The underwater soundscape of the North Sea.

As awareness on the impact of anthropogenic underwater noise on marine life grows, underwater noise measurement programs are needed to determine the current status of marine areas and monitor long-term trends. The Joint Monitoring Programme for Ambient Noise in the North Sea (JOMOPANS) collaborative project was funded by the EU Interreg to collect a unique dataset of underwater noise levels at 19 sites across the North Sea, spanning many different countries and covering the period from 2019 to 2020. The ambient noise from this dataset has been characterised and compared - setting a benchmark for future measurements in the North Sea area. By identifying clusters with similar sound characteristics in three broadband frequency bands (25-160 Hz, 0.2-1.6 kHz, and 2-10 kHz), geographical areas that are similarly affected by sound have been identified. The measured underwater sound levels show a persistent and spatially uniform correlation with wind speed at high frequencies (above 1 kHz) and a correlation with the distance from ships at mid and high frequencies (between 40 Hz and 4 kHz). Correlation with ocean current velocity at low frequencies (up to 200 Hz), which are susceptible to nonacoustic contamination by flow noise, was also evaluated. These correlations were evaluated and simplified linear scaling laws for wind and current speeds were derived. The presented dataset provides a baseline for underwater noise measurements in the North Sea and shows that spatial variability of the dominant sound sources must be considered to predict the impact of noise reduction measures.

Extending the viability of human precision-cut intestinal slice model for drug metabolism studies.

Human Precision-cut intestinal slices (hPCIS) are used to study intestinal physiology, pathophysiology, drug efficacy, toxicology, kinetics, and metabolism. However, the use of this ex vivo model is restricted to approximately a 24 h timeframe because of declining viability of the hPCIS during traditional culture. We hypothesized that we could extend the hPCIS viability by using organoid medium. Therefore, we cultured hPCIS for up to 72 h in organoid media [expansion medium (Emed) and differentiation medium (Dmed)]. After incubation, we assessed culture-induced changes on viability markers, specific cell type markers and we assessed the metabolic activity of enterocytes by measuring midazolam metabolite formation. We show that the adenosine triphosphate (ATP)/protein ratio of Emed-cultured hPCIS and morphology of both Emed- and Dmed-cultured hPCIS was improved compared to WME-cultured hPCIS. Emed-cultured hPCIS showed an increased expression of proliferation and stem cell markers, whereas Dmed-cultured hPCIS showed an increased expression of proliferation and enterocyte markers, along with increased midazolam metabolism. Using the Emed, the viability of hPCIS could be extended for up to 72 h, and proliferating stem cells remained preserved. Using Dmed, hPCS also remained viable for up to 72 h, and specifically rescued the metabolizing enterocytes during culture. In conclusion, by using two different organoid culture media, we could extend the hPCIS viability for up to 72 h of incubation and specifically steer stem cells or enterocytes towards their original function, metabolism, and proliferation, potentially allowing pharmacokinetic and toxicology studies beyond the 24 h timeframe.

Mental and physical health of international humanitarian aid workers on short-term assignments: Findings from a prospective cohort study.

Research findings show humanitarian work impacts one's health. We conducted a prospective observational study among 618 international humanitarian aid workers (iHAWs)' recruited from 76 countries to investigate health changes and ill-health risk factors after mostly short-term (<1 year) medical emergency assignments. The aid workers were assigned to 27 countries. Data collected between 2017 and 2020. We also compared a gold-standard clinical interview with self-report questionnaires to assess whether self-report scores overestimate the prevalence of clinical anxiety, depression and PTSD. Analyses consisted of repeated measures ANOVAs and adjusted odds ratios, using pre-assignment (T1), post-assignment (T2) and two-month follow-up data (T3). Humanitarian workers experienced on average, 2.6 experienced and witnessed potential traumatic events, and 4.8 male and 5.6 female assignment-related stressors. Self-report health indicators demonstrated a significant increase in emotional exhaustion, loss of vitality, decreased social functioning and emotional well-being between T1 and T2, all of which improved between T2 and T3. PTSD, depression, experienced role limitations, physical functioning, pain, and general health - remained stable. Anxiety levels decreased significantly between T1 and T2. The presence of DSM-5 disorders anxiety (6.6 %), depression (1.3 %) and PTSD (0.3 %) was low compared to norm populations, except for alcohol-use disorder (13 %). None of the reported T2 risk factors was significant at T3. Compared to the clinical interview, self-report cut-off thresholds inflated the presence of a potential anxiety disorder (3×), PTSD (8×) and depression (25×). Humanitarian work is highly stressful but most iHAWs remained healthy. Looking into how iHAWs stay healthy may be a more useful way forward.

Clinical relevant pancreatic fistula after pancreatoduodenectomy: when negative amylase levels tell the truth.

Drain Amylase level are routinely determined to diagnose pancreatic fistula after Pancreatocoduodenectomy. Consensus is lacking regarding the cut-off value of amylase to diagnosis clinically relevant postoperative pancreatic fistulae (POPF). The present study proposes a model based on Amylase Value in the Drain (AVD) measured in the first three postoperative days to predict a POPF. Amylase cut-offs were selected from a previous published systematic review and the accuracy were validated in a multicentre database from 12 centres in 2 countries. The present study defined POPF the 2016 ISGPS criteria (3 times the upper limit of normal serum amylase). A learning machine method was used to correlate AVD with the diagnosis of POPF. Overall, 454 (27%) of 1638 patients developed POPF. Machine learning excluded a clinically relevant postoperative pancreatic fistulae with an AUC of 0.962 (95% CI 0.940-0.984) in the first five postoperative days. An AVD at a cut-off of 270 U/L in 2 days in the first three postoperative days excluded a POPF with an AUC of 0.869 (CI 0.81-0.90, p < 0.0001). A single AVD in the first three postoperative days may not exclude POPF after pancreatoduodenectomy. The levels should be monitored until day 3 and have two negative values before removing the drain. In the group with a positive level, the drain should be kept in and AVD monitored until postoperative day five.

Influence of Promotion on the Growth of Anchored Colloidal Iron Oxide Nanoparticles during Synthesis Gas Conversion.

Using colloidal iron oxide nanoparticles with organic ligands, anchored in a separate step from the supports, has been shown to be beneficial to obtain homogeneously distributed metal particles with a narrow size distribution. Literature indicates that promoting these particles with sodium and sulfur creates an active Fischer-Tropsch catalyst to produce olefins, while further adding an H-ZSM-5 zeolite is an effective way to obtain aromatics. This research focused on the promotion of iron oxide colloids with sodium and sulfur using an inorganic ligand exchange followed by the attachment to H-ZSM-5 zeolite crystals. The catalyst referred to as FeP/Z, which consists of iron particles with inorganic ligands attached to a H-ZSM-5 catalyst, was compared to an unpromoted Fe/Z catalyst and an Fe/Z-P catalyst, containing the colloidal nanoparticles with organic ligands, promoted after attachment. A low CO conversion was observed on both FeP/Z and Fe/Z-P, originating from an overpromotion effect for both catalysts. However, when both promoted catalysts were washed (FeP/Z-W and Fe/Z-P-W) to remove the excess of promoters, the activity was much higher. Fe/Z-P-W simultaneously achieved low selectivity toward methane as part of the promoters were still present after washing, whereas for FeP/Z-W the majority of promoters was removed upon washing, which increased the methane selectivity. Moreover, due to the addition of Na+S promoters, the iron nanoparticles in the FeP/Z(-W) catalysts had grown considerably during catalysis, while those in Fe/Z-P(-W) and Fe/Z(-W) remained relatively stable. Lastly, as a large broadening of particle sizes for the used FeP/Z-W was found, where particle sizes had both increased and decreased, Ostwald ripening is suggested for particle growth accelerated by the presence of the promoters.

The role of abdominal drainage in pancreatic resection - A multicenter validation study for early drain removal.

BACKGROUND: Abdominal drainage and the timing of drain removal in patients undergoing pancreatic resection are under debate. Early drain removal after pancreatic resection has been reported to be safe with a low risk for clinical relevant postoperative pancreatic fistula (CR-POPF) when drain amylase on POD1 is < 5000U/L. The aim of this study was to validate this algorithm in a large national cohort. METHODS: Patients registered in the Dutch Pancreatic Cancer Audit (2014-2016) who underwent pancreatoduodenectomy, distal pancreatectomy or enucleation were analysed. Data on post-operative drain amylase levels, drain removal, postoperative pancreatic fistulae were collected. Univariate and multivariate analysis using a logistic regression model were performed. The primary outcome measure was grade B/C pancreatic fistula (CR-POPF). RESULTS: Among 1402 included patients, 433 patients with a drain fluid amylase level of <5000U/L on POD1, 7% developed a CR-POPF. For patients with an amylase level >5000U/L the CR-POPF rate was 28%. When using a cut-off point of 2000U/L or 1000U/L during POD1-3, the CR-POPF rates were 6% and 5% respectively. For patients with an amylase level of >2000U/L and >1000UL during POD 1-3 the CR-POPF rates were 26% and 22% respectively (n = 223). Drain removal on POD4 or thereafter was associated with more complications (p = 0.004). Drain amylase level was shown to be the most statistically significant predicting factor for CR-POPF (Wald = 49.7; p < 0.001). CONCLUSION: Our data support early drain removal after pancreatic resection. However, a cut-off of 5000U/L drain amylase on POD1 was associated with a relatively high CR-POPF rate of 7%. A cut-off point of 1000U/L during POD1-3 resulted in 5% CR-POPF and might be a safer alternative.

Development and validation of an UPLC-MS/MS method for the therapeutic drug monitoring of oral anti-hormonal drugs in oncology.

A liquid chromatography-mass spectrometry assay was developed and validated for simultaneous quantification of anti-hormonal compounds abiraterone, anastrozole, bicalutamide, Δ(4)-abiraterone (D4A), N-desmethyl enzalutamide, enzalutamide, Z-endoxifen, exemestane and letrozole for the purpose of therapeutic drug monitoring (TDM). Plasma samples were prepared with protein precipitation. Analyses were performed with a triple quadrupole mass spectrometer operating in the positive and negative ion-mode. The validated assay ranges from 2 to 200 ng/mL for abiraterone, 0.2-20 ng/mL for D4A, 10-200 ng/mL for anastrozole and letrozole, 1-20 ng/mL for Z-endoxifen, 1.88-37.5 ng/mL for exemestane and 1500-30,000 ng/mL for enzalutamide, N-desmethyl enzalutamide and bicalutamide. Due to low sensitivity for exemestane, the final extract of exemestane patient samples should be concentrated prior to injection and a larger sample volume should be prepared for exemestane patient samples and QC samples to obtain adequate sensitivity. Furthermore, we observed a batch-dependent stability for abiraterone in plasma at room temperature and therefore samples should be shipped on ice. This newly validated method has been successfully applied for routine TDM of anti-hormonal drugs in cancer patients.

Attachment of iron oxide nanoparticles to carbon nanofibers studied by in-situ liquid phase transmission electron microscopy.

By using liquid phase transmission electron microscopy (LP-TEM), the dynamics of iron oxide nanoparticle (Fe-NP) attachment to carbon nanofibers (CNFs) and oxygen functionalized CNFs (CNF-Ox) were studied in-situ. The beam effect on the stability of the sample in various liquids was examined, and it was found that toluene provided the highest stability and resolution to image both CNF supports and Fe-NPs. Flowing particles dispersed in toluene through the liquid cell allowed direct monitoring of the attachment process at ambient temperature. Using CNF-Ox as a support led to a large extent and irreversible attachment of iron nanoparticle compared to a lower extent and reversible attachment of Fe-NPs to pristine CNF, indicating the influence of surface functionalization on colloidal particle attachment. The results were confirmed by lab-scale experiments as well as experiments performed with the electron beam switched off, verifying the notion that beam effects did not affect the attachment. This study revealed previously unknown phenomena in colloidal particle - support interactions and demonstrates the power of LP-TEM technique for studying such nanoscale processes.

[The inter-rater reliability of the MINI-Plus]. / De interbeoordelaarsbetrouwbaarheid van het Mini-Internationaal Neuro­psychiatrisch Interview-Plus (MINI-Plus).

BACKGROUND The Mini-International Neuropsychiatric Interview-Plus (MINI-Plus) is a widely used diagnostic tool, yet research on the psychometric properties is limited. AIM To investigate the inter-rater reliability of the MINI-Plus and to explore the concordance between MINI-Plus diagnoses and clinician-rated diagnoses. METHOD MINI-Plus interviews were conducted with psychiatric outpatients and recorded using audio and video devices. Independent raters, blind to the assessments of the first raters, assessed the recordings in order to investigate the inter-rater reliability. To examine the degree of concordance between the MINI-Plus and the clinician, the diagnoses of the original interview and the clinical diagnoses were compared. RESULTS The inter-rater reliability was excellent for most diagnostic categories. A low correlation between the MINI-Plus diagnoses and the clinician-rated diagnoses was found. CONCLUSION This study confirmed the excellent inter-rater reliability of the instrument, although some modules could be further improved. The consensus between MINI-Plus diagnoses and clinician-rated diagnoses is limited. The MINI-Plus can therefore supplement information collected by clinicians and may help prevent clinicians from missing important information.

Inguinal endometriosis, a rare entity of which surgeons should be aware: clinical aspects and long-term follow-up of nine cases.

INTRODUCTION: Inguinal endometriosis is a rare disease and often misdiagnosed for other, more common groin pathology. We present nine cases of women with inguinal endometriosis with long-term follow-up. METHODS: In this retrospective case series, the Dutch PALGA system was searched for all patients diagnosed with extrapelvic endometriosis located in the groin in the OLVG hospital, Amsterdam, between 2000 and 2016. Relevant information regarding pre- and postoperative characteristics and symptoms was collected. Follow-up consisted of a telephone call from the attending surgeon. RESULTS: None of the patients had a history of pelvic endometriosis. Typically, they presented with a right-sided swelling in the groin. Preoperative ultrasound and MRI were in most cases inconclusive. In one of two patients fna indicated endometriosis. In only three patients the surgeon considered the diagnosis endometriosis preoperatively. Surgical removal was effective with no reported complications. A coexisting hernia sac was resected in four cases, and there was a suspicion of a persistent processus vaginalis (canal of Nuck) in three, suggesting that a persistent processus vaginalis is possibly an important key to the pathogenesis. In none of the cases there was an indication for mesh implantation. One patient was later diagnosed with pelvic endometriosis. CONCLUSION: Follow-up by a gynecologist is advised to check for intra-abdominal disease and inform patients on fertility perspective. Surgeons should be aware of the possibility of inguinal endometriosis in fertile women with a lump in the groin.

Maternal high fat diet induces early cardiac hypertrophy and alters cardiac metabolism in Sprague Dawley rat offspring.

BACKGROUND AND AIM: Maternal high fat diets (mHFD) have been associated with an increased offspring cardiovascular risk. Recently we found that the class IIa HDAC-MEF2 pathway regulates gene programs controlling fatty acid oxidation in striated muscle. This same pathway controls hypertrophic responses in the heart. We hypothesized that mHFD is associated with activation of signal controlling class II a HDAC activity and activation of genes involved in fatty acid oxidation and cardiac hypertrophy in offspring. METHODS AND RESULTS: Female Sprague Dawley rats were fed either normal fat diet (12%) or high fat diet (43%) three weeks prior to mating, remaining on diets until study completion. Hearts of postnatal day 1 (PN1) and PN10 pups were collected. Bioenergetics and respiration analyses were performed in neonatal ventricular cardiomyocytes (NVCM). In offspring exposed to mHFD, body weight was increased at PN10 accompanied by increased body fat percentage and blood glucose. Heart weight and heart weight to body weight ratio were increased at PN1 and PN10, and were associated with elevated signalling through the AMPK-class IIa HDAC-MEF2 axis. The expression of the MEF2-regulated hypertrophic markers ANP and BNP were increased as were expression of genes involved in fatty acid oxidation. However this was only accompanied by an increased protein expression of fatty acid oxidation enzymes at PN10. NVCM isolated from these pups exhibited increased glycolysis and an impaired substrate flexibility. CONCLUSION: Combined, these results suggest that mHFD induces signalling and transcriptional events indicative of reprogrammed cardiac metabolism and of cardiac hypertrophy in Sprague Dawley rat offspring.

Assembly and activation of supported cobalt nanocrystal catalysts for the Fischer-Tropsch synthesis.

The effect of oxidative treatments on the depostion of cobalt nanocrystals (Co-NC) onto a support and subsequent ligand removal was investigated. Deposition of ε-cobalt NC led to extensive clustering of NC and low Fischer-Tropsch synthesis activity. Low-temperature oxidation of ε-cobalt NC resulted in a very uniform CoO-NC distribution and high activity whereas high-temperature oxidation to Co3O4 led to less uniform NC distributions and lower activity.

Influence of precursor porosity on sodium and sulfur promoted iron/carbon Fischer-Tropsch catalysts derived from metal-organic frameworks.

Iron-based metal-organic frameworks (MOFs) with varying porosity are converted by pyrolysis into iron/carbon catalysts with predetermined composition and tailored pore structural features for the Fischer-Tropsch synthesis of lower C2-C4 olefins. Significantly higher activity arises for catalysts with higher porosity and decreased iron particle size derived from hierarchical MOF xerogel/aerogel precursors as compared to a purely microporous MOF. Post-synthetic functionalization using sodium and sulfur promoters further enhances the catalytic properties.

Genes and pathways underlying susceptibility to impaired lung function in the context of environmental tobacco smoke exposure.

BACKGROUND: Studies aiming to assess genetic susceptibility for impaired lung function levels upon exposure to environmental tobacco smoke (ETS) have thus far focused on candidate-genes selected based on a-priori knowledge of potentially relevant biological pathways, such as glutathione S-transferases and ADAM33. By using a hypothesis-free approach, we aimed to identify novel susceptibility loci, and additionally explored biological pathways potentially underlying this susceptibility to impaired lung function in the context of ETS exposure. METHODS: Genome-wide interactions of single nucleotide polymorphism (SNP) by ETS exposure (0 versus ≥1 h/day) in relation to the level of forced expiratory volume in one second (FEV1) were investigated in 10,817 subjects from the Dutch LifeLines cohort study, and verified in subjects from the Swiss SAPALDIA study (n = 1276) and the Dutch Rotterdam Study (n = 1156). SNP-by-ETS exposure p-values obtained from the identification analysis were used to perform a pathway analysis. RESULTS: Fourty Five SNP-by-ETS exposure interactions with p-values <10-4 were identified in the LifeLines study, two being replicated with nominally significant p-values (<0.05) in at least one of the replication cohorts. Three pathways were enriched in the pathway-level analysis performed in the identification cohort LifeLines, i.E. the apoptosis, p38 MAPK and TNF pathways. CONCLUSION: This unique, first genome-wide gene-by-ETS interaction study on the level of FEV1 showed that pathways previously implicated in chronic obstructive pulmonary disease (COPD), a disease characterized by airflow obstruction, may also underlie susceptibility to impaired lung function in the context of ETS exposure.

Short-Course Radiotherapy Followed by Neoadjuvant Bevacizumab, Capecitabine, and Oxaliplatin and Subsequent Radical Treatment in Primary Stage IV Rectal Cancer: Long-Term Results of a Phase II Study.

BACKGROUND: In a Dutch phase II trial conducted between 2006 and 2010, short-course radiotherapy followed by systemic therapy with capecitabine, oxaliplatin, and bevacizumab as neoadjuvant treatment and subsequent radical surgical treatment of primary tumor and metastatic sites was evaluated. In this study, we report the long-term results after a minimum follow-up of 6 years. METHODS: Patients with histologically confirmed rectal adenocarcinoma with potentially resectable or ablatable metastases in liver or lungs were eligible. Follow-up data were collected for all patients enrolled in the trial. Overall and recurrence-free survival were calculated using the Kaplan-Meier method. RESULTS: Follow-up data were available for all 50 patients. After a median follow-up time of 8.1 years (range 6.0-9.8), 16 patients (32.0%) were still alive and 14 (28%) were disease-free. The median overall survival was 3.8 years (range 0.5-9.4). From the 36 patients who received radical treatment, two (5.6%) had a local recurrence and 29 (80.6%) had a distant recurrence. CONCLUSIONS: Long-term survival can be achieved in patients with primary metastatic rectal cancer after neoadjuvant radio- and chemotherapy. Despite a high number of recurrences, 32% of patients were alive after a median follow-up time of 8.1 years.

[Liver transplantation in paediatric patients in the Netherlands; evolution over the past two decades]. / Levertransplantaties bij kinderen in Nederland.

OBJECTIVE: To evaluate the results of the national paediatric liver transplantation programme in the University Medical Centre (UMC) Groningen in the Netherlands during the past two decades. DESIGN: Retrospective cohort study. METHOD: We analysed data from paediatric patients who underwent liver transplantation at UMC Groningen in the period 1995-2016. We compared outcomes from children who had undergone a liver transplantation in the period 1995-2005 (cohort A; n = 126) and in the period 2006-2016 (cohort B; n = 169). We performed a subanalysis in cohort B between liver transplantations with deceased donor livers (n = 132) and living donor liver transplantations (LDLT; n = 37). RESULTS: In cohort A, almost all livers came from deceased donors (99%), whereas in cohort B, 37 LDLTs (22%) were performed. The median age of recipients was significantly higher in cohort A (4.4 vs. 2.5 years; p = 0.015). Postoperative complications were comparable for both cohorts. Re-transplantations within a year after transplantation were more often performed in cohort A than in cohort B (25% vs. 12%; p = 0.004). Following LDLT, there was 2 times (5.4%) an indication for re-transplantation. In cohort B the 5-year survival rate was better than in cohort A (83 vs. 71%; p = 0.014). In cohort B, 5-year survival was higher after LDLT than after transplantation with a deceased donor liver (95 vs. 81%; p = 0.025). CONCLUSION: Outcomes after paediatric liver transplantation in the Netherlands have further improved during the past two decades. With an actuarial 5-year survival of 83% in the most recent cohort, and as high as 95% following LDLT, we can say that the UMC Groningen has a successful national paediatric liver transplant programme.

Outcomes after resection and/or radiofrequency ablation for recurrence after treatment of colorectal liver metastases.

BACKGROUND: Repeat liver resection for colorectal liver metastases (CRLMs) is possible in a limited number of patients, with radiofrequency ablation (RFA) as an alternative for unresectable CRLMs. The aim of this study was to analyse survival rates with these interventions. METHODS: This was a database analysis of patients who underwent first and repeat interventions for synchronous and metachronous CRLMs between 2000 and 2013. Descriptive and survival statistics were calculated. RESULTS: Among 431 patients who underwent resection or RFA for CRLMs, 305 patients developed recurrences for which 160 repeat interventions (resection and/or RFA or ablative radiotherapy) were performed. In total, after 707 first or repeat interventions, 516 recurrences (73·0 per cent) developed, of which 276 were retreated curatively. At the time of first intervention, independent risk factors for death were lymph node-positive primary tumour (hazard ratio (HR) 1·40; P = 0·030), more than one CRLM (HR 1·53; P = 0·007), carcinoembryonic antigen level exceeding 200 ng/ml (HR 1·89; P = 0·020) and size of largest CRLM greater than 5 cm (HR 1·54; P = 0·014). The 5-year overall survival rates for liver resection and percutaneous RFA as first intervention were 51·9 and 53 per cent, with a median overall survival of 65·0 (95 per cent c.i. 47·3 to 82·6) and 62·1 (52·2 to 72·1) months, respectively. CONCLUSION: RFA had good oncological outcomes in patients with unresectable CRLMs. Radiofrequency ablation is progressively more applied with each additional intervention.

Resection of liver metastases in patients with gastrointestinal stromal tumors in the imatinib era: A nationwide retrospective study.

INTRODUCTION: Liver metastases are common in patients with gastrointestinal stromal tumors (GIST). In the absence of randomized controlled clinical trials, the effectiveness of surgery as a treatment modality is unclear. This study identifies safety and outcome in a nationwide study of all patients who underwent resection of liver metastases from GIST. METHODS: Patients were included using the national registry of histo- and cytopathology (PALGA) of the Netherlands from 1999. Kaplan Meier survival analysis was used for calculating survival outcome. Univariate and multivariate regression analyses were carried out for the assessment of potential prognostic factors. RESULTS: A total of 48 patients (29 male, 19 female) with a median age of 58 (range 28-81) years were identified. Preoperative and postoperative tyrosine kinase inhibitor therapy was given to 30 (63%) and 36 (75%) patients, respectively. A minor liver resection was performed in 32 patients, 16 patients underwent major liver resection. Median follow-up was 27 (range 1-146) months. Median progression-free survival (PFS) was 28 (range 1-121) months. One-, three-, and five-year PFS was 93%, 67%, and 59% respectively. Median overall survival (OS) was 90 (range 1-146) months from surgery. The one-, three-, and five-year OS was 93%, 80%, and 76% respectively. R0 resection was the only independent significant prognostic factor for DFS and OS at multivariate analysis. CONCLUSION: Resection of liver metastases in GIST patients combined with imatinib may be associated with prolonged overall survival when a complete resection is achieved.