Serum fasting GLP-1 and GLP-2 associate with intestinal adaptation in pediatric onset intestinal failure

Aim: Glukagon-like-peptide-1 (GLP-1) and -2 (GLP-2), produced by intestinal L-cells, are key hormones regulating intestinal transit, secretion, absorption, and mucosal growth. We evaluated nai ve fasting serum GLP-1 and GLP-2 levels in pediatric intestinal failure (IF). Methods: Fifty-five IF patients with median age 4.2 (IQR 1.3-12) years and 47 matched healthy controls underwent measurement of fasting serum GLP-1 and GLP-2. Results: Serum GLP-2 [19.9 (13.8-27.9) vs 11.6 (7.0-18.6) ng/mL, P <0.001], but not GLP-1 [6.1 (4.0-15.7) vs 6.4 (3.9-10.7) ng/mL, P = 0.976], levels were increased in IF patients. Serum GLP-2 concentrations were higher in patients with small bowel -colic continuity [21.1 (15.0-30.7) ng/mL] compared to patients with an endostomy [10.4 (6.6-17.9) ng/mL, P = 0.028], whereas no association with preservation of ileum or ileocecal valve was observed. During PN delivery, GLP-2 inversely associated with remaining small bowel length (r = -0.500, P = 0.041) and frequency of PN infusions (r = -0.549, P = 0.042). Serum GLP-1 levels were lower in patients receiving PN currently [4.1 (2.8-5.1)] compared to patients, who had weaned off PN [6.5 (5.1-21.1), P = 0.005],. and correlated positively with duration of PN (r = -0.763, P = 0.002) and negatively with percentage parenteral energy requirement (r = -0.716, P = 0.006). Conclusions: In pediatric IF, serum GLP-2 levels increase in patients with small bowel -colic continuity proportionally to the length of resected small intestine. Increase in serum GLP-1 and GLP-2 levels paralleled reducing requirement for parenteral support. These findings support regulation of intestinal adaption by GLP-2 and GLP-1 in children with IF. (C) 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.Peer reviewe

Nanoscale density fluctuations in swift heavy ion irradiated amorphous SiO2

We report on the observation of nanoscale density fluctuations in 2 μm thick amorphous SiO₂ layers irradiated with 185 MeV Au ions. At high fluences, in excess of approximately 5 × 10¹² ions/cm², where the surface is completely covered by ion tracks, synchrotron small angle x-ray scattering measurements reveal the existence of a steady state of density fluctuations. In agreement with molecular dynamics simulations, this steady state is consistent with an ion track “annihilation” process, where high-density regions generated in the periphery of new tracks fill in low-density regions located at the center of existing tracks.The authors acknowledge the Australian Research Council and the Australian Synchrotron Research Program for financial support and thank the staff at the ANU Heavy Ion facility for their continued technical assistance. O.P., F.D., and K.N. acknowledge financial support from the Academy of Finland under its Centre of Excellence program as well as the OPNA project, and grants of computer capacity from CSC

Infection Prevention and Management in Pediatric Short Bowel Syndrome

Short bowel syndrome (SBS) is a rare disease with potentially life-threatening consequences. In addition to intestinal failure-associated liver disease, infections and other complications related to central venous catheters (CVCs) cause a significant burden to patients with SBS and may even necessitate an intestinal transplant eventually. The need for long-term central venous access and the intestinal dysfunction associated with SBS drive the need for intestinal failure-specific approach to prevent and treat infections in patients with SBS. In bacterial infections, the line can often be salvaged with proficient antibiotic therapy. Repeated catheter replacements are predisposed to recurrent infections and thrombotic complications, which may limit the long-term survival of patients with SBS. Protocol-based CVC access procedures and daily care including taurolidine and ethanol catheter locks have been shown to reduce infection rates substantially. Compromised intestinal function in SBS predisposes to small bowel bacterial overgrowth, mucosal injury, and increased permeability. These pathophysiological changes are concentrated in a subset of patients with excessive bowel dilatation and frequent bowel-derived infections. In such patients, reconstructive intestinal surgery may be indicated. Probiotics have not been effective in infection prevention in SBS and carry a significant risk of complications. While more studies focusing on the prevention of infections and their complications are needed, protocol-based approach and multidisciplinary teams in the care of patients with SBS have been shown to reduce complications and improve outcomes.Peer reviewe

Outcome of Surgery for Pediatric Gastroesophageal Reflux : Clinical and Endoscopic Follow-up after 300 Fundoplications in 279 Consecutive Patients

Purpose: Clinical and endoscopic assessment of the outcome after fundoplication for pediatric gastroesophageal reflux. Basic procedures: Hospital records of 279 consecutive patients who underwent fundoplication for gastroesophageal reflux from 1991 to 2014 were reviewed. Underlying disorders, clinical and endoscopic findings, imaging studies, pH monitoring, and surgical technique were assessed. Main outcome measures were patency of fundoplication, control of symptoms and esophagitis, complications, redo operations, and predictive factors of failures. Main results: A total of 279 patients underwent 300 fundoplications (277 primaries and 23 redos). Underlying disorders in 217 (72%) patients included neurological impairment (28%) and esophageal atresia (22%). Indications for fundoplication included recalcitrant gastroesophageal reflux symptoms (44%), failure to thrive (22%), respiratory symptoms (15%), esophageal anastomotic stricture (4%), apneic spells (2%), and regurgitation (2%). Preoperative endoscopy was performed in 92% and pH monitoring in 49% of patients. Median age at primary fundoplication was 2.2 ((IQR = 0.5-7.5)) years. Fundoplication was open in 205 (74%; Nissen n=63, Boix-Ochoa n=97, Toupet n=39, and other n=6), laparoscopic in 72 (24%; Nissen n=67 and Toupet n=5), and included hiatoplasty in 73%. Clinical follow-up was a median of 3.9 (IQR = 1.2-9.9) years. Mortality related to surgery was 0.3%. Symptom control was achieved in 87% of patients, and esophagitis rate decreased from 65% to 29% (p Conclusion: The majority of patients who underwent fundoplication had an underlying disorder. Primary fundoplication provided control of symptoms in almost 90% of patients and also reduced the rate of esophagitis. Failure of primary fundoplication occurred in 15% of patients, and an underlying disorder, esophageal atresia, and hiatoplasty increased the risk of failure.Peer reviewe

Fragmented management of long-term parenteral support for adult intestinal failure in Finland

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.Peer reviewe

Long-term Outcomes and Health Perceptions in Pediatric-onset Portal Hypertension Complicated by Varices

Objectives: Outcomes of pediatric-onset portal hypertension are poorly defined. We aimed to assess population-based long-term outcomes of pediatric-onset portal hypertension complicated by varices. Methods: All children with esophageal varices (n = 126) were identified from 14,144 single nationwide referral center endoscopy reports during 1987 to 2013, and followed up through national health care and death registers. A questionnaire was sent to survivors (n = 94) of whom 65 (69%) responded. Results: Nineteen underlying disorders included biliary atresia (35%), extrahepatic portal vein obstruction (35%), autosomal recessive polycystic kidney disease (7%), and other disorders (23%). During median follow-up of 15.2 (range 0.5-43.1) years patients underwent median 9 (1-74) upper gastrointestinal endoscopies. Esophageal varices were first observed at a median age of 4.0 (0.3-18.2) years, 112 (89%) patients underwent median 6 (1-56) sclerotherapy/banding sessions, and 61 (48%) experienced median 2 (range 1-20) variceal bleeding episodes. Forty-eight surgical shunt procedures were performed to 41 (36%) patients and 38% underwent liver transplantation. Portal hypertensive biliopathy was diagnosed in 4 patients. Hepatopulmonary syndrome necessitated liver transplantation in 2 patients, hepatic encephalopathy in 2, and hepatorenal syndrome in 1. No patient died of variceal bleeding. Patient-reported perception of health on a scale of 1 to 10 was 9 (range 4-10), and 86% reported no current symptoms attributable to esophageal varices. Conclusions: Pediatric-onset portal hypertension is a heterogeneous disease with significant long-term morbidity, requiring multimodal approach with considerable resources and continuation of follow-up in adulthood. Although mortality to variceal bleeding was avoided, bleeding episodes recurred also in adulthood, while patient-reported health of long-term survivors was encouraging.Peer reviewe

Manometric findings in relation to functional outcomes in different types of anorectal malformations

Aims: To compare anorectal manometry (AM) in patients with different types of anorectal malformations (ARMs) in relation to functional outcomes. Methods: A single-institution, cross-sectional study. After ethical approval, all patients >= 7 years old treated for anterior anus (AA), perineal fistula (PF), vestibular fistula (VF), or rectourethral fistula (RUF) from 1983 onwards were invited to answer the Rintala bowel function score (BFS) questionnaire and to attend anorectal manometry (AM). Patients with mild ARMs (AA females and PF males) had been treated with minimally invasive perineal procedures. Females with VF/PF and males with RUF had undergone internal-sphincter saving sagittal repairs. Results: 55 of 132 respondents (42%; median age 12 (7-29) years; 42% male) underwent AM. Patients with mild ARMs displayed good anorectal function after minimally invasive treatments. The median anal resting and squeeze pressures among patients with mild ARMs(60 cm H2O and 116 cm H2O respectively) were significantly higher than among patients with more severe ARMs (50 cm H2O, and 80 cm H2O respectively; p Conclusions: Our findings support the appropriateness of our minimally invasive approaches to the management of mild ARMs, and IAS-saving anatomical repairs for patients with more severe malformations. (C) 2017 Elsevier Inc. All rights reserved.Peer reviewe

Combined management of perianal rhabdomyosarcoma with chemotherapy, radical surgery, and irradiation : A series of three consecutive children

Background and aim: We describe a series of three successive patients with perianal rhabdomyosarcoma (PRMS) from 2014 to 2017 managed with combined chemotherapy, radical surgery, and radiotherapy. Methods: Ethical consent was obtained. Data including tumor presentation, treatment, and survival was collected from hospital reports. Results: Two girls aged 15 and 16 years (patient #1 and #2) and one boy aged five years (patient #3) were referred because of a suspected perianal abscess. MRI showed large perianal tumors from 7 to 12 cm in diameter that surrounded or infiltrated the anal sphincters and were inconsistent with abscess. Tumor biopsies showed RMS of alveolar (#1 and #2) and embryonal (#3) types. Patient #1 had lymph node and bone metastases, patient #2 lymph node metastases, and patient # 3 no metastases. Pretreatment staging, IRS Clinical Group, and Risk Groups were: Stage 4, II, high; Stage 3, GII, intermediate; and Stage 3, I, low, respectively. All underwent colostomy before neoadjuvant chemotherapy (CWS-RMS 2009 program). Neoadjuvant chemotherapy failed to clear the tumors from anal sphincters preventing anus-saving surgery, and all patients underwent abdominoperineal excision. All removed specimens had freemargins with negative lymph nodes. After adjuvant chemotherapy and local radiation, the patients were tumor free after 48, 13, and 18 months. Conclusion: In PRMS local surgical control required abdominoperineal excision. Confusion between PRMS and abscess may cause unnecessary delay in management. (C) 2018 Elsevier Inc. All rights reserved.Peer reviewe

Risk factors and outcomes of tapering surgery for small intestinal dilatation in pediatric short bowel syndrome

Background: In remains unclear why in some short bowel syndrome (SBS) patients, the remaining small bowel (SB) dilates excessively leading to requirement of tapering surgery. Methods: Among SBS children, we retrospectively analyzed risk factors for tapering surgery with logistic regression and compared the outcome of operated patients (n = 16) to those managed conservatively (n = 44) with Cox proportional hazards regression. Results: SBS was caused by necrotizing enterocolitis (NEC) (n = 31), SB atresia (SBA) (n = 13), midgut volvulus (n = 12), or gastroschisis (n = 4). Patients with spontaneous symptomatic SB dilatation unable to wean parenteral nutrition (PN) underwent tapering surgery at median age of 1.04 (interquartile range 0.70-3.27) years. Missing ICV was related to an 8-fold (p = 0.003) increased risk while SBA diagnosis was related to a 13-fold risk of tapering surgery (p <0.001). Increasing SB length and NEC diagnosis were protective of tapering (p = 0.027-0.004). Of operated patients, 75% reached enteral autonomy during follow-up and their postoperative adjusted PN weaning rate was similar to nonoperated children (p = 0.842). Conclusion: SBS children with short remaining SB, missing ICV, and SBA etiology are more likely while NEC patients are less likely than others to necessitate tapering surgery. Postoperative PN weaning rates were comparable to patients who initially had more favorable intestinal anatomy and adapted without surgery. (C) 2017 Elsevier Inc. All rights reserved.Peer reviewe

Sexual Function, Fertility and Quality of Life after Modern Treatment of Anorectal Malformations

Purpose: Sexual dysfunction and impaired quality of life due to fecal incontinence are common after classic operations for anorectal malformations. We hypothesized that modern repairs may result in improved outcomes. Materials and Methods: Following ethical approval for this single institution cross-sectional study, all patients 16 years or older treated for rectourethral, vestibular or perineal fistula from 1983 onward were sent detailed postal questionnaires on sexual function and quality of life. Each respondent was age and gender matched to 3 controls randomly selected from the general population. Penoscrotal/gynecologic abnormalities were obtained from the records. Results: A total of 41 patients (62%) with a median age of 22 years participated in the study. Of the patients 20 were males with rectourethral fistula (prostatic in 60%), 10 were females with vestibular/perineal fistula and 11 were males with low malformations. Although experience of sexual relationships and orgasmic function were reported in comparable proportions to controls, age at coital debut was significantly delayed in all groups of patients (p Conclusions: While erectile and orgasmic function appear preserved after sagittal repair, further evaluation of fertility issues in males with rectourethral fistula is indicated. Larger multicenter studies are needed to confirm our findings.Peer reviewe