Brachytherapy: An overview for clinicians.

Brachytherapy is a specific form of radiotherapy consisting of the precise placement of radioactive sources directly into or next to the tumor. This technique is indicated for patients affected by various types of cancers. It is an optimal tool for delivering very high doses to the tumor focally while minimizing the probability of normal tissue complications. Physicians from a wide range of specialties may be involved in either the referral to or the placement of brachytherapy. Many patients require brachytherapy as either primary treatment or as part of their oncologic care. On the basis of high-level evidence from randomized controlled trials, brachytherapy is mainly indicated: 1) as standard in combination with chemoradiation in patients with locally advanced cervical cancer; 2) in surgically treated patients with uterine endometrial cancer for decreasing the risk of vaginal vault recurrence; 3) in patients with high-risk prostate cancer to perform dose escalation and improve progression-free survival; and 4) in patients with breast cancer as adjuvant, accelerated partial breast irradiation or to boost the tumor bed. In this review, the authors discuss the clinical relevance of brachytherapy with a focus on indications, levels of evidence, and results in the overall context of radiation use for patients with cancer.

Reappraisal of prognostic factors used in the European Pediatric Soft Tissue Sarcoma Study Group RMS 2005 study for localized rhabdomyosarcoma to optimize risk stratification and generate a prognostic nomogram.

BACKGROUND: The objective of this study was to investigate the role of clinical factors together with FOXO1 fusion status in patients with nonmetastatic rhabdomyosarcoma (RMS) to develop a predictive model for event-free survival and provide a rationale for risk stratification in future trials. METHODS: The authors used data from patients enrolled in the European Pediatric Soft Tissue Sarcoma Study Group (EpSSG) RMS 2005 study (EpSSG RMS 2005; EudraCT number 2005-000217-35). The following baseline variables were considered for the multivariable model: age at diagnosis, sex, histology, primary tumor site, Intergroup Rhabdomyosarcoma Studies group, tumor size, nodal status, and FOXO1 fusion status. Main effects and significant second-order interactions of candidate predictors were included in a multiple Cox proportional hazards regression model. A nomogram was generated for predicting 5-year event-free survival (EFS) probabilities. RESULTS: The EFS and overall survival rates at 5 years were 70.9% (95% confidence interval, 68.6%-73.1%) and 81.0% (95% confidence interval, 78.9%-82.8%), respectively. The multivariable model retained five prognostic factors, including age at diagnosis interacting with tumor size, tumor primary site, Intergroup Rhabdomyosarcoma Studies clinical group, and FOXO1 fusion status. Based on each patient's total score in the nomogram, patients were stratified into four groups. The 5-year EFS rates were 94.1%, 78.4%, 65.2%, and 52.1% in the low-risk, intermediate-risk, high-risk, and very-high-risk groups, respectively, and the corresponding 5-year overall survival rates were 97.2%, 91.5%, 74.3%, and 60.8%, respectively. CONCLUSIONS: The results presented here provide the rationale to modify the EpSSG stratification, with the most significant change represented by the replacement of histology with fusion status. This classification was adopted in the new international trial launched by the EpSSG.

Laparoscopic Treatment of Wilms' Tumor: Criteria of SIOP-UMBRELLA Protocol may be Updated.

INTRODUCTION: Total nephrectomies for the treatment of Wilms' tumor (WT) are more and more performed by laparoscopy, although indications for this approach following the UMBRELLA guidelines are currently very restrictive. The purpose of this study was to assess the compliance to the criteria of the UMBRELLA protocol for minimally invasive approach of WT. METHODS: This retrospective multicenter study included children operated on by laparoscopic total nephrectomy for suspected WT before 2020. Imaging was reviewed centrally. RESULTS: Fifty-six patients (50 WT and 6 nephrogenic rests) were operated on at a median age of 3.3 ± 2.6 years. Thirteen (23%) patients had metastasis at diagnosis. The mean operative time was 213 ± 84 min. There were eight (14.3%) conversions and five peroperative complications. A local stage III was confirmed in seven (12.5%) cases, including two for tumor rupture. Only one (1.8%) of the procedures followed the SIOP-UMBRELLA indications for laparoscopy. The criterion "ring of normal parenchyma" was met only once. Conservative surgery seemed possible in ten (17.9%) cases. The extension of the tumor beyond the ipsilateral edge of the vertebra after chemotherapy and a volume over 200 mL were associated with an increased risk of conversion (p = 0.0004 and p = 0.001 respectively). After a mean follow-up of 5.2 ± 4.0 years, although there was no local recurrence, one death occurred due to metastatic progression at 15 months postoperatively. CONCLUSIONS: The laparoscopic approach of WT beyond the UMBRELLA recommendations was feasible with low risk of local recurrence. Its indications may be updated and validated.

Surgical Management of Wilms Tumors with Intravenous Extension: A Multicenter Analysis of Clinical Management with Technical Insights.

BACKGROUND: About 5% of Wilms tumors present with vascular extension, which sometimes extends to the right atrium. Vascular extension does not affect the prognosis, but impacts the surgical strategy, which is complex and not fully standardized. Our goal is to identify elements of successful surgical management of Wilms tumors with vascular extensions. PATIENTS AND METHODS: A retrospective study of pediatric Wilms tumors treated at three sites (January 1999-June 2019) was conducted. The inclusion criterion was the presence of a renal vein and vena cava thrombus at diagnosis. Tumor stage, pre and postoperative treatment, preoperative imaging, operative report, pathology, operative complications, and follow-up data were reviewed. RESULTS: Of the 696 pediatric patients with Wilms tumors, 69 (9.9%) met the inclusion criterion. In total, 24 patients (37.5%) had a right atrial extension and two presented with Budd-Chiari syndrome at diagnosis. Two died at diagnosis owing to pulmonary embolism. All patients received neoadjuvant chemotherapy and thrombus regressed in 35.6% of cases. Overall, 14 patients had persistent intra-atrial thrombus extension (58%) and underwent cardiopulmonary bypass. Most thrombi (72%) were removed intact with nephrectomy. Massive intraoperative bleeding occurred during three procedures. Postoperative renal insufficiency was identified as a risk factor for patient survival (p = 0.01). With a median follow-up of 9 years (range: 0.5-20 years), overall survival was 89% and event-free survival was 78%. CONCLUSIONS: Neoadjuvant chemotherapy with proper surgical strategy resulted in a survival rate comparable to that of children with Wilms tumors without intravascular extension. Clinicians should be aware that postoperative renal insufficiency is associated with worse survival outcomes.

Outcome and late effects of patients treated for childhood vaginal malignant germ cell tumors.

PURPOSE: Vaginal malignant germ cell tumors (MGCT) are rare, occurring in children less than 2 years old and raise the question of the optimal local treatment. METHODS: We included children treated for vaginal MGCT according to the French TGM-95/2013 regimen. Patients were classified as standard risk (SR: localized disease and alpha-fetoprotein (AFP) < 10,000 ng/mL) or high risk (HiR: metastatic and/or AFP > 10,000 ng/mL) and were treated, respectively, with three to five VBP (vinblastine-bleomycin-cisplatin) or four to six VIP (etoposide-ifosfamide-cisplatin), followed by conservative surgery and/or brachytherapy in case of post-chemotherapy residuum. RESULTS: Fourteen patients were included (median age = 12 months), of which six (43%) were classified as HiR. AFP levels were normalized after first-line chemotherapy in all cases but one. A vaginal post-chemotherapy residuum (median size = 8 mm, range: 1-24 mm) was observed in 13/14 patients, treated by complete resection in seven of 13 (viable cells in three of seven), incomplete resection in four of 13 (viable cells in two of four), with adjuvant brachytherapy in two of 13, and exclusive brachytherapy in two of 13 (viable cells in one of six). Among the six patients with viable disease, four patients received adjuvant chemotherapy. One patient (SR) experienced immediate postoperative relapse despite presenting no viable residual cells and was treated with four VIP cycles and brachytherapy. At last follow-up (median = 4.6 years, range: 0.5-16), all patients were alive in complete remission. Five patients suffered from vaginal sequelae with synechiae and/or stenosis (of whom four had undergone brachytherapy). CONCLUSION: Childhood vaginal MGCTs show a highly favorable prognosis with risk-adapted chemotherapy and local treatment of post-chemotherapy residuum (preferably by conservative surgery with partial vaginectomy). Brachytherapy could be an alternative when conservative surgery is not deemed possible or in cases of incomplete resection with residual viable cells.

Outcome of patients with undifferentiated embryonal sarcoma of the liver treated according to European soft tissue sarcoma protocols.

BACKGROUND: To assess the outcomes of pediatric patients with undifferentiated embryonal sarcoma of the liver (UESL) and treatment including at least surgery and systemic chemotherapy. METHODS: This study included patients aged up to 21 years with a pathological diagnosis of UESL prospectively enrolled from 1995 to 2016 in three European trials focusing on the effects of surgical margins, preoperative chemotherapy, use of radiotherapy (RT), and chemotherapy. RESULTS: Out of 65 patients with a median age at diagnosis of 8.7 years (0.6-20.8), 15 had T2 tumors, and one had lymph node spread, 14 were Intergroup Rhabdomyosarcoma Study (IRS) I, nine IRS II, 38 IRS III, and four IRS IV. Twenty-eight upfront surgeries resulted in five operative spillages and 11 infiltrated surgical margins, whereas 37 delayed surgeries resulted in no spillages (p = .0119) and three infiltrated margins (p = .0238). All patients received chemotherapy, including anthracyclines in 47. RT was administered in 15 patients. With a median follow-up of 78.6 months, 5-year overall and event-free survivals (EFS) were 90.1% (95% confidence interval [CI]: 79.2-95.5) and 89.1% (95% CI: 78.4-94.6), respectively. Two out four local relapses had previous infiltrated margins and two out of three patients with metastatic relapses received reduced doses of alkylating agents. Infiltrated margins (p = .1607), T2 stage (p = .3870), use of RT (p = .8731), and anthracycline-based chemotherapy (p = .1181) were not correlated with EFS. CONCLUSIONS: Multimodal therapy improved the outcome of UESL. Neoadjuvant chemotherapy for pediatric patients increases the probability of complete surgical resection. The role of anthracyclines and RT for localized disease remains unclear.

Pediatric hepatic hemangiomas: spectrum and prognostic significance of initial ultrasound findings.

BACKGROUND: Hepatic hemangiomas may be associated with serious complications; however, it is unknown whether ultrasound (US) features can predict complications. OBJECTIVE: To analyze initial US features of hepatic hemangiomas predictive of complications. MATERIALS AND METHODS: This is a single-center retrospective cohort study of clinical, biological, and imaging data of infants with hepatic hemangioma between 2000 and 2018. Patients were categorized as having or not having any complication(s). Associations between initial US features and complications were analyzed through logistic regression. Receiver operating characteristic (ROC) curve analyses were performed to determine optimal cutoff values for continuous variables. Stepwise forward logistic regression was used to construct risk prediction models with training and validation sets. Model calibration and discrimination were evaluated using Hosmer-Lemeshow tests, area under the ROC curve, and overall accuracy. RESULTS: Of 112 infants with hepatic hemangioma, 67 (60%) had focal, 32 (28%) had multifocal, and 13 (12%) had diffuse lesions, with complication rates of 51%, 34%, and 92%, respectively, mostly cardiac (54/57, 95%). The US characteristics of the hemangiomas were diverse. Risk factors for complications included diffuse subtype; large tumor volume (focal forms); elevated peak systolic hepatic arterial velocity (PSV); and hepatic vein dilation. For focal forms, initial tumor volume >40 ml and PSV >100 cm/s had >70% sensitivity and specificity, respectively, to predict complications; a model including these variables had 75% overall accuracy in the validation set. For multifocal/diffuse forms, a PSV >115 cm/s had sensitivity and specificity to predict complications of >70%; a model including this variable had 78% overall accuracy in the validation set. CONCLUSION: Diffuse subtype, large tumor volume, elevated hepatic arterial PSV, and hepatic vein dilation are risk factors for complications of hepatic hemangiomas.

Long-term urological complications after conservative local treatment (surgery and brachytherapy) in children with bladder-prostate rhabdomyosarcoma: A single-team experience.

BACKGROUND: Outcome of children with bladder-prostate rhabdomyosarcoma (RMS) has improved with multimodal therapies, including surgery and/or radiotherapy for local treatment. Our aim was to report long-term urological complications after a conservative approach combining conservative surgery and brachytherapy. PATIENTS AND METHODS: Eighty-six patients, free of disease, were retrospectively reviewed. Symptoms related to urinary tract obstruction, incontinence, infection, and lithiasis were reported and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) classification. Only symptomatic patients underwent urodynamic studies. Risk factors for complications were analyzed. RESULTS: There were 76 males and 10 females. The median follow-up was 6.3 years (18 months to 24 years). Complications occurred after a median follow-up of 5 years (0-21). Twenty-two patients (26%) had long-term urological complications. Urinary tract obstruction was found in 15 patients (17%) and urinary incontinence in 14 patients (16%). Recurrent urinary tract infection occurred in four patients and urinary lithiasis in four (5%). The underlying physiopathology included bladder dysfunction in 15 patients (17%), urethral stenosis in six (7%), and ureterovesical junction stenosis in five (6%). On univariate analysis, posterior bladder wall dissection (p = .001), bladder neck trigone dissection (p = .010), and partial prostatectomy (p = .023) were significantly associated with an increased risk of bladder dysfunction; on multivariate analysis, only age ≤2 years (p = .028) at operation and posterior bladder wall dissection (p = .006) were found to be significant. CONCLUSION: The conservative surgical approach combined with brachytherapy for bladder-prostate RMS leads to long-term urological complications in 26% of survivors. Optimizing brachytherapy doses for young children and establishing a clear and long-term follow-up protocol could help to reduce these complications.

Perianal/perineal rhabdomyosarcoma: Results of the SIOP MMT 95, Italian RMS 96, and EpSSG RMS 2005 studies.

BACKGROUND/OBJECTIVES: Rhabdomyosarcoma of the perianal/perineal region (PRMS) is rare, with poor survival and limited understanding of the functional consequences of treatment. DESIGN/METHODS: International Society of Pediatric Oncology (SIOP) malignant mesenchymal tumor (MMT) 95, Italian RMS 96, and European paediatric Soft tissue sarcoma Study Group (EpSSG) RMS 2005 studies were interrogated to identify factors that impact survival; in RMS 2005, functional outcomes were analyzed. RESULTS: Fifty patients (nonmetastatic) were identified, median age 6.4 years (range: 0.1-19.6): 29 male, 21 female. Tumors were >5 cm in 33 patients. Histopathological subtype was alveolar in 35. Lymph nodes were involved in 23 patients. In RMS 2005, 16/21 (76%) tested alveolar tumors had positive FOXO1 fusion status. Diagnostic biopsy was performed in 37. Primary resection (13) was complete (R0) in one. Delayed primary excision (16) was complete in three. Radiotherapy (RT) in 34/50 patients included external beam (28), brachytherapy (3), and both (3). Nodal RT was given in 16/23 N1 patients (70%). Median follow-up of alive patients (29) was 84.1 months (range: 3.6-221.1). Relapse or progression occurred in 24 patients (48%), 87% were fatal and most events (63%) were locoregional. Five-year event-free survival (EFS) was 47.8 (95% CI: 32.8-61.3), and 5-year overall survival (OS) was 52.6 (95% CI: 36.7-66.2), with age ≥10 years and tumor size >5 cm impacting 5-year EFS and OS (p < .05). Functional outcome data showed bowel, genito-urinary, and psychological issues; fecal incontinence in four of 21 survivors, and urinary symptoms in two of 21. CONCLUSIONS: About 60% of patients with nonmetastatic PRMS survive; older patients and those with large tumors have the worst outcomes. Biopsy should be the initial procedure, and definitive local therapy individualized. Quality-of-life and functional studies are needed to better understand the consequences of treatment.

Clinical, pathologic, and molecular features of inflammatory myofibroblastic tumors in children and adolescents.

BACKGROUND: Inflammatory myofibroblastic tumors (IMT) are rare, intermediate malignant tumors harboring frequent somatic molecular rearrangements. The management of IMT has not been standardized. METHODS: A retrospective multicenter study was conducted on all pediatric patients treated for IMT between 2000 and 2019. RESULTS: This series included 39 cases of IMT, with a median age at diagnosis of 7 years (range 20 days to 16 years). Tumor location included pelvis-abdomen (n = 16), thorax (n = 14), head and neck (n = 7), and limbs (n = 2). One patient had metastatic disease. Immunochemistry showed 21/39 (54%) anaplastic lymphoma kinase (ALK)-positive tumors. Somatic tyrosine kinase rearrangement was present in 31/36 (86%) of the tumors analyzed: 21 ALK, five ROS1, and five NTRK. Immediate surgery was performed in 24 patients (62%), with adjuvant therapy for three patients. Delayed surgery after neoadjuvant therapy was possible in 10 cases. Exclusive systemic therapy was delivered to four patients; one patient with orbital IMT was managed by watchful waiting. After a median follow-up of 33 months (range 5-124), eight (20%) recurrences/progressions occurred after surgery (seven after primary surgery and one after delayed surgery), after a median interval of 7 months (range 2-21), all in thoracic locations. The 3-year overall and disease-free survivals were 96.8% (95% CI: 79.2%-94.0%) and 77.4% (95% CI: 59.6%-88.1%), respectively. Relapses/progressions were more common in patients with a thoracic primary (p < .001) or after incomplete surgery with no adjuvant therapy (p = .027). CONCLUSION: Surgery is effective in most cases of pediatric IMT. Systematic analysis of tyrosine kinase rearrangement is recommended. When the tumor is deemed only partially resectable to preserve organs and function, neoadjuvant therapy may be proposed to allow adequate conservative surgery.

Lessons from a large nationwide cohort of 350 children with ovarian mature teratoma: A study in favor of ovarian-sparing surgery.

BACKGROUND: Ovarian mature teratoma (OMT) is a common ovarian tumor found in the pediatric population. In 10%-20% of cases, OMT occurs as multiple synchronous or metachronous lesions on ipsi- or contralateral ovaries. Ovarian-sparing surgery (OSS) is recommended to preserve fertility, but total oophorectomy (TO) is still performed. DESIGN: This study reviews the clinical data of patients with OMT, and analyzes risk factors for second events. A national retrospective review of girls under 18 years of age with OMTs was performed. Data on clinical features, imaging, laboratory studies, surgical reports, second events and their management were retrieved. RESULTS: Overall, 350 children were included. Eighteen patients (5%) presented with a synchronous bilateral form at diagnosis. Surgery was performed by laparotomy (85%) and laparoscopy (15%). OSS and TO were performed in 59% and 41% of cases, respectively. Perioperative tumor rupture occurred in 23 cases, independently of the surgical approach. Twenty-nine second events occurred (8.3%) in a median time of 30.5 months from diagnosis (ipsilateral: eight cases including one malignant tumor; contralateral: 18 cases; both ovaries: three cases). A large palpable mass, bilateral forms, at diagnosis and perioperative rupture had a statistical impact on the risk of second event, whereas the type of surgery or approach did not. CONCLUSION: This study is a plea in favor of OSS as the first-choice treatment of OMT when possible. Close follow-up during the first 5 years is mandatory considering the risk of 8.3% of second events, especially in cases with risk factors.

Congenital Extrahepatic Portosystemic Shunts (Abernethy Malformation): An International Observational Study.

Congenital extrahepatic portosystemic shunt (CEPS) or Abernethy malformation is a rare condition in which splanchnic venous blood bypasses the liver draining directly into systemic circulation through a congenital shunt. Patients may develop hepatic encephalopathy (HE), pulmonary hypertension (PaHT), or liver tumors, among other complications. However, the actual incidence of such complications is unknown, mainly because of the lack of a protocolized approach to these patients. This study characterizes the clinical manifestations and outcome of a large cohort of CEPS patients with the aim of proposing a guide for their management. This is an observational, multicenter, international study. Sixty-six patients were included; median age at the end of follow-up was 30 years. Nineteen patients (28%) presented HE. Ten-, 20-, and 30-year HE incidence rates were 13%, 24%, and 28%, respectively. No clinical factors predicted HE. Twenty-five patients had benign nodular lesions. Ten patients developed adenomas (median age, 18 years), and another 8 developed HCC (median age, 39 years). Of 10 patients with dyspnea, PaHT was diagnosed in 8 and hepatopulmonary syndrome in 2. Pulmonary complications were only screened for in 19 asymptomatic patients, and PaHT was identified in 2. Six patients underwent liver transplantation for hepatocellular carcinoma or adenoma. Shunt closure was performed in 15 patients with improvement/stability/cure of CEPS manifestations. Conclusion: CEPS patients may develop severe complications. Screening for asymptomatic complications and close surveillance is needed. Shunt closure should be considered both as a therapeutic and prophylactic approach.

Paratesticular rhabdomyosarcoma-Impact of locoregional approach on patient outcome: A report from the European paediatric Soft tissue sarcoma Study Group (EpSSG).

BACKGROUND: Paratesticular rhabdomyosarcoma (PT RMS) is rare compared to benign scrotal pathology. Inappropriate first surgery (InFS) required supplementary treatment to maintain excellent outcomes. Initial staging of regional lymph nodes is important. The aim of this study was to determine to what extent the quality of locoregional approach impacted on patient morbidity and survival. DESIGN/METHODS: Analysis was performed on all nonmetastatic PT RMS patients enrolled in the European paediatric Soft tissue sarcoma Study Group (EpSSG) RMS 2005 protocol. Aspects assessed were adherence to surgical guidelines and impact of protocol violations, relapse analysis, and survival outcomes. RESULTS: Analysis was performed on 237 patients, with median follow up of 67.1 months. Median age was 9.0 years. InFS occurred in 75 of 237 (32%) patients. InFS required intensified chemotherapy (10) and local therapy. After InFS, 61 required primary reexcision and five delayed surgery. Of 26 recurrences, the risk of relapse was higher in patients ≥10 years (21/26) and was mainly locoregional in 16 of 26 recurrences (± metastatic). Sixteen of 26 died with 14 of 16 patients ≥10 years. Nodal relapse neither occurred when N1 nodes were identified at diagnosis, nor after surgical staging. Five-year overall survival (OS) at age <10 years versus ≥10 years was 98.1 and 86.7%, respectively (P = .0013). Event-free survival (EFS) at age <10 years versus ≥10 years was 95.8 and 79.6%, respectively (P = .0004). OS and EFS did not highlight a significant difference in patients undergoing appropriate versus InFS (P = .8479, P = .2780, respectively). CONCLUSIONS: InFS required intensified therapy to maintain excellent OS and EFS, so better anticipation of malignancy is required. Surgical staging of the retroperitoneal lymph nodes should be performed in patients ≥10 years old.

Outcome of localized liver-bile duct rhabdomyosarcoma according to local therapy: A report from the European Paediatric Soft-Tissue Sarcoma Study Group (EpSSG)-RMS 2005 study.

OBJECTIVES: To evaluate the impact of local therapies on the outcome of patients with liver-bile duct rhabdomyosarcoma (LBDRMS). METHODS: Data of 30 patients included in the EpSSG-RMS 2005 study were analyzed. RESULTS: The median age at diagnosis was 3 years (11 months-8 years). All patients had non-alveolar histology. Fifteen patients had a tumor > 5 cm and six had enlarged regional lymph nodes on imaging. Eight patients (27%) had primary surgery (1 R0). Six of them received external beam radiotherapy (EBRT). All are in first complete remission (CR1) except one (R1, EBRT+ , local relapse, death). Six patients (20%) received EBRT without surgery: one had local relapse and died. Sixteen patients (53%) underwent delayed surgery, with 12 achieving R0 margins, which were higher than those in the primary surgery group (P = 0.003). Three patients with R0 margins received EBRT; one had a metastatic relapse and died. Nine patients with R0 resection did not receive EBRT, three relapsed locally (two deaths). Four R1 patients received additional EBRT without relapses. Local relapse occurred in two among 19 patients with EBRT and three among 11 without EBRT (P = 0.326). At a median follow-up of 61 months (48-84 months), five patients died; all had a tumor size > 5 cm (P = 0.01). The five-year overall survival was 85% (95% CI, 65-94), and event-free survival was 76% (95% CI, 54-89). CONCLUSION: This analysis did not show any significant difference in outcome between irradiated and nonirradiated patients. Local relapse in LBDRMS is related to initial tumor size and is often fatal.

Congenital Portosystemic Shunts: Current Diagnosis and Management.

Congenital portosystemic shunts are increasingly recognized in several settings and at any age. The following are some of the most common presentations: prenatal ultrasound, neonatal cholestasis, incidental finding on abdominal imaging, or systemic complications such as unexplained cardiopulmonary or neurological disease, or the presence of liver nodules in a noncirrhotic liver. The purpose of the present review is to summarize clinical presentation and current recommendations for management, and highlight areas of future research. Illustrative examples from the veterinary literature complement our current lack of knowledge of this rare malformation often masquerading as a multisystem disease.

Management of Biliary Atresia in France 1986 to 2015: Long-term Results.

OBJECTIVES: This study analyses the prognosis of biliary atresia (BA) in France since 1986, when both Kasai operation (KOp) and liver transplantation (LT) became widely available. METHODS: The charts of all patients diagnosed with BA born between 1986 and 2015 and living in France were reviewed. RESULTS: A total of 1428 patients were included; 1340 (94%) underwent KOp. Total clearance of jaundice (total bilirubin ≤20 µmol/L) was documented in 516 patients (39%). Age at KOp (median 59 days, range 6-199) was stable over time. Survival with native liver after KOp was 41%, 35%, 26%, and 22% at 5, 10, 20, and 30 years, stable in the 4 cohorts. 25-year survival with native liver was 38%, 27%, 22%, and 19% in patients operated in the first, second, third month of life or later, respectively (P = 0.0001). Center caseloads had a significant impact on results in the 1986 to 1996 cohort only. 16%, 7%, 7%, and 8% of patients died without LT in the 4 cohorts (P = 0.0001). A total of 753 patients (55%) underwent LT. Patient survival after LT was 79% at 28 years. Five-year patient survival after LT was 76%, 91%, 88%, and 92% in cohorts 1 to 4, respectively (P < 0.0001). Actual BA patient survival (from diagnosis) was 81%. Five-year BA patient survival was 72%, 88%, 87%, and 87% in cohorts 1986 to 1996, 1997 to 2002, 2003 to 2009, and 2010 to 2015, respectively (P < 0.0001). CONCLUSIONS: In France, 87% of patients with BA survive nowadays and 22% reach the age of 30 years without transplantation. Improvement of BA prognosis is mainly due to reduced mortality before LT and better outcomes after LT.

First liver transplantation for biliary atresia in children: The hidden effects of non-centralization.

The aim of our study was to determine the impact of initial orientation for medical and surgical care of children with BA on procedures and outcomes of the first LT. We retrospectively analyzed charts of children with BA who underwent first LT between 2006 and 2015. Patients were divided into two groups for comparison: a single-center management group (from diagnosis to transplantation) and a secondarily referred group (children referred after failure of KP). We focused analysis on disease severity at transplantation, blood transfusion, and overall survival. One hundred and eighty-five children were included. The median delay between pretransplant check-up and transplantation was shorter in patients secondarily referred. A severe undernutrition was observed in 23.7% of children secondarily referred compared to 11.1% in children with a single-center management (P = .024). At transplantation, INR and factor V level were higher in single-center group patients (respectively, 67% vs 55%, P < .001 and 61% vs 49%, P = .002). The total of red blood cell and fresh frozen plasma administrated during procedure was two times higher in patients secondarily referred. Finally, patients with a single-center management had a higher overall 12 months of survival rate (92.1% vs 83.1%, P = .033). In a country without low-density population issues, the authors advocate an early referring to transplant center to further improving LT outcomes in children with BA.

Portal hypertension in children: High-risk varices, primary prophylaxis and consequences of bleeding.

BACKGROUND & AIMS: Primary prophylaxis of bleeding is debated for children with portal hypertension because of the limited number of studies on its safety and efficacy, the lack of a known endoscopic pattern carrying a high-risk of bleeding for all causes, and the assumption that the mortality of a first bleed is low. We report our experience with these issues. METHODS: From 1989 to 2014, we managed 1300 children with portal hypertension. Endoscopic features were recorded; high-risk varices were defined as: grade 3 esophageal varices, grade 2 varices with red wale markings, or gastric varices. Two hundred forty-six children bled spontaneously and 182 underwent primary prophylaxis. The results of primary prophylaxis were reviewed as well as bleed-free survival, overall survival and life-threatening complications of bleeding. RESULTS: High-risk varices were found in 96% of children who bled spontaneously and in 11% of children who did not bleed without primary prophylaxis (p<0.001), regardless of the cause of portal hypertension. Life-threatening complications of bleeding were recorded in 19% of children with cirrhosis and high-risk varices who bled spontaneously. Ten-year probabilities of bleed-free survival after primary prophylaxis in children with high-risk varices were 96% and 72% for non-cirrhotic causes and cirrhosis respectively. Ten-year probabilities of overall survival after primary prophylaxis were 100% and 93% in children with non-cirrhotic causes and cirrhosis respectively. CONCLUSION: In children with portal hypertension, bleeding is linked to the high-risk endoscopic pattern reported here. Primary prophylaxis of bleeding based on this pattern is fairly effective and safe. LAY SUMMARY: In children with liver disease, the risk of bleeding from varices in the esophagus is linked to their large size, the presence of congestion on their surface and their expansion into the stomach but not to the child's age nor to the cause of portal hypertension. Prevention of the first bleed in children with high-risk varices can be achieved by surgery or endoscopic treatment, and decreases mortality and morbidity.

Abdominal Arterial Anomalies in Children With Alagille Syndrome: Surgical Aspects and Outcomes of Liver Transplantation.

OBJECTIVES: Angiogenic defects secondary to gene mutations of JAG1 and NOTCH2, causing arterial anomalies in Alagille syndrome (AGS), are well described in the literature. The study analyzes the frequency of abdominal arterial anomalies in children with AGS with an emphasis on outcomes following liver transplantation (LT). METHODS: Between 1988 and 2013, 242 children with AGS were treated at our institution. We performed a retrospective analysis of 55 who underwent LT during the study period. Preoperative abdominal arterial findings, operative reports, arterial reconstruction technique, and early as well as late complications following LT were reviewed specifically focusing on arterial thrombosis. RESULTS: Twenty-five patients had preoperative imaging available for analysis. Twelve of these patients showed celiac trunk stenosis (48.0%), 2, a superior mesenteric artery stenosis (8.0%) and one a stenosis of both renal arteries. Twenty patients (36.3%) underwent standard hepatic reconstruction using the native recipient hepatic artery. Thirty-five patients (63.7%) underwent aortic conduit reconstruction (ACR) from the infrarenal aorta using donor arterial conduits. Hepatic artery thrombosis occurred in 9 patients (16.3%). This number was higher in the standard arterial anastomosis group 7/20 (35.0%) than in those with ACR 2/35 (5.7%, P = 0.0079). CONCLUSIONS: In this series, children with AGS pretransplant have a high prevalence of abdominal arterial anomalies. Preoperative abdominal vascular imaging makes it possible to anticipate whether or not a classical arterial revascularization can be performed or whether an ACR is required.