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Publisher Copyright: © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. Objectives: The development of intestinal failure-related complications in Finnish adults is unknown. This study aimed to investigate the incidence of catheter-related bloodstream infections (CRBSI), and the longitudinal changes in biochemical liver and kidney tests in a nationwide cohort. Materials and methods: The search for Finnish adults with intestinal failure (IF) utilized a survey to Finnish health-care providers (n = 111) with the potential to provide long-term parenteral support (PS) for adult IF. Our nationwide, cross-sectional cohort included all IF patients aged ≥ 18 years who had received PS for ≥ 120 d in 2017. Data regarding CRBSI and biochemical liver and kidney tests were collected from patient records at the start of PS up to the latest available measurement in 2017. Results: In the nationwide cohort of 52 patients, the CRBSI incidence was 1.35/1000 catheter days. Seventy-three percent of CRBSI in a long-term catheter led to catheter replacement. During a median PS duration of 27.5 (interquartile range [IQR] 11.3–57.3) months, a statistically significant median change occurred in estimated glomerular filtration rate (eGFR; −8.5 ml/min/1.73 m2, IQR −30–7, p =.005) and alkaline phosphatase (ALP; 26 U/l, IQR −11–95, p =.019). In a multiple regression model for eGFR at data collection, baseline eGFR and age were strong explanatory variables. Conclusions: Incidence of CRBSI, but not treatment strategies, in this nationwide adult IF population correspond well to those reported from specialized centers. Decreased kidney function and abnormal liver test results are frequent findings, and even more so over time, emphasizing the importance of regular monitoring.

Aim: We aimed to assess management, comorbidities, biliary histopathology and outcomes of choledochal malformations (CM) in adults. Methods: All adult CM patients managed during 1987–2021 at the Helsinki University Hospital were retrospectively reviewed. Results: Of the 39 patients (females 79%) identified, 19 (49%) underwent surgery, 5 (13%) therapeutic ERCP with papillotomy for type 3 CM and 15 (38%) were managed conservatively. Twenty-five (66%) patients had ≥1 comorbidity, and five (13%) patients had associated inflammatory bowel disease (IBD); ulcerative colitis (n = 3) and Crohn’s disease (n = 2). Most surgically treated patients underwent hepaticojejunostomy (n = 13) or pancreaticoduodenectomy (n = 3) and they were younger at presentation than other patients [29 (21 – 48) vs. 59 (41 – 71), p = 0.001]. Three patients (23%) suffered from pancreatitis following diagnostic ERCP. Early surgical complications occurred in six (32%) patients, including one anastomotic leakage. Biliary epithelial dysplasia was found in three (15%) patients in resected specimens, while no neoplastic changes were observed. Nine patients (47%) had long-term postoperative complications, cholangitis (n = 5) and anastomotic stricture (n = 3) being the most common ones. No evidence of malignant change was observed after median follow-up of 2.3 (0.60 − 4.5) years included all patient cohorts. Conservatively managed patients remained symptomless with unprogressive biliary tract imaging findings and normal liver biochemistry values during follow-up. Nearly half of operated patients developed long-term postoperative complications. A novel association between CMs and IBD was observed. Although no hepatobiliary malignancies regardless of treatment modality were encountered, the number of patients and length of follow-up remained limited.

Background: Information is needed regarding the complex relationships between long-term functional outcomes and health-related quality of life (HRQoL) in Hirschsprung's Disease (HSCR). We describe longterm outcomes across multiple domains, completing a core outcome set through to adulthood. Methods: HSCR patients operated at a single center over a 35-year period (1978-2013) were studied. Patients completed detailed questionnaires on bowel and urologic function, and HRQOL. Patients with learning disability (LD) were excluded. Outcomes were compared to normative data. Data are reported as median [IQR] or mean (SD). Results: 186 patients (median age 28 [18-32] years; 135 males) completed surveys. Bowel function was reduced (BFS 17 [14-19] vs. 19 [19-20], p < 0.0001;eta(2) = 0.22). Prevalence and severity of fecal soiling and fecal awareness improved with age ( p < 0.05 for both). Urinary incontinence was more frequent than controls, most of all in 13-26y females (65% vs. 31%, p = 0.003). In adults, this correlated independently with constipation symptoms (OR 3.18 [1.4-7.5], p = 0.008). HRQoL outcomes strongly correlated with functional outcome: 42% of children demonstrated clinically significant reductions in overall PedsQL score, and poor bowel outcome was strongly associated with impaired QOL (B = 22.7 [12.7- 32.7], p < 0.001). In adults, GIQLI scores were more often impacted in patients with extended segment disease. SF-36 scores were reduced relative to population level data in most domains, with large effect sizes noted for females in General Health (g = 1.19) and Social Wellbeing (g = 0.8). Conclusion: Functional impairment is common after pull-through, but bowel function improves with age. Clustering of poor functional outcomes across multiple domains identifies a need for early recognition and long-term support for these patients. (C) 2021 Elsevier Inc. All rights reserved.

An assessment of the clinical data and outcome of patients with oesophageal atresia (OA) with very low birth weight (VLBW) was completed.With ethical consent, we reviewed the records of 327 successive patients with OA from 1980 to 2020. Main outcome measures survival and oesophageal repair were compared between patients with VLBW(≤1500 g) and with BW1500 g.Thirty-four (10%) patients had VLBW. Gross types of OA in VLBW were similar as in other patients: A (15%/7%), B (3%/3%), C (78%/82%), D (3%/4%), E (0%/7%), F (0%/1%) (p = 0.16-0.99). In VLBW the incidence of congenital heart disease (CHD) (47%) and trisomy 13/18 and Cri du Chat (15%) were higher than in BW1500 g (23% and 1%), (p = 0.001 both). In VLBW one-month mortality was 35% vs 4% in patients with BW1500 g (p 0.001), overall mortality 56% and 8% (p 0.001), respectively. Cause of one-month mortality in VLBW (12 patients) were CHD w/wo chromosomal abnormality (n = 7), cerebral hemorrhage (n = 2), gastric perforation (n = 1), anastomotic leakage (n = 1) and pulmonary hemorrhage (n = 1). Of VLBW patients 79% and of other patients 99% underwent oesophageal repair (p 0.001). Repair in VLBW patients included early (n = 18) or delayed (n = 5) end-to-end anastomosis and reconstruction (n = 4). Anastomotic complications occurred in 24% of patients with VLBW and in 17% with BW1500 g, (p = 0.31). From 1980-2000 to 2001-2020 survival in VLBW changed from 11% to 81% (p = 0.002). During 2001 - 2020 all VLBW patients underwent repair.OA with VLBW had high incidence of life-threatening associated anomalies and decreased survival. Recently survival and rate of oesophageal repair have improved significantly.

Successful portoenterostomy (SPE) improves the short-term outcome of patients with biliary atresia (BA) by relieving cholestasis and extending survival with native liver. Despite SPE, hepatic fibrosis progresses in most patients, leading to cirrhosis and a deterioration of liver function. The goal of this study was to characterize the effects of SPE on the BA liver transcriptome. We used messenger RNA sequencing to analyze global gene-expression patterns in liver biopsies obtained at the time of portoenterostomy (n = 13) and 1 year after SPE (n = 8). Biopsies from pediatric (n = 2) and adult (n = 2) organ donors and other neonatal cholestatic conditions (n = 5) served as controls. SPE was accompanied by attenuation of inflammation and concomitant up-regulation of key extracellular matrix (ECM) genes. Highly overexpressed genes promoting biliary fibrosis and bile duct integrity, such as integrin subunit beta 6 and previously unreported laminin subunit alpha 3, emerged as candidates to control liver fibrosis after SPE. At a cellular level, the relative abundance of activated hepatic stellate cells and liver macrophages decreased following SPE, whereas portal fibroblasts (PFs) and cholangiocytes persisted. Conclusion: The attenuation of inflammation following SPE coincides with emergence of an ECM molecular fingerprint, a set of profibrotic molecules mechanistically connected to biliary fibrosis. The persistence of activated PFs and cholangiocytes after SPE suggests a central role for these cell types in the progression of biliary fibrosis.

Background GATA6, a transcription factor expressed in cholangiocytes, has been implicated in the response to liver injury. In biliary atresia, a disease characterized by extrahepatic bile duct obstruction, liver expression of GATA6 increases with pathological bile duct expansion and decreases after successful Kasai portoenterostomy. The aim of this study was to garner genetic evidence that GATA6 is involved in ductular formation/expansion. Methods The murine Gata6 gene was conditionally deleted using Alb-cre, a transgene expressed in hepatoblasts (the precursors of hepatocytes and cholangiocytes) and mature hepatocytes. Bile duct ligation (BDL) was used to model biliary obstruction. Results Alb-Cre;Gata6(flox/flox) mice were viable and fertile. Cre-mediated recombination of Gata6 in hepatocytes had little impact on cellular structure or function. GATA6 immunoreactivity was retained in a majority of biliary epithelial cells in adult Alb-Cre;Gata6(flox/flox) mice, implying that surviving cholangiocytes were derived from hepatoblasts that had escaped biallelic Cre-mediated recombination. Although GATA6 immunoreactivity was preserved in cholangiocytes, Alb-cre;Gata6(flox/flox) mice had a demonstrable biliary phenotype. A neutrophil-rich infiltrate surrounded newly formed bile ducts in neonatal Alb-Cre;Gata6(flox/flox) mice. Foci of fibrosis/necrosis, presumed to reflect patchy defects in bile duct formation, were observed in the livers of 37% of adult Alb-cre;Gata6(flox/flox) mice and 0% of controls (p

OBJECTIVE The aim of the study was to assess long-term morbidity in children operated for choledochal malformation (CM) by relating clinical complications to liver histopathology, follow-up imaging, liver stiffness, and biochemistry. METHODS A single-center retrospective follow-up study including all CM patients (n = 55, 71% girls) treated during 1976 to 2018 was performed. Mann-Whitney U test and Spearman rank correlation were used for statistical analyses. RESULTS During median follow-up of 5.8 (interquartile range, 2.5-12) years, 1 patient was lost to follow-up whereas all survived. Intraoperative liver biopsies showed fibrosis in 32%, and patients with Metavir stage ≥2 were younger at surgery (0.36 [0.11-1.9] vs 3.8 [0.72-10.5] years, P = 0.024) than those without fibrosis. Overall, 21% had long-term complications including cholangitis in 9 (>2 episodes in 5) patients, anastomotic stricture in 2 referred patients and adhesive volvulus or hepatocellular carcinoma in 1 each. Anastomotic strictures were successfully managed nonoperatively and hepatocellular carcinoma with thermoablation. In postoperative magnetic resonance cholangiography (MRCP) performed 6.4 (3.6-16) years after hepaticojejunostomy, diameters of both main intrahepatic ducts had decreased significantly to 3.0 (2.5-3.5) mm (P = 0.0001) but a distal cyst stump was remaining in 30% with a length of 6.0 (4.0-20) mm that associated with operation age (r = 0.71, P = 0.015) and fusiform CM type. Follow-up ultrasound revealed mild dilation of intrahepatic bile ducts in 6.3% and mildly to moderately elevated liver biochemistry in 23%, and liver stiffness (>7 kPa) in 22%. CONCLUSIONS Whilst cholangitis was the most common postoperative problem, individual patients experienced other more significant complications and one quarter of patients showed evidence of underlying liver dysfunction.

Steatosis is a common feature of intestinal failure-associated liver disease (IFALD) in adult and older pediatric patients receiving long-term parenteral nutrition (PN). There are limited clinical data concerning steatosis in infants with short bowel syndrome (SBS). We investigated early histopathological steatosis and its association to PN.In this retrospective study, 31 patients with SBS had a diagnostic liver biopsy taken at the median age of 5 (IQR 3-8) months. Follow-up biopsy was available for 24 patients at the median age of 29 (IQR 14-52) months. We evaluated the biopsies for steatosis and other histopathological signs of IFALD and compared results with patient characteristics, PN composition, and liver biochemistry.Diagnostic biopsies revealed steatosis in 8 (26%) patients. At the age of 3 months, patients with steatosis had received higher amounts of parenteral glucose: median 15.1 (IQR 12.4-17.2) vs 12.3 (8.7-14.4) g/kg/d (P = 0.04), amino acids: 2.9 (2.5-3.4) vs 2.2 (1.6-2.7) g/kg/d (P = 0.03), and energy: 87 (80-98) vs 73 (54-79) kcal/kg/d (P = 0.01) than those without steatosis. We detected no significant differences in parenteral lipid intake between the groups. Steatosis also associated with increased serum bile acid (P = 0.02), alanine aminotransferase (P = 0.0002), and aspartate aminotransferase (P = 0.001) levels.In this cohort, high parenteral glucose, amino acid, and energy provision associated with liver steatosis in infants with SBS. We recommend monitoring of bile acid and transaminase levels while aiming for PN with balanced macronutrient supply according to current recommendations to protect the liver from steatosis.

OBJECTIVES The aim of the study was to examine the frequency of rickets and bone fractures and to assess areal bone mineral density (aBMD) in childhood among patients with biliary atresia (BA). METHODS We gathered data on all patients diagnosed with BA in Finland that survived to ≥1 year of age between 1 January 2000 to 30 June 2018. Data on gestational age, birth weight, postsurgical medications, and history of rickets and bone fractures were collected retrospectively. Serum levels of 25-hydroxyvitamin D [25(OH)D] postportoenterostomy (PE) were collected. Plain radiographs and dual energy X-ray absorptiometry (DXA) measurements of study subjects were reviewed. RESULTS Out of 49 patients, 7 (14%) were diagnosed with rickets during infancy. Clearance of jaundice [odds ratio 0.055, 95% confidence interval [CI] 0.00266-0.393; P

Introduction Rare cholestatic liver diseases may cause debilitating pruritus in children. Partial biliary diversion (PBD) may relieve pruritus and postpone liver transplantation which is the only other alternative when conservative treatment fails. The aim was to report long-term outcome after PBD in a population of 26 million people during a 25-year period. Materials and Methods This is an international, multicenter retrospective study reviewing medical journals. Complications were graded according to the Clavien–Dindo classification system. Results Thirty-three patients, 14 males, underwent PBD at a median of 1.5 (0.3–13) years at four Nordic pediatric surgical centers. Progressive familial intrahepatic cholestasis was the most common underlying condition. Initially, all patients got external diversion, either cholecystojejunostomy (25 patients) or button placed in the gallbladder or a jejunal conduit. Early complications occurred in 14 (42%) patients, of which 3 were Clavien–Dindo grade 3. Long-term stoma-related complications were common (55%). Twenty secondary surgeries were performed due to stoma problems such as prolapse, stricture, and bleeding, or conversion to another form of PBD. Thirteen children have undergone liver transplantation, and two are listed for transplantation due to inefficient effect of PBD on pruritus. Serum levels of bile acids in the first week after PBD construction were significantly lower in patients with good relief of pruritus than in those with poor effect (13 [2–192] vs. 148 [5–383] μmol/L; p = 0.02). Conclusion PBD may ensure long-term satisfactory effect on intolerable pruritus and native liver survival in children with cholestatic liver disease. However, stoma-related problems and reoperations are common.

Background Surgery for total colonic aganglionosis (TCA) is designed to preserve continence and achieve satisfactory quality of life. This study evaluated a comprehensive group of clinical and social outcomes. Methods An international multicentre study from eight Nordic hospitals involving examination of case records and a patient‐reported questionnaire survey of all patients born with TCA between 1987 and 2006 was undertaken. Results Of a total of 116 patients, five (4·3 per cent) had died and 102 were traced. Over a median follow‐up of 12 (range 0·3–33) years, bowel continuity was established in 75 (73·5 per cent) at a median age of 11 (0·5–156) months. Mucosectomy with a short muscular cuff and straight ileoanal anastomosis (SIAA) (29 patients) or with a J pouch (JIAA) (26) were the most common reconstructions (55 of 72, 76 per cent). Major early postoperative complications requiring surgical intervention were observed in four (6 per cent) of the 72 patients. In 57 children aged over 4 years, long‐term functional bowel symptoms after reconstruction included difficulties in holding back defaecation in 22 (39 per cent), more than one faecal accident per week in nine (16 per cent), increased frequency of defaecation in 51 (89 per cent), and social restrictions due to bowel symptoms in 35 (61 per cent). Enterocolitis occurred in 35 (47 per cent) of 72 patients. Supplementary enteral and/or parenteral nutrition was required by 51 (55 per cent) of 93 patients at any time during follow‐up. Of 56 responders aged 2–20 years, true low BMI for age was found in 20 (36 per cent) and 13 (23 per cent) were short for age. Conclusion Reconstruction for TCA was associated with persistent bowel symptoms, and enterocolitis remained common. Multidisciplinary follow‐up, including continuity of care in adulthood, might improve care standards in patients with TCA., In a multicentre study, outcome of surgery for total colonic aganglionosis was evaluated in 116 patients. In long‐term follow‐up, patients with a J pouch reconstruction reported better faecal continence and those with a Duhamel reconstruction reported fewer episodes of enterocolitis. Nutritional support was needed extensively in all groups with various lengths of resected aganglionotic bowel. Problems persist into adulthood

Introduction Several surgical techniques are available for pediatric esophageal reconstruction. We started to use pedicled jejunum interposition graft (PJIG) because other techniques had significant long-term complications. In this retrospective study, the indications, surgical complications, and long-term outcomes were assessed in patients with PJIG. Materials and Methods With ethical consent, we reviewed the hospital records of 14 patients (7 females) who from 2005 to 2019 underwent a total of 16 esophageal reconstructions with PJIG. Results Median age at PJIG was 1.6 (range: 0.2–15) years. Underlying conditions were esophageal atresia (EA) (n = 11) or native esophagus lost by trauma or infection (n = 3). Eight patients with EA underwent PJIG as primary reconstruction and three as a rescue operation after complications in primary repair. Significant surgical complications occurred in 43% of patients. Major reoperations in six (43%) patients included resection and reanastomosis of strictured proximal PJIG (n = 1) and redo PJIG after failure of the first operation (n = 2). Surgical mortality was nil. After a median follow-up of 6.5 (range: 0.7–14) years, 13 (93%) patients survived, and 1 died of congenital heart disease. PJIG failed in three (23%) survivors of whom two underwent graft removal because of life-threatening aspiration and one did not start oral feeds at all. Ten survivors (77%) have full enteral feeds. Respiratory function in the survivors is satisfactory. Two patients have moderate and three mild gastroesophageal reflux symptoms. Conclusion PJIG was a functional option for a variety of conditions that required esophageal reconstruction. However, significant early and late complications required major surgical revisions.

Publisher Copyright: © 2021 The Author(s) Portoenterostomy (PE) has remained as the generally accepted first line surgical treatment for biliary atresia (BA) for over 50 years. Currently, close to half of BA patients survive beyond 10 years with their native livers, and most of them reach adulthood without liver transplantation (LT). Despite normalization of serum bilirubin by PE, ductular reaction and portal fibrosis persist in the native liver. The chronic cholangiopathy progresses to cirrhosis, complications of portal hypertension, recurrent cholangitis or hepatobiliary tumors necessitating LT later in life. Other common related health problems include impaired bone health, neuromotor development and quality of life. Only few high-quality trials are available for evidence-based guidance of post-PE adjuvant medical therapy or management of the disease complications. Better understanding of the pathophysiological mechanisms connecting native liver injury to clinical outcomes is critical for development of accurate follow-up tools and novel therapies designed to improve native liver function and survival.

Background There are limited data available to compare outcomes between surgical approaches for Hirschsprung’s disease. Duhamel and endorectal pull-through (ERPT) are two of the most common procedures performed worldwide. Methods Objective outcomes were compared between contemporary cohorts (aged 4–32 years) after Duhamel or ERPT using case–control methodology. Data were collected using prospectively administered standardized questionnaires on bowel and bladder function and quality of life (Pediatric Quality of Life Inventory, Short form 36 and Gastrointestinal Quality of Life Index). Patients were compared in two age groups (18 years and younger and older than 18 years) and reference made to normative control data. Multivariable analysis explored factors associated with poor outcomes. Results Cohorts were well matched by demographics, disease characteristics and incidence of postoperative complications (120 patients who underwent Duhamel versus 57 patients who had ERPT). Bowel function scores were similar between groups. Patients who underwent Duhamel demonstrated worse constipation and inferior faecal awareness scores (P Conclusion Outcomes from Duhamel and ERPT are good in the majority of cases, with comparable bowel function scores. Constipation and impaired faecal awareness were more prevalent after Duhamel, with differences sustained in adulthood. Recurrent enterocolitis was significantly more prevalent after ERPT. Clustering of poor QoL and poor functional outcomes were observed in both cohorts, with seemingly little effect by choice of surgical procedure in terms of QoL.

Simple Summary We investigated the increased prevalence of Barrett's esophagus in adults with esophageal atresia. A higher polygenic risk score and disturbances in inflammatory, stress response and oncological pathways upon acid exposure suggest a genetic susceptibility and increased induction of inflammatory processes. Although further research is required to explore this hypothesis, this could be a first-step into selecting patients that are more at risk to develop Barrett's esophagus and/or esophageal carcinoma. Currently, an endoscopic screening and surveillance program is in practice in our institution for patients born with esophageal atresia, to early detect (pre)malignant lesions. Since recurrent endoscopies can be a burden for the patient, selecting patients by for example genetic susceptibility would allow to only include those at risk in future practice. The prevalence of Barrett's esophagus (BE) in adults born with esophageal atresia (EA) is four times higher than in the general population and presents at a younger age (34 vs. 60 years). This is (partly) a consequence of chronic gastroesophageal reflux. Given the overlap between genes and pathways involved in foregut and BE development, we hypothesized that EA patients have an intrinsic predisposition to develop BE. Transcriptomes of Esophageal biopsies of EA patients with BE (n = 19, EA/BE); EA patients without BE (n = 44, EA-only) and BE patients without EA (n = 10, BE-only) were compared by RNA expression profiling. Subsequently, we simulated a reflux episode by exposing fibroblasts of 3 EA patients and 3 controls to acidic conditions. Transcriptome responses were compared to the differential expressed transcripts in the biopsies. Predisposing single nucleotide polymorphisms, associated with BE, were slightly increased in EA/BE versus BE-only patients. RNA expression profiling and pathway enrichment analysis revealed differences in retinoic acid metabolism and downstream signaling pathways and inflammatory, stress response and oncological processes. There was a similar effect on retinoic acid signaling and immune response in EA patients upon acid exposure. These results indicate that epithelial tissue homeostasis in EA patients is more prone to acidic disturbances.

This study describes functional and health-related quality of life (HRQoL) outcomes in patients with Hirschsprung’s disease (HSCR) with associated learning disability or neurodevelopmental delay (LD), completing a core outcome set for HSCR. This was a cross-sectional study from a tertiary pediatric surgery center. Patients treated between 1977 and 2013 were prospectively contacted to complete an outcomes survey. Children under 12 and older patients with LD were assisted to complete these by a proxy. Bowel and urologic function were assessed (Rintala’s BFS and modified DanPSS) along with HRQoL (PedsQL/GIQLI/SF-36). Thirty-two patients with LD were compared to 186 patients with normal cognition. Patients with LD had 76% survival over the follow-up period, compared to 99% in the remainder of the cohort. Poor functional outcomes were common in the patients with LD, considerably higher than cognitively normal patients: with weekly issues withholding stool, soiling and fecal accidents in over half of patients surveyed (44–60%), and urinary incontinence in 46%. Use of permanent stoma was significantly higher (22% vs. 4%; p = 0.001). HRQoL was worse in domains of physical functioning in adults and children but not for social or emotional domains in adults. Subgroup analysis of patients with Down syndrome suggested similar functional results but better QoL. Multivariate analysis demonstrated a dramatically higher incidence of poor continence outcomes in patients with LD (adjusted OR 9.6 [4.0–23]).Conclusions: We provide LD-specific outcomes showing inferior function but similar HRQoL to other patients with HSCR, this is much needed in the counselling of families of these children. What is Known:• Hirschsprung’s disease is commonly associated with syndromes or other anomalies with resultant cognitive impairments.• The outcomes for these patients specifically have been poorly described in the literature. What is New:• Objective functional and quality of life surveys demonstrate significant differences from patients without cognitive impairment.• Patients with learning disability Patients with associated LD were almost ten times more likely to have an associated poor functional outcome, with very little impact on proxy-reported quality of life.

Aim To assess the risk factors for anastomotic stricture (AS) in end-to-end anastomosis (EEA) in patients with esophageal atresia (EA). Methods With ethical consent, hospital records of 341 EA patients from 1980 to 2020 were reviewed. Patients with less than 3 months survival (n = 30) with Gross type E EA (n = 24) and with primary reconstruction (n = 21) were excluded. Outcome measures were revisional surgery for anastomotic stricture (RSAS) and number of dilatations required for anastomotic patency without RSAS. The factors that were tested for risk of RSAS or dilatations were distal tracheoesophageal fistula (TEF) at the carina in C-type EA (congenital TEF [CTEF]), type A/B EA, antireflux surgery (ARS), anastomotic leakage, recurrent TEF, and Spitz group and congenital heart disease. Main Results A total of 266 patients, Gross type A (n = 17), B (n = 3), C (n = 237), or D (n = 9) underwent EEA (early n = 240, delayed n = 26). Early anastomotic breakdown required secondary reconstruction in five patients. Of the remaining 261 patients, 17 (6.1%) had RSAS, whereas 244 patients with intact end to end required a median of five (interquartile range: 2–8) dilatations for anastomotic patency. Main risk factors for RSAS or (> 8) dilatations were CTEF, type A/B, ARS, and anastomotic leakage that increased the risk of RSAS or dilatations from 4.6- to 11-fold. Conclusion The risk of severe AS is associated with long-gap EA, significant gastroesophageal reflux, and anastomotic leakage.

Imaging-confirmed uncomplicated acute appendicitis can be effectively and safely treated with antibiotics in most adults and children. Symptomatic treatment may have similar efficacy and safety.The APPSYPP trial is a randomized national multicenter feasibility superiority pilot study comparing appendectomy with symptomatic treatment in children with imaging-confirmed uncomplicated acute appendicitis.1) age ≥ 7 and 16 years, 2) imaging-confirmed uncomplicated acute appendicitis and 3) CRP ≤ 65 mg/l. Patients are randomized to receive emergency laparoscopic appendectomy or symptomatic treatment. To ensure patient safety, symptomatically treated patients are hospitalized for at least 24 h receiving standard practice intravenous fluids and analgesics according to standard clinical practice. Primary outcome is 30-day treatment success defined by the absence of any treatment failure criteria. In appendectomy, treatment failure is defined as normal appendiceal histopathology or any postintervention complication requiring general anesthesia. In symptomatic treatment, treatment failure is defined as 1) inability for hospital discharge without appendectomy within 48 h after randomization with a finding of histopathologically inflamed appendix, 2) appendectomy during the initial hospital stay due to clinical progression of appendicitis with complicated acute appendicitis both histopathologically and surgically, 3) appendectomy with a histopathological finding of acute appendicitis after hospital discharge, or 4) any complication of appendicitis requiring general anesthesia. Detailed predefined secondary outcomes will be analyzed.Study was approved by Ethics Committee of Helsinki University Hospital (ID:HUS/1993/2021), conducted in compliance with the declaration of Helsinki with results disseminated in peer-reviewed scientific journals.ClinicalTrials.gov (NCT05289713).

Background This study evaluated the safety and efficacy of teduglutide in pediatric patients with short bowel syndrome-associated intestinal failure (SBS-IF). Methods A 24-week, phase III trial with 2 randomized, double-blind teduglutide dose groups and a nonblinded standard of care (SOC) arm was used; patients received 0.025 mg/kg or 0.05 mg/kg teduglutide once daily. Safety end points included treatment-emergent adverse events (TEAEs) and growth parameters. The primary efficacy/pharmacodynamic end point was the number of patients who achieved a >= 20% reduction in parenteral support (PS) from baseline at week 24. Results All 59 enrolled patients completed the study (0.025 mg/kg, n = 24; 0.05 mg/kg, n = 26; SOC, n = 9). Baseline demographics and disease characteristics were comparable among groups. TEAEs were reported by 98% and 100% of patients in the teduglutide and SOC groups, respectively. The most common TEAEs in the teduglutide-treated groups were pyrexia and vomiting. The primary end point was achieved by 13 (54.2%), 18 (69.2%), and 1 (11.1%) patients who received 0.025 mg/kg teduglutide, 0.05 mg/kg teduglutide, and SOC, respectively (P

Cholangitis and bile lakes are incompletely understood complications after portoenterostomy (PE). We investigated relationships between recurrent cholangitis, bile lakes, and clinical outcomes as well as surgical management of bile lakes.In this retrospective observational single institution study medical records and imaging studies of all patients who had undergone PE for biliary atresia during 1987 to 2016 (N = 61) were reviewed. We related occurrence of cholangitis episodes with the presence of intrahepatic bile lakes, patient characteristics, and PE outcomes. Risk factors for recurrent cholangitis and bile lakes, and management of bile lakes were analyzed.Despite routine antibiotic prophylaxis median of 3.0 cholangitis episodes (0.75 episodes/year) occurred in 48 (79%) patients. Intrahepatic bile lakes were discovered in 8 (13%) patients by 16 months after PE. Overall, 54% had survived with their native liver at median age of 7.3 years and 28 (46%) patients had ≥1 cholangitis episodes/year. Number and frequency of cholangitis episodes were5 times higher among patients with bile lakes (P 0.001). Six patients underwent Roux-en-Y bile lake-jejunostomy, resulting in regression/disappearance of bile lakes and normalization of serum bilirubin in 5 with reduction of median yearly cholangitis rate from 8.8 to 1.1 (P = 0.028) and native liver survival of 6.3 (range, 1.3-17) years after the operation.Bile lakes are a significant risk factor for recurrent cholangitis after PE and efficiently treated by operative intestinal drainage providing prolonged jaundice-free native liver survival. Bile lakes should be actively screened among patients presenting with recurrent cholangitis after PE.

Objectives: Parenteral support (PS) is the first-line therapy for intestinal failure (IF). Optimal patient outcomes require experienced multidisciplinary teams adhering to structured protocols. As practices to provide long-term PS for adult IF patients in Finland are unknown, this cross-sectional nationwide study aimed to evaluate current management of PS for adult IF across the country.Materials and methods: An internet-based survey was emailed to all Finnish hospitals and hospital-at-home services with the potential to provide PS for adult IF. The survey included 20 items addressing the provision of long-term PS for adult IF patients (aged >= 18years). Data were analysed using descriptive statistics.Results: Overall, 52 (47%) of the 111 identified units responded. Of responding units, 38 (73%) had at some point provided long-term (>= 120days) PS for adult IF, and 23 (44%) had done so during the preceding year. Only three units currently managed >= 3 adult patients. Most (65%) of the respondents worked in a hospital and were either physicians (38%) or dietitians (39%). Only 65% of respondents reported that their unit had an assigned physician responsible for PS provision, and 28% reported that a team was responsible for long-term PS. Only 26% of respondents reported having a written protocol to guide PS management.Conclusions: Health care providers with very limited experience and a fragmented approach manage most Finnish adult IF patients. Evidence-based protocols and multidisciplinary teams are scarce. The care for adult IF patients on long-term PS needs to be improved in Finland.

Background Although serial transverse enteroplasty (STEP) improves function of dilated short bowel, a significant proportion of patients require repeat surgery. To address underlying reasons for unsuccessful STEP, we compared small intestinal mucosal characteristics between initial and repeat STEP procedures in children with short bowel syndrome (SBS). Methods Fifteen SBS children, who underwent 13 first and 7 repeat STEP procedures with full thickness small bowel samples at median age 1.5 years (IQR 0.7–3.7) were included. The specimens were analyzed histologically for mucosal morphology, inflammation and muscular thickness. Mucosal proliferation and apoptosis was analyzed with MIB1 and Tunel immunohistochemistry. Results Median small bowel length increased 42% by initial STEP and 13% by repeat STEP (p = 0.05), while enteral caloric intake increased from 6% to 36% (p = 0.07) during 14 (12-42) months between the procedures. Abnormal mucosal inflammation was frequently observed both at initial (69%) and additional STEP (86%, p = 0.52) surgery. Villus height, crypt depth, enterocyte proliferation and apoptosis as well as muscular thickness were comparable at first and repeat STEP (p > 0.05 for all). Patients, who required repeat STEP tended to be younger (p = 0.057) with less apoptotic crypt cells (p = 0.031) at first STEP. Absence of ileocecal valve associated with increased intraepithelial leukocyte count and reduced crypt cell proliferation index (p Conclusions No adaptive mucosal hyperplasia or muscular alterations occurred between first and repeat STEP. Persistent inflammation and lacking mucosal growth may contribute to continuing bowel dysfunction in SBS children, who require repeat STEP procedure, especially after removal of the ileocecal valve. Level of evidence Level IV, retrospective study.

We investigated noninvasive follow‐up markers for histologic liver fibrosis and portal hypertension (PH) in patients with biliary atresia after successful portoenterostomy (PE). Among children with bilirubin 11 µmol/L in the youngest tertile (AUROC, 0.91; P < 0.001), bile acids was >80 µmol/L in the middle tertile (AUROC, 0.81; P = 0.009), and liver stiffness was >24 kPa in the oldest age tertile (AUROC, 0.96; P = 0.002). Conclusion: After successful PE, development of PH associates with progression of liver fibrosis and can be accurately detected by APRI and stiffness. Liver stiffness most accurately identified cirrhosis in older children, whereas biochemical markers of cholestasis closely reflected histologic cirrhosis in younger children.

OBJECTIVES The aim of the study was to evaluate the neurocognitive and motor development of biliary atresia (BA) patients in childhood and adolescence and to identify risk factors for impaired outcome. METHODS We invited all BA patients between ages 1 and 20 years followed up at Helsinki University Children's Hospital in Finland between 1 January 2019 to 31 January 2020 to participate. All participants underwent age-appropriate validated neurocognitive tests. Participants between 3.0 and 16.9 years of age were assessed with the Movement Assessment Battery for children, version 2. Guardians of participants between ages 5 and 17 years filled the Five-to-Fifteen-Revised (5-15R) parental questionnaire. RESULTS The mean (±standard deviation [SD]) total intelligence quotient (IQ) of the 39 participants was 91 ± 15, lower compared with test norms (mean IQ 100 ± 15, P

Interleukin (IL)-8 (CXCL8), a chemokine involved in neutrophil recruitment, has been implicated in ductular reaction and liver fibrogenesis. We studied liver and serum IL-8 expression in a large biliary atresia (BA) cohort and explored its prognostic and pathophysiological potential. IL-8 expression was assessed in liver utilizing quantitative polymerase chain reaction (qPCR), immunohistochemistry and in situ hybridization and in serum using an enzyme-linked immunosorbent assay, among 115 BA patients, 10 disease controls and 68 normal controls. Results were correlated to portoenterostomy (PE) outcomes, biochemical and histological liver injury, transcriptional markers of fibrosis and cholangiocytes, and expression of other related cytokines. IL-8 was markedly overexpressed in liver and serum of BA patients at PE (n = 88) and in serum samples obtained during postoperative follow-up (n = 40). IL-8 expression in the liver was predominantly in cholangiocytes within areas of ductular reaction. Liver IL-8 mRNA expression correlated positively with its serum concentration, bile ductular proliferation, Metavir fibrosis stage, and transcriptional markers of activated myofibroblasts (ACTA2) and cholangiocytes (KRT19). Taken together, IL-8 may mediate liver injury in BA by promoting ductular reaction and associated liver fibrogenesis. Prognostic value of serum IL-8 to predict native liver survival was limited and confined to the postoperative period after PE.

Background Unexplained graft fibrosis and inflammation are common after pediatric liver transplantation (LT). Objective We investigated the graft expression of fibrogenic genes and correlated the findings with transplant histopathology and outcome. Methods Liver biopsies from 29 recipients were obtained at a median of 13.1 (IQR: 5.0-18.4) years after pediatric LT. Control samples were from six liver-healthy subjects. Hepatic expression of 40 fibrosis-related genes was correlated to histological findings: normal histology, fibrosis with no inflammation, and fibrosis with inflammation. Liver function was evaluated after a subsequent follow-up of 9.0 years (IQR: 8.0-9.4). Results Patients with fibrosis and no inflammation had significantly increased gene expression of profibrotic TGF-beta 3 (1.17 vs. 1.02 p = .005), CTGF (1.64 vs. 0.66 p = .014), PDGF-alpha (1.79 vs. 0.98 p = .049), PDGF -beta (0.99 vs. 0.76 p = .006), integrin-subunit-beta 1 (1.19 vs. 1.02 p = .045), alpha-SMA (1.12 vs. 0.58 p = .013), type I collagen (0.82 vs. 0.53 p = .005) and antifibrotic decorin (1.15 vs. 0.99 p = .045) compared to patients with normal histology. mRNA expression of VEGF A (0.84 vs. 1.06 p = .049) was lower. Only a few of the studied genes were upregulated in patients with both fibrosis and inflammation. The gene expression levels showed no association with later graft outcome. Conclusions Altered hepatic expression of fibrosis-related genes is associated with graft fibrosis without concurrent inflammation.

Objectives Details of intestinal failure in the Finnish adult population are unknown. This study aimed to specify the intestinal failure prevalence and to clinically characterize the patient population in Finland. Methods All Finnish healthcare units with the potential of providing parenteral support received an electronic survey to report whether they had patient(s) aged ≥18 years on long-term (≥120 days) parenteral support due to intestinal failure. Patient details came from patient records. IBM SPSS v.25 was used to analyze descriptive statistics. Results Of the 74 patients, 52 were included after confirming parenteral support indication from the records. The adult intestinal failure prevalence for 2017 was 11.7 per million, 95% confidence interval: 8.9-15.3. Most patients were women (69%), and the median age was 62 (45-72) years. Short bowel syndrome was the most frequent intestinal failure mechanism (73%), and surgical complication the most frequent underlying diagnosis (29%). Of patients, 66% represented the clinical classification category parenteral nutrition 1 or parenteral nutrition 2. Median Charlson Comorbidity Index was one (0-2.8); hypertension (37%) and diabetes (23%) were the most frequent comorbidities. Patients received seven (3.5-7) parenteral support infusions weekly, and eight patients (15%) were on fluids and electrolytes only. The median duration of parenteral support was 27.5 (11.3-57.3) months. Ten patients ceased parenteral support during 2017 after a median of 20.0 (9.0-40.3) parenteral support months. Eight weaned off parenteral support, one ran out of catheter sites, and one died. Conclusion Prevalence and patient characteristics of adult intestinal failure in Finland are similar to those in other Western countries.

Introduction The aim of this study was retrospective assessment of late major reoperations after surgery for necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) in neonates. Materials and Methods Appropriate ethical consent was obtained. Data collection was by review of hospital records of 165 successive prematures who underwent surgery for NEC (n = 99) or SIP (n = 66) from 1986 to 2019. Outcome measures were late major abdominal surgeries or endoscopies that occurred after the primary surgical treatment, closure of enterostomies, and weaning from parenteral nutrition (PN). We assessed also risk factors for late abdominal surgeries. Results Hundred and twenty-six (76%) patients (NEC, n = 70, 71% and in SIP, n = 56, 85%) survived. Median follow-up was 13 (interquartile range: 5.9–23) years. Nineteen (15%) patients underwent late abdominal surgery with 0% mortality. Most common was surgery for small bowel obstruction (SBO) in 12(9.5%) patients (NEC, n = 5; 7.0%, SIP, n = 7; 13%, p = 0.36) with 10-year cumulative risk of 8.7 (95% confidence interval [CI]: 3.5–14). Long duration of PN and development of intestinal failure associated cholestasis (IFAC) increased the risk of SBO surgery, relative risk: 1.0–3.2 (95% CI: 1.0–9.1), p = 0.02–0.03. Other surgeries included serial transverse enteroplasty (NEC, n = 2), incisional hernia repair (n = 3), cholecystectomy (n = 1), and ovarian torsion (n = 1). Twenty (29%) NEC and four (7%) SIP patients required endoscopic assessment of postoperative symptoms (p = 0.003). Conclusion Late abdominal reoperations occurred in 15% of patients with NEC and SIP with nil mortality. SBO was the main indication. Risk of SBO was similar between NEC and SIP. Long PN and IFAC increased the risk of SBO.

Pediatric short bowel syndrome (SBS) is an increasingly encountered complex and devastating condition in which the remaining intestine is unable to absorb adequate amounts of fluid and nutrients leading to intestinal failure and need for long-term parenteral support (PS). The goal of SBS treatment is to ascertain normal growth and development while pursuing enteral autonomy (weaning off PS) with individualized treatment strategies. Children with SBS are at risk for multiple complications such as intestinal failure associated liver disease (IFALD), recurrent septic episodes, central line complications, intestinal bacterial overgrowth, metabolic bone disease, impaired renal function, failure to thrive and increased mortality.

Background: Subclinical graft inflammation and fibrosis after pediatric liver transplantation (LT) are common. Biomarkers are needed that precede and are associated with these changes and graft outcome. Material/Methods: We evaluated immunohistochemical expression of 6 biomarkers [alpha-smooth muscle actin (alpha-SMA), collagen I, decorin, vimentin, P-selectin glycoprotein ligand-1 (PSGL-1), and CD34] in biopsies taken intraoperatively at LT (baseline) (n=29) and at 11.3 years after LT (first follow-up) (n=51). Liver biochemistry and graft histology were assessed at the first follow-up and at final assessment (19.6 years after LT) (n=48). Second follow-up biopsies for histology were available from 24 patients. The immunostainings were correlated with liver histology, biochemistry, and outcome at these time-points. Results: Baseline levels of the biomarkers were unrelated to presence of fibrosis at follow-up. Increased a-SMA, collagen I levels, decorin, and vimentin were associated with simultaneous fibrosis at the first follow-up (p=0.001-0.027). Increased SMA, collagen I, decorin, vimentin, PSGL-1, and CD34 expression at first follow-up were associated with simultaneous portal inflammation (p=0.001-0.025). alpha-SMA, decorin, and vimentin expression were increased in patients without fibrosis at the first follow-up but who developed fibrosis in second follow-up (p=0.014 p=0.024 and p=0.024). Significant fibrosis (F2) and markedly increased alpha-SMA, collagen I, decorin, and vimentin levels at first follow-up were associated with suboptimal liver status at the final assessment (p=0.002-0.042). Conclusions: The expression of the biomarkers at LT was unrelated to later development of graft fibrosis. alpha-SMA, decorin, and vimentin were associated with later graft fibrosis and suboptimal liver status.

The incidence of Crohn's disease is increasing worldwide. The clinical course of childhood onset Crohn's disease is particularly aggressive with characteristic disease localization in the ileocecal region and colon, often associated with perianal disease. Severe complications of perianal disease include recurrent perianal sepsis, chronic fistulae, fecal incontinence, and rectal strictures that impair quality of life and may require fecal diversion. Care of patients with perianal Crohn's disease requires a multidisciplinary approach with systematic clinical evaluation, endoscopic assessment, and imaging studies followed by combined medical and surgical management. In this review, we provide an update of the epidemiology, pathophysiology, diagnostics, and management of perianal Crohn's disease in children and adolescents.

A plethora of diseases affecting liver parenchyma and vasculature underpin development of portal hypertension (PH) in children, although extrahepatic portal vein obstruction (EHPVO) and biliary atresia (BA) represent the majority of cases. With the addition of novel surgical and interventional radiology approaches to endoscopic management, the outlook of paediatric onset PH has markedly evolved during the last decades. Despite these advances, the long-term outcomes remain insufficiently characterised, as are natural history and progression risk of PH secondary to different underlying diseases.1 Typically, the first sign of complicated PH is bleeding from gastro-oesophageal varices, clinically presenting as haematemesis. Although the estimated overall mortality rate of the first variceal haemorrhage in children is low ranging from 1% to 3%, the incidence of spontaneous life-threatening bleeding episodes approaches 20% in children with cirrhosis and high-risk varices.2 Regardless of the underlying liver disease, endoscopic interventions remain the primary modality to control the first bleed and prevent further bleeding episodes. Endoscopic band ligation is replacing sclerotherapy also among children and is currently feasible in children over 10 kg of weight. Band ligation has been thought to outperform classic sclerotherapy as far as efficacy, safety and degree of standardisation are concerned, although high-quality comparative studies are few among children. Similarly, evidence-based treatment algorithms regarding the primary and secondary prophylaxis for variceal haemorrhage in children are still lacking, as prospective controlled (randomised) trials are challenging to accomplish in this young, relatively rare and heterogeneous patient population.3 Different centres tend to follow their local protocols as no uniformly accepted guidelines exist. Although prophylactic endoscopic treatment of high-risk varices (primary prophylaxis) has the potential to reduce the incidence of serious bleeding episodes and even lower the associated mortality, it is still common practice to start endoscopic interventions only …

GATA6, a transcription factor expressed in cholangiocytes, has been implicated in the response to liver injury. In biliary atresia, a disease characterized by extrahepatic bile duct obstruction, liver expression of GATA6 increases with pathological bile duct expansion and decreases after successful Kasai portoenterostomy. The aim of this study was to garner genetic evidence that GATA6 is involved in ductular formation/expansion.The murine Gata6 gene was conditionally deleted using Alb-cre, a transgene expressed in hepatoblasts (the precursors of hepatocytes and cholangiocytes) and mature hepatocytes. Bile duct ligation (BDL) was used to model biliary obstruction.Alb-Cre;Gata6GATA6 orchestrates intrahepatic biliary remodeling and mitigates liver injury following extrahepatic bile duct obstruction.