Outcome of bleomycin electrosclerotherapy of slow-flow malformations in adults and children.

OBJECTIVES: To evaluate the safety and clinical outcome of bleomycin electrosclerotherapy (BEST) for treating extracranial slow-flow malformations. METHODS: In this retrospective investigation of a multicenter cohort presenting symptomatic slow-flow malformations, patient records were analyzed with respect to procedural details and complications. A treatment-specific, patient-reported questionnaire was additionally evaluated, obtained 3-12 months after the last treatment, to assess the subjective outcomes, including mobility, aesthetic aspects, and pain, as well as the occurrence of postprocedural skin hyperpigmentation. All outcome parameters were compared according to patients' age. RESULTS: Overall, 325 BEST treatments were performed in 233 patients after intralesional and/or intravenous bleomycin injection. The total complication rate was 10.2% (33/325), including 29/352 (8.9%) major complications. Patient-reported mobility decreased in 10/133 (8.8%), was stable in 30/113 (26.5%), improved in 48/113 (42.5%), and was rated symptom-free in 25/113 (22.1%) patients. Aesthetic aspects were rated impaired compared to baseline in 19/113 (16.8%), stable in 21/133 (18.6%), improved in 62/113 (54.9%), and perfect in 11/133 (9.7%) patients. Postprocedural skin hyperpigmentation occurred in 78/113 (69%) patients, remaining unchanged in 24/78 (30.8%), reduced in 51/78 (65.5%), and completely resolved in 3/78 (3.8%) patients. The median VAS pain scale was 4.0 (0-10) preprocedural and 2.0 (0-9) postprocedural. Children/adolescents performed significantly better in all parameters compared to adults (≥ 16 years) (mobility, p = 0.011; aesthetic aspects, p < 0.001; pain, p < 0.001). CONCLUSIONS: BEST is effective for treating slow-flow vascular malformations, with few but potentially significant major complications. Regarding patient-reported outcomes, children seem to benefit better compared to older patients, suggesting that BEST should not be restricted to adults. CLINICAL RELEVANCE STATEMENT: Bleomycin electrosclerotherapy is a safe and effective approach and therapy should not be restricted to adults due to good clinical outcomes in children.

Second Malignant Neoplasms Following Treatment for Hepatoblastoma: An International Report and Review of the Literature.

Treatment intensification has improved survival in patients with hepatoblastoma (HB); however, these treatments are associated with an increased risk of late effects, including second malignant neoplasms (SMNs). Data is limited regarding SMNs following HB treatment. Cases of SMNs following treatment for HB reported in the literature and from personal communication were analyzed to further assess this late effect. Thirty-eight patients were identified. The median age at diagnosis of HB was 16 months (range: 3 to 168 mo). All patients had received a platinum agent, and almost all had anthracycline exposure. The SMNs reported were hematopoietic malignancies (n=19), solid tumors (n=12), and post-transplant lymphoproliferative disorder (n=7). Of the 36 patients with outcome data, 19 survived. SMNs following HB treatment were primarily seen in patients with chemotherapy exposure, a history of liver transplantation, hereditary tumor predisposition syndromes, and/or a history of radiation treatment. Hematopoietic malignancies were the most common SMN reported in this cohort and were diagnosed earlier than other SMNs. Prospective collection of data through a companion late effects study or international registry could be used to further evaluate the rates and risks of SMNs as well as tumor predisposition syndromes in patients treated for HB.

Consensus classification of pediatric hepatocellular tumors: A report from the Children's Hepatic tumors International Collaboration (CHIC).

BACKGROUND: Liver tumors are rare in children with histologic heterogeneity that makes diagnosis challenging. Systematic histopathological review, performed as part of collaborative therapeutic protocols, identified relevant histologic subtypes that are important to distinguish. The Children's Hepatic tumors International Collaboration (CHIC) was established to study pediatric liver tumors on a global scale and led to establishment of a provisional consensus classification for use in international clinical trials. The current study is the validation of this initial classification and first large-scale application by international expert reviewers. PROCEDURE: The CHIC initiative includes data from 1605 children treated on eight multicenter hepatoblastoma (HB) trials. Review of 605 available tumors was performed by seven expert pathologists from three consortia (US, EU, Japan). Cases with discordant diagnoses were collectively reviewed to reach a final consensus diagnosis. RESULTS: Of 599 cases with sufficient material for review, 570 (95.2%) were classified as HB by all consortia, and 29 (4.8%) as non-HB, which included "hepatocellular neoplasm, NOS" and malignant rhabdoid tumors. 453 of 570 HBs were classified as epithelial by final consensus. Some patterns (i.e., small cell undifferentiated, macrotrabecular, cholangioblastic) were selectively identified by reviewers from different consortia. All consortia identified a similar number of mixed epithelial-mesenchymal HB. CONCLUSIONS: This study represents the first large-scale application and validation of the pediatric malignant hepatocellular tumors consensus classification. It is a valuable resource to train future generations of investigators on accurate diagnosis of these rare tumors and provides a framework for further international collaborative studies and refinement of the current classification of pediatric liver tumors.

Additive value of transarterial embolization to systemic sirolimus treatment in kaposiform hemangioendothelioma.

Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor in children, which can be accompanied by life-threatening thrombocytopenia, referred to as Kasabach-Merritt phenomenon (KMP). The mTOR inhibitor sirolimus is emerging as targeted therapy in KHE. As the sirolimus effect on KHE occurs only after several weeks, we aimed to evaluate whether additional transarterial embolization is of benefit for children with KHE and KMP. Seventeen patients with KHE and KMP acquired from 11 hospitals in Germany were retrospectively divided into two cohorts. Children being treated with adjunct transarterial embolization and systemic sirolimus, and those being treated with sirolimus without additional embolization. Bleeding grade as defined by WHO was determined for all patients. Response of the primary tumor at 6 and 12 months assessed by magnetic resonance imaging (MRI), time to response of KMP defined as thrombocyte increase >150 × 103 /µL, as well as rebound rates of both after cessation of sirolimus were compared. N = 8 patients had undergone additive embolization to systemic sirolimus therapy, sirolimus in this group was started after a mean of 6.5 ± 3 days following embolization. N = 9 patients were identified who had received sirolimus without additional embolization. Adjunct embolization induced a more rapid resolution of KMP within a median of 7 days vs 3 months; however, tumor response as well as rebound rates were similar between both groups. Additive embolization may be of value for a more rapid rescue of consumptive coagulopathy in children with KHE and KMP compared to systemic sirolimus only.

Sarcopenia is a prognostic outcome marker in children with high-risk hepatoblastoma.

BACKGROUND: Children with hepatoblastoma (HB) are at risk of sarcopenia due to immobility, chemotherapy, and malnutrition. We hypothesized that children with HB have a low preoperative total psoas muscle area (tPMA), reflecting sarcopenia, which negatively impacts outcome. PROCEDURE: Retrospective study of children (1-10 years) with hepatoblastoma treated at a large university children's hospital from 2009 to 2018. tPMA was measured as the sum of the right and left psoas muscle area (PMA) at intervertebral disc levels L3-4 and L4-5. z-Scores were calculated using age- and gender-specific reference values and were compared to anthropometric measurements, clinical variables, and outcomes. Sarcopenia was defined as a tPMA z-score below -2. RESULTS: Thirty-three children were included. Mean tPMA z-score was -2.18 ± 1.08, and 52% were sarcopenic. A poor correlation between tPMA and weight was seen (r = 0.35; confidence interval [CI] 0.01, 0.62; P = .045), and most children had weights within the normal range (mean z-score -0.55 ± 1.39). All children categorized as high risk with relapse (n = 5/12) were sarcopenic before surgery. Relapse was significantly higher in the high-risk sarcopenic group compared to the nonsarcopenic group (P = .008). The change in tPMA z-score 1-4 months after surgery did not improve in patients with relapse, but did improve in 75% of children without relapse. CONCLUSIONS: The majority of children with HB were sarcopenic prior to surgery. Especially in children with high-risk hepatoblastoma, sarcopenia is an additional risk factor for relapse. Large multicenter studies are needed to confirm these preliminary results.

High Dose Chemotherapy with Autologous Stem Cell Transplantation in Hepatoblastoma does not Improve Outcome. Results of the GPOH Study HB99.

INTRODUCTION: The purpose of the German HB99 trial (1999-2008) for hepatoblastoma (HB), was primarily to analyse the effect of high dose (HD) chemotherapy with carboplatin/etoposide (CE) in high risk (HR) patients with extended tumors, vessel involvement, extrahepatic tumor or distant metastases. In standard risk (SR) patients the effect of treatment reduction was analysed. METHODS: HR patients received 2 cycles CE at conventional dose, followed by 2 at HD with subsequent autologous stem cell transplantation before delayed surgery. SR patients received 3-4 cycles of ifosfamide, cisplatin and doxorubicin (IPA) and delayed surgery. Analysis was on an intention to treat basis including resection rate, AFP decline, event free survival (EFS) and overall survival (OS). The patients with HD therapy were additionally analysed on an "as treated" basis. The results were compared to historical/published data. RESULTS: Of the 142 patients, the 5-y OS was 58% for the 57 HR patients and 94% for the 85 SR patients. The AFP decline after 2 cycles CE was ≥ 50% in > 90% of the patients. 12/18 (67%) patients treated with HD therapy showed an AFP decline after the first cycle (as treated). Tumor resection was possible in 89% of the patients. The median FU was 7.4 years. Late deaths occurred in 4 patients. CONCLUSION: Use of HD chemotherapy for HB did not improve patient outcomes, compared to contemporaneous and more recent trials (SIOPEL 4 trial). Reduction of therapy in SR patients was possible without worsening of results compared to previous trials. The tumor response to CE was good. CE can therefore be considered for relapse patients.

Multidisciplinary long-term care and modern surgical treatment of congenital melanocytic nevi - recommendations by the CMN surgery network.

In recent years, our knowledge of congenital melanocytic nevi (CMN) has greatly expanded. This has led to a paradigm shift. The present article represents a commentary by an interdisciplinary group of physicians from German-speaking countries with extensive experience in long-term care and surgical treatment of children and adults with CMN (CMN surgery network, "Netzwerk Nävuschirurgie", NNC). The authors address aspects such as the indication for treatment as well as treatment planning and implementation under these new premises. Adequate counseling of parents on conservative and/or surgical management requires an interdisciplinary exchange among physicians and individualized planning of the intervention, which frequently involves a multi-stage procedure. Today, the long-term aesthetic outcome is at the center of any therapeutic endeavor, whereas melanoma prevention plays only a minor role. The premise of "removal at any cost" no longer holds. Potential treatment-related adverse effects (hospitalization, wound healing disorders, and others) must be carefully weighed against the prospects of a beneficial outcome. In this context, the use of dermabrasion in particular must be critically evaluated. At a meeting of the NNC in September 2018, its members agreed on a consensus-based position on dermabrasion, stating that the procedure frequently leads to impaired wound healing and cosmetically unfavorable or hypertrophic scarring. Moreover, dermabrasion is considered to be commonly associated with considerable repigmentation that usually occurs a number of years after the procedure. In addition, the NNC members saw no benefit in terms of melanoma prevention. In the future, physicians should therefore thoroughly caution about the potential risks and often limited cosmetic benefits of dermabrasion.

Risk-stratified staging in paediatric hepatoblastoma: a unified analysis from the Children's Hepatic tumors International Collaboration.

BACKGROUND: Comparative assessment of treatment results in paediatric hepatoblastoma trials has been hampered by small patient numbers and the use of multiple disparate staging systems by the four major trial groups. To address this challenge, we formed a global coalition, the Children's Hepatic tumors International Collaboration (CHIC), with the aim of creating a common approach to staging and risk stratification in this rare cancer. METHODS: The CHIC steering committee-consisting of leadership from the four major cooperative trial groups (the International Childhood Liver Tumours Strategy Group, Children's Oncology Group, the German Society for Paediatric Oncology and Haematology, and the Japanese Study Group for Paediatric Liver Tumours)-created a shared international database that includes comprehensive data from 1605 children treated in eight multicentre hepatoblastoma trials over 25 years. Diagnostic factors found to be most prognostic on initial analysis were PRETreatment EXTent of disease (PRETEXT) group; age younger than 3 years, 3-7 years, and 8 years or older; α fetoprotein (AFP) concentration of 100 ng/mL or lower and 101-1000 ng/mL; and the PRETEXT annotation factors metastatic disease (M), macrovascular involvement of all hepatic veins (V) or portal bifurcation (P), contiguous extrahepatic tumour (E), multifocal tumour (F), and spontaneous rupture (R). We defined five clinically relevant backbone groups on the basis of established prognostic factors: PRETEXT I/II, PRETEXT III, PRETEXT IV, metastatic disease, and AFP concentration of 100 ng/mL or lower at diagnosis. We then carried the additional factors into a hierarchical backwards elimination multivariable analysis and used the results to create a new international staging system. RESULTS: Within each backbone group, we identified constellations of factors that were most predictive of outcome in that group. The robustness of candidate models was then interrogated using the bootstrapping procedure. Using the clinically established PRETEXT groups I, II, III, and IV as our stems, we created risk stratification trees based on 5 year event-free survival and clinical applicability. We defined and adopted four risk groups: very low, low, intermediate, and high. INTERPRETATION: We have created a unified global approach to risk stratification in children with hepatoblastoma on the basis of rigorous statistical interrogation of what is, to the best of our knowledge, the largest dataset ever assembled for this rare paediatric tumour. This achievement provides the structural framework for further collaboration and prospective international cooperative study, such as the Paediatric Hepatic International Tumour Trial (PHITT). FUNDING: European Network for Cancer Research in Children and Adolescents, funded through the Framework Program 7 of the European Commission (grant number 261474); Children's Oncology Group CureSearch grant contributed by the Hepatoblastoma Foundation; Practical Research for Innovative Cancer Control and Project Promoting Clinical Trials for Development of New Drugs and Medical Devices, Japan Agency for Medical Research; and Swiss Cancer Research grant.

Small cell undifferentiated (SCUD) hepatoblastomas: All malignant rhabdoid tumors?

Small cell undifferentiated (SCUD) hepatoblastoma is a rare variant of hepatoblastoma with poor outcome and loss of INI1 expression, sharing this with malignant rhabdoid tumors (MRT). We studied all tumors from the files of the Kiel Pediatric Tumor Registry (KTR) with the initial diagnosis of SCUD and MRT. After re-review, we performed immunistochemistry, fluorescence in situ hybridization, and multiplex ligation dependent probe amplification for loss of expression and deletion of INI1/SMARCB1 in 23 tumors. Morphologically, 12 of the tumors had a small cell morphology, 9 showed the typical picture of MRT, and 2 were composed of both small cells and rhabdoid cells. All but 1 of the 23 tumors showed loss of INI1 protein expression by immunohistochemistry. Nineteen of the INI1 negative tumors were analyzed by FISH technique and all showed a deletion of the INI1/SMARCB1 gene (17 homozygous deletions, 2 heterozygous deletions). We investigated 14 of these cases by multiplex ligation dependent probe amplification and verified the deletions in all cases. In conclusion, we postulate that SCUD hepatoblastoma is not a hepatoblastoma but represents a malignant rhabdoid tumor of the liver. © 2016 Wiley Periodicals, Inc.

Impact of postoperative complications on overall survival of patients with hepatoblastoma.

BACKGROUND: Complete resection of hepatoblastoma (HB) is a demanding procedure in advanced tumors. Perioperative complications are still common. The influence of complication rates on course of disease and survival of patients with HB has not been analyzed yet. PROCEDURES: Patients with high risk (HR) HB and standard-risk (SR) HB registered from 1999 to 2008 to the German prospective multicenter study HB99 were evaluated regarding perioperative complications, reasons (e.g., tumor size and vessel involvement) and impact on further treatment and overall survival (OS). RESULTS: Surgical data from 126 patients were available (47 HR-HB, 79 SR-HB). Postoperative complications occurred in 26 (21%) patients consisting of biliary leakage (n = 9), cholestasis (n = 5), deficit of liver perfusion (n = 5) and others (n = 7). Twenty of these 26 patients (77%) required a second operation. The rate of postoperative complications was higher in the HR-group (26%) compared to the SR-group (17%). Patients with vessel involvement had significantly more complications (17% vs. 54%, P = 0.01). Patients with PRETEXT I/II-tumors had the same rate of postoperative complications (19% vs. 20%) as patients with PRETEXT III/IV. Patients of HR-group with postoperative complications showed delayed start in adjuvant chemotherapy (>21 d) (75% vs. 25%, n.s.) combined with significant lower 5-year-OS (75% vs. 50%, P = 0.02). In multivariate analysis postoperative complications were an independent negative prognostic factor for HR-patients (HR 3.1, P = 0.04). CONCLUSIONS: Postoperative complications after HB resection are frequent and associated with worsened OS of patients with HR-HB. One possible reason is delay in postoperative chemotherapy. The approach to precarious liver resection should be carefully planned and executed by specialists.

The genomic landscape of hepatoblastoma and their progenies with HCC-like features.

BACKGROUND & AIMS: Hepatoblastoma (HB) is the most common childhood liver cancer and occasionally presents with histological and clinical features reminiscent of hepatocellular carcinoma (HCC). Identification of molecular mechanisms that drive the neoplastic continuation towards more aggressive HCC phenotypes may help to guide the new stage of targeted therapies. METHODS: We performed comprehensive studies on genetic and chromosomal alterations as well as candidate gene function and their clinical relevance. RESULTS: Whole-exome sequencing identified HB as a genetically very simple tumour (2.9 mutations per tumour) with recurrent mutations in ß-catenin (CTNNB1) (12/15 cases) and the transcription factor NFE2L2 (2/15 cases). Their HCC-like progenies share the common CTNNB1 mutation, but additionally exhibit a significantly increased mutation number and chromosomal instability due to deletions of the genome guardians RAD17 and TP53, accompanied by telomerase reverse-transcriptase (TERT) promoter mutations. Targeted genotyping of 33 primary tumours and cell lines revealed CTNNB1, NFE2L2, and TERT mutations in 72.5%, 9.8%, and 5.9% of cases, respectively. All NFE2L2 mutations affected residues of the NFE2L2 protein that are recognized by the KEAP1/CUL3 complex for proteasomal degradation. Consequently, cells transfected with mutant NFE2L2 were insensitive to KEAP1-mediated downregulation of NFE2L2 signalling. Clinically, overexpression of the NFE2L2 target gene NQO1 in tumours was significantly associated with metastasis, vascular invasion, the adverse prognostic C2 gene signature, as well as poor outcome. CONCLUSIONS: Our study demonstrates the importance of CTNNB1 mutations and NFE2L2-KEAP1 pathway activation in HB development and defines loss of genomic stability and TERT promoter mutations as prominent characteristics of aggressive HB with HCC features.

Hepatoblastoma state of the art: pathology, genetics, risk stratification, and chemotherapy.

PURPOSE OF REVIEW: As a rare pediatric tumor, hepatoblastoma presents challenges to the individual practitioner as no center will see more than a handful of cases each year. RECENT FINDINGS: The Children's Hepatic tumor International Collaborative (CHIC) effort has fostered international cooperation in this rare children's tumor, leading to the establishment of a large international collaborative dataset, the CHIC database, which has been interrogated to refine risk stratification and inform treatment options. Apace with this effort has been the international collaboration of pediatric pathologists working together to establish a new international histopathologic consensus classification for pediatric liver tumors as a whole, with particular focus on the histological subtypes of hepatoblastoma. SUMMARY: International collaborative efforts in hepatoblastoma have led to a new international histopathologic consensus classification, refinements in risk stratification, advances in chemotherapy, and a better understanding of surgical resection options forming the foundation for the development of an upcoming international therapeutic trial.

Fibro-Adipose Vascular Anomaly of the Lower Extremity.

Fibro-adipose vascular anomaly (FAVA) is characterized by intramuscular vascular malformation with secondary overgrowth of further mesenchymal elements, particularly fibro-adipose tissue. A rare disease complicated by nonspecific, overlapping clinical and imaging features, FAVA is often misdiagnosed, causing a dilemma in its diagnostic and therapeutical management. We present a case of FAVA of the lower extremity.

Complex Arterio-Portal-Venous Malformation of the Liver.

A neonatal female patient exhibited a congenital intricate vascular malformation affecting the liver, encompassing anomalies in the arterial, venous, and portal venous systems and notably including an aneurysm within the portal vein. The management strategy involved a staged endovascular approach, initially using retrograde embolization via the venous outflow tract. Subsequently, transarterial embolization was performed to address complications associated with pulmonary and portal hypertension.

Hepatoblastoma Relapse-Findings from the German HB99 Trial and the German Liver Tumor Registry.

Survival rates for HB patients have improved; however, outcomes for patients who relapse remain poor. A retrospective review of information gathered for the HB99 study and the German Liver Tumor Registry identified 25 relapse patients (6.9%, 25/362). The median time from initial diagnosis to first relapse was 13 months (range: 5-66 months). Two patients relapsed >36 months after initial diagnosis. A total of 68% (17/25) of relapses were metastatic, 24% local, and 8% combined. 67% of local relapses were alive at the last follow-up, in contrast to 53% of metastatic and 0% of combined relapses. At the last follow-up, 73% (8/11) of patients with lung relapses were still alive (0/4 with peritoneal, 1/2 with CNS involvement). A total of 20% of the patients had AFP-negative relapses, 64% of the relapse patients achieved a second complete remission, 69% were still in complete second remission at the last follow-up (median FU of 66 months), and 83% (5/6) of irinotecan-naïve patients who received relapse treatment including irinotecan were in second complete remission at the last follow-up. The 3-year overall survival/event-free survival from relapse was 63%/48% respectively. There is a good chance that HB patients will achieve a second remission despite a first relapse. However, patients who suffer further relapses tend to have a poorer prognosis.

Extracranial Vascular Anomalies Driven by RAS/MAPK Variants: Spectrum and Genotype-Phenotype Correlations.

BACKGROUND: We aimed to correlate alterations in the rat sarcoma virus (RAS)/mitogen-activated protein kinase pathway in vascular anomalies to the clinical phenotype for improved patient and treatment stratification. METHODS AND RESULTS: This retrospective multicenter cohort study included 29 patients with extracranial vascular anomalies containing mosaic pathogenic variants (PVs) in genes of the RAS/mitogen-activated protein kinase pathway. Tissue samples were collected during invasive treatment or clinically indicated biopsies. PVs were detected by the targeted sequencing of panels of genes known to be associated with vascular anomalies, performed using DNA from affected tissue. Subgroup analyses were performed according to the affected genes with regard to phenotypic characteristics in a descriptive manner. Twenty-five vascular malformations, 3 vascular tumors, and 1 patient with both a vascular malformation and vascular tumor presented the following distribution of PVs in genes: Kirsten rat sarcoma viral oncogene (n=10), neuroblastoma ras viral oncogene homolog (n=1), Harvey rat sarcoma viral oncogene homolog (n=5), V-Raf murine sarcoma viral oncogene homolog B (n=8), and mitogen-activated protein kinase kinase 1 (n=5). Patients with RAS PVs had advanced disease stages according to the Schobinger classification (stage 3-4: RAS, 9/13 versus non-RAS, 3/11) and more frequent progression after treatment (RAS, 10/13 versus non-RAS, 2/11). Lesions with Kirsten rat sarcoma viral oncogene PVs infiltrated more tissue layers compared with the other PVs including other RAS PVs (multiple tissue layers: Kirsten rat sarcoma viral oncogene, 8/10 versus other PVs, 6/19). CONCLUSIONS: This comparison of patients with various PVs in genes of the RAS/MAPK pathway provides potential associations with certain morphological and clinical phenotypes. RAS variants were associated with more aggressive phenotypes, generating preliminary data and hypothesis for future larger studies.

Outcomes for patients with congenital hepatoblastoma.

BACKGROUND: Congenital hepatoblastoma, diagnosed in the first month of life, has been reported to have a poor prognosis; however, a comprehensive evaluation of this entity is lacking. PROCEDURE: We retrospectively reviewed two patients from the senior authors' personal series and 25 cases identified in the databases of several multicenter group studies (INT-0098, P9645, 881, P9346, HB 89, HB94, and HB 99). We compared this series with cases of congenital hepatoblastoma previously published in the literature. RESULTS: The 3-year survival in our case series was 86% (18/21) with a follow-up of 44-230 months (median 85.5 months). Presentation and treatment were not substantially different from hepatoblastoma cohorts unselected for age. Survival was comparable to the reported disease free survival for a similar cohort of hepatoblastoma patients unselected for age between 1986 and 2002 (82.5%) [von Schweinitz et al., Eur J Cancer 1997; 33:1243-1249]. The 2-year survival of cases reported in the literature was 0% (0/9) and 42% (10/24) for patients reported before and after 1990, respectively. CONCLUSIONS: Congenital hepatoblastoma does not appear to confer a worse prognosis. The improved survival of our current series of patients, collected from the past 20 years of German and American multicenter trials and personal series, suggests that the outcome of hepatoblastoma at this young age is much better than has been historically reported. More rigorous analysis should be conducted in future multicenter trials. It is possible that congenital hepatoblastoma should be treated like all other patients with hepatoblastoma provided that the child is stable enough to proceed with surgery and chemotherapy.

Children with Localized Crohn's Disease Benefit from Early Ileocecal Resection and Perioperative Anti-Tumor Necrosis Factor Therapy.

INTRODUCTION: In pediatric Crohn's disease ileocecal resection is performed reluctantly as postoperative recurrence is frequent. Anti-tumor necrosis factor (TNF) therapy reduces postoperative recurrence rates but increases the risk for infections. MATERIALS AND METHODS: We retrospectively reviewed pediatric Crohn's disease patients who underwent ileocecal resection in our center. We compared disease activity and z-scores for height, weight, and body mass index of patients, who continuously received perioperative anti-TNF therapy (TNF + ), with those who did not (TNF-). RESULTS: Of 29 patients (48% females), 13 and 16 were grouped to TNF+ and TNF-, respectively. Patients' characteristics did not differ between groups, except a longer follow-up time in TNF-. We saw significant postoperative improvement but no normalization in z-scores for weight (1.78 vs. 0.77, p < 0.001), body mass index (1.08 vs. 0.22, p < 0.001), and height (0.88 vs. 0.66, p < 0.001). Disease activity improved significantly more in patients receiving anti-TNF therapy (moderate improvement in 83% vs. 31%, p = 0.02). Endoscopic recurrence was more frequent in patients without anti-TNF therapy (80% vs. 20%; p = 0.023), but endoscopic follow-up was incomplete. There was no increase of infections under perioperative anti-TNF therapy (1 patient each; p = 1.000). CONCLUSION: In patients with localized Crohn's disease an ileocecal resection leads to short-term postoperative improvement of disease activity, body mass index, weight, and growth. For relevant catch-up growth an earlier intervention is necessary. Continuous perioperative anti-TNF therapy had no increased risk of perioperative infections.

Use of Barbed Sutures for Congenital Diaphragmatic Hernia Repair.

BACKGROUND: Congenital diaphragmatic hernia (CDH) repair can be challenging, particularly when a larger defect is present. Barbed sutures prevent the suture from slipping back after approximation of the tissues. Although introduced almost 2 decades ago, barbed sutures have not been widely used for CDH repair. We report our initial experience and pitfalls. METHODS: All patients presenting with CDH from 2021 onward underwent repair using barbed sutures. Demographics, operative parameters, complications, and outcomes were prospectively recorded. RESULTS: A total of 13 patients underwent CDH repair during the study interval (median age 6 days, range 3 days to 5.75 years). Median operative time was 89 min (range 46 to 288 min). Five thoracoscopic and eight open procedures were performed. Severe pulmonary hypertension and ECMO (extracorporeal membrane oxygenation) were considered contraindications for thoracoscopic repair. The included patients were compared to a historic controlled group performed without barbed sutures. The barbed suture facilitated easy and quick closure of the defects in most cases and obviated the need for knot tying. One patient in the thoracoscopic group had a patch placed due to high tension after the barbed sutures tore the diaphragm. At a median follow-up time of 15 months (range 2 to 34 months), one patient had died, and one patient with complete diaphragmatic agenesis was home-ventilated. There were no recurrences. Median operative time trended lower (89 min) than in the historic control group repaired without barbed sutures (119 min, p < 0.06) after eliminating outliers with large, complex patch repairs. CONCLUSIONS: Barbed sutures simplify congenital diaphragmatic hernia repair regardless of whether a minimal-invasive or open approach is performed. Patch repair is not a contraindication for using barbed sutures. The resulting potential time savings make them particularly useful in patients with cardiac or other severe co-morbidities in which shorter operative times are essential. In cases with high tension, though, the barbs may tear through and produce a "saw" effect on the tissue with subsequent damage.