A retrospective case-control study of gastrostomy use in children undergoing hematopoietic cell transplantation.

BACKGROUND: Maintaining a good nutritional status during the hematopoietic cell transplantation (HCT) procedure is challenging in the pediatric population. METHODS: In a multicentric retrospective study, we compared the outcome of nutritional status and HCT-related parameters in 227 pediatric patients during and after HCT between 2005 and 2015. 112 patients received a gastrostomy before the start of HCT (GS group), and 115 did not receive a gastrostomy (NGS). Data collection was performed at HCT, 3, 6, and 12 months post-HCT. RESULTS: At time point of HCT the Standard Deviation Score (SDS) of weight was 0.17 in the NGS group, and 0.71 in the GS group (p = .01) Patients in the NGS group lost more weight during the first 3 months after HCT than patients in the GS group. At 12 months, patients in the NGS remained at a lower weight, while patients in the GS group slightly increased their weight. There were no differences between the groups in the incidence of acute graft-versus-host-disease (GvHD), overall survival, and non-relapse mortality. However, the number of febrile episodes requiring intravenous treatment with antibiotics, was higher in the GS group as compared to the NGS group, during the first 3 months post-HCT (p < .001). CONCLUSIONS: Our results indicate that gastrostomy can be utilized in children undergoing HCT without any negative effects on mortality. Therefore, the use of a gastrostomy appears to be a safe option to maintain a good nutritional status during the HCT procedure.

Diagnostic disagreement between clinical standard histopathological- and retrospective assessment of histopathology-based gastrointestinal graft-versus-host disease in children.

BACKGROUND: No previous paediatric study has evaluated the frequency of diagnostic disagreement between clinical standard histopathological assessment (CSHA) and retrospective, independent, histopathological assessment (RIHA) of gastrointestinal Graft-Versus-Host Disease (GI-GVHD) METHODS: In a retrospective cohort study, based on gastrointestinal biopsies collected from allogeneic HSCT-treated children (<18 years) with symptom-based GI-GVHD, we evaluated; disagreement of histopathology-based GI-GVHD diagnosis in CSHA vs RIHA, and potential clinical consequences of differences between the assessments. The CSHA-based diagnoses were retrieved from histopathology reports. The RIHA was performed by one pathologist, blinded to the CSHA outcomes and based on the minimal criteria for histopathology-based GI-GVHD diagnosis by the NIH 2014. RESULTS: Seventy children with 92 endoscopic occasions (including 22 re-endoscopies) were enrolled. GI-GVHD was observed in 73% (67/92) of the endoscopies in the RIHA and in 54% (50/92) in the CSHA (P = .014). The RIHA confirmed 94% (47/50) with GI-GVHD and 52% (22/42) with non-GI-GVHD diagnoses, established in the CSHA. Disagreement, that is endoscopic occasions with GI-GVHD solely detected in RIHA or detection of GI-GVHD in CSHA but not in RIHA, was observed in 20/42 (48%) and 3/50 (6%), respectively (McNemar's test, P = .0008). The risk of a subsequent re-endoscopy was higher in endoscopic occasions with GI-GVHD detected in RIHA but not in CSHA vs if non-GI-GVHD were detected in both readings (P = .005). CONCLUSION: Our results suggest that in children with symptom-based GI-GVHD without histopathological confirmation in CSHA, a second, NIH 2014 based histopathological assessment should be considered before performing a re-endoscopy.

Clinical relevance of endoscopy with histopathological assessment in children with suspected gastrointestinal graft-versus-host disease.

Endoscopy with histopathological assessment is an established practice to confirm gastrointestinal graft-versus-host disease (GI-GVHD). However, the clinical relevance of this approach in children is incompletely evaluated. In a retrospective cohort study, we investigated the frequency of treatment changes in response to histopathological findings in all children (<18 years) in Sweden who underwent endoscopy for suspected GI-GVHD (2000-2013) after receiving hematopoietic stem cell transplantation. Sixty-eight children with ninety-one endoscopic occasions were enrolled. At the time of endoscopy, anti-GI-GVHD treatment was ongoing in 71% (65/91). In 18% (12/65) with ongoing treatment, no histopathological evidence of GI-GVHD or another cause to justify anti-GI-GVHD treatment was found. In 48% (44/91), endoscopy with histopathological assessment led to changes in the treatment regimen. Re-endoscopy was more frequent among those with treatment changes, versus unchanged treatment, 39% (17/44) and 13% (6/47), respectively (P = .007). Histopathological findings generating treatment changes were as follows: GI-GVHD in 68% (30/44), normal histology in 25% (11/44), and an alternative diagnosis in 7% (3/44). In conclusion, this study supports that endoscopy with histopathological assessment should be considered in all children with suspected GI-GVHD.

Choice of Endoscopic Procedure in Children With Clinically Suspected Gastrointestinal Graft-versus-host Disease.

OBJECTIVES: Gastrointestinal graft-versus-host disease (GI-GVHD) is a potentially life-threatening complication after hematopoietic stem cell transplantation. Symptoms indicating GI-GVHD motivates endoscopy with biopsy sampling and histopathological confirmation. Optimal extent of endoscopy in children is, however, presently unknown. Therefore, we aimed to evaluate whether biopsies from the rectosigmoid area versus the rest of the colon/ileocolon with or without biopsies from simultaneous upper endoscopy, were equally reliable for detection of GI-GVHD and relevant differential diagnoses. METHODS: Retrospective multicenter study based on histopathological re-evaluation of biopsies and hospital record data, collected from children with suspected GI-GVHD. RESULTS: Forty-four children with 51 endoscopic occasions (81 procedures) were included. Thirty-nine of 51 (76.5%) were diagnosed as GI-GVHD, 14 (27.4%) received a differential diagnosis and 7 (13.7%) had normal histology findings. Comorbidity, that is, simultaneous detection of a differential diagnosis and GI-GVHD, was observed in 9 (23.1%) cases. Cytomegalovirus infection was the most frequent differential diagnosis, 6 of 7 were detected in biopsies from rectosigmoid and esophagogastroduodenal areas. Sensitivity for detection of GI-GVHD in biopsies collected from rectosigmoid-ileocolonic-, rectosigmoid-, or esophagogastroduodenal areas were 97.4%, 84.6%, 83.3%, respectively, and 97.4% when the latter 2 were merged. The difference, nondetected GI-GVHD in the rectosigmoid area versus detected elsewhere in the GI tract, was statistically significant (P = 0.03). CONCLUSIONS: Biopsies collected from the rectosigmoid area solely were not optimal for detection of pediatric GI-GVHD. When biopsy sampling from rectosigmoid and upper GI tract areas was combined, the sensitivity for GI-GVHD was, however, equally high as for ileocolonoscopy or full upper and lower endoscopy.

Tacrolimus without or with the addition of conventional immunosuppressive treatment in juvenile autoimmune hepatitis.

AIM: To investigate tacrolimus (Tac)-based treatment in juvenile autoimmune hepatitis (AIH). Twenty patients (13 girls; age, 8-17 years; median, 13.25 years) with AIH were treated with two daily oral doses of Tac. Six of them had advanced liver disease and/or cirrhosis. METHODS: Drug concentrations in blood were measured regularly, and the target trough levels were 2.5-5 ng/mL. The patients were followed up for 1 year. Their clinical, biochemical, immunological and histological status was obtained at baseline and after 1 year. RESULTS: In three cases, Tac alone led to complete remission. In 14 cases, additional low doses of prednisolone or azathioprine were used for a short time to achieve remission. In two cases, the treatment was discontinued: in one because of therapeutic failure, in another because of a suspected but unverified adverse event. Ten patients reported headache and/or recurrent abdominal pain. Two patients developed inflammatory bowel disease. Renal function remained intact. CONCLUSION: Tac is a promising alternative first line of treatment for AIH. Although monotherapy with Tac is usually not sufficient to achieve complete remission, the prednisolone and azathioprine doses can be drastically reduced, and most of their side effects avoided.

Exclusive enteral nutrition in the treatment of children with Crohn's disease in Sweden: a questionnaire survey.

AIM: The general use of exclusive enteral nutrition (EEN) as therapy for children with Crohn's disease (CD) in Sweden has not previously been studied. Thus, the aim of this study was to investigate how EEN is used as therapy in Sweden for children with CD. METHODS: A questionnaire was sent to all 37 paediatric units in Sweden that treat children with inflammatory bowel disease. RESULTS: The response rate was 78%, which covers nearly 90% of Sweden's paediatric population between 0 and 17 years of age. Ninety-six per cent of the units used EEN as a treatment option for children with CD, and 65% of the units used EEN as their primary therapy in newly diagnosed CD. The standard duration of EEN was 6 weeks, but the questionnaire revealed a span of 4-8 weeks. The use of polymeric formula was just as common as a combination of polymeric and elemental formulas. Fifty-seven per cent used oral nutrition supplements, and 81% allowed some extent of concomitant feeding, the addition of food and fluids, during EEN. All units used enteral nutrition to some extent as maintenance therapy after EEN was discontinued. CONCLUSIONS: In Sweden, EEN is used as therapy for children with Crohn's disease (CD), but the EEN protocols vary as to choice of formula and type of food and fluids allowed during EEN. Standardized EEN protocols would enable multicentre studies in Sweden, with the objective of investigating how EEN treatment can be improved and employed in the most efficient way.

Helicobacter species DNA in liver and gastric tissues in children and adolescents with chronic liver disease.

OBJECTIVE: Enterohepatic Helicobacter species (EHS) have previously been found in adults with hepatobiliary diseases. Here, we report the prevalence of Helicobacter pylori and EHS in liver and gastric tissue in children and adolescents with chronic liver disease (CLD). MATERIAL AND METHODS: Seventy-seven consecutive children and adolescents with CLD with or without ulcerative colitis or Crohn's disease (UC/CD) were investigated. Tissue samples were analysed using a Helicobacter genus-specific 16S rDNA polymerase chain reaction (PCR) assay and DNA-sequence analysis. Sera from 61 subjects were also analysed using enzyme immunoassay and immunoblotting. RESULTS: The Helicobacter PCR was positive in 3/23 (13%) livers from patients with primary sclerosing cholangitis and UC, and in 1/2 livers from patients with autoimmune hepatitis (AIH) and UC. Sequenced PCR products matched the 16S rDNA of H. hepaticus, H. muridarum, H. canis, and H. pylori, respectively. H. ganmani and H. bilis were detected in gastric tissues from two AIH patients. H. hepaticus and H. pullorum were found in livers from two patients with acute liver failure and intrahepatic cholestasis. Antibody reactivity to Helicobacter cell-surface proteins was negative. CONCLUSIONS: H. pylori and EHS can be detected in the livers of some patients with UC and concomitant liver disease, as well as in other children with liver diseases. Multicentre studies from different locations are needed to find out whether these bacteria play a pathogenetic role or whether their presence is an epiphenomenon.

Severe liver damage associated with celiac disease: findings in six toddler-aged girls.

OBJECTIVE: Light-to-moderate liver damage is often seen in children diagnosed with celiac disease, but severe liver damage is rarely observed. METHODS: During a 12-year-long period our center took care of six 13-36-month-old girls who developed severe liver damage 1-24 months after the diagnosis of celiac disease. RESULTS: Four girls had acute liver failure; two of them had to be liver transplanted. The other four girls recovered without transplantation and none of the six patients developed autoimmune disease during the 2-14-year-long follow-up period. Although adenovirus type 2 was found in the urine and stools of one girl, her liver histopathology did not resemble viral hepatitis. Certain autoimmune features could be observed initially in some of the children but finally none of them fulfilled the criteria for autoimmune liver disease and this pattern did not change during the several years of follow-up. Thorough investigation could not find any alternative pathogenetic cause and thus, the association with celiac disease is obvious. Histopathology showed various degrees of intralobular inflammation, necrosis, involvement of the small bile ducts, and in one case interface hepatitis; but in general, histopathology did not reveal a common pathogenetic mechanism. CONCLUSION: Although rare, severe hepatic damage or failure can develop in association with celiac disease. The etiology is varying and multifactorial. Consequently, children with newly onset celiac disease should be routinely checked for liver function and vice versa, children with severe liver damage should be investigated for untreated celiac disease.

Cerebral venous thrombosis and heparin-induced thrombocytopenia in an 18-year old male with severe ulcerative colitis.

The risk of thromboembolism is increased in inflammatory bowel disease and its symptoms may be overlooked. Furthermore, its treatment can be complex and is not without complications. We describe a case of an adolescent boy who developed a cerebral sinus venous thrombosis during a relapse of his ulcerative colitis and who, while on treatment with heparin, developed heparin-induced thrombocytopenia (HIT). The treatment was then switched to fondaparinux, a synthetic and selective inhibitor of activated factor X.

Vaccination of the immunocompromised child.

The development of vaccination is a major achievement in modern medicine. However, children treated with immunosuppression may not at all, or only in part, receive routine immunization due to uncertainty of its risks and effect. There is a substantial lack of pediatric studies concerning the efficacy and safety of vaccination in this patient group. Experience from similar adult groups and children with HIV infection can be used as a model for other disease categories. With increasing knowledge of the immunologic basis of vaccination and how immunosuppressive drugs interfere with the immune system, improved vaccines could be tailored, and adequate, individualized guidelines issued.

Concordance of Helicobacter pylori strains within families.

Helicobacter pylori infection is typically acquired in early childhood, and a predominantly intrafamilial transmission has been postulated. To what extent family members share the same strains is poorly documented. Our aim was to explore patterns of shared strains within families by using molecular typing. Family members of H. pylori-infected 10- to 12-year-old index children identified in a school survey were invited to undergo gastroscopy. Bacterial isolates were typed with random amplified polymorphic DNA and PCR-restriction fragment length polymorphism of the genes ureA-B, glmM, or flaA. The presence or absence of the cag pathogenicity island, a bacterial virulence factor, was determined by PCR. GelCompar II software, supplemented with visual inspection, was used in the cluster analysis. In 39 families, 104 individuals contributed 208 bacterial isolates from the antrum and corpus. A large proportion, 29 of 36 (81%) of the offspring in a sibship, harbored the same strain as at least one sibling. Mother-offspring strain concordance was detected in 10 of 18 (56%) of the families. Of 17 investigated father-offspring relations in eight families, none were strain concordant. Spouses were infected with the same strains in 5 of 23 (22%) of the couples. Different strains in the antrum and corpus were found in 8 of 104 (8%) of the subjects. Our family-based fingerprinting study demonstrates a high proportion of shared strains among siblings. Transmission between spouses seems to be appreciable. The data support mother-child and sib-sib transmission as the primary transmission pathways of H. pylori.

Ganciclovir treatment in infants with cytomegalovirus infection and cholestasis.

BACKGROUND: The authors have previously described an association between cytomegalovirus (CMV) infection and intrahepatic and extrahepatic forms of neonatal cholestasis. Pediatric use of the antiviral drug ganciclovir to treat patients with CMV infection has increased. In this study, infants with CMV infection and cholestasis were treated with ganciclovir. METHODS: Six infants with cholestasis (age, 3-16 weeks) and with signs of ongoing CMV infection were treated with intravenous ganciclovir for 3 to 7 weeks and observed for 4 to 31 months after treatment. Two patients had biliary atresia, one had suspected septo-optic dysplasia and three had no obvious cause for intrahepatic cholestasis other than ongoing CMV infection. RESULTS: Four patients, including one with biliary atresia, responded to the treatment, whereas two patients, including the one with septo-optic dysplasia did not. The latter patient had episodes of symptomatic hypoglycemia during the treatment, which was subsequently stopped. Liver function at the end of follow-up was good in four patients, intermediate in one, and poor in one. CONCLUSION: Ganciclovir treatment may be beneficial in infants with CMV-associated intrahepatic cholestasis, but controlled studies are needed. Because of the possible side effect of hypoglycemia, infants with cholestasis who have increased risk for such episodes should not be treated.