Publications by authors named "Otto M van Delden"

105 Publications

Liver Decompensation as Late Complication in HCC Patients with Long-Term Response following Selective Internal Radiation Therapy.

Cancers (Basel) 2021 Oct 29;13(21). Epub 2021 Oct 29.

Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.

Selective internal radiation therapy (SIRT) is used as a treatment for hepatocellular carcinoma (HCC). The aim of this study was to assess long-term liver-related complications of SIRT in patients who had not developed radioembolization-induced liver disease (REILD). The primary outcome was the percentage of patients without REILD that developed Child-Pugh (CP) ≥ B7 liver decompensation after SIRT. The secondary outcomes were overall survival (OS) and tumor response. These data were compared with a matched cohort of patients treated with sorafenib. Eighty-five patients were included, of whom 16 developed REILD. Of the remaining 69 patients, 38 developed liver decompensation CP ≥ B7. The median OS was 18 months. In patients without REILD, the median OS in patients with CP ≥ B7 was significantly shorter compared to those without CP ≥ B7; 16 vs. 31 months. In the case-matched analysis, the median OS was significantly longer in SIRT-treated patients; 16 vs. 8 months in sorafenib. Liver decompensation CP ≥ B7 occurred significantly more in SIRT when compared to sorafenib; 62% vs. 27%. The ALBI score was an independent predictor of liver decompensation (OR 0.07) and OS (HR 2.83). After SIRT, liver decompensation CP ≥ B7 often developed as a late complication in HCC patients and was associated with a shorter OS. The ALBI score was predictive of CP ≥ B7 liver decompensation and the OS, and this may be a valuable marker for patient selection for SIRT.
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http://dx.doi.org/10.3390/cancers13215427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8582376PMC
October 2021

Biliopancreatic and biliary leak after pancreatoduodenectomy treated by percutaneous transhepatic biliary drainage.

HPB (Oxford) 2021 Sep 6. Epub 2021 Sep 6.

Department of Hepato-Pancreato-Biliary Surgery, Regional Academic Cancer Center Utrecht, St. Antonius Hospital Nieuwegein and University Medical Center Utrecht, the Netherlands. Electronic address:

Background: Complementary to percutaneous intra-abdominal drainage, percutaneous transhepatic biliary drainage (PTBD) might ameliorate healing of pancreatic fistula and biliary leakage after pancreatoduodenectomy by diversion of bile from the site of leakage. This study evaluated technical and clinical outcomes of PTBD for this indication.

Methods: All patients undergoing PTBD for leakage after pancreatoduodenectomy were retrospectively evaluated in two tertiary pancreatic centers (2014-2019). Technical success was defined as external biliary drainage. Clinical success was defined as discharge with a resolved leak, without additional surgical interventions for anastomotic leakage other than percutaneous intra-abdominal drainage.

Results: Following 822 pancreatoduodenectomies, 65 patients (8%) underwent PTBD. Indications were leakage of the pancreaticojejunostomy (n = 25; 38%), hepaticojejunostomy (n = 15; 23%) and of both (n = 25; 38%). PTBD was technically successful in 64 patients (98%) with drain revision in 40 patients (63%). Clinical success occurred in 60 patients (94%). Leakage resolved after median 33 days (IQR 21-60). PTBD related complications occurred in 23 patients (35%), including cholangitis (n = 14; 21%), hemobilia (n = 7; 11%) and PTBD related bleeding requiring re-intervention (n = 4; 6%). In hospital mortality was 3% (n = 2).

Conclusion: Although drain revisions and complications are common, PTBD is highly feasible and appears to be effective in the treatment of biliopancreatic leakage after pancreatoduodenectomy.
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http://dx.doi.org/10.1016/j.hpb.2021.08.941DOI Listing
September 2021

Survival Benefit of Repeat Local Treatment in Patients Suffering From Early Recurrence of Colorectal Cancer Liver Metastases.

Clin Colorectal Cancer 2021 12 26;20(4):e263-e272. Epub 2021 Jul 26.

Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Surgery, Cancer Center Amsterdam, Amsterdam, the Netherlands.

Background: A uniform treatment strategy for patients suffering from early recurrence after local treatment of CRLM is currently lacking. The aim of this observational cohort study was to assess the potential survival benefit of repeat local treatment compared to systemic therapy in patients suffering from early recurrence of CRLM.

Patients And Methods: Patients who developed recurrent CRLM within 12 months after initial local treatment with curative intent were retrospectively identified in Amsterdam University Medical Centers between 2009-2019. Differences in overall and progression-free survival among treatment strategies were assessed using multivariable Cox regression analyses.

Results: A total of 135 patients were included. Median overall survival of 41 months [range 4-135] was observed in patients who received repeat local treatment, consisting of upfront or repeat local treatment after neoadjuvant systemic therapy, compared to 24 months [range 1-55] in patients subjected to systemic therapy alone (adjusted HR = 0.42 [95%-CI: 0.25-0.72]; P = .002). Prolonged progression-free survival was observed after neoadjuvant systemic therapy followed by repeat local treatment, as compared to upfront repeat local treatment in patients with recurrent CRLM within 4 months following initial local treatment of CRLM (adjusted HR = 0.36 [95%-CI: 0.15-0.86]; P = .021).

Conclusion: Patients with early recurrence of CRLM should be considered for repeat local treatment strategies. A multimodality approach, consisting of neoadjuvant systemic therapy followed by repeat local treatment, appeared favorable in patients with recurrence within 4 months following initial local treatment of CRLM.
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http://dx.doi.org/10.1016/j.clcc.2021.07.007DOI Listing
December 2021

Liver function after combined selective internal radiation therapy or sorafenib monotherapy in advanced hepatocellular carcinoma.

J Hepatol 2021 12 27;75(6):1387-1396. Epub 2021 Aug 27.

Liver Unit and HPB Oncology Area, Clinica Universidad de Navarra-IDISNA and CIBEREHD, Pamplona, Spain.

Background & Aims: SORAMIC is a previously published randomised controlled trial assessing survival in patients with advanced hepatocellular carcinoma who received sorafenib with or without selective internal radiation therapy (SIRT). Based on the per-protocol (PP) population, we assessed whether the outcome of patients receiving SIRT+sorafenib vs. sorafenib alone was affected by adverse effects of SIRT on liver function.

Methods: The PP population consisted of 109 (SIRT+sorafenib) vs. 173 patients (sorafenib alone). Comparisons were made between subgroups who achieved a significant survival benefit or trend towards improved survival with SIRT and the inverse group without a survival benefit: <65 years-old vs. ≥65 years-old, Child-Pugh 5 vs. 6, no transarterial chemoembolisation (TACE) vs. prior TACE, no cirrhosis vs. cirrhosis, non-alcohol- vs. alcohol-related aetiology. The albumin-bilirubin (ALBI) score was used to monitor liver function over time during follow-up.

Results: ALBI scores increased in all patient groups during follow-up. In the PP population, ALBI score increases were higher in the SIRT+sorafenib than the sorafenib arm (p = 0.0021 month 4, p <0.0001 from month 6). SIRT+sorafenib conferred a survival benefit compared to sorafenib alone in patients aged <65 years-old, those without cirrhosis, those with Child-Pugh 5, and those who had not received TACE. A higher increase in ALBI score was observed in the inverse subgroups in whom survival was not improved by adding SIRT (age ≥65 years-old, p <0.05; cirrhosis, p = 0.07; Child-Pugh 6, p <0.05; prior TACE, p = 0.08).

Conclusion: SIRT frequently has a negative, often subclinical, effect on liver function in patients with hepatocellular carcinoma, which may impair prognosis after treatment. Careful patient selection for SIRT as well as prevention of clinical and subclinical liver damage by selective treatments, high tumour uptake ratio, and medical prophylaxis could translate into better efficacy.

Clinical Trial Number: EudraCT 2009-012576-27, NCT01126645 LAY SUMMARY: This study of treatments in patients with hepatocellular carcinoma found that selective internal radiation therapy (SIRT) has an adverse effect on liver function that may affect patient outcomes. Patients should be carefully selected before they undergo SIRT and the treatment technique should be optimised for maximum protection of non-target liver parenchyma.
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http://dx.doi.org/10.1016/j.jhep.2021.07.037DOI Listing
December 2021

Assessment of Imaging Modalities Against Liver Biopsy in Nonalcoholic Fatty Liver Disease: The Amsterdam NAFLD-NASH Cohort.

J Magn Reson Imaging 2021 12 15;54(6):1937-1949. Epub 2021 May 15.

Department of Internal and Vascular Medicine, Amsterdam University Medical Centres, Amsterdam, The Netherlands.

Background: Noninvasive diagnostic methods are urgently required in disease stratification and monitoring in nonalcoholic fatty liver disease (NAFLD). Multiparametric magnetic resonance imaging (MRI) is a promising technique to assess hepatic steatosis, inflammation, and fibrosis, potentially enabling noninvasive identification of individuals with active and advanced stages of NAFLD.

Purpose: To examine the diagnostic performance of multiparametric MRI for the assessment of disease severity along the NAFLD disease spectrum with comparison to histological scores.

Study Type: Prospective, cohort.

Population: Thirty-seven patients with NAFLD.

Field Strength/sequence: Multiparametric MRI at 3.0 T consisted of magnetic resonance (MR) spectroscopy (MRS) with multi-echo stimulated-echo acquisition mode, magnitude-based and three-point Dixon using a two-dimensional multi-echo gradient echo, MR elastography (MRE) using a generalized multishot gradient-recalled echo sequence and intravoxel incoherent motion (IVIM) using a multislice diffusion weighted single-shot echo-planar sequence.

Assessment: Histological steatosis grades were compared to proton density fat fraction measured by MRS (PDFF ), magnitude-based MRI (PDFF ), and three-point Dixon (PDFF ), as well as FibroScan® controlled attenuation parameter (CAP). Fibrosis and disease activity were compared to IVIM and MRE. FibroScan® liver stiffness measurements were compared to fibrosis levels. Diagnostic performance of all imaging parameters was determined for distinction between simple steatosis and nonalcoholic steatohepatitis (NASH).

Statistical Tests: Spearman's rank test, Kruskal-Wallis test, Dunn's post-hoc test with Holm-Bonferroni P-value adjustment, receiver operating characteristic curve analysis. A P-value <0.05 was considered statistically significant.

Results: Histological steatosis grade correlated significantly with PDFF (r  = 0.66, P < 0.001), PDFF (r  = 0.68, P < 0.001), and PDFF (r  = 0.67, P < 0.001), whereas no correlation was found with CAP. MRE and IVIM diffusion and perfusion significantly correlated with disease activity (r  = 0.55, P < 0.001, r  = -0.40, P = 0.016, r  = -0.37, P = 0.027, respectively) and fibrosis (r  = 0.55, P < 0.001, r  = -0.46, P = 0.0051; r  = -0.53, P < 0.001, respectively). MRE and IVIM diffusion had the highest area-under-the-curve for distinction between simple steatosis and NASH (0.79 and 0.73, respectively).

Data Conclusion: Multiparametric MRI is a promising method for noninvasive, accurate, and sensitive distinction between simple hepatic steatosis and NASH, as well as for the assessment of steatosis and fibrosis severity.

Level Of Evidence: 2 TECHNICAL EFFICACY: 2.
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http://dx.doi.org/10.1002/jmri.27703DOI Listing
December 2021

Short- and long-term outcomes after hemihepatectomy for perihilar cholangiocarcinoma: does left or right side matter?

Hepatobiliary Surg Nutr 2021 Apr;10(2):154-162

Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, The Netherlands.

Background: The only potentially curative option for patients with perihilar cholangiocarcinoma (PHC) is resection, typically an extrahepatic bile duct resection in combination with (extended) liver resection. Complications such as bile leakage and liver failure have been suggested to be more common after right-sided resections compared to left-sided resections, whilst superior oncological outcomes have been reported after right-sided resections. However, data on outcomes after right-sided or left-sided liver resections in PHC are scarce. Therefore, we aimed to investigate short- and long-term outcomes after left and right hemihepatectomy in patients with PHC.

Methods: In this retrospective study, patients undergoing major liver resection for suspected PHC in a tertiary center between 2000-2018 were included. Patients who had undergone left-sided resections were compared to patients with right-sided resections in terms of complications (90-day mortality, overall and severe morbidity and specific complications). For long-term outcomes, only patients with pathologically proven PHC were included in the survival analysis.

Results: A total of 178 patients undergoing hemihepatectomy for suspected PHC were analysed, including 76 left-sided and 102 right-sided resections. Overall 90-day mortality was 14% (24 out of 178), with no significant difference after left-sided resection (11%; 8 out of 76) versus right-sided resection (16%; 16 out of 102) (P=0.319). Severe morbidity (Clavein Dindo ≥3) was also comparable in both groups: 54% versus 61% (P=0.361). No differences in specific complications including bile leakage were observed, although liver failure appeared to occur more frequently after right hemihepatectomy (22% versus 11%, P=0.052). Five-year overall survival for pathologically proven PHC, excluding in-hospital mortality, did not differ; 43.7% after left-sided resection . and 38.2% after right-sided resection (P=0.553).

Conclusions: Both short- and long-term outcomes between patients undergoing left and right hemihepatectomy for PHC were comparable. Post-hepatectomy liver failure was more common after right-sided resection.
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http://dx.doi.org/10.21037/hbsn-19-948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050564PMC
April 2021

Occurrence of seeding metastases in resectable perihilar cholangiocarcinoma and the role of low-dose radiotherapy to prevent this.

World J Hepatol 2020 Nov;12(11):1089-1097

Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam 1105 AZ, Netherlands.

Background: Preoperative biliary drainage in patients with presumed resectable perihilar cholangiocarcinoma (PHC) is hypothesized to promote the occurrence of seeding metastases. Seeding metastases can occur at the surgical scars or at the site of postoperative drains, and in case of percutaneous biliary drainage, at the catheter port-site. To prevent seeding metastases after resection, we routinely treated PHC patients with preoperative radiotherapy (RT) for over 25 years until January 2018.

Aim: To investigate the incidence of seeding metastases following resection of PHC.

Methods: All patients who underwent resection for pathology proven PHC between January 2000 and March 2019 were included in this retrospective study. Between 2000-January 2018, patients received preoperative RT (3 × 3.5 Gray). RT was omitted in patients treated after January 2018.

Results: A total of 171 patients underwent resection for PHC between January 2000 and March 2019. Of 171 patients undergoing resection, 111 patients (65%) were treated with preoperative RT. Intraoperative bile cytology showed no difference in the presence of viable tumor cells in bile of patients undergoing preoperative RT or not. Overall, two patients (1.2%) with seeding metastases were identified, both in the laparotomy scar and both after preoperative RT (one patient with endoscopic and the other with percutaneous and endoscopic biliary drainage).

Conclusion: The incidence of seeding metastases in patients with resected PHC in our series was low (1.2%). This low incidence and the inability of providing evidence that preoperative low-dose RT prevents seeding metastases, has led us to discontinue preoperative RT in patients with resectable PHC in our center.
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http://dx.doi.org/10.4254/wjh.v12.i11.1089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7701958PMC
November 2020

Hospital variation in combined liver resection and thermal ablation for colorectal liver metastases and impact on short-term postoperative outcomes: a nationwide population-based study.

HPB (Oxford) 2021 06 18;23(6):827-839. Epub 2020 Nov 18.

Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, the Netherlands.

Background: Combining resection and thermal ablation can improve short-term postoperative outcomes in patients with colorectal liver metastases (CRLM). This study assessed nationwide hospital variation and short-term postoperative outcomes after combined resection and ablation.

Methods: In this population-based study, all CRLM patients who underwent resection in the Netherlands between 2014 and 2018 were included. After propensity score matching for age, ASA-score, Charlson-score, diameter of largest CRLM, number of CRLM and earlier resection, postoperative outcomes were compared. Postoperative complicated course (PCC) was defined as discharge after 14 days or a major complication or death within 30 days of surgery.

Results: Of 4639 included patients, 3697 (80%) underwent resection and 942 (20%) resection and ablation. Unadjusted percentage of patients who underwent resection and ablation per hospital ranged between 4 and 44%. Hospital variation persisted after case-mix correction. After matching, 734 patients remained in each group. Hospital stay (median 6 vs. 7 days, p = 0.011), PCC (11% vs. 14.7%, p = 0.043) and 30-day mortality (0.7% vs. 2.3%, p = 0.018) were lower in the resection and ablation group. Differences faded in multivariable logistic regression due to inclusion of major hepatectomy.

Conclusion: Significant hospital variation was observed in the Netherlands. Short-term postoperative outcomes were better after combined resection and ablation, attributed to avoiding complications associated with major hepatectomy.
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http://dx.doi.org/10.1016/j.hpb.2020.10.003DOI Listing
June 2021

Trans-Arterial Embolization for Liver Hemangiomas: It's a New Dawn; It's a New Day; It's a New Life?

Cardiovasc Intervent Radiol 2021 01 17;44(1):92-94. Epub 2020 Nov 17.

Department of Interventional Radiology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

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http://dx.doi.org/10.1007/s00270-020-02707-yDOI Listing
January 2021

Systematic review on percutaneous aspiration and sclerotherapy versus surgery in symptomatic simple hepatic cysts.

HPB (Oxford) 2021 01 20;23(1):11-24. Epub 2020 Aug 20.

Department of Surgery, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC, University of Amsterdam, the Netherlands. Electronic address:

Background: Simple hepatic cysts (SHC) may cause pain and bloating and thus impair quality of life. Whereas current guidelines recommend laparoscopic cyst deroofing, percutaneous aspiration and sclerotherapy (PAS) may be used as a less invasive alternative. This review aimed to assess the efficacy of PAS and surgical management in patients with symptomatic SHC.

Methods: A systematic search in PubMed and Embase was performed according to PRISMA-guidelines. Studies reporting symptoms were included. Methodological quality was assessed by the MINORS-tool. Primary outcomes were symptom relief, symptomatic recurrence and quality of life, for which a meta-analysis of proportions was performed.

Results: In total, 736 patients from 34 studies were included of whom 265 (36%) underwent PAS, 348 (47%) laparoscopic cyst deroofing, and 123 (17%) open surgical management. During weighted mean follow-up of 26.1, 38.2 and 21.3 months, symptoms persisted in 3.5%, 2.1%, 4.2%, for PAS, laparoscopic and open surgical management, respectively. Major complication rates were 0.8%, 1.7%, and 2.4% and cyst recurrence rates were 0.0%, 5.6%, and 7.7%, respectively.

Conclusion: Outcomes of PAS for symptomatic SHC appear to be excellent. Studies including a step-up approach which reserves laparoscopic cyst deroofing for symptomatic recurrence after one or two PAS procedures are needed.
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http://dx.doi.org/10.1016/j.hpb.2020.07.005DOI Listing
January 2021

The utility of 99mTc-mebrofenin hepatobiliary scintigraphy with SPECT/CT for selective internal radiation therapy in hepatocellular carcinoma.

Nucl Med Commun 2020 Aug;41(8):740-749

Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centres, University of Amsterdam, Meibergdreef 9.

Background: Studies assessing the impact of selective internal radiation therapy (SIRT) on the regional liver function in patients with hepatocellular carcinoma (HCC) are sparse. This study assessed the changes in total and regional liver function using hepatobiliary scintigraphy (HBS) and investigated the utility of HBS to predict post-SIRT liver dysfunction.

Methods: Patients treated with SIRT for HCC between 2011 and 2019, underwent Tc-mebrofenin HBS with single-photon emission computed tomography/computed tomography (SPECT/CT) before and 6 weeks after SIRT. The corrected mebrofenin uptake rate (cMUR) and corresponding volume was measured in the total liver, and in treated and nontreated liver regions. Patients with and without post-SIRT liver dysfunction were compared.

Results: A total of 29 patients, all Child-Pugh-A and mostly intermediate (72%) stage HCC were included in this study. Due to SIRT, the cMURtotal declined from 5.8 to 4.5%/min/m (P < 0.001). Twenty-two patients underwent a lobar SIRT, which induced a decline in cMUR (2.9-1.7%/min/m, P < 0.001) and volume (1228-1101, P = 0.002) of the treated liver region, without a change in cMUR (2.4-2.0%/min/m, P = 0.808) or volume (632-644 mL, P = 0.661) of the contralateral nontreated lobe. There were no significant pre-SIRT differences in total or regional cMUR or volume between patients with and without post-SIRT liver dysfunction.

Conclusion: In patients treated with SIRT for HCC, HBS accurately identified changes in total and regional liver function and may have a complementary role to personalize lobar or selective SIRT. In this pilot study, there were no pre-SIRT differences in cMUR or volume to aid in predicting post-SIRT liver dysfunction.
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http://dx.doi.org/10.1097/MNM.0000000000001224DOI Listing
August 2020

Renal biopsies performed before versus during ablation of T1 renal tumors: implications for prevention of overtreatment and follow-up.

Abdom Radiol (NY) 2021 01 20;46(1):373-379. Epub 2020 Jun 20.

Department of Urology, OLVG, Oosterpark 9, 1091 AC, Amsterdam, The Netherlands.

Purpose: To assess the difference between renal mass biopsy (RMB) performed either before or during the ablation procedure.

Methods: A retrospective multicenter study was performed in patients with a cT1 renal mass treated with ablation between January 2007 and July 2019, including a search in the national pathology database for patients with a RMB planned for ablation. Patient and tumor characteristics and information on malignant, benign, and non-diagnostic biopsy results were collected to establish rates of overtreatment and number of ablations avoided in case of benign or non-diagnostic histology.

Results: RMB was performed in 714 patients, of which 231 patients received biopsy before planned ablation, and 483 patients at the time of ablation. Pathology results before ablation were malignant in 63% (145/231), benign in 20% (46/231) and non-diagnostic in 17% (40/231). Pathology results at the time of ablation were malignant in 67.5% (326/483), benign in 16.8% (81/483) and non-diagnostic in 15.7% (76/483), leading to a total of 32.5% of ablation of benign or non-diagnostic lesions. Of the patients with a benign biopsy obtained before ablation, 80.4% (37/46) chose not to undergo ablation. Patients with inconclusive biopsy before planned ablation chose an informed individualized approach including ablation, repeated biopsy, or no intervention in 56%, 34% and 10%.

Conclusion: This study emphasizes the importance of obtaining a biopsy prior to the ablation procedure in a separate session to lower the rate of potentially unnecessary ablations.
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http://dx.doi.org/10.1007/s00261-020-02613-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864836PMC
January 2021

Care after pancreatic resection according to an algorithm for early detection and minimally invasive management of pancreatic fistula versus current practice (PORSCH-trial): design and rationale of a nationwide stepped-wedge cluster-randomized trial.

Trials 2020 May 7;21(1):389. Epub 2020 May 7.

Department of Surgery, Regional Academic Cancer Center Utrecht, St. Antonius Hospital and University Medical Center Utrecht, PO Box 85500, Utrecht, 3508, GA, The Netherlands.

Background: Pancreatic resection is a major abdominal operation with 50% risk of postoperative complications. A common complication is pancreatic fistula, which may have severe clinical consequences such as postoperative bleeding, organ failure and death. The objective of this study is to investigate whether implementation of an algorithm for early detection and minimally invasive management of pancreatic fistula may improve outcomes after pancreatic resection.

Methods: This is a nationwide stepped-wedge, cluster-randomized, superiority trial, designed in adherence to the Consolidated Standards of Reporting Trials (CONSORT) guidelines. During a period of 22 months, all Dutch centers performing pancreatic surgery will cross over in a randomized order from current practice to best practice according to the algorithm. This evidence-based and consensus-based algorithm will provide daily multilevel advice on the management of patients after pancreatic resection (i.e. indication for abdominal imaging, antibiotic treatment, percutaneous drainage and removal of abdominal drains). The algorithm is designed to aid early detection and minimally invasive step-up management of postoperative pancreatic fistula. Outcomes of current practice will be compared with outcomes after implementation of the algorithm. The primary outcome is a composite of major complications (i.e. post-pancreatectomy bleeding, new-onset organ failure and death) and will be measured in a sample size of at least 1600 patients undergoing pancreatic resection. Secondary endpoints include the individual components of the primary endpoint and other clinical outcomes, healthcare resource utilization and costs analysis. Follow up will be up to 90 days after pancreatic resection.

Discussion: It is hypothesized that a structured nationwide implementation of a dedicated algorithm for early detection and minimally invasive step-up management of postoperative pancreatic fistula will reduce the risk of major complications and death after pancreatic resection, as compared to current practice.

Trial Registration: Netherlands Trial Register: NL 6671. Registered on 16 December 2017.
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http://dx.doi.org/10.1186/s13063-020-4167-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7206814PMC
May 2020

The value of sorafenib trough levels in patients with advanced hepatocellular carcinoma - a substudy of the SORAMIC trial.

Acta Oncol 2020 Sep 5;59(9):1028-1035. Epub 2020 May 5.

Department of Medical Oncology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.

: Sorafenib for advanced hepatocellular carcinoma (HCC) is dose adjusted by toxicity. Preliminary studies have suggested an association between plasma concentrations of sorafenib and its main metabolite (M2) and clinical outcomes. This study aimed to validate these findings and establish target values for sorafenib trough concentrations. Patients with advanced HCC were prospectively recruited within a multicenter phase II study (SORAMIC). Patients with blood samples available at trough level were included for this pharmacokinetic (PK) substudy. Trough plasma concentrations of sorafenib and its main metabolite (M2) were associated with sorafenib-related toxicity and overall survival (OS).: Seventy-four patients were included with a median OS of 19.7 months (95% CI 16.1-23.3). Patients received sorafenib for a median of 51 weeks (IQR 27-62) and blood samples were drawn after a median of 25 weeks (IQR 10-42). Patients had a median trough concentration of 3217 ng/ml (IQR 2166-4526) and 360 ng/ml (IQR 190-593) with coefficients of variation of 65% and 146% for sorafenib and M2, respectively. Patients who experienced severe sorafenib-related toxicity received a lower average daily dose (551 vs 730 mg/day,  = .003), but showed no significant differences in sorafenib (3298 vs 2915 ng/ml,  = .442) or M2 trough levels (428 vs 283 ng/ml,  = .159). Trough levels of sorafenib or M2 showed no significant association with OS. In patients with advanced HCC treated with sorafenib, the administered dose, trough levels of sorafenib or M2, and clinical outcomes were poorly correlated. Toxicity-adjusted dosing remains the standard for sorafenib treatment.
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http://dx.doi.org/10.1080/0284186X.2020.1759826DOI Listing
September 2020

Prediction of Survival Among Patients Receiving Transarterial Chemoembolization for Hepatocellular Carcinoma: A Response-Based Approach.

Hepatology 2020 07 27;72(1):198-212. Epub 2020 May 27.

Department of Internal Medicine and Gastroenterology, Klinikum Klagenfurt am Wörthersee, Klagenfurt, Austria.

Background And Aims: The heterogeneity of intermediate-stage hepatocellular carcinoma (HCC) and the widespread use of transarterial chemoembolization (TACE) outside recommended guidelines have encouraged the development of scoring systems that predict patient survival. The aim of this study was to build and validate statistical models that offer individualized patient survival prediction using response to TACE as a variable.

Approach And Results: Clinically relevant baseline parameters were collected for 4,621 patients with HCC treated with TACE at 19 centers in 11 countries. In some of the centers, radiological responses (as assessed by modified Response Evaluation Criteria in Solid Tumors [mRECIST]) were also accrued. The data set was divided into a training set, an internal validation set, and two external validation sets. A pre-TACE model ("Pre-TACE-Predict") and a post-TACE model ("Post-TACE-Predict") that included response were built. The performance of the models in predicting overall survival (OS) was compared with existing ones. The median OS was 19.9 months. The factors influencing survival were tumor number and size, alpha-fetoprotein, albumin, bilirubin, vascular invasion, cause, and response as assessed by mRECIST. The proposed models showed superior predictive accuracy compared with existing models (the hepatoma arterial embolization prognostic score and its various modifications) and allowed for patient stratification into four distinct risk categories whose median OS ranged from 7 months to more than 4 years.

Conclusions: A TACE-specific and extensively validated model based on routinely available clinical features and response after first TACE permitted patient-level prognostication.
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http://dx.doi.org/10.1002/hep.31022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496334PMC
July 2020

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

Liver Cancer 2019 Jul 2;8(4):255-270. Epub 2018 Nov 2.

Cancer Center Amsterdam, Amsterdam, The Netherlands.

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) ( = 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, = 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.
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http://dx.doi.org/10.1159/000493586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6738194PMC
July 2019

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

Liver Int 2020 01 18;40(1):215-228. Epub 2019 Nov 18.

Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK.

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.
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http://dx.doi.org/10.1111/liv.14270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6973249PMC
January 2020

Circulating tumor DNA quantity is related to tumor volume and both predict survival in metastatic pancreatic ductal adenocarcinoma.

Int J Cancer 2020 03 13;146(5):1445-1456. Epub 2019 Aug 13.

Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Circulating tumor DNA (ctDNA) is assumed to reflect tumor burden and has been suggested as a tool for prognostication and follow-up in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). However, the prognostic value of ctDNA and its relation with tumor burden has yet to be substantiated, especially in mPDAC. In this retrospective analysis of prospectively collected samples, cell-free DNA from plasma samples of 58 treatment-naive mPDAC patients was isolated and sequenced using a custom-made pancreatobiliary NGS panel. Pathogenic mutations were detected in 26/58 (44.8%) samples. Cross-check with droplet digital PCR showed good agreement in Bland-Altman analysis (p = 0.217, nonsignificance indicating good agreement). In patients with liver metastases, ctDNA was more frequently detected (24/37, p < 0.001). Tumor volume (3D reconstructions from imaging) and ctDNA variant allele frequency (VAF) were correlated (Spearman's ρ = 0.544, p < 0.001). Median overall survival (OS) was 3.2 (95% confidence interval [CI] 1.6-4.9) versus 8.4 (95% CI 1.6-15.1) months in patients with detectable versus undetectable ctDNA (p = 0.005). Both ctDNA VAF and tumor volume independently predicted OS after adjustment for carbohydrate antigen 19.9 and treatment regimen (hazard ratio [HR] 1.05, 95% CI 1.01-1.09, p = 0.005; HR 1.00, 95% CI 1.01-1.05, p = 0.003). In conclusion, our study showed that ctDNA detection rates are higher in patients with larger tumor volume and liver metastases. Nevertheless, measurements may diverge and, thus, can provide complementary information. Both ctDNA VAF and tumor volume were strong predictors of OS.
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http://dx.doi.org/10.1002/ijc.32586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004068PMC
March 2020

Diffusion-weighted imaging of hepatocellular carcinoma before and after transarterial chemoembolization: role in survival prediction and response evaluation.

Abdom Radiol (NY) 2019 08;44(8):2740-2750

Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, NL, The Netherlands.

Background: Survival outcomes of patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) are heterogeneous. Measuring the apparent diffusion coefficient (ADC) using diffusion-weighted imaging (DWI) may improve overall survival prediction.

Aim: To assess the value of measuring the ADC before and after TACE in predicting overall survival.

Methods: A retrospective analysis was performed in HCC patients treated with TACE at a tertiary referral center between 2008 and 2017. The ADC values and changes in ADC value (ΔADC) of HCC lesions (≥ 1 cm) and liver parenchyma were assessed by DWI ≤ 3 months before and after first TACE. Pre- and post-TACE ADC values were compared with tumor response according to mRECIST and correlated with overall survival (OS) in a univariable and multivariable Cox-regression analysis.

Results: A total of 89 patients were included, mostly Child-Pugh A (85%) and BCLC stage B (53%) with a median OS of 21.7 months (95% CI 17.6-25.9). Tumor ADC increased from 1081 mm/s before (IQR 964-1225) to 1328 mm/s (IQR 1197-1560) after TACE (p < 0.001). Responders according to mRECIST showed a higher ΔADC after first TACE than non-responders (26 vs. 14%, p = 0.048). Pre-TACE ADC and ΔADC were not significantly associated with OS in both univariable and multivariable analysis, whereas response according to mRECIST remained an independent predictor of OS.

Conclusion: mRECIST was confirmed as an independent prognostic factor of OS, but pre- or post-TACE ADC measurements were not. Response according to mRECIST was associated with a higher increase in ADC than non-response.
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http://dx.doi.org/10.1007/s00261-019-02030-2DOI Listing
August 2019

Chemoradiation induces epithelial-to-mesenchymal transition in esophageal adenocarcinoma.

Int J Cancer 2019 11 7;145(10):2792-2803. Epub 2019 May 7.

Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Multimodality treatment has advanced the outcome of esophageal adenocarcinoma (EAC), but overall survival remains poor. Therapeutic pressure activates effective resistance mechanisms and we characterized these mechanisms in response to the currently used neoadjuvant treatment against EAC: carboplatin, paclitaxel and radiotherapy. We developed an in vitro approximation of this regimen and applied it to primary patient-derived cultures. We observed a heterogeneous epithelial-to-mesenchymal (EMT) response to the high therapeutic pressure exerted by chemoradiation. We found EMT to be initiated by the autocrine production and response to transforming growth factor beta (TGF-β) of EAC cells. Inhibition of TGF-β ligands effectively abolished chemoradiation-induced EMT. Assessment of TGF-β serum levels in EAC patients revealed that high levels after neoadjuvant treatment predicted the presence of fluorodeoxyglucose uptake in lymph nodes on the post-chemoradiation positron emission tomography-scan. Our study shows that chemoradiation contributes to resistant metastatic disease in EAC patients by inducing EMT via autocrine TGF-β production. Monitoring TGF-β serum levels during treatment could identify those patients at risk of developing metastatic disease, and who would likely benefit from TGF-β targeting therapy.
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http://dx.doi.org/10.1002/ijc.32364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6767775PMC
November 2019

Added value of intra-operative ultrasound to determine the resectability of locally advanced pancreatic cancer following FOLFIRINOX chemotherapy (IMAGE): a prospective multicenter study.

HPB (Oxford) 2019 10 19;21(10):1385-1392. Epub 2019 Apr 19.

Department of Radiology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, the Netherlands. Electronic address:

Background: Determining the resectability of locally advanced pancreatic cancer (LAPC) after FOLFIRINOX chemotherapy is challenging because CT-scans cannot reliably assess vascular involvement. This study evaluates the added value of intra-operative ultrasound (IOUS) in LAPC following FOLFIRINOX induction chemotherapy.

Methods: Prospective multicenter study in patients with LAPC who underwent explorative laparotomy with IOUS after FOLFIRINOX chemotherapy. Resectability was defined according to the National Comprehensive Cancer Network guidelines. IOUS findings were compared with preoperative CT-scans and pathology results.

Results: CT-staging in 38 patients with LAPC after FOLFIRINOX chemotherapy defined 22 patients LAPC, 15 borderline resectable and one resectable. IOUS defined 19 patients LAPC, 13 borderline resectable and six resectable. In 12/38 patients, IOUS changed the resectability status including five patients from borderline resectable to resectable and five patients from LAPC to borderline resectable. Two patients were upstaged from borderline resectable to LAPC. Tumor diameters were significantly smaller upon IOUS (31.7 ± 9.5 mm versus 37.1 ± 10.0 mm, p = 0.001) and resectability varied significantly (p = 0.043). Ultimately, 20 patients underwent resection of whom 14 were evaluated as (borderline) resectable on CT-scan, and 17 on IOUS.

Discussion: This prospective study demonstrates that IOUS may change the resectability status up to a third of patients with LAPC following FOLFIRINOX chemotherapy.
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http://dx.doi.org/10.1016/j.hpb.2019.02.017DOI Listing
October 2019

A Pilot Study on Hepatobiliary Scintigraphy to Monitor Regional Liver Function in Y Radioembolization.

J Nucl Med 2019 10 6;60(10):1430-1436. Epub 2019 Apr 6.

Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.

Radioembolization is increasingly used as a bridge to resection (i.e., radiation lobectomy). It combines ipsilateral tumor control with the induction of contralateral hypertrophy to facilitate lobar resection. The aim of this pilot study was to investigate the complementary value of hepatobiliary scintigraphy (HBS) before and after radioembolization in the assessment of the future remnant liver. Consecutive patients with liver tumors who underwent HBS before and after Y radioembolization were included. Regional (treated/nontreated) and whole liver function and volume were determined on HBS and CT. Changes in regional liver function and volume were correlated with the functional liver absorbed doses, determined on Y PET/CT. In addition, the correlation between liver volume and function change was evaluated. Thirteen patients (10 hepatocellular carcinoma, 3 metastatic colorectal carcinoma) were included. Liver function of the treated part declined after radioembolization (HBS-pre, 4.0%/min/m; HBS-post, 1.9%/min/m; = 0.001), whereas the function of the nontreated part increased (HBS-pre, 1.4%/min/m; HBS-post, 2.8%/min/m; = 0.009). Likewise, treated volume decreased (pretreatment, 1,118.7 cm; posttreatment, 870.7 cm; = 0.003), whereas the nontreated volume increased (pretreatment, 412.7 cm; posttreatment, 577.6 cm; = 0.005). Bland-Altman analysis revealed a large bias (29%) between volume decrease and function decrease in the treated part and wide limits of agreement (-7.7%-65.6%). The bias between volume and function change was smaller (±6.0%) in the nontreated part of the liver, but limits of agreement were still wide (-117.9%-106.7%). Radioembolization induces regional changes in liver function that are accurately detected by HBS. Limits of agreement between function and volume changes were wide, showing large individual differences. This finding indicates that HBS may have a complementary role in the management of patients for radiation lobectomy.
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http://dx.doi.org/10.2967/jnumed.118.224394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6785787PMC
October 2019

Transarterial (Chemo-)Embolization and Lipiodolization for Hepatic Haemangioma.

Cardiovasc Intervent Radiol 2019 Jun 19;42(6):800-811. Epub 2019 Feb 19.

Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Background: Transarterial (chemo-)embolization/lipiodolization (TAE/TAL) might be an attractive minimally invasive alternative to surgery in the treatment of symptomatic hepatic haemangioma. This review assesses the efficacy and safety of TAE/TAL as primary treatment for symptomatic hepatic haemangioma.

Methods: A systematic search of the literature was performed by two reviewers following the PRISMA guidelines. Cohort studies and case reports were identified; outcomes of cohort studies were reported. The primary efficacy outcome was tumour size before and after TAE/TAL. Improvement of symptoms and quality of life (QoL) were secondary outcomes; the primary safety outcome was complications. The Downs and Black statement was used for quality assessment.

Results: Eighteen cohort studies were identified, including 1284 patients. TAE/TAL led to a decrease in tumour size in 1100/1223 (89.9%) patients and to improvement or disappearance of symptoms in 1080/1096 (98.5%) patients. A significant decrease in tumour size from 9.79 ± 0.79 cm to 4.00 ± 1.36 cm (p < 0.001) was shown. Grade 3 complications occurred in 37/1284 (2.9%) patients. Surgical treatment was necessary in 35/1284 (2.7%) of patients.

Conclusion: TAE/TAL appears to be a promising and safe treatment to decrease tumour size of hepatic haemangioma. The technique might also provide partial relief of symptoms, although no randomized clinical trials or prospective studies using validated QoL questionnaires are available. TAE/TAL may be considered as a viable alternative to resection.
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http://dx.doi.org/10.1007/s00270-019-02169-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503075PMC
June 2019

EBIR Evolution: Meeting the Challenge for Twenty-First-Century IR.

Cardiovasc Intervent Radiol 2019 Apr;42(4):485-486

Department of (Interventional) Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.

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http://dx.doi.org/10.1007/s00270-019-02172-2DOI Listing
April 2019

Stromal-derived interleukin 6 drives epithelial-to-mesenchymal transition and therapy resistance in esophageal adenocarcinoma.

Proc Natl Acad Sci U S A 2019 02 22;116(6):2237-2242. Epub 2019 Jan 22.

Laboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, 1105 AZ Amsterdam, The Netherlands;

Esophageal adenocarcinoma (EAC) has a dismal prognosis, and survival benefits of recent multimodality treatments remain small. Cancer-associated fibroblasts (CAFs) are known to contribute to poor outcome by conferring therapy resistance to various cancer types, but this has not been explored in EAC. Importantly, a targeted strategy to circumvent CAF-induced resistance has yet to be identified. By using EAC patient-derived CAFs, organoid cultures, and xenograft models we identified IL-6 as the stromal driver of therapy resistance in EAC. IL-6 activated epithelial-to-mesenchymal transition in cancer cells, which was accompanied by enhanced treatment resistance, migratory capacity, and clonogenicity. Inhibition of IL-6 restored drug sensitivity in patient-derived organoid cultures and cell lines. Analysis of patient gene expression profiles identified ADAM12 as a noninflammation-related serum-borne marker for IL-6-producing CAFs, and serum levels of this marker predicted unfavorable responses to neoadjuvant chemoradiation in EAC patients. These results demonstrate a stromal contribution to therapy resistance in EAC. This signaling can be targeted to resensitize EAC to therapy, and its activity can be measured using serum-borne markers.
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http://dx.doi.org/10.1073/pnas.1820459116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369811PMC
February 2019

Impact of expanding indications on surgical and oncological outcome in 1434 consecutive pancreatoduodenectomies.

HPB (Oxford) 2019 07 31;21(7):865-875. Epub 2018 Dec 31.

Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, The Netherlands. Electronic address:

Background: Over the years, high-volume pancreatic centers expanded their indications for pancreatoduodenectomy (PD) but with unknown impact on surgical and oncological outcome.

Methods: All consecutive PDs performed between 1992-2017 in a single pancreatic center were identified from a prospectively maintained database and analyzed according to three time periods.

Results: In total, 1434 patients underwent PD. Over time, more elderly patients underwent PD (P < 0.001) with increased use of vascular resection (10.4 to 16.0%, P < 0.001). In patients with cancer (n = 1049, 74.8%), the proportion pT3/T4 tumors increased from 54.3% to 70.6% over time (P < 0.001). The postoperative pancreatic fistula (16.0%), postpancreatectomy hemorrhage (8.0%) and delayed gastric emptying (31.0%) rate did not reduce over time, whereas median length of stay decreased from 16 to 12 days (P < 0.001). The overall failure-to-rescue rate (6.9%) and in-hospital mortality (2.2%) remained stable (P = 0.89 and P = 0.45). In 523 patients with pancreatic cancer (36.5%), the use of both adjuvant and neoadjuvant chemotherapy increased over time (both p<0.001), and the five-year overall survival improved from 11.0% to 17.4% (P < 0.001).

Conclusions: In a period where indications for PD expanded, with more elderly patients, more advanced cancers and increased use of vascular resections, surgical outcome remained favorable and five-year survival for pancreatic cancer improved.
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http://dx.doi.org/10.1016/j.hpb.2018.10.020DOI Listing
July 2019

Correction to: Reason of Discontinuation After Transarterial Chemoembolization Influences Survival in Patients with Hepatocellular Carcinoma.

Cardiovasc Intervent Radiol 2019 03;42(3):484

Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.

Toward the end of the second paragraph in the Discussion section, there is a word missing in the sentence.
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http://dx.doi.org/10.1007/s00270-018-2143-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6828183PMC
March 2019

Preoperative drainage for perihilar cholangiocarcinoma - Authors' reply.

Lancet Gastroenterol Hepatol 2019 01 6;4(1):11-12. Epub 2018 Dec 6.

Department of Surgery, Amsterdam University Medical Center, University of Amsterdam, Cancer Center Amsterdam, 1100DD Amsterdam, Netherlands.

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http://dx.doi.org/10.1016/S2468-1253(18)30346-7DOI Listing
January 2019

Feasibility and safety of irreversible electroporation (IRE) in patients with small renal masses: Results of a prospective study.

Urol Oncol 2019 03 30;37(3):183.e1-183.e8. Epub 2018 Nov 30.

Department of Radiology, Academic Medical Center, Amsterdam, the Netherlands.

Background: Irreversible electroporation (IRE) has the potential to overcome limitations of thermal ablation, enabling small renal mass (SRM) ablation near vital structures.

Purpose: To assess feasibility and safety of percutaneous IRE for the treatment of SRMs.

Materials And Methods: This prospective study is a phase 2 trial (NCT02828709) of IRE for patients with SRMs. Primary endpoints are feasibility and safety. Device- and procedural-adverse events were assessed by Clavien-Dindo and Common Terminology Criteria for Adverse Events version 4.0 grading systems. Technical feasibility was assessed by recording the technical success of the procedures. Technical success was evaluated by performing a CT immediately after ablation where complete tumor coverage and nonenhancement were evaluated. Tumor charcateristics and patient characteristics, procedural and anesthesia details, postprocedural events, and perioperative complications were recorded.

Results: Ten SRMs were included with a mean tumor size of 2.2 cm (range 1.1-3.9 cm) were treated with IRE. Renal mass biopsies revealed 7 clear cell and 1 papillary renal cell carcinoma. Two renal mass biopsies were nondiagnostic. The median follow-up was 6 months (range 3-12 months). Technical success was achieved in 9 out of 10 cases. One patient had a grade 3 Clavien-Dindo complication (1/10, 95% Confidence interval (CI) 0.0179-0.4041). Mean anesthesia time was 3.7 hours (range 3-5 hours), mean procedural time was 2.1 hours (range 1 hour 45 minutes-2 hours 30 minutes) and mean ablation time was 50 minutes (range 20 minutes-1 hour 45 minutes). The creatinine preoperative and postoperative (1 week, 3 months, 6 months, and 12 months) did not significantly differ. In total, 8 out of 10 cases did not experience postoperative pain.

Conclusion: IRE in SRMs is safe and feasible. Renal function is not affected by IRE and postoperative pain is rare. Anesthesia time and procedural time are a potential concern.
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http://dx.doi.org/10.1016/j.urolonc.2018.11.008DOI Listing
March 2019

Reason of Discontinuation After Transarterial Chemoembolization Influences Survival in Patients with Hepatocellular Carcinoma.

Cardiovasc Intervent Radiol 2019 Feb 28;42(2):230-238. Epub 2018 Nov 28.

Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.

Background: Transarterial chemoembolization (TACE) for intermediate-stage hepatocellular carcinoma (HCC) is often repeated until unTACEable progression (UTP) occurs. There is little data on the various reasons for stopping TACE and its consequences for subsequent treatment and survival.

Aim: To assess the impact of the various reasons of UTP on survival and consequences for subsequent treatments.

Methods: Consecutive HCC patients who underwent TACE between 2003 and 2016 were analyzed retrospectively for the reason of TACE discontinuation. UTP was defined according to the EASL guidelines, considering radiological pattern of progression, liver function and performance status (PS). Overall and post-progression survival (OS, PPS) for different reasons of TACE discontinuation were compared. The correlation between time to untreatable progression by chemoembolization (TTUPc) and OS was analyzed.

Results: One hundred and sixty-six patients (BCLC-A 40%, BCLC-B 54%, BCLC-C: 7%) were included, undergoing a median of 2 TACE procedures with a median OS of 22.1 months (95% CI 17.4-26.7). UTP occurred in 116 patients (70%) after a median TTUPc of 11.6 months (95% CI 7.8-15.4). There was a strong positive correlation (ρ = 0.816, p < 0.001) between TTUPc and OS. The main reason of UTP was radiological progression (61%), which was mostly intrahepatic (75%). Hepatic decompensation and worsening of PS were independent predictors of OS and PPS.

Conclusion: The majority of HCC patients treated with TACE have UTP due to intrahepatic tumor progression with preserved liver function and PS, making them potential candidates for subsequent liver-directed or systemic treatment. TTUPc may be a valuable surrogate endpoint for OS in patients treated with TACE.

Level Of Evidence: Level II, prognosis study.
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http://dx.doi.org/10.1007/s00270-018-2118-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6344387PMC
February 2019
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