Percutaneous transhepatic interventional therapy of portal vein stenosis in paediatric liver transplantation: A systematic review of efficacy and safety.

PURPOSE OF THE SYSTEMATIC REVIEW: To determine the efficacy and safety of percutaneous trans-hepatic balloon and/or stent angioplasty (PTA) in the management of portal vein (PV) stenosis following paediatric liver transplantation. METHODS: Articles were included from a systematic search of Medline, Embase, Cochrane CENTRAL, ClinicalTrials.gov and International Clinical Trials Registry from inception to the 29th of August 2020. RESULTS: There were 213 paediatric liver recipients who underwent PTA for PV stenosis in 19 included studies published between 1991 and 2019. Balloon angioplasty was the initial treatment in the majority (n = 153). Primary stent placement (n = 34) was performed for elastic recoil, intimal tears and PV kinks and rescue stent placement (n = 14) for recurrent PV stenosis following primary balloon angioplasty. The technical success was 97.6%-100% overall, 97.6%-100% for balloon-angioplasty-only and 100% for primary stenting. The clinical success was 50%-100% overall, 50%-100% for balloon-angioplasty-only and 100% for primary stenting. Long-term PV patency was 50%-100% overall, 37.5%-100% for balloon-angioplasty-only and 100% for primary stenting. Primary balloon angioplasty was successful in 78% of the cases. Of the recurrent PV stenoses, 9% resolved with stent placement and one required a meso-Rex shunt. There was one re-transplantation without stenting. The complication rate was 2.6% for balloon-angioplasty-only (bleeding, liver abscess, 2 PV thromboses) and 5.9% for primary stenting (bleeding, stent-fracture). There was no procedure-related mortality. CONCLUSION: Percutaneous transhepatic balloon angioplasty may be the initial management of portal vein stenosis in paediatric liver recipients. Stent placement may be a primary option in selected cases and a reliable rescue option for recurrent portal vein stenosis following balloon-angioplasty-only.

Hyperammonemia in ornithine transcarbamylase-deficient recipients following living donor liver transplantation from heterozygous carrier donors.

Ornithine transcarbamylase deficiency (OTCD) is a urea cycle disorder of X-linked inheritance, affecting the detoxification of excess nitrogen and leading to hyperammonemia (hyper-NH3 ). Living donor liver transplantation (LDLT) has been applied for the treatment of OTCD. This case series retrospectively reviewed two OTCD patients who experienced hyper-NH3 following LDLT. The first case was a 5-year-old girl who had onset of OTCD at 2 years of age. Ornithine transcarbamylase (OTC) enzyme activity was 62% for the donor and 15% for the recipient. The patient suffered from recurrence of hyper-NH3 within 2 months following LDLT. The second case was a 5-year-old girl who had onset of OTCD at 3 years of age. OTC enzyme activity was 42.6% for the donor and 9.7% for the recipient. The patient suffered hyper-NH3 for 12 days starting on the date of surgery. Both of the patients transiently required continuous veno-venous hemodialysis; however, they are currently doing well without intensive medical treatment. The use of asymptomatic OTCD heterozygous donors in LDLT has been accepted with careful examination. However, an OTCD heterozygous carrier donor should be avoided if there is another donor candidate, due to the potentially fatal condition of hyper-NH3 following LDLT.

Successful resumption of peritoneal dialysis following living donor liver transplantation in children with end-stage renal disease.

Children with ESRD in need of RRT are commonly managed by PD due to difficulty with vascular access for HD and the relatively large extracorporeal blood volume required. Major abdominal surgery may result in injury to the peritoneum and consequent adhesion, thereby resulting in a reduction in the anatomical capacity and transport capability across the peritoneal membrane. Here, we report successful resumption of PD after LDLT in two pediatric patients. The causes of ESRD were PH1 and juvenile nephronophthisis, respectively. Both patients were managed by PD prior to LDLT. PD was converted to HD starting three days before LDLT and was continued postoperatively until resumption of PD on days 13 and 28, respectively. The PD weekly Kt/V urea was maintained before and after LDLT. The patients continued to do well on PD without complications. Meticulous intra-operative techniques during LDLT allow postoperative PD resumption by preservation of peritoneal integrity with effective transport capability and without added risk of peritonitis.

Reno- and splenoportal anastomosis for a retransplant patient with situs inversus.

PV thrombosis following pediatric LT is a serious complication that may lead to graft loss. LDLT poses limitations with regard to the availability of vein grafts for complex PV reconstructions. We herein report a unique reconstruction of the PV inflow in a one-yr-old boy with situs inversus undergoing re-LDLT. The inflow was derived from the SPV and the RRV. A common channel was created utilizing a donor IMV and the recipient explant LHV as vascular conduits. With the application of innovative surgical reconstructions, pre-existing portomesenteric thrombosis may be amenable to re-LDLT in the pediatric population.

Chemotherapy-induced B-cell depletion in hepatoblastoma patients undergoing ABO-incompatible living donor liver transplantation.

LT from ABO-I donors requires preconditioning regimens to prevent postoperative catastrophic AMR. NAC for HBL is known to cause myelosuppression leading to a reduction in the number and function of lymphocytes. We investigated this chemotherapy-induced myelosuppression in HBL patients listed for LT from ABO-I donors with reference to the kinetics of B, T cells, and anti-ABO blood type isoagglutinin titers. Between 2005 and 2015, of the 319 patients who underwent LDLT at our institute, 12 were indicated for unresectable HBL. Three patients with unresectable HBL who underwent LDLT from ABO-I donors are included in this study. Immunosuppression consisted of a standard regime of tacrolimus and low-dose steroids as in ABO compatible/identical LDLT. No additional preoperative therapies for B-cell depletion were used. Absolute lymphocyte counts, lymphocyte subsets (including CD20+ B cells, CD3+CD4+ T cells and CD3+CD8+ T cells), and anti-ABO blood type isoagglutinin titers were measured before LDLT and postoperatively. The median age at diagnosis was 19 months (range, 3-31 months). The median follow-up was seven months (range, 6-15 months). The median interval from the last NAC to LDLT was 33 days (range, 25-52 days). The median interval from LDLT to adjuvant chemotherapy was 28 days (range, 22-36 days). The counts of CD20+ B cells before LDLT were depleted to median 5 cells/mm(3) (range, 0-6 cells/mm(3)). There was a transient rebound in the CD20+ B cell counts on day seven (maximum of 82 cells/mm(3)) followed by a decline starting at 14 days after LDLT that was sustained for the duration of adjuvant chemotherapy. Anti-ABO blood type isoagglutinin titers were lowered to between 1:1 and 1:16 before LDLT and remained low for the duration of follow-up in this study. All of the three patients remained in good health without either acute cellular or AMR after LDLT. The B-cell depletion that occurs after cisplatin-based chemotherapy for HBL may help accomplish safe ABO-I LDLT in children without the use of additional conditioning regimens for prevention of AMR.

Navigating Inconclusive Upper-Gastrointestinal Series in Infantile Bilious Vomiting: A Case Series on Intestinal Malrotation.

BACKGROUND Bilious vomiting in a child potentially portends the dire emergency of intestinal malrotation with volvulus, necessitating prompt surgical management, with differentials including small-bowel atresia, duodenal stenosis, annular pancreas, and intussusception. Although the upper-gastrointestinal series (UGI) is the diagnostic investigation of choice, up to 15% of the studies are inconclusive, thereby posing a diagnostic challenge. CASE REPORT We report a case series of 3 children referred for bilious vomiting, whose initial UGI was inconclusive and who were eventually confirmed to have intestinal malrotation at surgery. The first child was a female born at 37 weeks with antenatally diagnosed situs inversus and levocardia, who developed bilious vomiting on day 1 of life. The duodenojejunal flexure (DJ) could not be visualized on the UGI because of faint opacification on first pass of the contrast and subsequent overlap with the proximal jejunal loops. The second child was a male born at 36 weeks, presenting at age 4 months with bilious vomiting of 2 days duration. The third child was a female born at 29 weeks, presenting with bilious aspirates on day 3 of life. UGI for all 3 showed persistent hold-up of contrast at the proximal duodenum with no opacification of the distal duodenum or small bowel.Adjunctive techniques during the UGI and ultrasound examination helped achieve a preoperative diagnosis of malrotation in these children. CONCLUSIONS Application of diagnostic adjuncts to an inconclusive initial UGI may help elucidate a preoperative diagnosis of intestinal malrotation in infantile bilious vomiting.

An Intelligent Customer-Driven Digital Solution to Improve Perioperative Health Outcomes Among Children Undergoing Circumcision and Their Parents: Development and Evaluation.

BACKGROUND: Circumcision as a common elective pediatric surgery worldwide is a stressful and anxiety-inducing experience for parents and children. Although current perioperative interventions proved effective, such as reducing preoperative anxiety, there are limited holistic solutions using mobile apps. OBJECTIVE: This paper aims to describe the development and primary evaluation of an intelligent customer-driven smartphone-based app program (ICory-Circumcision) to enhance health outcomes among children undergoing circumcision and their family caregivers. METHODS: Based on the review of the literature and previous studies, Bandura's self-efficacy theory was adopted as the conceptual framework. A multidisciplinary team was built to identify the content and develop the apps. Semistructured interviews were conducted to evaluate the ICory-Circumcision. RESULTS: The ICory-Circumcision study was carried out from March 2019 to January 2020 and comprised 2 mobile apps, BuddyCare app and Triumf Health mobile game app. The former provides a day-by-day perioperative guide for parents whose children are undergoing circumcision, while the latter provides emotional support and distraction to children. In total, 6 participants were recruited to use the apps and interviewed to evaluate the program. In total, 4 main categories and 10 subcategories were generated from content analysis. CONCLUSIONS: ICory-Circumcision seemed to lean toward being useful. Revisions to ICory-Circumcision are necessary to enhance its contents and features before advancing to the randomized controlled trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT04174404; https://clinicaltrials.gov/ct2/show/NCT04174404.

Enhanced recovery after surgery in children undergoing abdominal surgery: meta-analysis.

BACKGROUND: Enhanced recovery after surgery (ERAS) is a multimodal approach that streamlines patient processes before, during, and after surgery. The goal is to reduce surgical stress responses and improve outcomes; however, the impact of ERAS programmes in paediatric abdominal surgery remains unclear. The authors aimed to review the effectiveness of ERAS on clinical outcomes in children undergoing abdominal surgery. METHOD: CINAHL, CENTRAL, Embase, ProQuest, PubMed, and Scopus were searched for relevant studies published from inception until January 2021. The length of hospital stay (LOS), time to oral intake, time to stool, complication rates, and 30-day readmissions were measured. Meta-analyses and subgroup analyses were conducted using RevMan 5.4 with a random-effects model. RESULTS: Among 2371 records from the initial search, 111 articles were retrieved for full-text screening and 12 were included for analyses. The pooled mean difference (MD) demonstrated reduced LOS (MD -1.96; 95 per cent c.i. -2.75 to -1.17), time to oral intake (MD -3.37; 95 per cent c.i. -4.84 to -1.89), and time to stool (MD -4.19; 95 per cent c.i. -6.37 to -2.02). ERAS reduced postoperative complications by half and 30-day readmission by 36 per cent. Subgroup analyses for continuous outcomes suggested that ERAS was more effective in children than adolescents. CONCLUSION: ERAS was effective in improving clinical outcomes for paediatric patients undergoing abdominal surgery.

Comparing the Performance of Multiple Small-Data Personalized Tacrolimus Dosing Models for Pediatric Liver Transplant: A Retrospective Study.

Tacrolimus is a potent immunosuppressant used after pediatric liver transplant. However, tacrolimus's narrow therapeutic window, reliance on physicians' experience for the dose titration, and intra- and inter-patient variability result in liver transplant patients falling out of the target tacrolimus trough levels frequently. Existing personalized dosing models based on the area-under-the-concentration over time curves require a higher frequency of blood draws than the current standard of care and may not be practically feasible. We present a small-data artificial intelligence-derived platform, CURATE.AI, that uses data from individual patients obtained once daily to model the dose and response relationship and identify suitable doses dynamically. Retrospective optimization using 6 models of CURATE.AI and data from 16 patients demonstrated good predictive performance and identified a suitable model for further investigations.Clinical Relevance- This study established and compared the predictive performance of 6 personalized tacrolimus dosing models for pediatric liver transplant patients and identified a suitable model with consistently good predictive performance based on data from pediatric liver transplant patients.

Prevalence, management and efficacy of treatment in portal vein obstruction after paediatric liver transplantation: protocol of the retrospective international multicentre PORTAL registry.

INTRODUCTION: Portal vein obstruction (PVO) consists of anastomotic stenosis and thrombosis, which occurs due to a progression of the former. The aim of this large-scale international study is to assess the prevalence, current management practices and efficacy of treatment in patients with PVO. METHODS AND ANALYSIS: The Portal vein Obstruction Revascularisation Therapy After Liver transplantation registry will facilitate an international, retrospective, multicentre, observational study, with 25 centres around the world already actively involved. Paediatric patients (aged <18 years) with a diagnosed PVO between 1 January 2001 and 1 January 2021 after liver transplantation will be eligible for inclusion. The primary endpoints are the prevalence of PVO, primary and secondary patency after PVO intervention and current management practices. Secondary endpoints are patient and graft survival, severe complications of PVO and technical success of revascularisation techniques. ETHICS AND DISSEMINATION: Medical Ethics Review Board of the University Medical Center Groningen has approved the study (METc 2021/072). The results of this study will be disseminated via peer-reviewed publications and scientific presentations at national and international conferences. TRIAL REGISTRATION NUMBER: Netherlands Trial Register (NL9261).

Anterior urethral valves.

We studied the clinical presentation and management of four patients with anterior urethral valves; a rare cause of urethral obstruction in male children. One patient presented antenatally with oligohydramnios, bilateral hydronephrosis and bladder thickening suggestive of an infravesical obstruction. Two other patients presented postnatally at 1 and 2 years of age, respectively, with poor stream of urine since birth. The fourth patient presented at 9 years with frequency and dysuria. Diagnosis was established on either micturating cystourethrogram (MCU) (in 2) or on cystoscopy (in 2). All patients had cystoscopic ablation of the valves. One patient developed a postablation stricture that was resected with an end-to-end urethroplasty. He had an associated bilateral vesicoureteric junction (VUJ) obstruction for which a bilateral ureteric reimplantation was done at the same time. On long-term follow-up, all patients demonstrated a good stream of urine. The renal function is normal. Patients are continent and free of urinary infections. Anterior urethral valves are rare obstructive lesions in male children. The degree of obstruction is variable, and so they may present with mild micturition difficulty or severe obstruction with hydroureteronephrosis and renal impairment. Hence, it is important to evaluate the anterior urethra in any male child with suspected infravesical obstruction. The diagnosis is established by MCU or cystoscopy and the treatment is always surgical, either a transurethral ablation or an open resection. The long-term prognosis is good.

Benefit of early inflow exclusion during living donor liver transplantation for unresectable hepatoblastoma.

BACKGROUND: Hepatoblastoma (HB) is a highly malignant primary liver tumor in children. Although liver transplantation (LT) is an effective treatment for unresectable HB with good long-term outcomes, post-transplant survival is mainly affected by recurrence, despite adjuvant chemotherapy. Novel strategies are needed to improve the outcomes in patients undergoing LT for unresectable HB. PATIENTS AND METHODS: Twelve children received LT for unresectable HB. In 9 patients, we applied early exclusion of hepatic inflow (hepatic artery and portal vein) and creation of a temporary portocaval shunt during LT. RESULT: There were differences in the duration of and the blood loss during operation as compared with previously reports. The estimated glomerular filtration rate was well preserved at 3, 6, and 12months and the latest follow-up after LT, and the recurrence-free survival was 88.9%. CONCLUSION: Early inflow control during LT for unresectable HB may benefit recurrence-free survival by minimizing blood loss and tumor dissemination, preserving renal function and allowing early adjuvant chemotherapy.

Recurrent acute thyroid swellings because of pyriform sinus fistula.

Anterior neck abscesses are not rare; but their origin from within the usually infection-resistant thyroid gland is not thought of in the first instance. We encountered 3 patients with differing presentations (tender nodule over anterior neck, recurrent abscess overlying the thyroid gland, and nonhealing fistula with inflammation of the anterior neck). These were caused by persistent embryological communication from the pyriform sinus to the thyroid gland to the left lobe. Excluding the first patient in whom an abnormal communication with oropharynx was suspected when actinomyces was detected in the aspiration cytology of a thyroid nodule, the other 2 patients underwent drainage as for any neck abscess. Fistulous communication was confirmed on barium swallow (in 2 patients) or computed tomographic scan (in 1 patient). En bloc excision of the affected thyroid along with the fistulous tract was performed in all patients. Long-term follow-up confirmed a cure.

Foregut atresias and bile duct anomalies: rare, infrequent or common?!

The association of foregut atresias and bile duct anomalies is reportedly rare. We encountered five referrals within 2 years where the secondary diagnosis was missed at operation. Four patients initially presented on antenatal scans as a foregut atresia whereas the fifth presented at nine years with abdominal pain due to a choledochal cyst. The biliary anomalies (cholecysto-hepatic duct, liver cyst and choledochal cysts) in the first four presented as postoperative jaundice during infancy whereas the fifth patient developed subacute intestinal obstruction due to congenital duodenal stenosis at fifteen years. In the patients with duodenal atresia neither did the preoperative X ray reveal any distal bowel gas nor did the subsequent intraoperative cholangiograms reveal bifid common bile duct or pancreato-biliary malunion. Atresias were corrected by primary repair (duodenoduodenostomy for congenital duodenal obstruction in four patients and disconnection/ligation of tracheo-oesophageal fistula with oesophageal anastomosis in one patient). The biliary anomalies were corrected by excision of the abnormal bile ducts (choledochal cyst/liver cyst/cholecystectomy) with Roux en Y hepaticojejunostomy. All patients are asymptomatic and liver function and biliary dilatation has normalised. The association of foregut atresias and bile duct anomalies is not as rare as previously reported. Antenatal ultrasound suggesting either a foregut or a biliary anomaly should alert one to the association. Full radiological and/or imaging investigation may be indicated prior to corrective surgery of the primary anomaly.