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Objective. Decrease in skeletal muscle index (SMI) during neoadjuvant chemotherapy (NACT) has been associated with worse outcome in patients with advanced ovarian cancer. To validate these findings, we tested if a decrease in SMI was a prognostic factor for a homogenous cohort of patients who received NACT in the randomized phase 3 OVHIPEC-trial.Methods. CT-scans were performed at baseline and after two cycles of neoadjuvant chemotherapy in stage III ovarian cancer patients. The SMI (skeletal muscle area in cm(2) divided by body surface area in m(2)) was calculated using SliceOMatic software. The difference in SMI between both CT-scans (Delta SMI) was calculated. Cox-regression analyses were performed to analyze the independent effect of a difference in SMI (Delta SMI) on outcome. Log-rank tests were performed to plot recurrence-free (RFS) and overall survival (OS). The mean number of adverse events per patient were compared between groups using t-tests.Results. Paired CT-scans were available for 212 out of 245 patients (87%). Thirty-four of 74 patients (58%) in the group with a decrease in Delta SMI and 73 of 138 of the patients (53%) in the group with stable/increase in Delta SMI had died. Median RFS and OS did not differ significantly (p = 0.297 and p = 0.764) between groups. Patients with a decrease in SMI experienced more pre-operative adverse events, and more grade 3-4 adverse events.Conclusion. Decreased SMI during neoadjuvant chemotherapy was not associated with worse outcome in patients with stage III ovarian cancer included in the OVHIPEC-trial. However, a strong association between decreasing SMI and adverse events was found. (C) 2020 Elsevier Inc. All rights reserved.

Objective. Decrease in skeletal muscle index (SMI) during neoadjuvant chemotherapy (NACT) has been associated with worse outcome in patients with advanced ovarian cancer. To validate these findings, we tested if a decrease in SMI was a prognostic factor for a homogenous cohort of patients who received NACT in the randomized phase 3 OVHIPEC-trial.Methods. CT-scans were performed at baseline and after two cycles of neoadjuvant chemotherapy in stage III ovarian cancer patients. The SMI (skeletal muscle area in cm(2) divided by body surface area in m(2)) was calculated using SliceOMatic software. The difference in SMI between both CT-scans (Delta SMI) was calculated. Cox-regression analyses were performed to analyze the independent effect of a difference in SMI (Delta SMI) on outcome. Log-rank tests were performed to plot recurrence-free (RFS) and overall survival (OS). The mean number of adverse events per patient were compared between groups using t-tests.Results. Paired CT-scans were available for 212 out of 245 patients (87%). Thirty-four of 74 patients (58%) in the group with a decrease in Delta SMI and 73 of 138 of the patients (53%) in the group with stable/increase in Delta SMI had died. Median RFS and OS did not differ significantly (p = 0.297 and p = 0.764) between groups. Patients with a decrease in SMI experienced more pre-operative adverse events, and more grade 3-4 adverse events.Conclusion. Decreased SMI during neoadjuvant chemotherapy was not associated with worse outcome in patients with stage III ovarian cancer included in the OVHIPEC-trial. However, a strong association between decreasing SMI and adverse events was found. (C) 2020 Elsevier Inc. All rights reserved.

Critical illness is associated with a disturbed regulation of gastrointestinal hormones resulting in functional and metabolic anomalies. Fibroblast growth factor 19 (FGF19) is an ileum-derived metabolic hormone induced by bile salts upon gallbladder emptying after enteral nutrient stimulation. Our aim was to study the nutrient-stimulated FGF19 response in 24 patients admitted to the intensive care unit (ICU) compared with 12 healthy controls. All subjects received intraduodenal high-lipid nutrient infusion for 120 minutes. Blood was collected every 30 minutes until 1 hour after infusion, and gallbladder emptying was studied by ultrasound. Serum levels of bile salts and FGF19 were assessed. ICU patients had significantly higher fasting bile salt serum levels compared with controls, whereas FGF19 serum levels were similar. In both groups, nutrient infusion elicited substantial bile salt elevations (P <0.001), peaking at 90 minutes, albeit with a significantly lower peak in the ICU patients (P = 0.029). In controls, FGF19 was significantly elevated relative to baseline from 120 minutes onward (P <0.001). In ICU patients, the FGF19 response was blunted, as reflected by significantly lower FGF19 elevations at 120, 150, and 180 minutes (P <0.05) and significantly lower area under the curve (AUC) values compared with controls (P <0.001). Gallbladder dysmotility was associated with the impaired FGF19 response in critical illness. The gallbladder ejection fraction correlated positively with FGF19 AUC values (rho = +0.34, P = 0.045). In 10 of 24 ICU patients, gallbladder emptying was disturbed. These patients had significantly lower FGF19 AUC values (P <0.001). Gallbladder emptying and the FGF19 response were respectively disturbed or absent in patients receiving norepinephrine. Conclusion: The nutrient-stimulated FGF19 response is impaired in ICU patients, which is mechanistically linked to gallbladder dysmotility in critical illness. This may contribute to

Background In patients with resectable perihilar cholangiocarcinoma, biliary drainage is recommended to treat obstructive jaundice and optimise the clinical condition before liver resection. Little evidence exists on the preferred initial method of biliary drainage. We therefore investigated the incidence of severe drainage-related complications of endoscopic biliary drainage or percutaneous transhepatic biliary drainage in patients with potentially resectable perihilar cholangiocarcinoma.Methods We did a multicentre, randomised controlled trial at four academic centres in the Netherlands. Patients who were aged at least 18 years with potentially resectable perihilar cholangiocarcinoma requiring major liver resection, and biliary obstruction of the future liver remnant (defined as a bilirubin concentration of >50 mu mol/L [2.9 mg/dL]), were randomly assigned (1:1) to receive endoscopic biliary drainage or percutaneous transhepatic biliary drainage through the use of computer-generated allocation. Randomisation, done by the trial coordinator, was stratified for previous (attempted) biliary drainage, the extent of bile duct involvement, and enrolling centre. Patients were enrolled by clinicians of the participating centres. The primary outcome was the number of severe complications between randomisation and surgery in the intention-to-treat population. The trial was registered at the Netherlands National Trial Register, number NTR4243.Findings From Sept 26, 2013, to April 29, 2016, 261 patients were screened for participation, and 54 eligible patients were randomly assigned to endoscopic biliary drainage (n=27) or percutaneous transhepatic biliary drainage (n=27). The study was prematurely closed because of higher mortality in the percutaneous transhepatic biliary drainage group (11 [41%] of 27 patients) than in the endoscopic biliary drainage group (three [11%] of 27 patients; relative risk 3.67, 95% CI 1.15-11.69; p=0.03). Three of the 11 deaths

Background: Myosteatosis, characterized by inter-and intramyocellular fat deposition, is strongly related to poor overall survival after surgery for periampullary cancer. It is commonly assessed by calculating the muscle radiation attenuation on computed tomography (CT) scans. However, since magnetic resonance imaging (MRI) is replacing CT in routine diagnostic work-up, developing methods based on MRI is important. We developed a new method using MRI-muscle signal intensity to assess myosteatosis and compared it with CT-muscle radiation attenuation.Methods: Patients were selected from a prospective cohort of 236 surgical patients with periampullary cancer. The MRI-muscle signal intensity and CT-muscle radiation attenuation were assessed at the level of the third lumbar vertebra and related to survival.Results: Forty-seven patients were included in the study. Inter-observer variability for MRI assessment was low (R-2 = 0.94). MRI-muscle signal intensity was associated with short survival: median survival 9.8 (95%-CI: 1.5-18.1) vs. 18.2 (95%-CI: 10.7-25.8) months for high vs. low intensity, respectively (p = 0.038). Similar results were found for CT-muscle radiation attenuation (low vs. high radiation attenuation: 10.8 (95%-CI: 8.5-13.1) vs. 15.9 (95%-CI: 10.2-21.7) months, respectively; p = 0.046). MRI-signal intensity correlated negatively with CT-radiation attenuation (r=-0.614, p <0.001).Conclusions: Myosteatosis may be adequately assessed using either MRI-muscle signal intensity or CT-muscle radiation attenuation.

Background: An inverse relation between chemotherapy-associated liver injury (CALI) and tumour response to chemotherapy has been reported. The aim was to validate these findings, and further investigate the impact of CALI on survival in patients who underwent partial hepatectomy for colorectal liver metastases (CRLM).Methods: Patients who received neoadjuvant chemotherapy and underwent partial hepatectomy for CRLM between 2008 and 2014 were included. Liver and tumour specimens were histologically examined for CALI (steatosis, steatohepatitis, sinusoidal dilatation [SD], nodular regeneration) and tumour regression grade (TRG). TRG 1-2 was defined as complete tumour response.Results: 166 consecutive patients were included with a median survival of 30 and 44 months for recurrence-free and overall survival, respectively. Grade 2-3 SD was found in 44 (27%) and TRG 1-2 was observed in 33 (20%) patients. Of studied CALI, only grade 2-3 SD was associated with increased TRG 3-5 (odds ratio 3.99, 95% CI 1.17-13.65, p = 0.027). CALI was not significantly related to survival. TRG 1-2 was associated with prolonged recurrence-free (hazard ratio 0.47, 95% CI 0.25-0.89, p = 0.020) and overall survival (hazard ratio 0.35, 95% CI 0.18-0.68, p = 0.002).Conclusion: CALI was not directly related to survival. CALI was, however, associated with diminished complete tumour response, and diminished complete tumour response, in turn, was associated with decreased survival.

Adaptation of the smooth muscle cell (SMC) phenotype is essential for homeostasis and is often involved in pathologies of visceral organs (e.g., uterus, bladder, gastrointestinal tract). In vitro studies of the behavior of visceral SMCs under (patho)-physiological conditions are hampered by a spontaneous, uncontrolled phenotypic modulation of visceral SMCs under regular tissue culture conditions. We aimed to develop a new visceral SMC culture model that allows controlled phenotypic modulation. Human uterine SMCs [ULTR and telomerase-immortalized human myometrial cells (hTERT-HM)] were grown to confluency and kept for up to 6 days on regular tissue culture surfaces or basement membrane (BM) matrix-coated surfaces in the presence of 0-10% serum. mRNA and protein expression and localization of SMC-specific phenotype markers and their transcriptional regulators were investigated by quantitative PCR, Western blotting, and immunofluorescence. Maintaining visceral SMCs confluent for 6 days increased alpha-smooth muscle actin (1.9-fold) and smooth muscle protein 22-alpha (3.1-fold), whereas smooth muscle myosin heavy chain was only slightly upregulated (1.3-fold). Culturing on a BM matrix-coated surface further increased these proteins and also markedly promoted mRNA expression of gamma-smooth muscle actin (15.0-fold), smoothelin (3.5-fold), h-caldesmon (5.2-fold), serum response factor (7.6-fold), and myocardin (8.1-fold). Whereas additional serum deprivation only minimally affected contractile markers, platelet-derived growth factor- BB and transforming growth factor beta 1 consistently reduced versus increased their expression. In conclusion, we present a simple and reproducible visceral SMC culture system that allows controlled phenotypic modulation toward both the synthetic and the contractile phenotype. This may greatly facilitate the identification of factors that drive visceral SMC phenotypic changes in health and disease.

Background and Aims: Human gut microbiota play an important role in maintaining human health. Dietary fibers, i.e. prebiotics, are fermented by human gut microbiota into the short-chain fatty acids (SCFAs) acetate, propionate, and butyrate. SCFAs promote fat oxidation and improve metabolic health. Therefore, the prebiotic inulin might be an effective dietary strategy to improve human metabolism. We aimed to investigate the acute metabolic effects of ingesting inulin compared with digestible carbohydrates and to trace inulin-derived SCFAs using stable isotope tracer methodology.Methods: In a double-blind, randomized, placebo-controlled crossover design, 14 healthy, overweight to obese men consumed a high-fat milkshake containing A) 24 g inulin of which 0.5 g was U-C-13-inulin (INU) or B) 24 g maltodextrin placebo (PLA), with a wash-out period of at least five days. Fat oxidation was measured via an open-circuit ventilated hood and blood samples were collected up to 7 h after ingestion. Plasma, breath, and fecal samples were collected, and appetite and satiety scores were assessed.Results: Fat oxidation increased in the early postprandial phase (0-3 h), and both plasma glucose and insulin were lower after INU ingestion compared with PLA (all P <0.05). Plasma free fatty acids were higher in the early, and lower in the late postprandial period after INU ingestion. Inulin was fermented into SCFAs as indicated by higher plasma acetate concentrations after INU compared with PLA (P <0.05). In addition, we found continuous increases in plasma C-13-SCFA enrichments (P <0.05 from t = 120 onwards) and breath (CO2)-C-13 enrichments after INU intake. There were no effects on plasma triglycerides, free glycerol, satiety hormones GLP-1 and PYY, and appetite and satiety scores.Conclusions: Ingestion of the prebiotic inulin improves fat oxidation and promotes SCFA production in overweight to obese men. Overall, replacing digestible carbohydrates with

Background: An inverse relation between chemotherapy-associated liver injury (CALI) and tumour response to chemotherapy has been reported. The aim was to validate these findings, and further investigate the impact of CALI on survival in patients who underwent partial hepatectomy for colorectal liver metastases (CRLM).Methods: Patients who received neoadjuvant chemotherapy and underwent partial hepatectomy for CRLM between 2008 and 2014 were included. Liver and tumour specimens were histologically examined for CALI (steatosis, steatohepatitis, sinusoidal dilatation [SD], nodular regeneration) and tumour regression grade (TRG). TRG 1-2 was defined as complete tumour response.Results: 166 consecutive patients were included with a median survival of 30 and 44 months for recurrence-free and overall survival, respectively. Grade 2-3 SD was found in 44 (27%) and TRG 1-2 was observed in 33 (20%) patients. Of studied CALI, only grade 2-3 SD was associated with increased TRG 3-5 (odds ratio 3.99, 95% CI 1.17-13.65, p = 0.027). CALI was not significantly related to survival. TRG 1-2 was associated with prolonged recurrence-free (hazard ratio 0.47, 95% CI 0.25-0.89, p = 0.020) and overall survival (hazard ratio 0.35, 95% CI 0.18-0.68, p = 0.002).Conclusion: CALI was not directly related to survival. CALI was, however, associated with diminished complete tumour response, and diminished complete tumour response, in turn, was associated with decreased survival.

Adaptation of the smooth muscle cell (SMC) phenotype is essential for homeostasis and is often involved in pathologies of visceral organs (e.g., uterus, bladder, gastrointestinal tract). In vitro studies of the behavior of visceral SMCs under (patho)-physiological conditions are hampered by a spontaneous, uncontrolled phenotypic modulation of visceral SMCs under regular tissue culture conditions. We aimed to develop a new visceral SMC culture model that allows controlled phenotypic modulation. Human uterine SMCs [ULTR and telomerase-immortalized human myometrial cells (hTERT-HM)] were grown to confluency and kept for up to 6 days on regular tissue culture surfaces or basement membrane (BM) matrix-coated surfaces in the presence of 0-10% serum. mRNA and protein expression and localization of SMC-specific phenotype markers and their transcriptional regulators were investigated by quantitative PCR, Western blotting, and immunofluorescence. Maintaining visceral SMCs confluent for 6 days increased alpha-smooth muscle actin (1.9-fold) and smooth muscle protein 22-alpha (3.1-fold), whereas smooth muscle myosin heavy chain was only slightly upregulated (1.3-fold). Culturing on a BM matrix-coated surface further increased these proteins and also markedly promoted mRNA expression of gamma-smooth muscle actin (15.0-fold), smoothelin (3.5-fold), h-caldesmon (5.2-fold), serum response factor (7.6-fold), and myocardin (8.1-fold). Whereas additional serum deprivation only minimally affected contractile markers, platelet-derived growth factor- BB and transforming growth factor beta 1 consistently reduced versus increased their expression. In conclusion, we present a simple and reproducible visceral SMC culture system that allows controlled phenotypic modulation toward both the synthetic and the contractile phenotype. This may greatly facilitate the identification of factors that drive visceral SMC phenotypic changes in health and disease.

Background: Myosteatosis, characterized by inter-and intramyocellular fat deposition, is strongly related to poor overall survival after surgery for periampullary cancer. It is commonly assessed by calculating the muscle radiation attenuation on computed tomography (CT) scans. However, since magnetic resonance imaging (MRI) is replacing CT in routine diagnostic work-up, developing methods based on MRI is important. We developed a new method using MRI-muscle signal intensity to assess myosteatosis and compared it with CT-muscle radiation attenuation.Methods: Patients were selected from a prospective cohort of 236 surgical patients with periampullary cancer. The MRI-muscle signal intensity and CT-muscle radiation attenuation were assessed at the level of the third lumbar vertebra and related to survival.Results: Forty-seven patients were included in the study. Inter-observer variability for MRI assessment was low (R-2 = 0.94). MRI-muscle signal intensity was associated with short survival: median survival 9.8 (95%-CI: 1.5-18.1) vs. 18.2 (95%-CI: 10.7-25.8) months for high vs. low intensity, respectively (p = 0.038). Similar results were found for CT-muscle radiation attenuation (low vs. high radiation attenuation: 10.8 (95%-CI: 8.5-13.1) vs. 15.9 (95%-CI: 10.2-21.7) months, respectively; p = 0.046). MRI-signal intensity correlated negatively with CT-radiation attenuation (r=-0.614, p <0.001).Conclusions: Myosteatosis may be adequately assessed using either MRI-muscle signal intensity or CT-muscle radiation attenuation.

Background In patients with resectable perihilar cholangiocarcinoma, biliary drainage is recommended to treat obstructive jaundice and optimise the clinical condition before liver resection. Little evidence exists on the preferred initial method of biliary drainage. We therefore investigated the incidence of severe drainage-related complications of endoscopic biliary drainage or percutaneous transhepatic biliary drainage in patients with potentially resectable perihilar cholangiocarcinoma.Methods We did a multicentre, randomised controlled trial at four academic centres in the Netherlands. Patients who were aged at least 18 years with potentially resectable perihilar cholangiocarcinoma requiring major liver resection, and biliary obstruction of the future liver remnant (defined as a bilirubin concentration of >50 mu mol/L [2.9 mg/dL]), were randomly assigned (1:1) to receive endoscopic biliary drainage or percutaneous transhepatic biliary drainage through the use of computer-generated allocation. Randomisation, done by the trial coordinator, was stratified for previous (attempted) biliary drainage, the extent of bile duct involvement, and enrolling centre. Patients were enrolled by clinicians of the participating centres. The primary outcome was the number of severe complications between randomisation and surgery in the intention-to-treat population. The trial was registered at the Netherlands National Trial Register, number NTR4243.Findings From Sept 26, 2013, to April 29, 2016, 261 patients were screened for participation, and 54 eligible patients were randomly assigned to endoscopic biliary drainage (n=27) or percutaneous transhepatic biliary drainage (n=27). The study was prematurely closed because of higher mortality in the percutaneous transhepatic biliary drainage group (11 [41%] of 27 patients) than in the endoscopic biliary drainage group (three [11%] of 27 patients; relative risk 3.67, 95% CI 1.15-11.69; p=0.03). Three of the 11 deaths

Background and Aims: Human gut microbiota play an important role in maintaining human health. Dietary fibers, i.e. prebiotics, are fermented by human gut microbiota into the short-chain fatty acids (SCFAs) acetate, propionate, and butyrate. SCFAs promote fat oxidation and improve metabolic health. Therefore, the prebiotic inulin might be an effective dietary strategy to improve human metabolism. We aimed to investigate the acute metabolic effects of ingesting inulin compared with digestible carbohydrates and to trace inulin-derived SCFAs using stable isotope tracer methodology. Methods: In a double-blind, randomized, placebo-controlled crossover design, 14 healthy, overweight to obese men consumed a high-fat milkshake containing A) 24 g inulin of which 0.5 g was U-C-13-inulin (INU) or B) 24 g maltodextrin placebo (PLA), with a wash-out period of at least five days. Fat oxidation was measured via an open-circuit ventilated hood and blood samples were collected up to 7 h after ingestion. Plasma, breath, and fecal samples were collected, and appetite and satiety scores were assessed. Results: Fat oxidation increased in the early postprandial phase (0-3 h), and both plasma glucose and insulin were lower after INU ingestion compared with PLA (all P < 0.05). Plasma free fatty acids were higher in the early, and lower in the late postprandial period after INU ingestion. Inulin was fermented into SCFAs as indicated by higher plasma acetate concentrations after INU compared with PLA (P < 0.05). In addition, we found continuous increases in plasma C-13-SCFA enrichments (P < 0.05 from t = 120 onwards) and breath (CO2)-C-13 enrichments after INU intake. There were no effects on plasma triglycerides, free glycerol, satiety hormones GLP-1 and PYY, and appetite and satiety scores. Conclusions: Ingestion of the prebiotic inulin improves fat oxidation and promotes SCFA production in overweight to obese men. Overall, replacing digestible carbohydrates with the fermentable in

Background: Detection of early-stage cancer significantly improves patient survival. As platelets play an important role in cancer progression, we aimed to investigate whether platelets can be used for the discovery of early-stage cancer.Methods: Patients with lung (n = 86) or head of pancreas (n = 42) cancer were included, as were healthy sex-and age-matched controls (n = 92). Blood was collected before initiation of treatment. Platelet count, volume and activation status were quantified in whole blood. Next, concentrations of vascular endothelial growth factor, platelet-derived growth factor, platelet factor 4, thrombospondin-1 and connective tissue-activating peptide III were measured in both platelets and plasma. Using the results, two multivariable diagnostic models were developed and internally validated.Findings: Multiple platelet features, including platelet count, volume and protein content, were significantly changed in lung and head of pancreas cancer patients. However, the pattern of changes differed between both groups. The diagnostic model developed for lung cancer discriminated very well between patients and controls (AUC = 88.7%). Addition of smoking as a variable significantly increased the AUC of the model to 94.5%. The diagnostic model for head of pancreas cancer also performed well (AUC = 82.7%). Both models were internally validated, resulting in optimism-corrected AUC's of 86.8% and 80.8%, respectively.Interpretation: In patients with lung or head of pancreas cancer, several platelet characteristics are changed compared to healthy sex-and age-matched controls. A cancer type-specific combination of these platelet features can be used to discriminate between patients with early-stage cancer and healthy individuals. (C) 2017 Elsevier Ltd. All rights reserved.

Background: Detection of early-stage cancer significantly improves patient survival. As platelets play an important role in cancer progression, we aimed to investigate whether platelets can be used for the discovery of early-stage cancer.Methods: Patients with lung (n = 86) or head of pancreas (n = 42) cancer were included, as were healthy sex-and age-matched controls (n = 92). Blood was collected before initiation of treatment. Platelet count, volume and activation status were quantified in whole blood. Next, concentrations of vascular endothelial growth factor, platelet-derived growth factor, platelet factor 4, thrombospondin-1 and connective tissue-activating peptide III were measured in both platelets and plasma. Using the results, two multivariable diagnostic models were developed and internally validated.Findings: Multiple platelet features, including platelet count, volume and protein content, were significantly changed in lung and head of pancreas cancer patients. However, the pattern of changes differed between both groups. The diagnostic model developed for lung cancer discriminated very well between patients and controls (AUC = 88.7%). Addition of smoking as a variable significantly increased the AUC of the model to 94.5%. The diagnostic model for head of pancreas cancer also performed well (AUC = 82.7%). Both models were internally validated, resulting in optimism-corrected AUC's of 86.8% and 80.8%, respectively.Interpretation: In patients with lung or head of pancreas cancer, several platelet characteristics are changed compared to healthy sex-and age-matched controls. A cancer type-specific combination of these platelet features can be used to discriminate between patients with early-stage cancer and healthy individuals. (C) 2017 Elsevier Ltd. All rights reserved.

A Summary background data: Hepatic sinusoidal dilatation (SD) is a histopathological entity that occurs in up to 75% of patients undergoing oxaliplatin-based chemotherapy for colorectal liver metastases (CRLM). Objective: To study the influence of SD on outcome after partial hepatectomy in patients with CRLM. Methods: Medline, Embase, CENTRAL, LILACS and CINAHL were searched for studies published between 01.01.2004 and 09.06.2015 with keywords: "sinusoidal obstruction syndrome", "hepatic veno-occlusive disease", and "Stuart-Bras syndrome". Studies comprising adults who underwent partial hepatectomy for CRLM with grading of SD and registration of postoperative morbidity and/or mortality were included. Risk of bias and quality of studies were evaluated with the Quality In Prognosis Studies Instrument (QUIPS) and modified GRADE framework. Results: Search strategies produced 2007 hits from which 23 and 13 articles were extracted for qualitative and quantitative analyses, respectively. Meta-analysis on the influence of SD grade 2-3 vs. SD grade 0-1 on postoperative overall morbidity showed an odds ratio (OR) of 1.26 [95% CI 0.74, 2.15](p = 0.40), an OR of 1.03 [0.15, 6.89]( p = 0.98) for liver failure, an OR of 1.21 [0.23, 6.35](p = 0.82) for overall mortality, and an OR of 3.52 [0.31, 39.91](p = 0.31) for liver-related morbidity. QUIPS showed a low to high risk of bias for studies, and GRADE showed very low quality of evidence per outcome. Conclusions: No significant effect of SD grade 2-3 on short-term outcome after partial hepatectomy was found. However, the data on which this conclusionwas based were not very robust and therefore no solid conclusions could be drawn.

A Summary background data: Hepatic sinusoidal dilatation (SD) is a histopathological entity that occurs in up to 75% of patients undergoing oxaliplatin-based chemotherapy for colorectal liver metastases (CRLM). Objective: To study the influence of SD on outcome after partial hepatectomy in patients with CRLM. Methods: Medline, Embase, CENTRAL, LILACS and CINAHL were searched for studies published between 01.01.2004 and 09.06.2015 with keywords: "sinusoidal obstruction syndrome", "hepatic veno-occlusive disease", and "Stuart-Bras syndrome". Studies comprising adults who underwent partial hepatectomy for CRLM with grading of SD and registration of postoperative morbidity and/or mortality were included. Risk of bias and quality of studies were evaluated with the Quality In Prognosis Studies Instrument (QUIPS) and modified GRADE framework. Results: Search strategies produced 2007 hits from which 23 and 13 articles were extracted for qualitative and quantitative analyses, respectively. Meta-analysis on the influence of SD grade 2-3 vs. SD grade 0-1 on postoperative overall morbidity showed an odds ratio (OR) of 1.26 [95% CI 0.74, 2.15](p = 0.40), an OR of 1.03 [0.15, 6.89]( p = 0.98) for liver failure, an OR of 1.21 [0.23, 6.35](p = 0.82) for overall mortality, and an OR of 3.52 [0.31, 39.91](p = 0.31) for liver-related morbidity. QUIPS showed a low to high risk of bias for studies, and GRADE showed very low quality of evidence per outcome. Conclusions: No significant effect of SD grade 2-3 on short-term outcome after partial hepatectomy was found. However, the data on which this conclusionwas based were not very robust and therefore no solid conclusions could be drawn.