknown, n = 12). Median age was 40 years (range 18-70) and 81% were female. The majority of patients (99/123) underwent extrahepatic bile duct resection, with additional liver parenchyma resections in eight patients, only exploration in two, and a local cyst resection in eight patients. Postoperative 30-day mortality was 2% (2/123) and limited to patients who underwent liver resection. Severe morbidity occurred in 24%. In 14 of the 123 patients (11%), a malignancy was found in the resected specimen. One patient developed a periampullary malignancy 7 years later. Conclusions In a large Western series of CM patients, 11% were found to have a malignancy. This justifies resection in these patients, despite the risk of morbidity (24%) and mortality (2%). Show less
Nieuwenhuizen, S.; Puijk, R.S.; Bemd, B. van den; Aldrighetti, L.; Arntz, M.; Boezem, P.B. van den; ... ; Meijerink, M.R. 2020
The guidelines for metastatic colorectal cancer crudely state that the best local treatment should be selected from a 'toolbox' of techniques according to patient- and treatment-related factors. We... Show moreThe guidelines for metastatic colorectal cancer crudely state that the best local treatment should be selected from a 'toolbox' of techniques according to patient- and treatment-related factors. We created an interdisciplinary, consensus-based algorithm with specific resectability and ablatability criteria for the treatment of colorectal liver metastases (CRLM). To pursue consensus, members of the multidisciplinary COLLISION and COLDFIRE trial expert panel employed the RAND appropriateness method (RAM). Statements regarding patient, disease, tumor and treatment characteristics were categorized as appropriate, equipoise or inappropriate. Patients with ECOG <= 2, ASA <= 3 and Charlson comorbidity index <= 8 should be considered fit for curative-intent local therapy. When easily resectable and/or ablatable (stage IVa), (neo)adjuvant systemic therapy is not indicated. When requiring major hepatectomy (stage IVb), neo-adjuvant systemic therapy is appropriate for early metachronous disease and to reduce procedural risk. To downstage patients (stage IVc), downsizing induction systemic therapy and/or future remnant augmentation is advised. Disease can only be deemed permanently unsuitable for local therapy if downstaging failed (stage IVd). Liver resection remains the gold standard. Thermal ablation is reserved for unresectable CRLM, deep-seated resectable CRLM and can be considered when patients are in poor health. Irreversible electroporation and stereotactic body radiotherapy can be considered for unresectable perihilar and perivascular CRLM 0-5cm. This consensus document provides per-patient and per-tumor resectability and ablatability criteria for the treatment of CRLM. These criteria are intended to aid tumor board discussions, improve consistency when designing prospective trials and advance intersociety communications. Areas where consensus is lacking warrant future comparative studies. Show less
Background Conditional survival is the survival probability after already surviving a predefined time period. This may be informative during follow-up, especially when adjusted for tumor... Show moreBackground Conditional survival is the survival probability after already surviving a predefined time period. This may be informative during follow-up, especially when adjusted for tumor characteristics. Such prediction models for patients with resected pancreatic cancer are lacking and therefore conditional survival was assessed and a nomogram predicting 5-year survival at a predefined period after resection of pancreatic cancer was developed. Methods This population-based study included patients with resected pancreatic ductal adenocarcinoma from the Netherlands Cancer Registry (2005-2016). Conditional survival was calculated as the median, and the probability of surviving up to 8 years in patients who already survived 0-5 years after resection was calculated using the Kaplan-Meier method. A prediction model was constructed. Results Overall, 3082 patients were included, with a median age of 67 years. Median overall survival was 18 months (95% confidence interval 17-18 months), with a 5-year survival of 15%. The 1-year conditional survival (i.e. probability of surviving the next year) increased from 55 to 74 to 86% at 1, 3, and 5 years after surgery, respectively, while the median overall survival increased from 15 to 40 to 64 months at 1, 3, and 5 years after surgery, respectively. The prediction model demonstrated that the probability of achieving 5-year survival at 1 year after surgery varied from 1 to 58% depending on patient and tumor characteristics. Conclusions This population-based study showed that 1-year conditional survival was 55% 1 year after resection and 74% 3 years after resection in patients with pancreatic cancer. The prediction model is available via to inform patients and caregivers. Show less
Background: While most of the evidence on minimally invasive liver surgery (MILS) is derived from expert centers, nationwide outcomes remain underreported. This study aimed to evaluate the... Show moreBackground: While most of the evidence on minimally invasive liver surgery (MILS) is derived from expert centers, nationwide outcomes remain underreported. This study aimed to evaluate the implementation and outcome of MILS on a nationwide scale.Methods: Electronic patient files were reviewed in all Dutch liver surgery centers and all patients undergoing MILS between 2011 and 2016 were selected. Operative outcomes were stratified based on extent of the resection and annual MILS volume.Results: Overall, 6951 liver resections were included, with a median annual volume of 50 resections per center. The overall use of MILS was 13% (n = 916), which varied from 3% to 36% (P < 0.001) between centers. The nationwide use of MILS increased from 6% in 2011 to 23% in 2016 (P < 0.001). Outcomes of minor MILS were comparable with international studies (conversion 0- 13%, mortality <1%). In centers which performed >= 20 MILS annually, major MILS was associated with less conversions (14 (11%) versus 41 (30%), P < 0.001), shorter operating time (184 (117- 239) versus 200 (139-308) minutes, P = 0.010), and less overall complications (37 (30%) versus 58 (42%), P = 0.040).Conclusion: The nationwide use of MILS is increasing, although large variation remains between centers. Outcomes of major MILS are better in centers with higher volumes. Show less
