Recurrence After Liver Resection of Colorectal Liver Metastases: Repeat Resection or Ablation Followed by Hepatic Arterial Infusion Pump Chemotherapy

Background: The aim of this study was to investigate the effectiveness of adjuvant hepatic arterial infusion pump (HAIP) chemotherapy after complete resection or ablation of recurrent colorectal liver metastases (CRLM). Methods: A retrospective cohort study was conducted of patients from two centers who were treated with resection and/or ablation of recurrent CRLM only between 1992 and 2018. Overall survival (OS) and hepatic disease-free survival (hDFS) were estimated using the Kaplan–Meier method. The Cox regression method was used to calculate hazard ratios (HRs) with corresponding 95% confidence intervals (CI). Results: Of 374 eligible patients, 81 (22%) were treated with adjuvant HAIP chemotherapy. The median follow-up for survivors was 65 months (IQR 32–118 months). Patients receiving adjuvant HAIP were more likely to have multifocal disease and receive perioperative systemic chemotherapy at time of resection for recurrence. A median hDFS of 46 months (95% CI 29–81 months) was found in patients treated with adjuvant HAIP compared with 18 months (95% CI 15–26 months) in patients treated with resection and/or ablation alone (p = 0.001). The median OS and 5-year OS were 89 months (95% CI 52–126 months) and 66%, respectively, in patients treated with adjuvant HAIP compared with 57 months (95% CI 47–67 months) and 47%, respectively, in patients treated with resection and/or ablation only (p = 0.002). Adjuvant HAIP was associated with superior hDFS (adjusted HR 0.599, 95% CI 0.38–0.93, p = 0.02) and OS (adjusted HR 0.59, 95% CI 0.38–0.92, p = 0.02) in multivariable analysis. Conclusion: Adjuvant HAIP chemotherapy after resection and/or ablation of recurrent CRLM is associated with superior hDFS and OS

Salinity-gradient power: Evaluation of pressure-retarded osmosis and reverse electrodialysis

A huge potential to obtain clean energy exists from mixing water streams with different salt concentrations. Two membrane-based energy conversion techniques are evaluated: pressure-retarded osmosis and reverse electrodialysis. From the literature, a comparison is not possible since the reported performances are not comparable. A method was developed which allows for a comparison of both techniques at equal conditions, with respect to power density and energy recovery. Based on the results from the model calculations, each technique has its own field of application. Pressure-retarded osmosis seems to be more attractive for power generation using concentrated saline brines because of the higher power density combined with higher energy recovery. Reverse electrodialysis seems to be more attractive for power generation using seawater and river water. These conclusions are valid for present and latent performances of both techniques. According to the model, the potential performances of both techniques are much better than the current performances. In order to achieve these potential performances, the development of pressure-retarded osmosis must focus on membrane characteristics, i.e. increasing the water permeability of the membrane skin and optimization of the porous support. The development of reverse electrodialysis, however, must focus on system characteristics, i.e. optimization of the internal resistance, which is mainly determined by the width of the spacers

Predicting 10-year survival after resection of colorectal liver metastases; an international study including biomarkers and perioperative treatment

Background: The aim of this study was to develop a prediction model for 10-year overall survival (OS) after resection of colorectal liver metastasis (CRLM) based on patient, tumour and treatment characteristics.Methods: Consecutive patients after complete resection of CRLM were included from two centres (1992-2019). A prediction model providing 10-year OS probabilities was developed using Cox regression analysis, including KRAS, BRAF and histopathological growth patterns. Discrimination and calibration were assessed using cross-validation. A web-based calculator was built to predict individual 10-year OS probabilities.Results: A total of 4112 patients were included. The estimated 10-year OS was 30% (95% CI 29 -32). Fifteen patient, tumour and treatment characteristics were independent prognostic factors for 10-year OS; age, gender, location and nodal status of the primary tumour, disease-free interval, number and diameter of CRLM, preoperative CEA, resection margin, extrahepatic disease, KRAS and BRAF mutation status, histopathological growth patterns, perioperative systemic chemotherapy and hepatic arterial infusion pump chemotherapy. The discrimination at 10-years was 0.73 for both centres. A simplified risk score identified four risk groups with a 10-year OS of 57%, 38%, 24%, and 12%.Conclusions: Ten-year OS after resection of CRLM is best predicted with a model including 15 patient, tumour, and treatment characteristics. The web-based calculator can be used to inform patients. This model serves as a benchmark to determine the prognostic value of novel biomarkers. (C) 2022 The Author(s). Published by Elsevier Ltd.Development and application of statistical models for medical scientific researc

Adjuvant hepatic arterial infusion pump chemotherapy and resection versus resection alone in patients with low-risk resectable colorectal liver metastases - the multicenter randomized controlled PUMP trial

Background: Recurrences are reported in 70% of all patients after resection of colorectal liver metastases (CRLM), in which half are confined to the liver. Adjuvant hepatic arterial infusion pump (HAIP) chemotherapy aims to reduce the risk of intrahepatic recurrence. A large retrospective propensity score analysis demonstrated that HAIP chemotherapy is particularly effective in patients with low-risk oncological features. The aim of this randomized controlled trial (RCT) -the PUMP trial- is to investigate the efficacy of adjuvant HAIP chemotherapy in low-risk patients with resectable CRLM. Methods: This is an open label multicenter RCT. A total of 230 patients with resectable CRLM without extrahepatic disease will be included. Only patients with a clinical risk score (CRS) of 0 to 2 are eligible, meaning: patients are allowed to have no more than two out of five poor prognostic factors (disease-free interval less than 12 months, node-positive colorectal cancer, more than 1 CRLM, largest CRLM more than 5 cm in diameter, serum Carcinoembryonic Antigen above 200 μg/L). Patients randomized to arm A undergo complete resection of CRLM without any adjuvant treatment, which is the standard of care in the Netherlands. Patients in arm B receive an implantable pump at the time of CRLM resection and start adjuvant HAIP chemotherapy 4-12 weeks after surgery, with 6 cycles of floxuridine scheduled. The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival, hepatic PFS, safety, quality of life, and cost-effectiveness. Pharmacokinetics of intra-arterial administration of floxuridine will be investigated as well as predictive biomarkers for the efficacy of HAIP chemotherapy. In a side study, the accuracy of CT angiography will be compared to radionuclide scintigraphy to detect extrahepatic perfusion. We hypothesize that adjuvant HAIP chemotherapy leads to improved survival, improved quality of life, and a reduction of costs, compared to resection alone. Discussion: If this PUMP trial demonstrates that adjuvant HAIP chemotherapy improves survival in low-risk patients, this treatment approach may be implemented in the standard of care of patients with resected CRLM since adjuvant systemic chemotherapy alone has not improved survival. Trial registration: The PUMP trial is registered in the Netherlands Trial Register (NTR), number: 7493 . Date of registration September 23, 2018

The National Immunisation Programme in the Netherlands: surveillance and developments in 2016-2017.

Surveillance and developments in 2016-2017 In 2016, about 760,000 children aged 0 to 19 years received a total of 2,140,000 vaccinations within the National Immunisation Programme (NIP). Participation in the NIP was high (more than 90% depending on the vaccine), but dropped by around 0.5% for newborns for the third consecutive year. The participation in vaccinations against human papillomavirus (HPV) declined from 61 to 53 per cent. The number of reports (1,483) of adverse events following immunisation (in total 3,665) in 2016 was comparable to the number of reports in 2015. NIP target diseases The number of reported cases of most NIP target diseases was again low. However, the number of cases of Haemophilus influenzae type b (Hib) disease in 2016 (n=44) was considerably higher than in the previous five years (22-34 cases), with the highest incidence occurring among children under five years of age. Pertussis incidence in 2016 fits within the usual fluctuations. However, six people died from pertussis in 2016.The incidence of cervical cancer cases increased in 2016 (9.3 per 100,000 compared with 7.7 per 100,000 in 2015). In 2017, two fully vaccinated employees were exposed to a wild poliovirus type 2 (WPV2). Due to strict isolation, no transmission was detected. Potential NIP target diseases An increase in the number of meningococcal (Men) disease was observed after more than two decades of decrease. An ongoing increase in the number of cases of MenW disease has been observed (9, 50 and 34, respectively, in 2015, 2016 and the first five months of 2017). Dutch Health Council recommendations The RIVM facilitate the Dutch Health Council with their recommendations on vaccinations and therefore has collected and structured relevant national and international information in background documents concerning rotavirus, meningococcal disease and HPV.The Health Council has advised earlier that maternal pertussis vaccination should be provided. The Ministry of Health, Welfare and Sport (VWS) has expressed a positive attitude towards the advice but still has to make a decision. In 2017, the Health Council also advised that all employees who are in close contact with young infants during work should be offered vaccination against pertussis. In addition, the Dutch Health Council advised in September 2017 positive on vaccination against rotavirus and the minister decided to vaccinate against MenACWY in 2018. (aut. ref.

The National Immunisation Programme in the Netherlands : surveillance and developments in 2017-2018.

In 2017, about 760,000 children aged 0 to 19 years received a total of 2,140,000 vaccinations within the National Immunisation Programme (NIP). Participation in the NIP was high among children under 10 years of age, despite the drop by around 2-3% for most vaccinations since 2014. An exception in the high participation is the number of girls who was vaccinated against human papillomavirus (HPV), which has declined by 15% since 2016. The number of reports (1,383) of possible adverse events following immunisation in 2017 was lower than the number of reports in 2016 (1,483). NIP target diseases There is an ongoing increase in the number of cases with meningococcal serogroup W (MenW) disease with 80 cases reported in 2017 and 78 up to August 2018. Because of this increase, since May 2018, the MenC vaccination given at 14 months of age has been replaced by a quadrivalent MenACWY vaccination. The case fatality of MenW disease (17%) was substantially higher than for other serogroups. In 2017, the number of measles cases was low (16 reported cases) but higher than in the previous two years. The number of pertussis reports in 2017 was comparable with 2016 (28.7 compared with 32.6 per 10,000). Three people died from pertussis, one infant and two elderly. The number of reports of acute hepatitis B infections stayed stable (0.7 per 100,000 population). Also, the incidence of vaccine type invasive pneumococcal disease (IPD) remained very low in 2017/2018. Once again, the number of reported cases were in 2017 low for mumps (46), Haemophilus influenzae type b (Hib; 46), meningococcal serogroep C (MenC; 9), diphtheria (4), tetanus (1), rubella (0) and polio (0). The inhabitants of Bonaire, St. Eustatius and Saba are predominantly well protected against NIP diseases. However, protection against measles and diphtheria is suboptimal for some age groups. Awareness is needed to prevent these diseases from spreading from neighboring countries, where outbreaks currently are observed. New advice and decisions In July 2018, the Ministry of Health, Welfare and Sports decided to expand the MenACWY vaccination outbreak programme to 13-14 year olds. In 2019, there will be a catch up campaign for all 15-18 year olds. Furthermore, it was decided that vaccination against disease caused by rotavirus will be included in the NIP for risk groups, and that maternal pertussis vaccination in the NIP will be organised by youth health care organisations. The Dutch Health Council advises to offer vaccination against pneumococcal disease to the people 60 years and older. (aut. ref.

The National Immunisation Programme in the Netherlands : surveillance and developments in 2015-2016.

Surveillance en ontwikkelingen in 2015-2016 In 2015 kregen bijna 770.000 kinderen van 0 tot 19 jaar samen 1.547.000 vaccinaties binnen het Rijksvaccinatieprogramma (RVP). De deelname aan het RVP is met 92 tot 99 procent (afhankelijk van de vaccinatie) nog steeds hoog. Een uitzondering daarop is de vaccinatie tegen het humaan papillomavirus (HPV) met 61 procent. De deelname voor pasgeborenen is voor het tweede achtereenvolgende jaar met ongeveer 0,5 procent gedaald. Meldingen van RVP-ziekten Het aantal gemelde gevallen van de meeste ziekten waartegen via het RVP wordt ingeënt, was wederom laag. Dit gold ook voor het aantal meldingen van mazelen (7) na de grote epidemie in 2013/2014. Kinkhoest kwam in 2015 minder vaak voor (39 per 100.000) dan in het epidemische jaar 2014 (55 per 100.000). Eén zuigeling overleed aan kinkhoest. Het aantal gevallen van ernstige pneumokokkenziekte - veroorzaakt door de drie typen waarmee het pneumokokkenvaccin werd uitgebreid in 2011 - bleef bij kinderen jonger dan 5 jaar zeer laag (0,5 per 100.000). Door de indirecte bescherming kwam het bij andere leeftijdsgroepen ook minder vaak voor. In 2015 en de eerste helft van 2016 kwam de bof vaker voor dan in 2014 (bij respectievelijk 89, 45 en 40 mensen). Meldingen van mogelijke bijwerkingen van vaccins In 2015 is het aantal meldingen van mogelijke bijwerkingen van vaccins gestegen (1494 ten opzichte van 982 in 2014). Het betrof vooral meldingen van (heftige) lokale ontstekingsreacties en koorts bij 4-jarigen. Ook nam het aantal meldingen van vermoeidheid bij 12-jarige meisjes toe na media-aandacht over eventuele bijwerkingen van de HPV vaccinatie. De aard van de gemelde bijwerkingen was in vergelijking met voorgaande jaren niet ernstiger. Meldingen van ziekten voor potentiële RVP-vaccins In 2015 en 2016 steeg het aantal gevallen van meningokokkenziekte veroorzaakt door serogroep W (MenW); meestal waren dit personen van 65 jaar of ouder. Na het extreem lage aantal gevallen in 2014 had 2015 een gemiddeld rotavirus seizoen, met de piek in maart. Tot en met juni 2016 was het aantal gevallen van rotavirus weer laag, waarbij het ‘seizoen’ ook later begon dan normaal. (aut. ref.