Author Correction: Targeted therapy in patients with PIK3CA-related overgrowth syndrome.

The 'Competing interests' statement of this Article has been updated; see accompanying Amendment for further details.

Identification of liver transplant biopsy phenotypes associated with distinct liver biological markers and allograft survival.

The intricate association between histologic lesions and circulating antihuman leucocyte antigen donor-specific antibodies (DSA) in liver transplantation (LT) requires further clarification. We conducted a probabilistic, unsupervised approach in a comprehensively well-annotated LT cohort to identify clinically relevant archetypes. We evaluated 490 pairs of LT biopsies with DSA testing from 325 recipients transplanted between 2010 and 2020 across 3 French centers and an external cohort of 202 biopsies from 128 recipients. Unsupervised archetypal analysis integrated all clinico-immuno-histologic parameters of each biopsy to identify biopsy archetypes. The median time after LT was 1.17 (interquartile range, 0.38-2.38) years. We identified 7 archetypes distinguished by clinico-immuno-histologic parameters: archetype #1: severe T cell-mediated rejection (15.9%); #2: chronic rejection with ductopenia (1.8%); #3: architectural and microvascular damages (3.5%); #4: (sub)normal (55.9%); #5: mild T cell-mediated rejection (4.9%); #6: acute antibody-mediated rejection (6.5%); and #7: chronic rejection with DSA (11.4%). Cell infiltrates vary in the archetype. These archetypes were associated with distinct liver biological markers and allograft outcomes. These findings remained consistent when stratified using the patient's age or indications for LT, with good performance in the external cohort (mean highest probability assignment = 0.58, standard deviation ± 0.17). In conclusion, we have identified clinically meaningful archetypes, providing valuable insights into the intricate DSA-histology association, which may help standardize liver allograft pathology classification.

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.

Comparative histological analysis of spleens in pediatric patients with hemolytic anemias: Insights into the pathophysiological mechanisms of spleen destruction in sickle cell anemia.

While sickle cell anemia (SCA) and hereditary spherocytosis (HS) share common features of increased spleen erythrophagocytosis due to increased red blood cell (RBC) turnover, SCA is specifically characterized by susceptibility to infections. In this study, histological lesions in the spleens of pediatric patients with SCA were analyzed, in close correlation with past clinical history and comparatively to HS, healthy and transfused ß-thalassemia patients (TDT). An evaluation of red pulp elementary lesions (red pulp fibrosis, iron deposition, number of Gandy-Gamna, and RBC trapping) combined into a severity score was established, as well as B-cell follicles analysis. Quantification on digitalized slides of iron deposition, RBC trapping, and red pulp fibrosis was additionally performed. Spleens from 22 children with SCA, eight with HS, eight with TDT, and three healthy controls (HC) were analyzed. Median age at splenectomy was not different between SCA and HS patients, 6.05 years (range: 4.5-16.0) versus 4.75 (range: 2.2-9.5). Marked heterogeneity was found in SCA spleens in contrast to other conditions. Contrary to previous reports, B-cell follicles were generally preserved in SCA. While RBC trapping was significantly increased in both SCA and HS (compared to TDT and HC), quantitative fibrosis and overall red pulp severity score were significantly increased in SCA spleens compared to other conditions. Moreover, there was an inverse correlation between quantitative fibrosis and number of B-cell follicles, linking these two compartments as well as spleen fibrosis to infectious susceptibility in SCA, potentially through impaired red pulp macrophage scavenging and B-cell subpopulations defects.

Modern surgical strategies in pediatric neuroblastoma: Evolving approaches and treatment principles.

Neuroblastoma, the most common extracranial solid tumor in children under the age of 5, has been described as early as the 19th century, and its complexity has continued to intrigue researchers, as well as medical and surgical specialists. At one end of the phenotypic spectrum, neuroblastoma is self-limiting with minimal to no intervention required, while on the opposite end exists the challenge of refractory disease despite aggressive management and toxic systemic treatments. The goal of this review is to describe a comprehensive surgical perspective and contemporary approach to neuroblastoma.

Childhood pancreatic neuroendocrine neoplasms: A national experience.

Pancreatic neuroendocrine neoplasms (pNENs) diagnosed in childhood are very rare, with few data available. The aim was to describe the clinical presentation and behavior of children with pNENs at a national level. METHODS: National multicenter retrospective study of all patients, aged from 0 to 17 years at diagnosis, treated from 2011 to 2020 for a pNEN and registered in the French National Registry of Childhood Cancers or FRACTURE database. RESULTS: Fifteen patients, 13 well-differentiated pancreatic neuroendocrine tumors (pNETs) and two neuroendocrine carcinomas (pNECs), were selected. Median age at diagnosis was 14 years (range, 7-17). Eight patients, all with localized disease, had a cancer predisposition syndrome (CPS), including five cases diagnosed during systematic screening. Five (31%) had metastatic disease at diagnosis: three grade 2 pNETs and two pNECs. First line therapy included exclusive pancreatectomy (seven cases, all M0), active surveillance (three cases, all M0), medical therapies (somatostatin analogues, chemotherapy; four cases, all M1), and surgery with medical therapy (one M1 case). Three-year progression-free survival was 57% (confidence interval [CI] 95%: 27-78) and was significantly better for patients with low-grade well differentiated (73 vs. 0%; p < 10-4) and localized (76 vs. 20%; p = .02) tumors. The two patients with pNECs died. Three-year overall survival was 92% (CI95%: 59-99) and was significantly better in patients with low-grade tumor (100 vs. 50%; p = 10-4). CONCLUSION: Childhood pNENs occur more frequently in adolescents with CPS. Localized low-grade pNETs in children have a very good prognosis, whereas the treatment of high-grade and metastatic pNETs/pNECs should be better defined.

A subset of image-defined risk factors predict completeness of resection in children with high-risk neuroblastoma: An international multicenter study.

BACKGROUND: Image-defined risk factors (IDRFs) were promulgated for predicting the feasibility and safety of complete primary tumor resection in children with neuroblastoma (NB). There is limited understanding of the impact of individual IDRFs on resectability of the primary tumor or patient outcomes. A multicenter database of patients with high-risk NB was interrogated to answer this question. DESIGN/METHODS: Patients with high-risk NB (age <20 years) were eligible if cross-sectional imaging was performed at least twice prior to resection. IDRFs and primary tumor measurements were recorded for each imaging study. Extent of resection was determined from operative reports. RESULTS: There were 211 of 229 patients with IDRFs at diagnosis, and 171 patients with IDRFs present pre-surgery. A ≥90% resection was significantly more likely in the absence of tumor invading or encasing the porta hepatis, hepatoduodenal ligament, superior mesenteric artery (SMA), renal pedicles, abdominal aorta/inferior vena cava (IVC), iliac vessels, and/or diaphragm at diagnosis or an overlapping subset of IDRFs (except diaphragm) at pre-surgery. There were no significant differences in event-free survival (EFS) and overall survival (OS) when patients were stratified by the presence versus absence of any IDRF either at diagnosis or pre-surgery. CONCLUSION: Two distinct but overlapping subsets of IDRFs present either at diagnosis or after induction chemotherapy significantly influence the probability of a complete resection in children with high-risk NB. The presence of IDRFs was not associated with significant differences in OS or EFS in this cohort.

The rationale for nephron-sparing surgery in unilateral non-syndromic Wilms tumour.

The central question of nephron-sparing surgery in unilateral non-syndromic Wilms tumour sits at a crossroads between surgery, oncology, and nephrology. There has been a significant paradigm shift in paediatric oncology towards reducing toxicity and addressing long-term treatment-related sequalae amongst childhood cancer survivors. After paediatric nephrectomy and 30-50 years of follow-up, 40% of patients will have chronic kidney disease, including 22% with hypertension and 23% with albuminuria. It is difficult to predict which patients will progress to develop hypertension, reduced glomerular filtration rate, albuminuria, and a higher cardiovascular risk. For these reasons, nephron-sparing surgery when it is technically feasible must be considered. To decrease the incidence of positive surgical margins (viable tumour present at a resection margin), incomplete lymph node sampling, and complications, these procedures should be performed at specialist and experienced reference centres. Based on the impacts of individual treatment pathways, survivors of childhood WT need to be followed through adulthood for early detection of chronic kidney disease, hypertension, and prevention of cardiovascular events.

Targeted therapy in patients with PIK3CA-related overgrowth syndrome.

CLOVES syndrome (congenital lipomatous overgrowth, vascular malformations, epidermal naevi, scoliosis/skeletal and spinal syndrome) is a genetic disorder that results from somatic, mosaic gain-of-function mutations of the PIK3CA gene, and belongs to the spectrum of PIK3CA-related overgrowth syndromes (PROS). This rare condition has no specific treatment and a poor survival rate. Here, we describe a postnatal mouse model of PROS/CLOVES that partially recapitulates the human disease, and demonstrate the efficacy of BYL719, an inhibitor of PIK3CA, in preventing and improving organ dysfunction. On the basis of these results, we used BYL719 to treat nineteen patients with PROS. The drug improved the disease symptoms in all patients. Previously intractable vascular tumours became smaller, congestive heart failure was improved, hemihypertrophy was reduced, and scoliosis was attenuated. The treatment was not associated with any substantial side effects. In conclusion, this study provides the first direct evidence supporting PIK3CA inhibition as a promising therapeutic strategy in patients with PROS.

Radiation-free and injection-free imaging of the paediatric chest using a magnetic resonance imaging protocol including zero time echo sequence (3D-ZTE).

Computed tomography (CT) is commonly used for paediatric thoracic diseases but involves radiation exposure and often requires intravenous contrast. We evaluated the performance of a magnetic resonance imaging (MRI) protocol including a 3D zero echo time (3D-ZTE) sequence for radiation-free and contrast-free imaging of the paediatric chest. In this prospective, single-centre study, children aged 6-16 years underwent chest CT and MRI within 48 h. CT and MRI exams were independently assessed by two paediatric radiologists. The primary outcome was the image quality of the 3D-ZTE sequence using a scoring system based on the acceptability of the images obtained and visibility of bronchial structures, vessels and fissures. Secondary outcomes included radiologists' ability to detect lung lesions on 3D-ZTE MRI images compared with CT images. Seventy-two children were included. Overall, the image quality achieved with the 3D-ZTE MRI sequence was inferior to that of CT for visualising pulmonary structures, with satisfactory lung image quality observed for 81.9% (59/72) and 100% (72/72) of patients, respectively. However, MRI sensitivity was excellent (above 90%) for the detection of certain lesions such as lung consolidation, proximal mucoid impactions, pulmonary cysts, ground glass opacities and honeycombing. Intermodality agreement (MRI versus CT) was consistently higher for the senior reader compared to the junior reader. CONCLUSION: Despite its overall lower image quality compared to CT, and the additional years of experience required for accurate interpretation, the 3D-ZTE MRI sequence demonstrated excellent sensitivity for several lesions, making it an appropriate imaging method in certain indications. WHAT IS KNOWN: • Chest radiography and CT are the main imaging modalities for paediatric thoracic diseases but involve radiation exposure and CT often requires IV contrast. • MRI is promising for radiation-free lung imaging in children but faces challenges of low signal-to-noise ratio and motion artefacts. WHAT IS NEW: • An MRI protocol including a 3D zero echo time (ZTE) sequence allows satisfactory visualisation of lung parenchyma in 82% of children. • Despite overall inferior image quality compared to CT, MRI demonstrated excellent sensitivity for several lesions, making it an appropriate imaging method in certain indications.

Ovarian tissue cryopreservation for fertility preservation before hematopoietic stem cell transplantation in patients with sickle cell disease: safety, ovarian function follow-up, and results of ovarian tissue transplantation.

PURPOSE: To describe the experience of performing ovarian tissue cryopreservation (OTC) before hematopoietic stem cell transplantation (HSCT), among girls/women with severe sickle cell disease (SCD)(SS or S/ß0-thalassemia) who are, besides the usual surgical risk, at risk of SCD-related complications during the fertility preservation procedure for improving their counseling and management. METHODS: This retrospective study included 75 patients (girls/women) with SCD who have had OTC before myeloablative conditioning regimen (MAC) for HSCT. Characteristics of patients and data on OTC, ovarian status follow-up, and results of ovarian tissue transplantation (OTT) were collected in medical records. RESULTS: At OTC, the median (IQR 25-75; range) age of the patients was 9.6 (6.9-14.1; 3.6-28.3) years, 56/75 were prepubertal, and no SCD or surgery-related complications occurred. The median follow-up post-HSCT was > 9 years. At the last follow-up, among prepubertal patients at HSCT, 26/56 were ≥ 15 years old and presented with a premature ovarian insufficiency (POI), except 2, including the patient who had received an OTT to induce puberty. Eight were 13-15 years old and presented for POI. The remaining 22 patients were under 13. Among the 19 patients who were menarche at HSCT, 2 died 6 months post-HSCT and we do not have ovarian function follow-up for the other 2 patients. All the remaining patients (n = 15) had POI. Five patients had OTT. All had a return of ovarian function. One patient gave birth to a healthy baby. CONCLUSION: OTC is a safe fertility preservation technique and could be offered before MAC independent of the patient's age.

Adverse Events and Morbidity in a Multidisciplinary Pediatric Robotic Surgery Program. A prospective, Observational Study.

OBJECTIVE: To report one-year morbidity of robotic-assisted laparoscopic surgery (RALS) in a dedicated, multidisciplinary, pediatric robotic surgery program. Summary Background Data. RALS in pediatric surgery is expanding, but data on morbidity in children is limited. METHODS: All children who underwent RALS (Da Vinci Xi, Intuitive Surgical, USA) were prospectively included (October 2016 to May 2020; follow-up ≥1 year). Analyzed data: patient characteristics, surgical indication/procedure, intraoperative adverse events (ClassIntra classification), blood transfusion, hospital stay, postoperative complications (Clavien-Dindo). RESULTS: Three hundred consecutive surgeries were included: urology/gynecology (n=105), digestive surgery (n=83), oncology (n=66), ENT surgery (n=28), thoracic surgery (n=18). Median age and weight at surgery were 9.5 [interquartile range (IQR)=8.8] years and 31 [IQR=29.3] kg, respectively. Over one year, 65 (22%) children presented with ≥1 complication, with Clavien-Dindo ≥III in 14/300 (5%) children at ≤30 days, 7/300 (2%) at 30-90 days, and 12/300 (4%) at >90 days. Perioperative transfusion was necessary in 15 (5%) children, mostly oncological (n=8). Eight (3%) robotic malfunctions were noted, one leading to conversion (laparotomy). Overall conversion rate was 4%. ASA ≥3, weight ≤15 kg, and surgical oncology did not significantly increase the conversion rate, complications, or intraoperative adverse events (ClassIntra ≥2). ASA score was significantly higher in children with complications (Clavien-Dindo ≥III) than without (p=0.01). Median hospital stay was 2 [IQR=3] days. Three children died after a median follow-up of 20 [IQR=16] months. CONCLUSIONS: RALS is safe, even in the most vulnerable children with a wide scope of indications, age, and weight. Robot-specific complications or malfunctions are scarce.

Pediatric Tumors and Developmental Anomalies: A French Nationwide Cohort Study.

OBJECTIVE: To assess the associations between congenital abnormalities and pediatric malignancies and evaluate the potential underlying molecular basis by collecting information on pediatric patients with cancer and congenital abnormalities. STUDY DESIGN: Tumeur Et Développement is a national, prospective, and retrospective multicenter study recording data of children with cancer and congenital abnormalities. When feasible, blood and tumoral samples are collected for virtual biobanking. RESULTS: From June 2013 to December 2019, 679 associations between pediatric cancers and congenital abnormalities were recorded. The most represented cancers were central nervous system tumors (n = 139; 20%), leukemia and myelodysplastic syndromes (n = 123; 18.1%), and renal tumors (n = 101; 15%). Congenital abnormalities were not related to any known genetic disorder in 66.5% of cases. In this group, the most common anomaly was intellectual disability (22.3%), followed by musculoskeletal (14.2%) and genitourinary anomalies (12.4%). Intellectual disability was mostly associated with hematologic malignancies. Embryonic tumors (neuroblastoma, Wilms tumor, and rhabdomyosarcoma) were associated with consistent abnormalities, sometimes with a close anatomical neighborhood between the abnormality and the neoplasm. CONCLUSIONS: In the first Tumeur Et Développement analysis, 3 major themes have been identified: (1) germline mutations with or without known cancer predisposition, (2) postzygotic events responsible for genomic mosaicism, (3) coincidental associations. New pathways involved in cancer development need to be investigated to improve our understanding of childhood cancers.

Identification of Pediatric Tumors Intraoperatively Using Indocyanine Green (ICG).

BACKGROUND: Fluorescence-guided surgery (FGS) with indocyanine green (ICG) is increasingly applied in pediatric surgical oncology. However, FGS has been mostly reported in case studies of liver or renal tumors. Applying novel technologies in pediatric surgical oncology is more challenging than in adult surgical oncology due to differences in tumor histology, biology, and fewer cases. No consensus exists on ICG-guided FGS for surgically managing pediatric solid tumors. Therefore, we reviewed the literature and discuss the limitations and prospects of FGS. METHODS: Using PRISMA guidelines, we analyzed articles on ICG-guided FGS for childhood solid tumors. Case reports, opinion articles, and narrative reviews were excluded. RESULTS: Of the 108 articles analyzed, 17 (14 retrospective and 3 prospective) met the inclusion criteria. Most (70.6%) studies used ICG to identify liver tumors, but the timing and dose of ICG administered varied. Intraoperative outcomes, sensitivity and specificity, were reported in 23.5% of studies. Fluorescence-guided liver resections resulted in negative margins in 90-100% of cases; lung metastasis was detected in 33% of the studies. In otolaryngologic malignancies, positive margins without fluorescence signal were reported in 25% of cases. Overall, ICG appeared effective and safe for lymph node sampling and nephron-sparing procedures. CONCLUSIONS: Despite promising results from FGS, ICG use varies across the international pediatric surgical oncology community. Underreported intraoperative imaging outcomes and the diversity and rarity of childhood solid tumors hinder conclusive scientific evidence supporting adoption of ICG in pediatric surgical oncology. Further international collaborations are needed to study the applications and limitations of ICG in pediatric surgical oncology.

Retrospective evaluation of clinical and molecular data of 148 cases of esophageal atresia.

Developmental abnormalities provide a unique opportunity to seek for the molecular mechanisms underlying human organogenesis. Esophageal development remains incompletely understood and elucidating causes for esophageal atresia (EA) in humans would contribute to achieve a better comprehension. Prenatal detection, syndromic classification, molecular diagnosis, and prognostic factors in EA are challenging. Some syndromes have been described to frequently include EA, such as CHARGE, EFTUD2-mandibulofacial dysostosis, Feingold syndrome, trisomy 18, and Fanconi anemia. However, no molecular diagnosis is made in most cases, including frequent associations, such as Vertebral-Anal-Cardiac-Tracheo-Esophageal-Renal-Limb defects (VACTERL). This study evaluates the clinical and genetic test results of 139 neonates and 9 fetuses followed-up at the Necker-Enfants Malades Hospital over a 10-years period. Overall, 52 cases were isolated EA (35%), and 96 were associated with other anomalies (65%). The latter group is divided into three subgroups: EA with a known genomic cause (9/148, 6%); EA with Vertebral-Anal-Cardiac-Tracheo-Esophageal-Renal-Limb defects (VACTERL) or VACTERL/Oculo-Auriculo-Vertebral Dysplasia (VACTERL/OAV) (22/148, 14%); EA with associated malformations including congenital heart defects, duodenal atresia, and diaphragmatic hernia without known associations or syndromes yet described (65/148, 44%). Altogether, the molecular diagnostic rate remains very low and may underlie frequent non-Mendelian genetic models.

A Novel Standard for Systematic Reporting of Neuroblastoma Surgery: The International Neuroblastoma Surgical Report Form (INSRF): A Joint Initiative by the Pediatric Oncological Cooperative Groups SIOPEN∗, COG∗∗, and GPOH∗∗∗.

OBJECTIVE: To create the first structured surgical report form for NBL with international consensus, to permit standardized documentation of all NBL-related surgical procedures and their outcomes. SUMMARY OF BACKGROUND DATA: NBL, the most common extracranial solid malignant tumor in children, covers a wide spectrum of tumors with significant differences in anatomical localization, organ or vessel involvement, and tumor biology. Complete surgical resection of the primary tumor is an important part of NBL treatment, but maybe hazardous, prone to complications and its role in high-risk disease remains debated. Various surgical guidelines exist within the protocols of the different cooperative groups, although there is no standardized operative report form to document the surgical treatment of NBL. METHODS: After analyzing the treatment protocols of the SIOP Europe International Neuroblastoma Study Group, Children's Oncology Group, and Gesellschaft fuer Paediatrische Onkologie und Haematologie - German Association of Pediatric Oncology and Haematology pediatric cooperative groups, important variables were defined to completely describe surgical biopsy and resection of NBL and their outcomes. All variables were discussed within the Surgical Committees of SIOP Europe International Neuroblastoma Study Group, Children's Oncology Group, and Gesellschaft fuer Paediatrische Onkologie und Haematologie - German Association of Pediatric Oncology and Haematology. Thereafter, joint meetings were organized to obtain intercontinental consensus. RESULTS: The "International Neuroblastoma Surgical Report Form" provides a structured reporting tool for all NBL surgery, in every anatomical region, documenting all Image Defined Risk Factors and structures involved, with obligatory reporting of intraoperative and 30 day-postoperative complications. CONCLUSION: The International Neuroblastoma Surgical Report Form is the first universal form for the structured and uniform reporting of NBL-related surgical procedures and their outcomes, aiming to facilitate the postoperative communication, treatment planning and analysis of surgical treatment of NBL.

Predicting Factors of Protracted Intestinal Failure in Children with Gastroschisis.

OBJECTIVE: To identify prenatal and neonatal predictors of short bowel syndrome-related intestinal failure (SBS-IF) in gastroschisis. STUDY DESIGN: This retrospective study included all patients with gastroschisis born between 2000 and 2017 who were enrolled in our home parenteral nutrition program, and all patients with gastroschisis born in our institution who survived 2 weeks, during the same time period. Prenatal ultrasound features, neonatal status, anatomic features, oral feeding, and parenteral nutrition dependency were analyzed. RESULTS: Among 180 patients, 35 required long-term parenteral nutrition (SBS-IF group) and 145 acquired full oral feeding within 6 months (oral feeding group). The mean follow-up was 7.9 years (IQR, 1.6-17.5 years) and 5.0 years (IQR, 0.1-18.2 years), respectively. Both bowel matting (OR, 14.23; 1.07-16.7; P = .039) and secondarily diagnosed atresia or stenosis (OR, 17.78; 3.13-100.98; P = .001) were independent postnatal predictors of SBS-IF. Eighteen children (51% of the SBS-IF group) were still dependent on artificial nutrition at the last follow-up. patients with SBS-IF who achieved full oral feeding had a median residual small-bowel length of 74 cm (IQR, 51-160 cm) vs 44 cm (IQR, 10-105 cm) for those still dependent on artificial nutrition (P = .02). An initial residual small bowel length of more than 50 cm was the best predictive cut-off for nutritional autonomy, with a sensitivity of 67% and a specificity of 100%. CONCLUSIONS: Bowel matting, complex gastroschisis, and secondary intestinal obstruction were associated with SBS-IF in gastroschisis. For patients with SBS-IF, a small bowel length of more than 50 cm was predictive of secondary nutritional autonomy.

Robotic Surgery in Pediatric Oncology: Lessons Learned from the First 100 Tumors-A Nationwide Experience.

BACKGROUND: While robotics has become commonplace in adult oncology, it remains rare in pediatric oncology due to the rarity of childhood cancers. We present the results of a large nationwide experience with robotic oncology, with the aim of providing practical and feasible guidelines for child selection. METHODS: This was a prospective analysis performed over a period of 4 years. Treatment was delivered according to the Société Internationale d'Oncologie Pédiatrique/International Society of Paediatric Oncology Europe Neuroblastoma Group (SIOP/SIOPEN) protocols. Indications were approved by a certified tumor board. RESULTS: Overall, 100 tumors were resected during 93 procedures (abdomen, 67%; thorax, 17%; pelvis, 10%; retroperitoneum, 6%) in 89 children (56 girls). The median age at surgery was 8.2 years (range 3.6-13); 19 children (21%) harbored germinal genetic alterations predisposing to cancer. No intraoperative tumor ruptures occurred. Seven conversions (8%) to an open approach were performed. Neuroblastic tumors (n = 31) comprised the main group (18 neuroblastomas, 4 ganglioneuroblastomas, 9 ganglioneuromas) and renal tumors comprised the second largest group (n = 24, including 20 Wilms' tumors). The remaining 45 tumors included neuroendocrine (n = 12), adrenal (n = 9), germ-cell (n = 7), pancreatic (n = 4), thymic (n = 4), inflammatory myofibroblastic (n = 4), and different rare tumors (n = 5). Overall, 51 tumors were malignant, 2 were borderline, and 47 were benign. The median hospital stay was 3 days (2-4), and five postoperative complications occurred within the first 30 days. During a median follow-up of 2.4 years, one child (Wilms' tumor) presented with pleural recurrence. One girl with Wilms' tumor died of central nervous system metastasis. CONCLUSIONS: Robotic surgery for pediatric tumors is a safe option in highly selected cases. Indications should be discussed by tumor boards to avoid widespread and uncontrolled application.

Prognostic impact of pulmonary nodules diagnosed at initial presentation in patients with osteosarcoma.

BACKGROUND: Resection of all lung metastases in patients with osteosarcoma improves survival. The increased computed tomography (CT) scan quality allows detecting smaller nodules. We aimed to evaluate the prognostic impact of those nodules that do not meet the classical criteria for lung metastases. METHODS: A central radiology review (CRR) on lung CT scans performed during the treatment of patients included in OS2006 trial and treated with a high-dose methotrexate-based chemotherapy from 2007 to 2013 was realized in three centers. RESULTS: At trial enrollment, among 77 patients, six (8%) had nodules meeting the trial's criteria for metastatic disease, 46 (60%) were classified as having localized disease, and 25 (32%) as having doubtful nodules. After CRR, 218 nodules were found at diagnosis (all in patients classified as "metastatic or doubtful" and 13 patients classified as "localized") (median two nodules per patient [1-52]). The 5-year event-free survival/overall survival (EFS/OS) of patients with at least one nodule versus no nodule were similar (67.7%/79.2% vs. 81.8%/91%). After histological analysis, two of 46 (4.3%) "localized" and eight of 25 (32.0%) "doubtful" patients were re-classified as "metastatic," whereas there was no change in patients initially "metastatic." The 5-year OS of confirmed histological metastatic versus nonmetastatic patients were different (56% vs. 92%, p < .01). CONCLUSION: Central review of lung CT scan increased the detection of nodules in osteosarcoma. Patients with small lung nodules classified as doubtful had a quite similar outcome as those with a localized disease. However, patients with confirmed metastatic nodules have a poorer prognosis, even if considered as "localized" at diagnosis.

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.