Human precision-cut cystic duct and gallbladder slices: a novel method for studying cholangiopathies.

Background and aims: Precision-cut tissue slices (PCTS) are widely used as an ex vivo culture tissue culture technique to study pathogeneses of diseases and drug activities in organs in vitro. A novel application of the PCTS model may be in the field of translational research into cholangiopathies such as biliary atresia. Therefore, the aim of this study was to apply the precision-cut slice technique to human bile duct and gallbladder tissue. Methods: Cystic duct and gallbladder tissue derived from patients undergoing a cholecystectomy were collected, preserved and used for preparation of precision-cut cystic duct slices (PCCDS) and precision-cut gallbladder slices (PCGS). The PCCDS and PCGS were prepared using a mechanical tissue slicer and subsequently incubated for 24 and 48 h respectively in William's Medium E (WME) culture medium. Viability was assessed based on ATP/protein content and tissue morphology [hematoxylin and eosin (H&E) staining]. Results: It was shown that viability, assessed by the ATP/protein content and morphology, of the PCCDS (n = 8) and PCGS (n = 8) could be maintained over the 24 and 48 h incubation period respectively. ATP/protein content of the PCCDS increased significantly from 0.58 ± 0.13 pmol/µg at 0 h to 2.4 ± 0.29 pmol/µg after 24 h incubation (P = .0003). A similar significant increase from 0.94 ± 0.22 pmol/µg at 0 h to 3.7 ± 0.41 pmol/µg after 24 h (P = .0005) and 4.2 ± 0.47 pmol/µg after 48 h (P = .0002) was observed in the PCGS. Morphological assessment of the PCCDS and PCGS showed viable tissue at 0 h and after 24 and 48 h incubation respectively. Conclusion: This study is the first to report on the use of the PCTS model for human gallbladder and cystic duct tissue. PCCDS and PCGS remain viable for an incubation period of at least 24 h, which makes them suitable for research purposes in the field of cholangiopathies, including biliary atresia.

Outcome Reporting in Interventional Necrotizing Enterocolitis Studies: A Systematic Review.

BACKGROUND: Despite an increasing necrotizing enterocolitis (NEC) incidence, treatment strategies have failed to make major advancements towards improved NEC outcomes. Heterogeneity in outcome reporting and a lack of treatment efficacy studies potentially hamper these advancements. We aimed to analyze outcome reporting in recent interventional NEC studies. METHODS: We performed a systematic review identifying interventional studies on NEC between 1st of January 2016 and 1st of June 2023 in MEDLINE, Embase, CENTRAL and Cochrane reviews. Systematic reviews, clinical trials and change-in-practice cohort studies reporting any therapeutic intervention for NEC patients (Bell's stage ≥ IIa) were eligible. We excluded studies on NEC diagnostics or prevention and non-English publications. Outcomes were categorized into five core areas and presented descriptively. The review was registered with PROSPERO (CRD42022302712). RESULTS: Out of 1.642 screened records, 65 were eligible for full-text review and 15 were finally included for data extraction. Median number of reported outcomes per article was six (range 1-19). We identified 66 unique outcomes, which were mapped to 53 outcome terms. Thirty-four out of the 53 of the outcome terms (64%) were only reported in a single article. Mortality was the most reported outcome (11/15 articles, 73%). Core area 'Adverse outcomes' contained the most outcome terms (n = 19), whereas 'Life impact' contained the least outcome terms (n = 4) and was represented in 3 articles (20%). CONCLUSIONS: Considerable heterogeneity in outcome reporting and a paucity of outcomes concerning 'Life impact' exist in interventional NEC studies. Development of a NEC core outcome set may improve consistency and patient-relevance in outcome reporting. STUDY TYPE: Systematic Review and Meta-Analyses. LEVEL OF EVIDENCE: III.

Surgery or comfort care for neonates with surgical necrotizing enterocolitis: Lessons learned from behavioral artificial intelligence technology.

Background: Critical decision making in surgical necrotizing enterocolitis (NEC) is highly complex and hard to capture in decision rules due to case-specificity and high mortality risk. In this choice experiment, we aimed to identify the implicit weight of decision factors towards future decision support, and to assess potential differences between specialties or centers. Methods: Thirty-five hypothetical surgical NEC scenarios with different factor levels were evaluated by neonatal care experts of all Dutch neonatal care centers in an online environment, where a recommendation for surgery or comfort care was requested. We conducted choice analysis by constructing a binary logistic regression model according to behavioral artificial intelligence technology (BAIT). Results: Out of 109 invited neonatal care experts, 62 (57%) participated, including 45 neonatologists, 16 pediatric surgeons and one neonatology physician assistant. Cerebral ultrasound (Relative importance = 20%, OR = 4.06, 95% CI = 3.39-4.86) was the most important factor in the decision surgery versus comfort care in surgical NEC, nationwide and for all specialties and centers. Pediatric surgeons more often recommended surgery compared to neonatologists (62% vs. 57%, p = 0.03). For all centers, cerebral ultrasound, congenital comorbidity, hemodynamics and parental preferences were significant decision factors (p < 0.05). Sex (p = 0.14), growth since birth (p = 0.25), and estimated parental capacities (p = 0.06) had no significance in nationwide nor subgroup analyses. Conclusion: We demonstrated how BAIT can analyze the implicit weight of factors in the complex and critical decision for surgery or comfort care for (surgical) NEC. The findings reflect Dutch expertise, but the technique can be expanded internationally. After validation, our choice model/BAIT may function as decision aid.

Genotype-phenotype relationships of truncating mutations, p.E297G and p.D482G in bile salt export pump deficiency.

Background & Aims: Bile salt export pump (BSEP) deficiency frequently necessitates liver transplantation in childhood. In contrast to two predicted protein truncating mutations (PPTMs), homozygous p.D482G or p.E297G mutations are associated with relatively mild phenotypes, responsive to surgical interruption of the enterohepatic circulation (siEHC). The phenotype of patients with a compound heterozygous genotype of one p.D482G or p.E297G mutation and one PPTM has remained unclear. We aimed to assess their genotype-phenotype relationship. Methods: From the NAPPED database, we selected patients with homozygous p.D482G or p.E297G mutations (BSEP1/1; n = 31), with one p.D482G or p.E297G, and one PPTM (BSEP1/3; n = 30), and with two PPTMs (BSEP3/3; n = 77). We compared clinical presentation, native liver survival (NLS), and the effect of siEHC on NLS. Results: The groups had a similar median age at presentation (0.7-1.3 years). Overall NLS at age 10 years was 21% in BSEP1/3 vs. 75% in BSEP1/1 and 23% in BSEP3/3 (p <0.001). Without siEHC, NLS in the BSEP1/3 group was similar to that in BSEP3/3, but considerably lower than in BSEP1/1 (at age 10 years: 38%, 30%, and 71%, respectively; p = 0.003). After siEHC, BSEP1/3 and BSEP3/3 were associated with similarly low NLS, while NLS was much higher in BSEP1/1 (10 years after siEHC, 27%, 14%, and 92%, respectively; p <0.001). Conclusions: Individuals with BSEP deficiency with one p.E297G or p.D482G mutation and one PPTM have a similarly severe disease course and low responsiveness to siEHC as those with two PPTMs. This identifies a considerable subgroup of patients who are unlikely to benefit from interruption of the enterohepatic circulation by either surgical or ileal bile acid transporter inhibitor treatment. Impact and implications: This manuscript defines the clinical features and prognosis of individuals with BSEP deficiency involving the combination of one relatively mild and one very severe BSEP deficiency mutation. Until now, it had always been assumed that the mild mutation would be enough to ensure a relatively good prognosis. However, our manuscript shows that the prognosis of these patients is just as poor as that of patients with two severe mutations. They do not respond to biliary diversion surgery and will likely not respond to the new IBAT (ileal bile acid transporter) inhibitors, which have recently been approved for use in BSEP deficiency.

Safety and Feasibility of Indocyanine Green Fluorescence Angiography in Pediatric Gastrointestinal Surgery: A Systematic Review.

BACKGROUND: Although ICG-FA may be valuable in assessing anastomotic perfusion, reliable data on its use in pediatric gastrointestinal surgery is lacking. This systematic review analyzes whether ICG is useful for intestinal perfusion assessment in pediatric gastrointestinal surgery and safe to use in neonates. METHODS: Systematic searches of PubMed, EMBASE & MEDLINE and CENTRAL were performed (last conducted December 6, 2021). The main inclusion criteria were (1) use of ICG for intestinal perfusion assessment and (2) use of ICG in young infants. Exclusion criteria were lack of an English or Dutch full-text and MINORS quality score <60%. Data was presented in overview tables. The usefulness in pediatric gastrointestinal surgery was assessed by surgical outcome. Safety of ICG in neonates was assessed by complication or adverse event occurrence. RESULTS: Regarding intestinal perfusion assessment, four studies were included, reporting 45 patients (median age 1.5 years). ICG was considered useful for anastomotic blood flow evaluation and intraoperative determination of resection length. Regarding ICG safety in neonates, eight studies were included, reporting 46 infants (median age 24.9 days), of which 18 neonates. All but one studies reported the absence of complications or adverse events. Two studies reported subcutaneous dye retention, which fully disappeared within two weeks. CONCLUSION: Although the number of available studies is small, ICG might be useful for intraoperative intestinal perfusion assessment, perhaps even more than conventional clinical assessment. Furthermore, its safety profile looks promising in neonates. Larger prospective studies are necessary to confirm these assumptions and seem warranted given the safety profile. LEVELS OF EVIDENCE: Since this is a systematic review, a Level of Evidence for clinical studies cannot be determined for this manuscript.

Biliary Atresia in 2021: Epidemiology, Screening and Public Policy.

Biliary atresia (BA) is a rare newborn liver disease with significant morbidity and mortality, especially if not recognized and treated early in life. It is the most common cause of liver-related death in children and the leading indication for liver transplantation in the pediatric population. Timely intervention with a Kasai portoenterostomy (KPE) can significantly improve prognosis. Delayed disease recognition, late patient referral, and untimely surgery remains a worldwide problem. This article will focus on biliary atresia from a global public health perspective, including disease epidemiology, current national screening programs, and their impact on outcome, as well as new and novel BA screening initiatives. Policy challenges for the implementation of BA screening programs will also be discussed, highlighting examples from the North American, European, and Asian experience.

Controversies in Choledochal Malformation in Children: An International Survey among Pediatric Hepatobiliary Surgeons and Gastroenterologists.

BACKGROUND: While congenital choledochal malformation (CCM) is relatively well known within the pediatric surgical and pediatric gastroenterological communities, many controversies and questions remain. METHODS: In this paper, we will discuss the results of an international Delphi survey among members of the European Reference Network RARE-LIVER and of the faculty of the Biliary Atresia and Related Diseases (BARD) network to identify the most common practices as well as controversies regarding diagnosis, treatment and follow-up of this still enigmatic disease. RESULTS: Twenty-two individual respondents completed the survey. While there seems to be agreement on the definitions of CCM, preoperative workup, surgical approach and follow-up still vary considerably. The mainstay of treatment remains the removal of the entire extrahepatic biliary tract, clearance of debris both proximally and distally, followed by reconstruction with (according to 86% of respondents) a Roux-en-Y hepaticojejunostomy. Nonetheless, both laparoscopic and robotic-assisted resections are gaining ground with the suggestion that this might be facilitated by concentration of care and resources in specialized centers. However, long-term outcomes are still lacking. CONCLUSIONS: As even post-surgical CCM has to be considered as having premalignant potential, follow-up should be well-organized and continued into adulthood. This seems to be lacking in many centers. International cooperation for both benchmarking and research is paramount to improving care for this rare disease.

Intestinal Oxygenation and Survival After Surgery for Necrotizing Enterocolitis: An Observational Cohort Study.

OBJECTIVE: To assess whether regional intestinal oxygen saturation (rintSO2) and regional cerebral oxygen saturation (rcSO2) measurements aid in estimating survival of preterm infants after surgery for NEC. SUMMARY OF BACKGROUND DATA: Predicting survival after surgery for NEC is difficult yet of the utmost importance for counseling parents. METHODS: We retrospectively studied prospectively collected data of preterm infants with surgical NEC who had available rintSO2 and rcSO2 values measured via near-infrared spectroscopy 0-24 hours preoperatively. We calculated mean rintSO2 and rcSO2 for 60-120 minutes for each infant. We analyzed whether preoperative rintSO2 and rcSO2 differed between survivors and non-survivors, determined cut-off points, and assessed the added value to clinical variables. RESULTS: We included 22 infants, median gestational age 26.9 weeks [interquartile range (IQR): 26.3-28.4], median birth weight 1088 g [IQR: 730-1178]. Eleven infants died postoperatively. Preoperative rintSO2, but not rcSO2, was higher in survivors than in non-survivors [median: 63% (IQR: 42-68) vs 29% (IQR: 21-43), P < 0.01), with odds ratio for survival 4.1 (95% confidence interval, 1.2-13.9, P = 0.02) per 10% higher rintSO2. All infants with rintSO2 values of >53% survived, whereas all infants with rintSO2 <35% died. Median C-reactive protein [138 mg/L (IQR: 83-179) vs 73 mg/L (IQR: 12-98), P < 0.01), lactate [1.1 mmol/L (IQR: 1.0-1.6) vs 4.6 mmol/L (IQR: 2.8-8.0), P < 0.01], and fraction of inspired oxygen [25% (IQR: 21-31) vs 42% (IQR: 30-80), P < 0.01] differed between survivors and non-survivors. Only rintSO2 remained significant in the multiple regression model. CONCLUSIONS: Measuring rintSO2, but not rcSO2, seems of added value to clinical variables in estimating survival of preterm infants after surgery for NEC. This may help clinicians in deciding whether surgery is feasible and to better counsel parents about their infants' chances of survival.

Parental wellbeing after diagnosing a child with biliary atresia: A prospective cohort study.

PURPOSE: To determine anxiety, stress, and quality of life (QoL) in parents of children who are diagnosed with biliary atresia (BA). METHODS: Parents of BA patients (0-3 years) completed validated questionnaires at three time points: at first hospitalization (T0); 1-2 months post diagnosis (T1); and 2-3 years post diagnosis (T2). Results are presented in medians (min-max). RESULTS: We included 52 parents (age 31 [24-51 y], 31 females) of 30 BA patients. In fathers, neither anxiety nor stress levels significantly differed from reference values. Mothers reported significantly higher anxiety levels compared to reference values (T0: 48 vs 35, p = 0.001; T1: 43 vs 35, p = 0.03; T2: 37 vs 35, p = 0.04), which significantly decreased over time (-23% between T0 and T2: p = 0.04). Stress in mothers was significantly higher at T1 than at T2 (+35%, p = 0.02), but was not significantly different from reference values at each time point (T0: 17 vs 14, p = 0.07; T1: 18 vs 14, p = 0.09; T2: 13 vs 14, p = 0.52).The overall QoL in mothers and fathers was rather unaffected. CONCLUSIONS: Particularly mothers of infants diagnosed with BA report high anxiety levels up to three years after diagnosis. The overall QoL of parents is rather unaffected after diagnosing BA in their child. LEVEL OF EVIDENCE: Level 2.

Blood group AB is associated with poor outcomes in infants with necrotizing enterocolitis.

BACKGROUND: Necrotizing enterocolitis (NEC) is a neonatal disease associated with necrosis and perforation of the bowel. We investigated the association between blood group and NEC outcomes and the potential contribution of fetal-maternal blood group incompatibility. METHODS: Retrospective study including all preterm-born infants with NEC (≥ Bell's stage IIa) admitted to our NICU between January 2008 and October 2019. We analyzed the association between infants' blood groups and fetal-maternal blood group incompatibility with Bell stage severity, need for surgery, and mortality due to NEC. RESULTS: We included 237 NEC patients. In univariable analyses both AB blood group and fetal-maternal blood group incompatibility increased infants' risk of severe outcomes, with odds ratios (OR) ranging from 6.57 to 12.06 and 1.97 to 2.38, respectively. When adjusted for gestational age only AB blood group remained significant with OR 7.47 (95% confidence interval, 1.95-28.53, P = 0.003), 12.37 (2.63-58.20, P = 0.001), and 8.16 (2.28-29.14, P = 0.001) for NEC Bell's stage III, need for surgery, and NEC related mortality, respectively. Blood group incompatibility adjusted for gestational age was not related to worse outcomes with OR 1.84 (0.87-3.89, P = 0.11, 2.08 (0.98-4.41, P = 0.06) 1.52 (0.68-3.42, P = 0.31), for NEC Bell's stage III, need for surgery, and NEC related mortality, respectively. CONCLUSION: Our data confirm an association between blood group AB and worse outcomes in NEC infants, but this is not based on fetal-maternal blood group incompatibility.

Impact of Genotype, Serum Bile Acids, and Surgical Biliary Diversion on Native Liver Survival in FIC1 Deficiency.

BACKGROUND AND AIMS: Mutations in ATPase phospholipid transporting 8B1 (ATP8B1) can lead to familial intrahepatic cholestasis type 1 (FIC1) deficiency, or progressive familial intrahepatic cholestasis type 1. The rarity of FIC1 deficiency has largely prevented a detailed analysis of its natural history, effects of predicted protein truncating mutations (PPTMs), and possible associations of serum bile acid (sBA) concentrations and surgical biliary diversion (SBD) with long-term outcome. We aimed to provide insights by using the largest genetically defined cohort of patients with FIC1 deficiency to date. APPROACH AND RESULTS: This multicenter, combined retrospective and prospective study included 130 patients with compound heterozygous or homozygous predicted pathogenic ATP8B1 variants. Patients were categorized according to the number of PPTMs (i.e., splice site, frameshift due to deletion or insertion, nonsense, duplication), FIC1-A (n = 67; no PPTMs), FIC1-B (n = 29; one PPTM), or FIC1-C (n = 34; two PPTMs). Survival analysis showed an overall native liver survival (NLS) of 44% at age 18 years. NLS was comparable among FIC1-A, FIC1-B, and FIC1-C (% NLS at age 10 years: 67%, 41%, and 59%, respectively; P = 0.12), despite FIC1-C undergoing SBD less often (% SBD at age 10 years: 65%, 57%, and 45%, respectively; P = 0.03). sBAs at presentation were negatively associated with NLS (NLS at age 10 years, sBAs < 194 µmol/L: 49% vs. sBAs ≥ 194 µmol/L: 15%; P = 0.03). SBD decreased sBAs (230 [125-282] to 74 [11-177] µmol/L; P = 0.005). SBD (HR 0.55, 95% CI 0.28-1.03, P = 0.06) and post-SBD sBA concentrations < 65 µmol/L (P = 0.05) tended to be associated with improved NLS. CONCLUSIONS: Less than half of patients with FIC1 deficiency reach adulthood with native liver. The number of PPTMs did not associate with the natural history or prognosis of FIC1 deficiency. sBA concentrations at initial presentation and after SBD provide limited prognostic information on long-term NLS.

A Higher Incidence of Isolated Biliary Atresia in Rural Areas: Results From an Epidemiological Study in The Netherlands.

OBJECTIVES: Environmental factors may be involved in the pathogenesis of biliary atresia (BA). This epidemiological study aimed to analyze the relationships between the incidence of BA, the incidence of confirmed viral or bacterial infections and population density, and geographical and temporal clustering of BA in the Netherlands. STUDY DESIGN: Correlations between the monthly incidence of BA and the number of confirmed infections were assessed. BA incidence per province was calculated and compared to the province with highest population density. Birthplaces were classified as rural or urban. Temporal clustering of month of birth and month of conception were analyzed. We performed analyses for isolated BA (IBA) and syndromic BA (SBA) separately. Chi2, logistic regression, and Walter and Elwood test were used. RESULTS: A total of 262 IBA and 49 SBA patients, born between 1987 and 2018, were included. IBA incidence correlated to the number of confirmed infections of, for example, Chlamydia trachomatis (R = 0.14; P = 0.02) and adenovirus (R = 0.22; P = 0.005). We observed a higher incidence of IBA (0.75/10,000; odds ratio [OR] = 1.86; P = 0.04) and SBA (0.27/10,000; OR = 6.91; P = 0.001) in Groningen and a higher incidence of SBA in Gelderland (0.13/10,000; OR = 3.35; P = 0.03). IBA incidence was 68% higher in rural (0.67/10,000) versus urban areas (0.40/10,000) (P = 0.02). The estimated month of conception of patients with SBA clustered in November (85% increase compared to average SBA incidence [0.09/10,000; P = 0.04]). CONCLUSIONS: IBA incidence correlated weakly with national confirmed infections. IBA and SBA incidence varied geographically in the Netherlands. IBA incidence was higher in rural than in urban areas, which may be explained decreased exposure to pathogens. Our results provide support for a role of environmental factors in the pathogenesis of IBA.

Plasma citrulline during the first 48 h after onset of necrotizing enterocolitis in preterm infants.

BACKGROUND: Levels of plasma citrulline (citrulline-P), a biomarker for enterocyte function, might be useful for the monitoring the course of necrotizing enterocolitis (NEC). Our aim was to evaluate whether citrulline-P levels during the first 48 h (h) after NEC onset were associated with need for surgery, survival, and intestinal recovery. METHODS: In preterm infants with NEC (Bell's stage ≥2) we measured citrulline-P levels during the first 48 h after NEC onset. Categorizing the measurements into 0-8 h, 8-16 h, 16-24 h, 24-36 h, and 36-48 h, we determined the course of citrulline-P using linear regression analyses. Next, we analyzed whether citrulline-P levels measured at 0-24 h and 24-48 h differed between conservative and surgical treatment, survivors and nonsurvivors, and equal/below and above total group's median time to full enteral feeding (FEFt). RESULTS: We included 48 infants, median gestational age 28.3 [IQR:26.0-31.4] weeks, birth weight 1200 [IQR:905-1524] grams. Citrulline-P levels decreased the first 48 h (B per time interval: -1.40 µmol, 95% CI, -2.73 to -0.07, p = 0.04). Citrulline-P was not associated with treatment, nor with survival. Citrulline-P at 0-24 h, but not 24-48 h, was higher in infants with FEFt ≤20 days than in infants with FEFt >20 days (20.7 [IQR:19.9-25.3] µmol/L (n = 13) vs. 11.1 [IQR:8.4-24.0] µmol/L (n = 11), p = 0.049), with a citrulline-P cut-off value of 12.3 µmol/L. CONCLUSION: Citrulline-P levels decreased the first 48 h after NEC onset, suggesting on-going intestinal injury. In survivors, measuring citrulline-P in the first 24 h after NEC onset may provide an indication for intestinal recovery rate.

The Dutch Incidence of Infantile Hypertrophic Pyloric Stenosis and the Influence of Seasons.

INTRODUCTION: Studies report contradicting results on the incidence of infantile hypertrophic pyloric stenosis (IHPS) and its association with seasons. We aim to assess the IHPS incidence in the Netherlands and to determine whether seasonal variation is present in a nationwide cohort. MATERIALS AND METHODS: All infants with IHPS hospitalized in the Netherlands between 2007 and 2017 were included in this retrospective cohort study. Incidence rates per 1,000 livebirths (LB) were calculated using total number of LB during the matched month, season, or year, respectively. Seasonal variation based on month of birth and month of surgery was analyzed using linear mixed model and one-way ANOVA, respectively. RESULTS: A total of 2,479 infants were included, of which the majority was male (75.9%). Median (interquartile range) age at surgery was 34 (18) days. The average IHPS incidence rate was 1.28 per 1,000 LB (variation: 1.09-1.47 per 1,000 LB). We did not find a conclusive trend over time in IHPS incidence. Differences in incidence between season of birth and season of surgery were not significant (p = 0.677 and p = 0.206, respectively). CONCLUSION: We found an average IHPS incidence of 1.28 per 1,000 LB in the Netherlands. Our results showed no changing trend in incidence and no seasonal variation.

Intra-abdominal hypertension and abdominal compartment syndrome in patients admitted to the ICU.

BACKGROUND: Intra-abdominal hypertension is frequently present in critically ill patients and is an independent predictor for mortality. Risk factors for intra-abdominal hypertension and abdominal compartment syndrome have been widely investigated. However, data are lacking on prevalence and outcome in high-risk patients. Our objectives in this study were to investigate prevalence and outcome of intra-abdominal hypertension and abdominal compartment syndrome in high-risk patients in a prospective, observational, single-center cohort study. RESULTS: Between March 2014 and March 2016, we included 503 patients, 307 males (61%) and 196 females (39%). Patients admitted to the intensive care unit with a diagnosis of pancreatitis, elective or emergency open abdominal aorta surgery, orthotopic liver transplantation, other elective or emergency major abdominal surgery and trauma were enrolled. One hundred and sixty four (33%) patients developed intra-abdominal hypertension and 18 (3.6%) patients developed abdominal compartment syndrome. Highest prevalence of abdominal compartment syndrome occurred in pancreatitis (57%) followed by orthotopic liver transplantation (7%) and abdominal aorta surgery (5%). Length of intensive care stay increased by a factor 4 in patients with intra-abdominal hypertension and a factor 9 in abdominal compartment syndrome, compared to patients with normal intra-abdominal pressure. Rate of renal replacement therapy was higher in abdominal compartment syndrome (38.9%) and intra-abdominal hypertension (8.2%) compared to patients with normal intra-abdominal pressure (1.2%). Both intensive care mortality and 90-day mortality were significantly higher in intra-abdominal hypertension (4.8% and 15.2%) and abdominal compartment syndrome (16.7% and 38.9%) compared to normal intra-abdominal pressure (1.2% and 7.1%). Body mass index (odds ratio 1.08, 95% confidence interval 1.03-1.13), mechanical ventilation at admission (OR 3.52, 95% CI 2.08-5.96) and Apache IV score (OR 1.03, 95% CI 1.02-1.04) were independent risk factors for the development of intra-abdominal hypertension or abdominal compartment syndrome. CONCLUSIONS: The prevalence of abdominal compartment syndrome was 3.6% and the prevalence of intra-abdominal hypertension was 33% in this cohort of high-risk patients. Morbidity and mortality increased when intra-abdominal hypertension or abdominal compartment syndrome was present. The patient most at risk of IAH or ACS in this high-risk cohort has a BMI > 30 kg/m2 and was admitted to the ICU after emergency abdominal surgery or with a diagnosis of pancreatitis.

Health-Related Quality of Life in Biliary Atresia Patients with Native Liver or Transplantation.

INTRODUCTION: We aimed to assess health-related quality of life (HrQoL) in biliary atresia (BA) patients, based on original data and a literature review, and to determine factors associated with their HrQoL. MATERIALS AND METHODS: We reviewed available studies describing HrQoL in BA patients. We assessed HrQoL in Dutch BA patients (6-16 years) using the validated Child Health Questionnaire. We compared HrQoL scores in BA patients with healthy peers and with children who had undergone major surgery in infancy or children with chronic conditions. We determined the relationship between specific patient-related factors and HrQoL. RESULTS: Literature data indicated that HrQoL in children with BA is lower than in healthy peers. In Dutch BA patients (n = 38; age 10 ± 3 years), parent-proxy physical HrQoL (48 ± 11) was significantly lower compared with two reference groups of healthy peers (59 ± 4 and 56 ± 6, respectively, each p < 0.001), and lower than in children with attention deficit hyperactivity disorder (60 ± 5), asthma (54 ± 6), attending a cardiology clinic (52 ± n/r), congenital diaphragmatic hernia (53 ± 7) or D-transposition of the great arteries (54 ± 6; all p < 0.05). Psychosocial HrQoL (50 ± 9) was lower than in healthy peers (54 ± 6, p = 0.02, and 53 ± 6, p = 0.07) and children with asthma (54 ± 6, p = 0.02), and largely comparable to children with other chronic conditions. Parent-proxy physical HrQoL was adversely related to adverse medical event in the past year, special education, and motor impairments; psychosocial HrQoL was adversely related to behavioral problems. CONCLUSION: Children with BA are at risk of impaired HrQoL. Special attention is warranted for children with adverse medical events and special education.

Choledochal malformations in adults in the Netherlands: Results from a nationwide retrospective cohort study.

BACKGROUND AND AIMS: Patients with a choledochal malformation, formerly described as cysts, are at increased risk of developing a cholangiocarcinoma and resection is recommended. Given the low incidence of choledochal malformation (CM) in Western countries, the incidence in these countries is unclear. Our aim was to assess the incidence of malignancy in CM patients and to assess postoperative outcome. METHODS: In a nationwide, retrospective study, all adult patients who underwent surgery for CM between 1990 and 2016 were included. Patients were identified through the Dutch Pathology Registry and local patient records and were analysed to determine the incidence of malignancy, as well as postoperative mortality and morbidity. RESULTS: A total of 123 patients with a CM were included in the study (Todani Type I, n = 71; Type II, n = 10; Type III, n = 3; Type IV, n = 27; unknown, n = 12). Median age was 40 years (range 18-70) and 81% were female. The majority of patients (99/123) underwent extrahepatic bile duct resection, with additional liver parenchyma resections in eight patients, only exploration in two, and a local cyst resection in eight patients. Postoperative 30-day mortality was 2% (2/123) and limited to patients who underwent liver resection. Severe morbidity occurred in 24%. In 14 of the 123 patients (11%), a malignancy was found in the resected specimen. One patient developed a periampullary malignancy 7 years later. CONCLUSIONS: In a large Western series of CM patients, 11% were found to have a malignancy. This justifies resection in these patients, despite the risk of morbidity (24%) and mortality (2%).

Genotype correlates with the natural history of severe bile salt export pump deficiency.

BACKGROUND & AIMS: Mutations in ABCB11 can cause deficiency of the bile salt export pump (BSEP), leading to cholestasis and end-stage liver disease. Owing to the rarity of the disease, the associations between genotype and natural history, or outcomes following surgical biliary diversion (SBD), remain elusive. We aimed to determine these associations by assembling the largest genetically defined cohort of patients with severe BSEP deficiency to date. METHODS: This multicentre, retrospective cohort study included 264 patients with homozygous or compound heterozygous pathological ABCB11 mutations. Patients were categorized according to genotypic severity (BSEP1, BSEP2, BSEP3). The predicted residual BSEP transport function decreased with each category. RESULTS: Genotype severity was strongly associated with native liver survival (NLS, BSEP1 median 20.4 years; BSEP2, 7.0 years; BSEP3, 3.5 years; p <0.001). At 15 years of age, the proportion of patients with hepatocellular carcinoma was 4% in BSEP1, 7% in BSEP2 and 34% in BSEP3 (p = 0.001). SBD was associated with significantly increased NLS (hazard ratio 0.50; 95% CI 0.27-0.94: p = 0.03) in BSEP1 and BSEP2. A serum bile acid concentration below 102 µmol/L or a decrease of at least 75%, each shortly after SBD, reliably predicted NLS of ≥15 years following SBD (each p <0.001). CONCLUSIONS: The genotype of severe BSEP deficiency strongly predicts long-term NLS, the risk of developing hepatocellular carcinoma, and the chance that SBD will increase NLS. Serum bile acid parameters shortly after SBD can predict long-term NLS. LAY SUMMARY: This study presents data from the largest genetically defined cohort of patients with severe bile salt export pump deficiency to date. The genotype of patients with severe bile salt export pump deficiency is associated with clinical outcomes and the success of therapeutic interventions. Therefore, genotypic data should be used to guide personalized clinical care throughout childhood and adulthood in patients with this disease.