Indocyanine green is a sensitive adjunct in the identification and surgical management of local and metastatic hepatoblastoma.

BACKGROUND: Hepatoblastoma is the most common primary pediatric liver malignancy. Indocyanine green (ICG) has been described as an adjunct to resection in small series. Its utility remains undefined in larger cohorts. METHODS: Records for 29 patients diagnosed with hepatoblastoma who received ICG prior to surgical resection from 2017 to 2020 at a single institution were retrospectively reviewed. The primary outcome was correlation between intraoperative ICG-avidity and histologic presence of hepatoblastoma. A secondary outcome included the histologic margin designation for resected liver specimens. RESULTS: ICG sensitivity was 91% for 120 resected thoracic specimens from 21 patients. Specificity was 57%. In 10% of operations, HB-positive specimens were resected solely on ICG-avidity. In an additional 40% of cases, ICG assisted in localizing a preoperatively diagnosed lesion. ICG sensitivity during thoracotomy and thoracoscopic surgery was 95 and 74%, respectively; primary and relapsed disease demonstrated sensitivity of 94 and 73%, respectively. Sensitivity was 92% for 25 resected liver specimens from nine patients with all parenchymal margins grossly negative for disease. Four multifocal lesions were identified with two resected solely by ICG-avidity. CONCLUSIONS: ICG is a sensitive adjunct for identifying local and metastatic hepatoblastoma, including lesions not visualized on preoperative imaging, and delineating margins during liver resection. False positives limit specificity; however, there were no adverse outcomes from additional resections. We noted that thoracoscopic surgery can be completed safely in patients with less significant disease burden, and conversion to thoracotomy, if necessary, is straightforward.

Natural Course of Pediatric Portal Hypertension.

The etiology of portal hypertension (pHTN) in children differs from that of adults and may require different management strategies. We set out to review the etiology, management, and natural history of pHTN at a pediatric liver center. From 2008 to 2018, 151 children and adolescents with pHTN were identified at a free-standing children's hospital. Patients were stratified by etiology of pHTN (intrahepatic disease [IH], defined as cholestatic disease and fibrotic or hepatocellular disease; extrahepatic disease [EH], defined as hepatic vein obstruction and prehepatic pHTN). Patients with EH were more likely to undergo an esophagoduodenscopy for a suspected gastrointestinal bleed (77% vs. 41%; P < 0.01). Surgical interventions differed based on etiology (P < 0.01), with IH more likely resulting in a transplant only (65%) and EH more likely to result in a shunt only (43%); 30% of patients with IH and 47% of patients with EH did not undergo an intervention for pHTN. Kaplan-Meier analysis revealed a significant increase in mortality in the group that received no intervention compared to shunt, transplant, or both and lower mortality in patients with prehepatic pHTN compared to other etiologies (P < 0.01 each). Multivariate analysis revealed increased odds of mortality in patients with refractory ascites (odds ratio [OR], 4.34; 95% confidence interval [CI], 1.00, 18.88; P = 0.05) and growth failure (OR, 13.49; 95% CI, 3.07, 58.99; P < 0.01). Conclusion: In this single institution study, patients with prehepatic pHTN had better survival and those who received no intervention had higher mortality than those who received an intervention. Early referral to specialized centers with experience managing these complex disease processes may allow for improved risk stratification and early intervention to improve outcomes.

The role of surgical shunts in the treatment of pediatric portal hypertension.

BACKGROUND: Portal diversion by surgical shunt plays a major role in the treatment of medically refractory portal hypertension. We evaluate our center's experience with surgical shunts for the treatment of pediatric portal hypertension. METHODS: All patients who underwent surgical shunt at a single institution from 2008 to 2017 were reviewed. The primary outcome was intervention-free shunt patency. RESULTS: In this study, 34 pediatric patients underwent portal shunt creation. The median age was 7.7 years (interquartile range 4.3-12.0). Twenty-nine patients (85%) had prehepatic portal hypertension and 5 patients (15%) had intrahepatic portal hypertension. The primary manifestations of portal hypertension were esophageal varices (97%) and gastrointestinal bleeding (77%). Eighteen patients (53%) underwent meso-Rex bypass, 10 patients (29%) underwent splenorenal shunt, and 6 patients (18%) underwent mesocaval shunt. Outcomes were notable for minimal wound complications (9%), rebleeding events (12%), and mortality (3%). In the postoperative setting, 10 patients (29%) experienced a shunt complication (occlusion or stenosis), 4 of which occurred in the early postoperative period and required urgent intervention. The 1-year and 5-year "primary patency" patency rates were 71% and 66%, respectively. CONCLUSION: Children suffer significant morbidity from the sequelae of portal hypertension. Our experience reinforces the feasibility of surgical shunts as an effective treatment option associated with low rates of morbidity and mortality.

Esophageal dysmotility: An intrinsic feature of megacystis, microcolon, hypoperistalsis syndrome (MMIHS).

OBJECTIVES: Megacystis-microcolon-hypoperistalsis syndrome (MMIHS) also called Berdon's Syndrome, is a smooth muscle myopathy that results in an enlarged bladder, microcolon, and small bowel hypoperistalsis. In our series of six patients with this disorder, all had disordered swallowing. Therefore, we prospectively characterized esophageal structure and function in all. METHODS: Diagnoses had been established by contrast radiography, small bowel manometry, and urodynamic studies. To investigate the esophagus, we endoscoped and biopsied the esophagus of each patient on multiple occasions. All patients also underwent water soluble contrast esophagography and esophageal manometry. RESULTS: Upon careful questioning, all patients had swallowing dysfunction, and the majority of their enteral intake was via gastrostomy or gastrojejunostomy. All took some oral alimentation, but eating was slow and none could aliment themselves completely by the oral route, receiving 50% or less of their calories by mouth. Four had megaesophagus whereas the esophagus of the two youngest was of normal caliber. All had eosinophilic esophagitis and/or esophageal Candidiasis from time to time, but successful treatment of these findings failed to improve their symptoms. Manometry revealed normal lower esophageal sphincter (LES) resting tone and normal LES relaxation, but for all, peristalsis was absent in the esophageal body. CONCLUSIONS: This series expands the spectrum of findings in MMIHS, to include a primary motility disorder of the esophageal body. As patients age, the esophageal caliber appears to increase. Successful treatment of neither esophageal eosinophilia nor Candidiasis is effective in ameliorating the motility disorder. If our findings are confirmed in more patients with MMIHS, this disorder should be renamed, megacystis-microcolon-intestinal-and esophageal hypoperistalsis syndrome. TYPE OF STUDY: Prognosis study, Level IV (case series).

Extracorporeal Membrane Oxygenation in a Patient with Biliary Atresia: Case and Review of Extracorporeal Life Support Organization Data.

Biliary atresia is a newborn cholangiopathy that may lead to portopulmonary hypertension and cirrhosis-induced cardiomyopathy while awaiting liver transplantation. Extracorporeal life support and hepatic toxin filtration are life-saving interventions that provide cardiopulmonary support and hepatic dialysis to allow resolution of a child's illness. We utilized a combination of these extreme measures to bridge an infant with biliary atresia to transplantation. We reviewed cases of extracorporeal life support utilization in transplantation recipients in the Extracorporeal Life Support Organization database and determined that ours was the only use of pretransplant extracorporeal life support in biliary atresia.

Laparoscopic donor nephrectomy for the pediatric recipient population: Risk factors for adverse outcomes.

Kidney transplantation is the optimal treatment of ESRD in children. Some studies have reported inferior outcomes in recipients of LDN allografts who are ≤ 5 yr of age. We performed a retrospective review of pediatric recipient outcomes of 110 LDN allografts at our institution and examined predictors of adverse outcomes. Subgroup analysis was performed by dividing recipients into three age categories: 0-5 yr, 6-17 yr, and ≥ 18 yr. There was no significant difference between incidences of DGF or ARE between groups. Kaplan-Meier analysis demonstrated 100% allograft survival in 0- to 5-yr-old recipients, nearly reaching statistical significance (p = 0.07) for outcome superior to that of the two older age groups. Pretransplant HD was associated with increased risk of DGF (p = 0.05). Significant risk factors for ARE were recipient weight >15 kg (p = 0.033) and multiple renal arteries (p = 0.047). Previous ARE was associated with an increased risk of allograft failure (p = 0.02). LDN is not associated with increased risk of DGF, ARE, or allograft failure in the youngest recipients. These findings support an aggressive pursuit of preemptive transplantation even in the youngest pediatric allograft recipients.

Limited surgical resection for graft salvage following recovery from complicated exfoliative rejection in pediatric intestinal recipients.

Complications of ER contribute significantly to morbidity and mortality following intestinal transplantation. The surgical management of three pediatric patients who experienced complications of late ER after composite LSB transplantation is described, highlighting the potential for allograft salvage after limited surgical resection. A retrospective case series was compiled. Data collected included time to ER from transplant, medical management of ER, complications, and surgical management of ER complications. All patients had undergone composite LSB transplantation between one and two yr of age. Time to ER after transplantation was 9.5-26.5 months. ER complications included ileal allograft stricture, intramural hematoma with perforation of jejunal allograft, and massive GI hemorrhage secondary to focal ulceration and pseudopolyp formation. With evidence of mucosal regeneration, all three patients underwent limited segmental allograft resection. Two patients continue to maintain satisfactory allograft function 39-44 months following operation. The third patient retained adequate allograft function until he developed PTLD, subsequently dying from disseminated Adenovirus infection 51 months after resection. Severe disruption of intestinal allograft integrity in ER can lend itself to medically refractory complications. Prompt recognition and surgical correction of complications can play a crucial role in allograft salvage and patient survival after ER.

Micronutrient deficiencies in pediatric and young adult intestinal transplant patients.

Intestinal transplant recipients are at risk of micronutrient deficiency due to the slow process of post-transplant adaptation. Another contributing factor is calcineurin inhibitor-induced renal tubular dysfunction. Patients are typically supplemented with micronutrients during PN; however, the risk of deficiency may persist even after a successful transition to FEN. The goal was to determine the prevalence of, and associated risk factors for, iron, zinc, magnesium, phosphorus, selenium, copper, folate, and vitamins A, D, E, and B12 deficiency in pediatric intestinal transplant recipients after successful transition to FEN. A retrospective review of prospectively collected data from children who underwent intestinal transplantation at Cincinnati Children's Hospital Medical Center was done. Deficiencies of various micronutrients were defined using the hospital reference values. Twenty-one intestinal transplant recipients, aged one to 23 yr, who were successfully transitioned to FEN were included in the study. The prevalence of micronutrient deficiency was 95.2%. The common deficient micronutrients were iron (94.7%) and magnesium (90.5%). Age ≤ 10 yr (p = 0.002) and tube feeding (p = 0.02) were significant risk factors for micronutrient deficiencies. Pediatric intestinal transplant recipients have a high risk of micronutrient and mineral deficiencies. These deficiencies were more common among younger patients and those who received jejunal feeding.

Management and long-term consequences of portal vein thrombosis after liver transplantation in children.

Portal vein thrombosis (PVT) occurs in ≤12% of pediatric recipients of liver transplantation (LT). Known complications of PVT include portal hypertension, allograft loss, and mortality. The management of PVT is varied. A single-center, case-control study of pediatric LT recipients with portal vein (PV) changes after LT was performed. Cases were categorized as early PVT (if PVT was detected within 30 days of transplantation) or late PVT (if PVT was detected more than 30 days after transplantation or if early PVT persisted beyond 30 days). Two non-PVT control patients were matched on the basis of the recipient weight, transplant indication, and allograft type to each patient with PVT. Thirty-two of the 415 LT recipients (7.7%) received 37 allografts and developed PVT. In comparison with control patients, a higher proportion of patients with PVT had PVT present before LT (13.3% versus 0%, P = 0.01). Patients with early PVT usually returned to the operating room, and 9 of 15 patients (60%) had PV flow restored. Patients with late PVT had lower white blood cell (4.9 [1000/µL] versus 6.8 [1000/µL], P < 0.01) and platelet counts (140 [1000/µL] versus 259 [1000/µL], P < 0.01), an elevated international normalized ratio (1.2 versus 1.0, P < 0.001), and more gastrointestinal bleeding (25% versus 8.3%, P = 0.03) compared to controls. Patients with PVT were also less frequently at the expected grade level (52% versus 88%, P < 0.001). The patient survival rates were 84%, 78%, and 78% and 91%, 84%, and 79% for cases and controls at 1, 5, and 10 years, respectively. The allograft survival rates were 90%, 80%, and 80% for cases and 94%, 89%, and 87% for controls at 1, 5, and 10 years, respectively. In conclusion, patients with early and late PVT had preserved allograft function, and there was no impact on mortality. Patients diagnosed with early PVT often underwent operative interventions with successful restoration of flow. Patients diagnosed with late PVT experienced variceal bleeding, and some required portosystemic shunting procedures. Academic delays were also more common. In late PVT, the clinical presentation dictates care because the optimal management algorithm has not yet been determined. Multi-institutional studies are needed to confirm these findings and improve patient outcomes.

The beneficial impact of revision of Kasai portoenterostomy for biliary atresia: an institutional study.

OBJECTIVE: To determine whether portoenterostomy (PE) revision in patients afflicted with biliary atresia (BA) is a viable treatment option and, if so, identify which patients may benefit. BACKGROUND: BA, the most common cause of neonatal liver disease, results in biliary tract obstruction and hepatic fibrosis. Kasai PE is the initial surgical intervention performed and, if successful, restores drainage and preserves the native liver. Portoenterostomy failure warrants liver transplantation, but because of complications related to transplantation, treatment strategies to salvage the native liver may be beneficial. Using uniformly applied criteria, we have revised PEs to delay or avoid transplantation. METHODS: A retrospective review of medical records of patients diagnosed with BA since 1983 was performed. Patient demographics, symptoms, indications for revision, laboratory values, and outcomes were recorded. A cohort of patients who underwent revision after initial PE was identified. Survival rates were assessed using the Kaplan-Meier method. For patients who required transplantation, operative data from the revised PE cohort were compared with those from the unrevised PE cohort. A Cox proportional hazards model was used to determine covariates predictive of a favorable outcome. RESULTS: Of 181 children who underwent PE, 24 underwent revision. Adequate biliary drainage, as evidenced by normalized conjugated bilirubin levels, was achieved in 75% of revised patients. Overall survival in patients who underwent revision, regardless of transplantation, was 87%. Among patients who underwent PE revision, 46% have survived with their native liver. CONCLUSION: Experience at our center suggests that with appropriate patient selection, PE revision may delay the need for liver transplanation yielding encouraging patient outcomes.

Anatomic and histologic variability of epithelial apoptosis in small bowel transplants.

Surveillance ileoscopies are performed regularly immediately post-transplantation to prevent allograft rejection. We investigated whether variability in apoptosis exists between proximal and distal intestinal limbs of double-barreled ileostomies, and if detection varies according to number of biopsies taken and sections prepared for evaluation. We retrospectively analyzed endoscopy/pathology reports of patients who underwent simultaneous proximal and distal ileoscopies during surveillance. We re-reviewed three sections of selected biopsies for the presence of apoptotic bodies and viral inclusions. Seven patients underwent 26 endoscopies in which both distal and proximal limbs were investigated simultaneously. Apoptosis was identified in each limb simultaneously in 21/26 cases (81%). Of the discrepant results, 3/5 (60%) revealed apoptosis in the proximal limb with normal distal limb and 2/5 (40%) had apoptotic bodies identified in the distal limb and normal proximal biopsies. Re-reviewing discrepant biopsies, two patients had at least one piece of mucosa without apoptosis and apoptotic bodies were seen in only 47% of sections. Histologic variability exists between proximal and distal limbs of double-barreled ileostomies and detection of apoptosis increases with number of pieces obtained and sections examined. Investigating both limbs with adequate sample size and rigorous processing may have clinical implications.

Spectrum of hepatic hemangiomas: management and outcome.

PURPOSE: Infants with multiple cutaneous hemangiomas often present with hepatic hemangiomas. They can follow a benign clinical course or require complex management. We reviewed our experience in the management of hepatic hemangiomas. METHODS: We performed a retrospective review of patients (1996-2007) with hepatic hemangiomas treated in our institution. RESULTS: Twenty-six patients were diagnosed with hepatic hemangiomas as follows: 8 focal, 12 multiple, and 6 diffuse lesions. Nineteen (73%) patients had associated cutaneous hemangiomas. Sixteen patients had multiple and 3 patients had single cutaneous hemangiomas. All patients with multiple or diffuse liver lesions were screened for heart failure and hypothyroidism. Congestive heart failure developed in 4 patients, 3/4 of these patients had diffuse lesions. Two patients required thyroid replacement because of elevated thyroid-stimulating hormone. Because of progression of disease, 9 patients required steroid treatment. Two patients were treated with vincristine and 3 patients received alpha-interferon because of poor response to steroid treatment. Two patients went on to surgical resection for failed response to medical management and worsening heart failure (left lobectomy, liver transplant). Both patients had uncomplicated postoperative courses. Five patients had a previously undescribed constellation of rapidly involuting cutaneous hemangiomas (gone by 3 months, glut-1-negative) with associated liver lesions also resolving at a faster pace (mean resolution of cutaneous hemangiomas, 1.9 vs 7.9 months; P = .001; liver, 5.8 vs 25.3 months; P = .004). All patients in our series survived. CONCLUSION: Patients with multiple cutaneous hemangiomas should be screened for hepatic lesions. Patients with diffuse or multifocal liver hemangiomas should be screened for congestive heart failure and hypothyroidism. A subgroup of rapidly involuting cutaneous hemangiomas have a significantly shorter time for involution of hepatic lesions. The status of cutaneous lesions can be used as indicators for the liver hemangiomas.

Isolated liver and multivisceral transplantation for total parenteral nutrition-related end-stage liver disease.

PURPOSE: Total parenteral nutrition (TPN) has prolonged survival in children with intestinal failure; however, end-stage liver disease owing to TPN-induced cholestasis (ESLD-TPN) may preclude its use. ESLD-TPN is an indication for isolated liver transplantation (ILT) or multivisceral transplantation (MVT). Isolated liver transplantation for ESLD-TPN should only be considered in patients who have the potential for enteral autonomy. METHODS: We retrospectively reviewed the records of patients with ESLD-TPN who underwent ILT (n = 7) or MVT (n = 5) between 1994 and 2005. The median age at the time of transplantation was 10.0 months. Intestinal failure followed necrotizing enterocolitis (n = 3), gastroschisis (n = 3), gastroschisis with volvulus (n = 3), gastroschisis with atresia (n = 1), malrotation (n = 1), and megacystis microcolon intestinal hypoperistalsis syndrome (n = 1). RESULTS: Isolated liver transplant patients had a median length of small bowel of 70 cm and tolerated a median of 50% of enteral calories. The median length of small bowel in patients who underwent MVT was 29 cm, and none tolerated more than 30% of goal enteral feeds. Reduced-size (n = 5) and whole-liver (n = 2) allografts were used for patients undergoing ILT. Patients undergoing MVT received liver-small bowel-pancreas (n = 4) or liver-small bowel-pancreas-colon (n = 1). Overall patient survival was 57% in ILT (median follow-up = 25.1 months); 3 survivors are TPN independent, and the fourth patient requires TPN 3 days/wk. Patient survival was 40% after MVT (median follow-up = 13.0 months); 1 MVT patient died of abuse 16.9 months after transplant and was TPN independent at the time of death. Both survivors are TPN independent. Bilirubin levels are within normal range in all survivors. CONCLUSION: Isolated liver transplantation for ESLD-TPN in the setting of intestinal failure is a viable option in patients who have the potential for enteral autonomy. Multivisceral transplantation is the only alternative in patients without the potential for intestinal recovery. Survival can be achieved in patients with ESLD-TPN, but mortality remains high for both procedures.

Pediatric liver transplantation.

Liver transplantation has become the accepted standard of care in the treatment of a child with a failing liver. Advances in the management of critical care and immunosuppression along with the development of innovative operative procedures have improved outcome such that 5-year survival rates of 80% to 90% are expected following liver transplantation. Organ allocation schemes have evolved in an effort to better stratify recipient risk thereby more appropriately distributing deceased donor grafts. A persistent shortage of appropriate donors continues to contribute to patient mortality. The consequences of long-term immunosuppression have become increasingly apparent such that health care providers need to be aware of the side effects of chronic immunosuppression. New strategies need to be defined to minimize the need of continuous immunosuppression. The continued success of pediatric liver transplantation will require multi-disciplinary health care teams comprised of general pediatricians, pediatric hepatologists, transplant surgeons, and transplant coordinators who focus on the complex needs of the transplant recipient.

The effect of a right-sided aortic arch on outcome in children with esophageal atresia and tracheoesophageal fistula.

UNLABELLED: During repair of an esophageal atresia with tracheoesophageal fistula (EA/TEF), a right-sided aortic arch (RAA) presents a technical challenge. We reviewed our experience with EA/TEF focusing on the impact of RAA. METHODS: A retrospective review of patients with EA/TEF at our institution from 1990 to 2004 was performed. Of 61 patients, 53 had a left aortic arch (LAA) and 8 had RAA. RESULTS: The mean gestational age and birth weight were similar between patients with LAA and RAA. There were more vascular rings in patients with RAA than with LAA (37.5% vs 3.8%, P = .009). A preoperative echocardiogram correctly identified the location of the arch in all with LAA but only 62.5% of those with RAA. Operative complications occurred in 25% of patients with RAA and 11% of patients with LAA. CONCLUSIONS: Management of a child with RAA and EA/TEF is technically challenging. Preoperative identification of the great vessel anomalies may impact operative decision making. Therefore, careful diagnostic evaluation of a patient with an aortic arch that cannot be easily defined by ECHO should be considered before definitive repair.

Cecal volvulus: a rare cause of bowel obstruction in a pediatric patient diagnosed pre-operatively by conventional imaging studies.

Cecal volvulus is an acute surgical condition that is extremely rare in children, with a mortality rate of up to 40%. The clinical symptoms are often non-specific, and pediatric patients frequently have neurological deficits with associated communication difficulties, making the clinical diagnosis extremely challenging. Conventional radiographic imaging studies play a key role in the prospective diagnosis in children. We report a rare case of cecal volvulus in a 12-year-old boy who was diagnosed pre-operatively by abdominal radiographs and a contrast enema.

Determination of risk factors for Epstein-Barr virus-associated posttransplant lymphoproliferative disorder in pediatric liver transplant recipients using objective case ascertainment.

BACKGROUND: Previous studies have suggested an increased risk of Epstein-Barr virus-associated posttransplant lymphoproliferative disorder (EBV-PTLD) in patients receiving tacrolimus for immunosuppression. We hypothesized that after correction for confounding variables, immunosuppression with tacrolimus is not associated with an increased risk of EBV-PTLD. METHODS: Potential cases of EBV-PTLD, identified by chart review, were independently ascertained by three clinicians and defined using published criteria. Agreement in diagnosing EBV-PTLD was measured using Kappa coefficients. Unadjusted and adjusted relative risk estimates were determined using proportional hazards regression. RESULTS: Twenty-three cases of EBV-PTLD were identified in 221 patients, a proportion of 10.4% (95% confidence interval [CI]: 6.4%-14.4%). Multivariable analysis revealed that immunosuppression with tacrolimus was associated with an increased risk of EBV-PTLD (relative risk 3.10: 95% CI: 1.21-7.92), as was age at transplantation as a continuous variable (parameter estimate -0.15, P=0.03). Kappa coefficients in diagnosing EBV-PTLD and subclassifying as neoplastic and non-neoplastic EBV-PTLD were 0.73 (95% CI: 0.54-0.93) and 0.54 (95% CI: 0.40-0.68), respectively. Patients with neoplastic PTLD demonstrated a lower probability of survival than patients with non-neoplastic PTLD and non-cases. CONCLUSIONS: Immunosuppression with tacrolimus and young age at transplantation are associated with an increased risk of EBV-PTLD in children undergoing liver transplantation, although we cannot exclude detection bias as an explanation for this observed increase. Good agreement between observers can be achieved using previously published criteria for defining EBV-PTLD. Patients with neoplastic EBV-PTLD may have a worse prognosis, and thus identification of risk factors for the development of this subtype of the disorder may be more important.