Managing giant omphalocele: A systematic review of surgical techniques and outcomes.

AIM: We analysed closure techniques in the treatment of giant omphalocele. A challenging pathology where there lacks consensus. METHODS: Cochrane, MEDLINE and EMBASE were searched between 1 January 1992 and 31 December 2022 using terms and variations: omphalocele, exomphalos, giant, closure and outcome. Papers were selected using Preferred Reporting Items for Systematic review and Meta-Analyses 2020 criteria. Data collected included demographics, timing and technique of surgical repair, morbidity and mortality. RESULTS: We identified 342 papers; 34 met inclusion criteria with a total 356 neonates. Initial non-operative management was described in 26 papers (14 dressings, eight silo, four serial sac-ligation). Operative techniques by paper were as follows: Early closure: nine primary suture closure without patch, two primary closure with patch and four mixed methods. Delayed closure: five simple, four-component separation technique, four tissue expanders, one Botox/pneumoperitoneum and two with patch. Median number of procedures was two (1-6) in the early group versus three (1-4) in the delayed. The most favourable was early primary closure with biological patch. The most unfavourable was delayed closure with patch. Cumulative reported mortality remained high, mostly due to non-surgical causes. CONCLUSION: Definitions of giant omphalocele in the literature were heterogeneous with a variety of management approaches described.

Implementation and validation of a novel instrument for the grading of unexpected events in paediatric surgery: Clavien-Madadi classification.

BACKGROUND: Inconsistent definitions of complications and unexpected events have limited accurate analysis of surgical outcomes. Perioperative outcome classifications currently used for adult patients have limitations when used for children. METHODS: A multidisciplinary group of experts modified the Clavien-Dindo classification to increase its utility and accuracy in paediatric surgery cohorts. Organizational and management errors were considered in the novel Clavien-Madadi classification, which focuses on procedural invasiveness rather than anaesthetic management. Unexpected events were prospectively documented in a paediatric surgery cohort. Results of the Clavien-Dindo and Clavien-Madadi classifications were compared and correlated with procedure complexity. RESULTS: Unexpected events were prospectively documented in a cohort of 17 502 children undergoing surgery between 2017 and 2021. The results of both classifications were highly correlated (ρ = 0.95), although the novel Clavien-Madadi classification identified 449 additional events (organizational and management errors) over the Clavien-Dindo classification, increasing the total number of events by 38 per cent (1605 versus 1158 events). The results of the novel system correlated significantly with the complexity of procedures in children (ρ = 0.756). Furthermore, grading of events > grade III according to the Clavien-Madadi classification showed a higher correlation with procedure complexity (ρ = 0.658) than the Clavien-Dindo classification (ρ = 0.198). CONCLUSION: The Clavien-Madadi classification is a tool for the detection of surgical and non-medical errors in paediatric surgery populations. Further validation in paediatric surgery populations is required before widespread use.

Pediatric Intestinal Pseudo-Obstruction: An International Survey on Diagnostic and Management Strategies in the European Reference Network for Rare Inherited and Congenital Anomalies Intestinal Failure Teams.

OBJECTIVES: Pediatric intestinal pseudo-obstruction (PIPO) management is based on nutritional, medical, and surgical care while available evidence is scarce. The aim of this study was to outline the current diagnostic and management strategies in intestinal failure (IF) teams of the European Reference Network for rare Inherited and Congenital Anomalies (ERNICA) and to compare these practices to the latest PIPO international guidelines. METHODS: An online survey on institutional diagnostic and management strategies of PIPO was conducted among the ERNICA IF teams. RESULTS: In total, 11 of 21 ERNICA IF centers from 8 countries participated. On average, 64% of teams had ≥6 and 36% had 1-5 PIPO patients under active follow-up. In total, 80 of 102 PIPO patients were parenteral nutrition (PN) dependent while each IF team had median 4 (range 0-19) PN dependent PIPO patients under follow-up. On average, each center received 1-2 new PIPO patients per year. Diagnostics mostly followed current guidelines while medical and surgical management strategies were diverse. CONCLUSIONS: Numbers of PIPO patients are low and management strategies are diverse among ERNICA IF teams. To improve PIPO patient care, regional reference centers with specialized multidisciplinary IF teams and continuous collaboration across centers are needed.

Long-Term Outcomes After Autologous Intestinal Reconstructive Surgery in Children With Short Bowel Syndrome.

OBJECTIVES: Autologous intestinal reconstructive (AIR) surgery is frequently utilized in the management of pediatric short bowel syndrome (SBS). However, little is known about the long-term sequela of these procedures. METHODS: We undertook a retrospective follow-up study addressing parenteral nutrition (PN) dependence, nutritional status, intestinal morbidity, and related complications in SBS patients having undergone AIR surgery (SBS-AIR, n = 19). We compared results with conservatively treated control SBS patients (SBS-C, n = 45). Eligible patients were identified from our institutional intestinal failure registry during 1985-2019. RESULTS: After median 11.4 follow-up years, 42% of SBS-AIR patients received PN in relation to 36% in SBS-C group ( P = 0.6210), and overall PN duration was significantly longer (35.4 vs 10 months, P = 0.0004) in SBS-AIR group. Although symptoms of intestinal dysfunction improved in majority (62%) of patients after AIR surgery, their symptoms remained more frequent and severe at latest follow-up compared to SBS-C group (39% vs 5%, P = 0.0015). Although bacterial overgrowth was more frequent in SBS-AIR group (53% vs 24%, P = 0.0416), latest endoscopy findings and fecal calprotectin levels as well as occurrence of anastomotic/staple line ulcerations were comparable between groups. Histological liver steatosis (50% vs 18%, P = 0.042) and impaired bone health (26% vs 6.7%, P = 0.042) were more frequent in SBS-AIR patients. CONCLUSIONS: While AIR surgery improved gastrointestinal symptoms and transition to enteral autonomy in majority of patients, a noteworthy proportion of them continued to suffer from clinically significant intestinal dysfunction and related complications. Close long-term follow-up of pediatric AIR surgery patients is mandatory.

Cutoffs and Characteristics of Abnormal Bowel Dilatation in Pediatric Short Bowel Syndrome.

OBJECTIVES: Although excessive intestinal dilatation associates with worsened outcomes in pediatric short bowel syndrome (SBS), little is known about the natural history and definition of pathological dilatation. We addressed fore-, mid-, and hind-gut dilatation in children with SBS, who had not undergone autologous intestinal reconstructive (AIR) surgery, in relation to controls. METHODS: SBS children without history of AIR surgery (n = 59) and age-matched controls without any disclosed intestinal pathology (n = 140) were included. Maximum diameter of duodenum, small bowel (SB), and colon were measured in each intestinal contrast series during 2002 to 2020 and expressed as diameter ratio (DR) to L5 vertebrae height. Predictive ability of DR for weaning off parenteral nutrition (PN) was analyzed with Cox proportional hazards regression models using multiple cutoffs. RESULTS: Duodenum (DDR), SB (SBDR), and colon (CDR) DR were 53%, 183%, and 23% higher in SBS patients compared to controls ( P < 0.01 for all). The maximal DDR and SBDR measured during follow-up is associated with current PN dependence and young age. DDR correlated with SBDR ( r = 0.586, P < 0.01). Patients with maximal DDR less than 1.5, which was also the 99th percentile for controls, were 2.5-fold more likely to wean off PN ( P = 0.005), whereas SBDR and CDR were not predictive for PN duration. CONCLUSIONS: All segments of remaining bowel, especially SB, dilate above normal levels in children with SBS. In SBS children without AIR surgery, PN dependence and young age is associated with duodenal and small intestinal dilatation, while duodenal dilatation also predicted prolonged PN.

Prediction, identification and progression of histopathological liver disease activity in children with intestinal failure.

BACKGROUND & AIMS: Diagnostic criteria, progression risk and optimal monitoring for intestinal failure (IF)-associated liver disease (IFALD) remain undefined. We assessed predictors, non-invasive markers and progression of histopathological liver disease in patients with IF. METHODS: In total, 77 children with IF and median age of 1.7 years underwent diagnostic liver biopsy, which was repeated in 48 patients after 2.9 years with simultaneous evaluation of liver biochemistry, liver stiffness, serum citrulline (a surrogate for viable enterocyte mass), spleen size, esophageal varices and clinical data. Patients were staged according to histopathological liver disease activity: active IFALD (cholestasis and/or inflammation), chronic IFALD (significant fibrosis and/or steatosis), or no IFALD (none of these features). RESULTS: Diagnostic liver biopsy revealed active, chronic or no IFALD in 48%, 21% and 31% of patients. Active IFALD was segregated by low serum citrulline, parenteral nutrition (PN) dependency and young age, while weaning off PN and older age predicted chronic IFALD. Although the liver histopathology in most patients either normalized (52%) or transformed to a less reactive (chronic) disease stage (23%), 19% of patients retained and 6.3% progressed to an active cholestatic/inflammatory IFALD phenotype. Decreased serum citrulline and PN-dependency also predicted active IFALD in follow-up biopsies. Increased median liver biochemistry values and liver stiffness only associated with active IFALD, which was accurately identified by gamma-glutamyltransferase (GGT), citrulline and liver stiffness, their combinations reaching diagnostic and follow-up AUROC values above 0.90. CONCLUSIONS: Active IFALD, essentially predicted by intestinal disruption and PN-dependency, was accurately detected by GGT, liver stiffness and citrulline, which together with recent advances in clinical management options, provides new avenues for monitoring and targeted liver protection in patients with IF. LAY SUMMARY: Liver disease is a common and critical complication in patients with intestinal failure, who require intravenous nutrition for survival due to severe intestinal dysfunction. We showed that both intravenous nutrition dependency and intestinal disruption essentially predicted development of active histopathological liver disease, which persisted in 25% of patients during long-term follow-up and could be accurately detected without the need for liver biopsy. Identification of the active and potentially progressive histopathology offers new possibilities for monitoring and targeted liver protection in patients with intestinal failure.

Altered Bile Transporter Expression and Cholesterol Metabolism in Children With Cholesterol and Pigment Gallstones.

OBJECTIVES: We elucidated pathophysiology of pediatric gallstone disease by assessing liver expression of bile transporters in relation to bile acids and surrogates of cholesterol absorption and synthesis in serum and gallstones. METHODS: RNA expression of canalicular bile transporters in liver biopsies from 32 pediatric gallstone patients and from 6 liver donors (controls) was measured by qRT-PCR (quantitative real-time reverse transcription polymerase chain reaction). Concentrations of cholesterol and precursors, plant sterols and bile acids in gallstones, and in serum of the patients and 82 healthy children were measured. Primary outcomes were the difference in RNA expressions and serum sterol profiles between patients and controls. RESULTS: Cholesterol stones (CS; n = 15) contained cholesterol >42% and pigment stones (PS; n = 17) <9% of weight. CS patients had markedly lower serum plant sterols (absorption) and higher cholesterol precursors (synthesis) than PS patients or healthy controls. CS contained several times more cholesterol precursors and less plant sterols relative to cholesterol than PS, which were enriched by primary bile acids (12-5.2-fold, P < 0.001). Liver RNA expression of ABCG5/G8 was similarly increased 2.5- to 1.8-fold (P < 0.002) in CS and PS patients, whereas PS patients had higher ABCB11 expression (P < 0.05). In PS bile acid concentration correlated with gallstone plant sterols (R = 0.83, P < 0.0001), and ABCG5 expression with ABCB11 expression (R = 0.27, P = 0.03). CONCLUSIONS: In CS, upregulation of ABCG5/G8 expression associates with low absorption and high gallstone content of cholesterol. In PS, activation of bile acid transport by ACBC11 interconnects with hepatic upregulation of ABCG5/G8 enriching PS with bile acids and plant sterols.

Autologous Intestinal Reconstructive Surgery in the Management of Total Intestinal Aganglionosis.

OBJECTIVES: Total/near total intestinal aganglionosis (TIA/NTIA) is the most uncommon and life-threatening form of Hirschsprung disease (HD). The management of TIA/NTIA is challenging and the role of autologous intestinal reconstructive (AIR) surgery is controversial. The objective is to evaluate the effectiveness of AIR in patients with TIA/NTIA. METHODS: Records from children affected by TIA and enrolled in the multicenter international Pediatric Intestinal Rehabilitation and Transplantation Registry were retrospectively reviewed. RESULTS: Fourteen patients with TIA were identified. TIA diagnosis was confirmed histologically at the median age of 14 days of life. All received a proximal decompressive jejunostomy. Two patients died, 4 patients had satisfactory stoma output with enteral tolerance without additional procedures, 8 underwent 10 AIR procedures (4 Ziegler myotomy-myectomy, 3 transposition of aganglionic ileum with or without myotomy, 2 simple tapering, 1 longitudinal lengthening and tailoring procedure with associated myotomy). AIR significantly reduced median stoma output, from 197 to 31 mL ·â€Škg ·â€Šday (P = 0.0001). The reduction was seen in all patients. In addition, AIR improved enteral tolerance in the long term in 5 of 8 patients (63%), and temporarily in 1, leading to a reduction of parenteral nutrition requirement from 100% to 70% (P = 0.0231). CONCLUSIONS: AIR surgery in carefully selected patients may be useful and effective way to enhance residual bowel absorptive function and to reduce parenteral nutrition requirements. AIR and intestinal transplantation are complementary surgical tools in the complex treatment algorithm of TIA/NTIA.

Liver Inflammation Relates to Decreased Canalicular Bile Transporter Expression in Pediatric Onset Intestinal Failure.

OBJECTIVE: Although liver disease is a major complication of parenteral nutrition (PN) for intestinal failure (IF), its pathogenesis remains unclear. We investigated potential molecular mechanisms of liver injury in pediatric onset IF. METHODS: Liver expression of canalicular phospholipid (ABCB4), bile acid (ABCB11), and sterol (ABCG5/8) transporters, their upstream regulators LXR and FXR as well as pro-inflammatory cytokines interleukin-6 (IL6) and tumor necrosis factor (TNF) were investigated among patients with IF [age median 3.8 (IQR 1.2 to 11)] in relation to biochemical and histologic liver injury, PN, serum plant sterols, fibroblast growth factor 19, and α-tocopherol. RESULTS: Patients receiving PN currently (n = 18) showed more advanced liver injury than patients after weaning off PN (n = 30). Histologic portal inflammation strongly segregated PN-dependent (44%) from weaned off patients (3%, P = 0.001) and coupled with progression of cholestasis and liver fibrosis. Patients with portal inflammation demonstrated markedly induced liver RNA expression of IL6 and TNF, repression of FXR and its canalicular bile transporter target gene RNA expression, including ABCB4 and ABCB11 as well as decreased protein expression of ABCB11 and ABCB4. Furthermore, upregulation of LXR and ABCG5/8 RNA expression was suppressed in patients with portal inflammation. Current PN, increased serum levels of plant sterols stigmasterol, avenasterol, and sitosterol along with serum citrulline, a marker of enterocyte mass, predicted portal inflammation. CONCLUSIONS: In pediatric onset IF, current PN delivery synergistically with intestinal compromise promote liver inflammation, which associates with progression of biochemical and histologic liver injury, while reducing expression of canalicular bile transporters.

Duodenal Disaccharidase Activities During and After Weaning off Parenteral Nutrition in Pediatric Intestinal Failure.

OBJECTIVES: Data on factors affecting absorptive function in children with intestinal failure (IF) are sparse. We evaluated duodenal disaccharidase activities and inflammation in relation to parenteral nutrition (PN) and intestinal resection in pediatric onset IF. METHODS: Disaccharidase (maltase, sucrase, and lactase) activities and histologic inflammation were evaluated from duodenal biopsies in 58 patients during PN (n = 23) or full enteral nutrition (n = 40) and in 43 matched controls. The first and the last postresection biopsies were analyzed separately after 4.3 (1.2-9.7) years and 6.5 (2.3-12.4) years, respectively. RESULTS: During PN, maltase and sucrase activities were 1.6-fold lower and mucosal inflammation more frequent (22% vs 3%) when compared to matched controls (P < 0.05 for both). In patients on full enteral nutrition, activities of maltase and sucrase were significantly higher than that in patients receiving PN and comparable to those of matched controls. Postresection time correlated positively (r = 0.448 and r = 0.369) and percentage length of the remaining small intestine inversely (r = -0.337 and r = -0.407) with maltase and sucrase activity in patients on full enteral nutrition (P < 0.05 for all), whereas proportional length of remaining colon correlated positively with maltase and lactase activity (r = 0.424-0.544, P < 0.05) in patients receiving PN. CONCLUSIONS: In children with IF, PN dependency associated with decreased duodenal maltase and sucrase activities and mucosal inflammation, which may disturb intestinal absorptive function. Localization and extent of intestinal resection and post-resection time correlated with duodenal disaccharidase activities.

Transient elastography and aspartate aminotransferase to platelet ratio predict liver injury in paediatric intestinal failure.

BACKGROUND & AIMS: We aimed to evaluate the value of AST to platelet ratio (APRI) and transient elastography (TE) as predictors of liver histopathology in children with intestinal failure (IF). METHODS: Altogether 93 liver biopsies from 57 children with parenteral nutrition (PN) duration ≥3 months were analysed. APRI measurement and TE (n = 46) were performed at the time of biopsy. RESULTS: IF was caused by short bowel syndrome in 75% of patients. At the time of liver biopsy, PN dependent patients (n = 42) were younger with longer PN duration compared to those weaned off PN (n = 51) (2.2 vs. 7.6 years, P < 0.001; 26 vs. 10.5 months, P = 0.043). Elevated transaminase or bilirubin levels were found in 51%, splenomegaly in 26%, and oesophageal varices in 3.5%. Histological fibrosis was present in 61% (Metavir stage F1; 27%, F2; 26%, F3-4; 9%), cholestasis in 25% and steatosis in 22% of biopsy specimens. TE was superior to APRI in prediction of any liver histopathology (fibrosis, cholestasis or steatosis) with areas under the receiving operating curve (AUROC) of 0.86 (95% CI 0.74-0.97) and 0.67 (95% CI 0.58-0.78) respectively. For prediction of ≥F1 and ≥F2 fibrosis, AUROC values for TE were 0.78 (95% CI 0.64-0.93) and 0.73 (95% CI 0.59-0.88), whereas APRI did not correlate with fibrosis stages. For detection of histological cholestasis, the AUROC for APRI was 0.77 (95% CI 0.64-0.89). CONCLUSIONS: Both TE and APRI are promising noninvasive methods for monitoring the development of IF-related liver histopathology. TE values reflected the degree of fibrosis better while APRI detected histological cholestasis more accurately.

Loss of ileum decreases serum fibroblast growth factor 19 in relation to liver inflammation and fibrosis in pediatric onset intestinal failure.

BACKGROUND & AIMS: The pathogenesis of intestinal failure (IF) associated liver disease (IFALD) is uncertain, we therefore investigated the role of FGF19 and pro-inflammatory cytokines has on this disease state. METHODS: Serum FGF19, IL-6 and, TNF-α were measured in 52 IF patients at median age 6.0 years (IQR 2.2-13) after 10 months (4.1-39) on parenteral nutrition (PN). Thirty-nine patients underwent liver biopsies. RESULTS: In IF patients, FGF19 concentrations were lower and those of IL-6 and TNF-α higher compared to healthy matched controls (p ⩽ 0.001 for all). FGF19 concentrations were further decreased in patients without a remaining ileum [37 pg/ml (IQR 30-68) vs. 74 (35-135) p=0.028], and correlated with remaining ileum length (r = 0.333, p = 0.018) and markers of cholesterol synthesis (r = -0.552 to -0.643, p < 0.001). Patients with histological portal inflammation [30 pg/ml (28-45) vs. 48 (33-100), p = 0.019] or fibrosis [35 pg/ml (30-66) vs. 99 (38-163), p = 0.013] had lower serum FGF19 concentrations than others. FGF19 negatively correlated with portal inflammation grade (r = -0.442, p = 0.005), serum TNF-α (r = -0.318, p = 0.025), METAVIR fibrosis stage (r = -0.441, p = 0.005) and APRI (r = -0.328, p = 0.028). IL-6 was higher during PN [6 pg/ml (2-31)] than after weaning off PN [2 pg/ml (1-5), p = 0.009], correlated weakly with cholestasis grade (r = 0.328, p = 0.044), and tended to associate with histological cholestasis [n = 5, 5 pg/ml (5-267) vs. n=34, 2 pg/ml (1-7), p = 0.058]. CONCLUSIONS: In pediatric onset of IF, total or partial loss of ileum decreases serum FGF19 concentration corresponding to hepatic inflammation and fibrosis, along with increased cholesterol synthesis. In contrast, serum IL-6 increases during PN and may associate with concurrent cholestasis. These data suggests that FGF19 may contribute to the pathogenesis of IFALD.

Surgical rehabilitation of short and dysmotile intestine in children and adults.

AIMS: This is a descriptive study aiming to compare outcomes of intestinal rehabilitation surgery among pediatric and adult intestinal failure (IF) patients with either primary intestinal motility disorders or short bowel syndrome (SBS) treated by our nationwide program. METHODS: Medical records of IF patients (n = 31, 71% children) having undergone autologous intestinal reconstructions (AIR) (n = 25), intestinal transplantation (ITx) (n = 5), or being listed for ITx (n = 2) between 1994 and 2014 were reviewed. RESULTS: At surgery, median age was 3.4 (interquartile range, 1.0-22.1) in SBS (n = 22) and 16.5 (3.2-26.7) years in dysmotility patients (n = 9) who received median 60% and 83% of energy requirement parenterally, respectively. Median small bowel length was shorter in SBS than dysmotility patients (34 versus 157 cm, p < 0.001). Following AIR, none of the dysmotility patients achieved permanent intestinal autonomy, whereas 68% of SBS patients weaned off parenteral nutrition (PN) (p = 0.022) and none required listing for ITx. Five dysmotility patients who underwent ITx achieved intestinal autonomy. Regarding both AIR and ITx procedures, no significant difference in PN weaning was observed between the two subgroups. At last follow-up, 3.3 (0.6-8.0) years postoperatively, median plasma bilirubin was 6 (4-16) µmol/l, while liver biopsy showed fibrosis (Metavir stage 1-2) in 50% and cholestasis in 8%. Proportion of PN energy requirement had reduced significantly (p = 0.043) among PN-dependent SBS (n = 7) but not among dysmotility patients (n = 5). Overall survival was 90%. CONCLUSION: AIR surgery was beneficial among selected SBS patients, whereas in intestinal dysmotility disorders, permanent PN weaning was only achieved by ITx.

[Diaphragmatic rupture: case report of a rare complication of labor]. / Synnyttäjän pallearuptuura.

A diaphragmatic rupture associated with labor is a rare complication of pregnancy with high fetal and maternal mortality. Due to non-specific symptoms and rareness of the disease the diagnosis can be challenging. We present a case of a healthy 26-year old woman with one previous childbirth who presented upper abdominal pain, tachycardia and dyspnea during labor. Immediately after labor, a left-sided diaphragmatic rupture complicated with ventricle perforation was diagnosed. After prompt diagnosis and immediate surgical care, including thoracotomy and laparotomy, both patient and child experienced a full recovery.

Serum FGF21 increases with hepatic fat accumulation in pediatric onset intestinal failure.

BACKGROUND & AIMS: Previously, FGF21 has been related to glucose and lipid metabolism and liver steatosis. Our aim was to evaluate serum FGF21 levels in pediatric onset intestinal failure (IF). METHODS: Serum FGF21 was measured in 35 IF patients at median age of 7.8 years (range 0.2-27) and 59 matched healthy controls. Thirty patients underwent liver biopsy. RESULTS: Serum FGF21 levels were increased in patients compared to controls [229 pg/ml (21-20,345) vs. 133 pg/ml (7-1607), p=0.018]. Frequency of liver steatosis (60% vs. 50%, p=0.709) was similar during (6/10) and after (10/20) weaning off parenteral nutrition (PN). Patients with steatosis had markedly higher serum FGF21 concentration [626 pg/ml (21-20,345) vs. 108 pg/ml (32-568), p=0.002] and more advanced liver fibrosis [Metavir stage 1.6 (0-4) vs. 0.7 (0-3), p=0.020] without associated inflammation or Mallory body formation. Serum FGF21 levels reflected the degree of steatosis [FGF21 in grade 3 vs. grades 0-2, p<0.001; grade 1 vs. controls, p=0.002], and correlated with steatosis grade (r=0.589, p=0.001). Hepatic steatosis and serum FGF21 showed similar associations with duration of PN and remaining small bowel length (p<0.05 for all). In a multivariate regression model, liver steatosis grade (ß=0.630, p=0.001) predicted serum FGF21 concentration. CONCLUSIONS: In pediatric IF increased serum FGF21 levels reflect liver steatosis, while both are exclusively associated with duration of PN and extent of small intestinal resection. Liver steatosis is coupled with progression of fibrosis without accompanying inflammation. Serum FGF21 assay may be useful for diagnosing liver steatosis in IF patients.

Persistent abnormal liver fibrosis after weaning off parenteral nutrition in pediatric intestinal failure.

UNLABELLED: The aim of this study was to evaluate the long-term effects of pediatric intestinal failure (IF) on liver histology. Altogether, 38 IF patients (median age: 7.2 years; range, 0.2-27) underwent liver biopsy, gastroscopy, abdominal ultrasound, and laboratory tests. Sixteen patients were on parenteral nutrition (PN) after 74 PN months (range, 2.5-204). Twenty-two had weaned off PN 8.8 years (range, 0.3-27) earlier, after 35 PN months (range, 0.7-250). Fifteen transplant donor livers served as controls. Abnormal liver histology was found in 94% of patients on PN and 77% of patients weaned off PN (P = 0.370). During PN, liver histology weighted with cholestasis (38% of patients on PN versus 0% of patients weaned off PN; P = 0.003) and portal inflammation (38% versus 9%; P = 0.050) were found. Fibrosis (88% versus 64%; P = 0.143; Metavir stage: 1.6 [range, 0-4] versus 1.1 [range, 0-2]; P = 0.089) and steatosis (50% versus 45%; P = 1.000) were equally common during and after weaning off PN. Plasma alanine aminotransferase (78 U/L [range, 19-204] versus 34 [range, 9-129]; P = 0.009) and conjugated bilirubin (43 µmol/L [range, 1-215] versus 4 [range, 1-23]; P = 0.037) were significantly higher during than after weaning off PN. Esophageal varices were encountered in 1 patient after weaning off PN. Metavir stage was associated with small bowel length (r = -0.486; P = 0.002) and number of septic episodes (r = 0.480; P = 0.002). In a multivariate analysis, age-adjusted small bowel length (ß = -0.533; P = 0.001), portal inflammation (ß = 0.291; P = 0.030), and absence of an ileocecal valve (ß = 0.267; P = 0.048) were predictive for fibrosis stage. CONCLUSION: Despite resolution of cholestasis and portal inflammation, significant liver fibrosis and steatosis persist after weaning off PN. Extensive small intestinal resection was the major predictor for liver fibrosis stage.

Validation of the Clavien-Madadi Classification for Unexpected Events in Pediatric Surgery: A Collaborative ERNICA Project.

BACKGROUND: The Clavien-Madadi classification is a novel instrument for the assessment and grading of unexpected events in pediatric surgery, based on the Clavien-Dindo classification. The system has been adjusted to better fit the pediatric population in a prospective single-center study. There is a need now to validate the Clavien-Madadi classification within an international expert network. METHODS: A pediatric surgical working group created 19 case scenarios with unexpected events in a multi-staged process. Those were circulated within the European Reference Network of Inherited and Congenital Anomalies (ERNICA) and surgeons were instructed to rate the scenarios according to the Clavien-Madadi vs. Clavien-Dindo classification. RESULTS: 59 surgeons from 12 European countries completed the questionnaire. Based on ratings of the case scenarios, the Clavien-Madadi classification showed significantly superior agreement rates of the respondents (85.9% vs 76.2%; p < 0.05) and was less frequently considered inaccurate for rating the pediatric population compared to Clavien-Dindo (2.1% vs 11.1%; p = 0.05). Fleiss' kappa analysis showed slightly higher strength of agreement using the Clavien-Madadi classification (0.74 vs 0.69). Additionally, intraclass correlation coefficient was slightly higher for the Clavien-Madadi compared to the Clavien-Dindo classification (ICCjust 0.93 vs 0.89; ICCunjust 0.93 vs 0.89). More pediatric surgeons preferred the Clavien-Madadi classification for the case scenarios (43.0% vs 11.8%; p = 0.002) and advantages of the Clavien-Madadi were confirmed by 81.4% of the surgeons. CONCLUSION: The Clavien-Madadi classification is an accurate and reliable instrument for the grading of unexpected events in pediatric surgery. We therefore recommend its application in clinical and academic pediatric surgical practice. LEVEL OF EVIDENCE: III.

Featuring molecular regulation of bile acid homeostasis in pediatric short bowel syndrome.

BACKGROUND: Disturbed bile acid homeostasis may foster development of short bowel syndrome (SBS) associated liver disease during and after weaning off parenteral nutrition (PN). Our aim was to study hepatic molecular regulation of bile acid homeostasis in relation to serum and fecal bile acid profiles in pediatric SBS. METHODS: Liver histopathology and mRNA expression of genes regulating synthesis, uptake and export of bile acids, and cellular receptors involved in bile acid signaling were measured in SBS patients (n = 33, median age 3.2 years). Simultaneously, serum (n = 24) and fecal (n = 10) bile acid profiles were assessed. Sixteen patients were currently on PN. Results of patients were compared to healthy control subjects. RESULTS: Nine of ten (90 %) patients with histological cholestasis received current PN, while portal inflammation was present in 60 % (6/10) of patients with cholestasis compared to 13 % (3/23) without cholestasis (P = 0.01). In all SBS patients, hepatic synthesis and uptake of bile acids was increased. Patients on current PN showed widespread repression of hepatic FXR target genes, including downregulated canalicular (BSEP, MDR3) and basolateral (MRP3) bile acid exporters. Serum and fecal primary bile acids were increased both during and after weaning off PN. CONCLUSIONS: Bile acid homeostasis in SBS is characterized by interrupted enterohepatic circulation promoting increased hepatic synthesis and conservation of bile acids. In PN dependent SBS patients with hepatic cholestasis and inflammation, the molecular fingerprint of downregulated hepatocyte canalicular and basolateral bile acid export with simultaneously increased synthesis and uptake of bile acids could favor their accumulation in hepatocytes and predispose to liver disease.

Distal Recurrent Tracheoesophageal Fistula after Repair of Esophageal Atresia-Incidence, Risk Factors, and Outcome.

OBJECTIVE: The aim of this study was to assess incidence, risk factors, and outcomes of distal recurrent tracheoesophageal fistula (RTEF) after repair of esophageal atresia (EA). METHODS: Ethical consent was obtained. Data collection was done by review of hospital records of 286 patients (268 in-house and 18 referred) who underwent repair of type C or D EA from 1980 to 2021. Spitz class, long-gap (tracheoesophageal fistula at carina), fundoplication, leakage, and stricture were assessed as RTEF risk factors. Outcome measures were long-term closure of RTEF, retainment of native esophagus, and survival. RESULTS: RTEF occurred in 23 patients (19 in-house) with type C (n = 22) or type D (n = 1) EA with median 4.4 (interquartile range [IQR]: 1.7-13) months after repair. Five patients had late RTEF 3.5 to 16 years after repair. Nineteen (7.3%) in-house patients developed RTEF. Presenting symptoms, age at diagnosis, and presence of anastomotic stricture (AS) are listed. No statistically significant risk factors were found, risk ratio of 0.5 to 2.7 (IQR: 0.1-8.7), p-value of 0.25 to 0.75. Detached closure clip and esophageal foreign body contributed to RTEF in two patients. Sixteen patients underwent rethoracotomy for closure of RTEF, 5 (22%) with AS eventually underwent esophageal reconstruction after a period with cervical esophagostomy. Two patients with late-manifested RTEFs underwent closure with laser cauterization. In 22 patients, treatment of RTEF succeeded, whereas 1 (4%) premature patient died of instant re-RTEF. CONCLUSION: RTEF had an incidence of 7% with diverse patterns of manifestation and predicting factors. Closure rate and patient survival were excellent, but RTEF with AS predicted loss of native esophagus.