Budd-Chiari syndrome in children: Radiological intervention and role of shear wave elastography in monitoring response.

OBJECTIVES: Radiological intervention (RI) is the preferred treatment in children with Budd-Chiari syndrome (BCS). We studied the comparative long-term outcome of BCS children, with and without RI and utility of liver and splenic stiffness measurement (LSM, SSM) by 2-dimensional shear wave elastography (2D-SWE) in assessing response. METHODS: Sixty children (40 boys, median age 10.5 [6.5-15.25] years) with BCS (29 newly diagnosed, 31 follow-up) were evaluated. LSM and SSM by 2D-SWE and vascular patency were monitored pre- and postprocedure (≥ 6 months postprocedure) in those undergoing RI. Medical therapy without anticoagulation and monitoring was done in subjects without RI. The RI and no-RI groups were compared. RESULTS: Ascites (54,90%), hepatomegaly (56,93%) and prominent abdominal-veins (42,70%), were the commonest features. The majority (46,78%) had isolated hepatic vein block. 44 (73%) cases underwent RI, while 16 (27%) were managed conservatively. Both groups were similar at baseline. Post-RI subjects showed significant improvement in clinical findings, liver functions and portal hypertension. LSM [33 (32-34.5) to 19.2 (18-20.67) kPa] and SSM [54.5 (52.3-57.6) to 28.9 (27.6-30.25) kPa] showed a significant decline from baseline value over a follow-up of 12 (6-13) months. Gradual reduction occurred in the LSM and SSM over 1-5 years, with near-normal LSM [10.2 (9.2-11.5) kPa] and SSM [22.3 (20.5-24.3) kPa] values in patients (n-16) with > 5 years follow-up. Patients without RI showed worsening in LSM and SSM. Hepatopulmonary syndrome and hepatocellular carcinoma developed in 4 (8%) and 1 (1.7%) cases respectively. CONCLUSION: RI leads to clinical recovery and reduction with near normalization of LSM and SSM over long-term follow-up in children with BCS. 2D-SWE is a promising tool to monitor outcomes.

Relative Adrenal Insufficiency in Decompensated Cirrhotic Children: Does It Affect Outcome?

INTRODUCTION: Relative adrenal insufficiency (RAI) is associated with poor outcome in adult cirrhotics. So far, pediatric studies are not available on the same. We aimed to prospectively study the presence and outcome of RAI in children with decompensated cirrhosis over 180 days. METHODS: Hemodynamically stable children with decompensated cirrhosis were sampled for serum basal cortisol and peak cortisol (after 30 minutes of 1-µg intravenous Synacthen) at day 1 and day 21. RAI was diagnosed as peak cortisol <500 nmol/L. Serum cytokines (interleukin-6 and tumor necrosis factor-α) and lipid profile were correlated with RAI. Cohort was followed up for outcomes over 180 days for complications and survival. With the identified risk factors, prognostic models were derived and compared with pediatric end-stage liver disease (PELD) and Child-Turcotte-Pugh scores. RESULTS: Prevalence of RAI was 54% at baseline and 61% at day 21 in the enrolled patients (n = 63, aged 128 ± 48 months, male 78%). No significant differences in cytokines and serum lipid levels were seen between RAI and normal adrenal function groups. Patients with RAI at baseline (D1-RAI) developed higher complications at follow-up as compared to the normal adrenal function group (53% vs 24%, P = 0.02). The PELD score (odds ratio 1.08, confidence interval 1.05-1.12, P < 0.01) and D1-RAI (odds ratio 3.19, confidence interval 1.32-7.73, P = 0.01) were independent predictors of follow-up complications. The PELD-delta cortisol model (area under the receiver operating curve 0.84, P < 0.001, 92% sensitivity; 60% specificity) predicted morbidity better than isolated PELD or Child-Turcotte-Pugh scores. DISCUSSION: RAI is a risk factor for development of complications in pediatric cirrhosis over short-term follow-up. The PELD-delta cortisol score is a promising prognostic model for predicting follow-up complications.

Efficacy of amitriptyline in pediatric functional abdominal pain disorders: A randomized placebo-controlled trial.

BACKGROUND AND AIM: Amitriptyline improves symptoms in functional abdominal pain disorders (FAPD) in adults with variable results in pediatric studies. The study aims to evaluate the efficacy of amitriptyline in pediatric FAPD. METHODS: In this open-label trial, children (≤ 18 years) diagnosed as FAPD based on ROME IV criteria were randomized to amitriptyline or placebo for 12 weeks. Post-treatment improvement of pain and quality of life (QOL) from the baseline were compared between the two groups. RESULTS: The mean age of 149 children (amitriptyline 75, placebo 74) was 11.3 ± 3.5 years (79 boys). There was a significant difference in pain improvement in terms of reduction in scores for intensity (3.4 vs 0.9), frequency (3.6 vs 0.6), duration (3.5 vs 0.9), and QOL (2.3 vs 0.9) between amitriptyline and placebo group (P < 0.001 in all). Responders (> 50% reduction) in pain was seen in 76% in amitriptyline compared with 14.9% in the placebo group (P < 0.001). On multivariate analysis, the use of amitriptyline was the only factor predictive of response (odds ratio 24.1, 95% confidence interval: 9.1-64.6, P < 0.001). Minor adverse events were comparable between the groups (25.3% vs 13.5%, respectively, P = 0.07). Eighty-nine percent of children (24/27) who had extended treatment duration (6.8 ± 1.8 months) had pain improvement. After discontinuation of amitriptyline, 70% had sustained response over a mean follow up of 15.84 ± 5.6 months. CONCLUSIONS: A 3-month trial of amitriptyline gives sustained relief of pain in two-thirds of children with FAPD. The safety profile of the drug and its efficacy necessitate more frequent use in the clinical settings.

An unusual cause of obstructive jaundice in childhood: Intra-choledochal malignant neuroendocrine tumour.

The extrahepatic biliary apparatus is a rare site for neuroendocrine tumours. A 13-year-old child presented with cholestatic symptoms of jaundice and pruritus with soft hepatomegaly and mild ascites. Magnetic resonance imaging and endoscopic ultrasound revealed a mid-common bile duct mass, and dilated intrahepatic biliary system. An en-bloc resection of the extrahepatic biliary apparatus, showed malignant cells disposed in lobules in a desmoplastic stroma with intramural invasion, staining positive for cytokeratin, chromogranin, synaptophysin and negative for CD56. At 3 months post-resection, whole body positron emission tomography scan was normal with no recurrence at 24 months.

Gastrointestinal Polyps and Polyposis in Children: Experience of Endoscopic and Surgical Outcomes.

INTRODUCTION: There are gaps in the literature regarding outcome of multiple polyps and dilemmas in the management issues in polyposis syndromes in children. OBJECTIVE: We aimed to study the clinical behaviour of gastrointestinal (GI) polyps with emphasis on therapeutic outcomes of polyposis syndrome. METHODS: Proven cases of GI polyp(s) on endoscopy were classified as single polyp, multiple polyps, and polyposis syndrome. Complex presentation was defined as 1 or more of the following: severe anaemia, anasarca, intussusception, rectal mucosal prolapse, and diarrhoea. A clinico-endoscopic criterion was applied in polyposis syndrome patients for the decision of surgery versus endoscopic therapy with surveillance. RESULTS: Of total 240 patients, there were no significant differences between single (52.5%, n = 126) versus multiple polyps (27.5%, n = 66) with respect to age, symptoms, histology, and recurrence. Polyposis syndrome (20%, n = 48) presented with complex symptoms (50%), higher family history, significantly lower haemoglobin, total protein, and albumin as compared to single and multiple polyps (p < 0.01). Nineteen polyposis patients with favourable clinico-endoscopic criteria were endoscopically eradicated for polyps in 3 (1-4) sessions with sustenance of laboratory parameters at 1 year and 30% symptomatic recurrence at follow-up of 23.5 (7-40) months. There were no major endoscopic complications. Nineteen patients required proctocolectomy with improvement in laboratory parameters 6 months post-surgery. CONCLUSIONS: Multiple polyps behave similar to single polyps in children. A clinico-endoscopic criterion may guide for optimal management of polyposis syndrome. Colectomy may be effectively deferred in a large proportion of polyposis syndrome patients if maintained on an endoscopic protocol.

Late-Onset Hepatic Failure in Children: Risk Factors that Determine the Outcome.

BACKGROUND: Late-onset hepatic failure (LOHF) is a distinct entity of intractable liver diseases with limited pediatric experience. We aimed to identify the etiology and risk factors that determine the poor outcome (PO) of pediatric LOHF. METHODS: LOHF was defined as liver failure occurring 5-24 weeks after onset of jaundice and without any evidence of underlying chronic liver disease. PO (death or liver transplantation within 160 days) was compared with spontaneous recovery (SR; complete normalization of liver functions in the native liver). Pediatric end-stage liver disease (PELD) score and King's College Criteria (KCC) were applied to investigate their prognostic value. RESULTS: We enrolled 47 children (6 [2-16] years) with LOHF. Hepatitis A was the most common etiology (15, 32%) and 64% complicated with infections. Twelve children (25%) had SR over 6 (1-24) months, while 28 (60%) children had PO. Univariate analysis showed indeterminate etiology, hepatic encephalopathy (HE), infection, acute kidney injury, and high PELD score determined PO. On multivariate regression analysis, only PELD score with a cutoff 32 (area under curve 0.833, sensitivity 68%, specificity 92%) predicted PO. KCC showed a sensitivity of 85.7%, specificity of 41.7% to determine PO in our cohort. CONCLUSION: Indeterminate etiology, presence of HE, occurrence of infection at any site, and acute kidney injury lead to the PO. PELD score ≥32 can be utilized to optimize the listing for liver transplantation. A significant proportion survives with the native liver.

Solitary Rectal Ulcer Syndrome in Children: A Report of 140 Cases.

OBJECTIVES: Solitary rectal ulcer syndrome (SRUS) is said to be rare in children (largest series so far; 55 in children, 116 in adults). We analyzed our experience to look at its clinical presentations, endoscopic appearance, and treatment outcome in a large cohort of children. METHODS: Clinical and endoscopic data were collected between 2000 and 2018. Children (18 years or younger) diagnosed to have SRUS on colonoscopy and confirmed by histopathology were included. All children with SRUS were treated with behavioral modification, bulk laxative. Most with ulcer received steroid enema and some sulfasalazine or sucralfate enema. RESULTS: The median age of 140 children was 12 (interquartile range [IQR]: 10-14) years, 79% were boys. The median symptom duration was 21 (IQR: 9-36) months. Rectal bleeding was the presenting feature in 131 (93.6%); constipation in 38 (27%); and small, frequent stools in 79 (56%). Most children had features of dyssynergic defecation such as prolonged sitting in the toilet (131, 93.6%), excessive straining (138, 98.6%), a feeling of incomplete evacuation (130, 92.8%), and rectal digitation (71, 50.7%). Rectal prolapse was noted in 24 (17%) cases. Colonoscopy documented rectal ulcer in 101 (72%) [Single: 84]. Over a median follow-up of 6 (IQR: 4-18) months, 27 patients were lost to follow-up and of the remaining 113 cases, 71 (62.8%) showed clinical improvement (healing of ulcer documented in 36/82, 44%). CONCLUSIONS: The majority of cases of SRUS presented in second decade with rectal bleeding and features of dyssynergic defecation. Ulcer was noted in three fourths of cases. The outcome of medical treatment with behavioral modification and local therapy was modest.

Non-variceal gastrointestinal bleed in children: surgical experience with emphasis on management challenges.

PURPOSE: This exclusively surgical series on pediatric non-variceal gastrointestinal bleed (NVGIB) defines three levels of bleed site and describes etiology, bleed severity, diagnostic algorithm, and surgical management for each bleed site. Management challenges are detailed. METHODS: Patients aged ≤ 18 years treated surgically for NVGIB were analysed. RESULTS: Bleed site (n = 87) was classified as: upper gastrointestinal bleed (UGIB; n = 11); small bowel bleed (SBB: n = 52); and lower GIB (n = 24). Four etiology-based groups were identified: lesions with ectopic gastric mucosa (EGM; n = 33), tumours (n = 23), ulcers (n = 21), and vascular pathology (n = 8). Bleed severity spectrum was: acute severe bleed (n = 12); subacute overt bleed (n = 59); and occult GIB (n = 16). Preoperative diagnosis was obtained in all UGIB and LGIB lesions. Eighty-two percent of surgical SB lesions were diagnosed preoperatively on Tc99m pertechnetate scan, computed tomography enterography-angiography, and capsule endoscopy; remaining 18% were diagnosed at laparotomy with intra-operative enteroscopy (IOE). Surgical management was tailored to bleed site, severity, and etiology. Indications of IOE and approach to management challenges are detailed. CONCLUSIONS: The commonest site-specific bleed etiologies were duodenal ulcers for UGIB, EGM lesions for SBB, and tumours for LGIB. SBB presented diagnostic challenge. Diagnostic algorithm was tailored to bleed site, age-specific etiology, bleed severity, and associated abdominal/systemic symptoms. Management challenges were acute severe bleed, occult GIB, SBB, obscure GIB, and rare etiologies. IOE has a useful role in SBB management.

Prognostic scoring systems and outcome of endovascular radiological intervention of chronic Budd-Chiari syndrome in children.

BACKGROUND AND AIM: Prognostic scoring systems (PSS) have not been validated in children with chronic Budd-Chiari syndrome (BCS). We aimed to analyse the long-term outcome of radiological intervention (RI) and validate the PSS in children. METHODS: Chronic BCS children were analysed in four subgroups: (i) SI: successful intervention (primary or secondary stent patency) (ii) PO: poor outcome (refractory stent block or requirement of liver transplantation), (iii) NU: naïve unintervened (awaiting RI) and (iv) DBI: died before intervention. PSS analysed included Paediatric end-stage liver disease (PELD), Rotterdam, BCS-Transjuglar intrahepatic Portosystemic shunt (BCS-TIPS) index, Zeitoun, Child-Pugh and Model for end-stage liver disease. RESULTS: Of 113 BCS children, 48 children underwent 53 successful primary RI. Actuarial probability of vascular patency was 87% at 1 year and 82% at 5 years follow-up. Four groups (SI: n = 40, PO: n = 7, NU: n = 13, DBI: n = 6) were analysed. Univariate analysis showed pre-intervention PELD score [PO: 11 (-1-23) vs SI: 2 (-8-25), P = .009] with a cut-off of 4 (AUC: 0.809, 86% sensitivity, 75% specificity) determined PO following intervention. In unintervened group (NU vs DBI), multivariate analysis demonstrated that Zeitoun score predicted death independently (OR 15.4, 95% CI: 1.17-203.56, P = .04) with a cut-off of 4.3 (AUC: 0.923, 83% sensitivity and 77% specificity). CONCLUSIONS: Children with BCS have a favourable long-term outcome. Among those undergoing RI, pre-intervention PELD score determines the outcome. Survival is determined by Zeitoun score in those unintervened.

Safety, complications and outcome of large volume paracentesis with or without albumin therapy in children with severe ascites due to liver disease.

BACKGROUND & AIMS: There are currently no published data on post-paracentesis circulatory dysfunction (PPCD) or its prevention in children. Our study was aimed to analyze the safety and complications of large volume paracentesis (LVP) in children with severe ascites due to chronic liver disease with or without albumin therapy. METHODS: A prospective longitudinal observational study enrolled children with severe ascites who underwent single time LVP at admission. They were divided into albumin infused (AI) and albumin non-infused (ANI) groups. Hemodynamic monitoring and laboratory parameters including plasma renin activity (PRA) were compared between baseline, 48 h and day 6 of LVP. Their outcome at 3 months and maximal follow-up were noted. RESULTS: 32 children (AI, n=17; ANI, n=15) had comparable baseline characteristics and 90.6% had high PRA at onset. The incidence of PPCD was 37.5% (ANI: 67%; AI: 12%, p=0.003), occurred if ascitic fluid extraction was >197.5 ml/kg (sensitivity: 90%; specificity: 50%, p=0.01) and if flow rate was higher in ANI group (1224 ± 476 vs. 678 ± 214 ml/h, p=0.009). ANI patients were susceptible to asymptomatic, persistent hyponatremia (baseline vs. day 6, 131 ± 4 vs. 128 ± 6 mEq/L; p=0.04) and had higher rates of recurrent ascites (42%) and hospital readmission (67%) within 3 months. No survival benefit among the AI or non-PPCD groups was demonstrated. CONCLUSIONS: LVP is safe in all age groups, best performed under albumin cover to overcome the problems of PPCD and hyponatremia. It is prudent to restrict volume extraction to less than 200 ml/kg actual dry weight for all and flow rate of 680 ml/h in ANI.