Paediatric oncology surgeons play a crucial role in diagnosing, staging, and treating malignant solid tumors. In recent years, many solid tumour protocols have advocated for a more tailored surgical approach to both the primary tumour site and metastatic disease. The integration of Minimally Invasive Surgery (MIS) into paediatric oncology practice has gained popularity over the past few decades. While the benefits of MIS are well established in non-oncologic surgery, its role in paediatric solid tumours is still evolving and, in many cases, lacks high-quality evidence. These IPSO-MIS guidelines guidelines aim to provide practical surgical recommendations for diverse clinical scenarios, addressing the needs of both High-Income Countries (HICs) and Low- and Middle-Income Countries (LMICs). The contributing authors represent both settings, ensuring a comprehensive and inclusive perspective. We hope that these guidelines will contribute to improving outcomes for children with cancer worldwide. Israel Fernandez-Pineda, IPSO Education Committee Chair Abdelhafeez H Abdelhafeez, IPSO Education Committee Member.

Background The Kasai portoenterostomy (KPE) is the only option to achieve native liver survival for patients with biliary atresia and yet technical variations exist. We surveyed members of three American pediatric surgery research consortia regarding their approach to the KPE. Methods Members from the Eastern Pediatric Surgery Network (EPSN), Midwestern Pediatric Surgery Consortium (MWPSC), and Western Pediatric Surgery Research Consortium (WPSRC) developed the survey which was distributed via REDCap to consortia member institutions. Results The survey was completed by 44/45 institutions. KPE is performed by pediatric surgeons at 41 sites (93%), a transplant surgeon at one (2%), and both at two (5%). Twenty-six sites (59%) transected into the liver capsule, 10 (23%) into the liver, two (5%) into the fibrous cord, and 6 (14%) reported variance. One site (2%) reported use of cautery in addition to sharp dissection for porta hepatis transection. The most common length for the Roux limb was 25-35 cm (16, 36%), with 14 sites (32%) creating a Roux limb < 25 cm, eight sites (18%) > 35 cm, and 6 sites (14%) responding that length varies between surgeons. Surgical diagnosis with intraoperative cholangiogram (IOC) was always performed at 33 sites (75%), and twenty-eight sites (64%) obtain both preoperative percutaneous and intraoperative biopsies. Two sites (5%) offer partially laparoscopic KPE. Conclusion In the first survey of American surgical practices for KPE, we found consensus regarding some technical aspects of the operation. However, the responses to most questions demonstrated variability. Future studies will analyze how technical variations impact national KPE outcomes.

ABSTRACTBackgroundLiver transplantation is the standard therapy for end‐stage liver disease in pediatric patients with biliary atresia (BA), congenital and metabolic conditions, and for an unresectable malignant tumor like hepatoblastoma (HB). BA is the leading indication for pediatric liver transplantation, while HB is the most common childhood liver cancer. Despite improved outcomes through advanced surgical techniques and novel immunosuppression, pediatric liver transplantation (pLT) is complicated by post‐transplant infections.MethodsA retrospective review was performed of pLT recipients at Cincinnati Children's Hospital Medical Center (CCHMC) and stratified patients by underlying disease to assess impact on post‐transplant infectious events.ResultsBA patients were youngest at pLT (12.5 months; p < 0.001) compared to other disease cohorts (HB 30.8, other 43.7). All HB patients received organs from deceased donors. In the year following pLT, 93% of the patients experienced at least one infectious event (IE). HB patients had the highest mean number of IE across disease groups (5.5 IE/patient vs. BA 4.5, other 4.0; p = 0.055), with significantly more patients with fever and neutropenia (p < 0.001) and EBV infections (p = 0.012). HB patients were more likely to develop IE earlier after pLT than non‐HB groups (p = 0.013), especially Clostridioides difficile (p < 0.01) and fever and neutropenia (p < 0.01). Despite having variable IE experiences, 1‐and‐5‐year survival across disease groups were similar.ConclusionsIE were frequently observed in HB patients after pLT, possibly related to pre‐and‐postoperative chemotherapy and associated neutropenia. Underlying disease may help inform targeted infection‐related patient management following pLT.

Solid tumors with vascular involvement in pediatric patients are challenging to address. They are rare with limited data to guide treatment recommendations. Multidisciplinary management with a pediatric oncologist, pediatric surgeon, vascular surgeon and on occasion cardiac surgeon is paramount. Below, we review the scope of this problem in specific for treatment of Wilms tumor, hepatoblastoma, hepatocellular carcinoma, neuroblastoma, and sarcoma with involvement of the adjoining major vascular structures. Included in this manuscript is the role of vascular reconstruction principles as it applies to pediatric patients. We highlight the importance of individualized treatment plans taking into consideration the nature of the tumor, histology, and extent of disease; the role of neoadjuvant therapy in minimizing extent of resection; and discuss the variety of options that exist for vascular reconstruction.

Malignant liver tumors affecting children and adolescents are rare. In order to adequately study liver tumors occurring in this patient population and establish a more uniform approach to therapy, the three primary liver tumor consortia, SIOPEL (mainly European), COG (mainly North American) and JCCG (Japan), in concert, designed an international prospective clinical trial [PHITT (Paediatric Hepatic International Tumour Trial)/COGAHEP1531/JPLT4 – to be referred to as PHITT from this point forth] for the study of hepatoblastoma and hepatocellular carcinoma in children and adolescents. Recruitment to PHITT has recently concluded. The major results from this trial will be published in the next 2–3 years, therefore in the interim, we sought to provide a consensus statement on evidence-based chemotherapy guidance for hepatoblastoma and hepatocellular carcinoma of all stages.

OBJECTIVE:Chronic pancreatitis (CP) and acute recurrent pancreatitis (ARP) cause significant morbidity in pediatric patients and may be candidates for total pancreatectomy with islet auto-transplantation (TPIAT). We examined opioid use and pain outcomes in a large cohort of pediatric patients post-TPIAT at a single institution. METHODS:Prospective data was collected from 105 pediatric patients from 2015 to 2023 with at least 12 months post-operative data available, up to 5 years. Number of patients at each time point dependent on time from surgery, with median time point 36 months post-TPIAT (70.5 % of patients). RESULTS:Opioid use significantly decreased from 55 % of patients pre-TPIAT (58/105) to 4 % at 12 months post-TPIAT (4/103, p < 0.001), sustained over time with no patients requiring opioids at 60 months (0/23). 60 % of patients with abdominal pain pre-TPIAT (93/105) reported complete resolution of pain at 3 months (48/102, p < 0.001), with downtrend over time, sustained through 60 months (4/25, 16 %). SF-36 physical component summary and SF-10 physical health and psychosocial summaries showed significant improvement over time post-TPIAT (p < 0.0001). Univariable analysis showed no significant association between post-TPIAT opioid use at 12 months and age at TPIAT, gender, duration from first pancreatitis attack to TPIAT, number of endoscopic retrograde cholangiopancreatographies pre-TPIAT, or diagnosis of CP. PRSS1 mutation more likely to have resolution of abdominal pain at 12 months (p = 0.005). CONCLUSIONS:Utilizing a standardized multidisciplinary approach to TPIAT in pediatric patients with pancreatitis showed significant decreases in opioid use and abdominal pain, regardless of severity of disease, pain, or opioid use pre-TPIAT.

Hepatoblastoma (HB) is the most common pediatric liver malignancy. However, its cellular origin and molecular drivers remain poorly defined. Using single-nuclear RNA sequencing (snRNA-seq), we identified a proliferative, hepatocyte-derived tumor cell population (cycling HepT) enriched for Enhancer of Zeste Homolog 2 (EZH2) expression, particularly in the aggressive embryonal subtype. Integrative genomic and transcriptomic profiling confirmed EZH2 overexpression. Disruption of the PRC2 complex was evident through mislocalization and reduced expression of SUZ12, a core component. EZH2 overexpression correlated with upregulation of mitotic regulators such as AURKB and Ki67 in human HB gene expression analysis as compared to background liver. Targeted sequencing identified variants of uncertain significance in EZH2 and SUZ12 in 11 of 11 patient tumors. Pharmacologic inhibition of EZH2 with EPZ-6438 reduced proliferation and sensitized HB cells to cisplatin through gene regulation, potentially modulating platinum accumulation both in vitro and in vivo. In summary, EZH2 promotes HB progression through epigenetic silencing and noncanonical signaling pathways. These findings support EZH2's contribution to HB pathogenesis, therefore identifying it as a novel therapeutic target.

Minimally invasive surgical techniques are increasingly adopted for the management of hepatic masses in children. Laparoscopic liver biopsy can be used to obtain tissue diagnosis while avoiding the risks of open surgery and providing improved cosmesis. Laparoscopic or robotic liver resection has more gradually been adopted in children than in adults but can be utilized for appropriately located tumours as long as oncologic principles are maintained. Patient size is a factor when choosing whether to perform liver resection via a minimally invasive approach. Laparoscopic radiofrequency ablation offers an alternative strategy to surgery for paediatric patients with small masses or can serve as a bridge to transplant.

Purpose: Early Kasai portoenterostomy (KPE) for infants with biliary atresia (BA) increases the chance of transplant-free survival (TFS). However, early timing of KPE is not consistently achieved in the United States. Clearance of jaundice at three months is predictive of TFS. Among a cohort of patients with BA, we investigated institutional variability in the initiation of hyperbilirubinemia evaluation and operative timing to identify factors associated with successful jaundice clearance. Methods: A multi-institutional, retrospective study was performed at eleven U.S. tertiary children's hospitals. Infants diagnosed with BA between 10/1/2015-10/1/2020 were identified. Age at initiation of diagnostic workup and age at KPE were collected. Adjusted multivariable logistic regression was used to determine factors associated with direct bilirubin normalization at three months following KPE. Results: In 161 infants, the median age at initiation of jaundice evaluation was 35 days (IQR 8-60). Among 148 patients who underwent KPE, median age at surgery was 53 days (IQR 37.3-67.5). Each 10day increase in age at KPE was associated with a 18.8 % decrease in odds of normalizing bilirubin at three months (OR 0.81, 95 % CI 0.66-0.99), with infants who underwent KPE <50 days significantly more likely to normalize bilirubin (OR 2.6, CI 1.1-6.1) compared to KPE >50 days. There was significant variation among institutions in the time from initiation of workup to KPE (range 0-24.5 days, p = 0.02) and the odds of patients normalizing direct bilirubin at three months (range 0.04-0.89, p = 0.044). Conclusion: Our results confirmed that increasing age at KPE decreases the odds of clearing bilirubin at three months post-KPE. We identified significant institutional variability in the time from workup to KPE that may have impacted the likelihood of successful biliary drainage. Level of Evidence: IV (Well-designed case-control or cohort study). (c) 2025 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and

Background/Purpose: Studies have demonstrated existing racial and ethnic disparities in multiple aspects of pediatric oncology. The purpose of this study was to examine how racial and ethnic disparities in mortality among pediatric oncology patients have changed over time. We examined mortality by race and ethnicity over time within the Surveillance, Epidemiology, and End Results (SEER) registry. Methods: Patients <20 years-old from 1975 to 2016 (n = 49,861) were selected for the analysis. Demographic characteristics, cancer diagnosis, and mortality data were extracted. Patients were divided by race and ethnicity: 1) non-Latino White, 2) Black, 3) Latino, and 4) Other Race. The interaction between race/ethnicity and decade was evaluated to better understand how disparities in mortality have changed over time. Results: Unadjusted mortality among all cancers improved significantly, with 5-year mortality decreasing from the 1970s to the 2010s (log-rank: p < 0.001) for all race/ethnicity groups. However, improvements in mortality were not equal, with 5-year overall survival (OS) improving from 62.7 % in the 1970s to 87.5 % (Delta = 24.8 %) in the 2010s for White patients but only improving from 59.9 % to 80.8 % (Delta = 20.9 %) for Black patients (p < 0.01). The interaction between Race/Ethnicity and decade demonstrated that the Hazard Ratio (HR) for mortality worsened for Black [HR (95 % Confidence Interval): 1.10 (1.05-1.15) and Latino [1.11 (1.07-1.17)] patients compared to White, non-Latino patients. Conclusion: There has been a dramatic improvement in survival across pediatric oncology patients since 1975. However, the improvement has not been shared equally across racial/ethnic categories, with overall survival worsening over time for racial/ethnic minorities compared to White patients. Level of Evidence: III. (c) 2024 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

BACKGROUND:Acute Recurrent Pancreatitis (ARP) and Chronic Pancreatitis (CP) may cause abdominal pain, malnutrition, opioid dependency, and impairment in quality of life. Total Pancreatectomy with Islet Autotransplantation (TPIAT) is an option when other measures fail. Pancreatitis gastroparesis can be potentiated by surgery. Botulinum toxin (BT) injections into the pylorus have been used in children for gastroparesis. We evaluated outcomes of pyloric injection of BT for TPIAT in children. METHODS:Retrospective cohort of children who underwent TPIAT (2021-2023). Twenty with-BT and 20 without-BT were evaluated for time to achieve full oral nutrition, percent weight change at discharge, days with emesis through post op day 14 (POD14), days when gastrostomy tube (G) required drainage for vomiting through POD14, length of stay (LOS). We hypothesized that pyloric BT during TPIAT would decrease post-operative gastroparesis symptoms. RESULTS:CP diagnosis present in 80 % of with-BT & 65 % of the without-BT patients. The groups were similar by sex (with-BT, 45 % male vs 50 % in without-BT). With-BT patients had fewer days to full PO (29.4 (18.3) vs. 40.9 (15.9), p < 0.01), and fewer G tube days (mean 7.2 SD (2.6) vs 10.1(3.4)) (p < 0.01) but no significant difference in emesis days (2.7 (2.8) vs 4.2 (2.9)) (p = 0.21), percent weight change at discharge (-2.9 % (2.7) vs. -4.6 % (2.7)) (p = 0.07) and LOS (median 15.5 IQR(14-16.5) vs. 16 (13.5-19)) (p = 0.46). CONCLUSION:Pyloric BT may improve postoperative gastroparesis symptoms among pediatric patients undergoing TPIAT. To our knowledge, this is the first pediatric study evaluating morbidity associated with gastroparesis after TPIAT in an already high-risk population due to ARP or CP. TYPE OF STUDY:Retrospective Cohort Study LEVEL OF EVIDENCE: III.

The Kasai portoenterostomy (KPE) can provide a surgical cure for children with biliary atresia (BA), without the need for a liver transplant (OLTxp). Revision KPE can be attempted following a failed initial KPE where biliary clearance is not achieved. The most common indications for revision KPE are recurrent jaundice or recurrent cholangitis, although it has also been performed for persistent jaundice or bile lakes. Outcomes are heterogenous but the best results appear to be with recurrent jaundice or limited episodes of recurrent cholangitis. In the setting of a failed KPE, providers must make a patient-specific decision about whether to attempt revision KPE versus proceed with OLTxp. While the choice is multifactorial, patients who undergo revision KPE likely do not have worse long-term outcomes than patients who undergo a single KPE.

Temporal trends demonstrate improved survival for many types of common pediatric cancer. Studies have not examined improvement in very rare pediatric cancers or compared these improvements to more common cancers. In this cohort study of the Surveillance, Epidemiology, and End Results (SEER) registry, we examined patients from 1975 to 2016 who were 0-19 years of age at the time of diagnosis. Cancers were grouped by decade of diagnosis and 3 cancer frequency groups: Common, Intermediate, and Rare. Trends in mortality across decades and by cancer frequency were compared using Kaplan-Meier curves and adjusted Cox proportional hazards models. A total of 50,222 patients were available for analysis, with the top 10 cancers grouped as Common (67%), 13 cancers grouped with Intermediate (24%), and 37 cancers as Rare (9%). Rare cancers had higher rates of children who were older and Black. 5-year survival increased from 63% to 86% across all cancers from the 1970s to the 2010s. The hazard ratio (HR) for mortality decreased from the reference point of 1 in the 1970s to 0.27 (95% CI: 0.25-0.30) in the 2010s in Common cancers, while the HR only dropped to 0.60 (0.49-0.73) over that same period for rare cancers. Pediatric oncology patients have experienced dramatic improvement in mortality since the 1970s, with mortality falling by nearly 75% in common cancers. Unfortunately, rare pediatric cancers continue to lag behind more common and therefore better studied cancers, highlighting the need for a renewed focus on research efforts for children with these rare diseases.

Fibrosing cholangiopathies, including biliary atresia and primary sclerosing cholangitis, involve immune-mediated bile duct epithelial injury and hepatic bile acid (BA) retention (cholestasis). Regulatory T-cells (Tregs) can prevent auto-reactive lymphocyte activation, yet the effects of BA on this CD4 lymphocyte subset are unknown. Gene regulatory networks for hepatic CD4 lymphocytes in a murine cholestasis model revealed Tregs are polarized to Th17 during cholestasis. Following bile duct ligation, Stat3 deletion in CD4 lymphocytes preserved hepatic Treg responses. While pharmacological reduction of hepatic BA in MDR2-/- mice prompted Treg expansion and diminished liver injury, this improvement subsided with Treg depletion. A cluster of patients diagnosed with biliary atresia showed both increased hepatic Treg responses and improved 2-year native liver survival, supporting that Tregs might protect against neonatal bile duct obstruction. Together, these findings suggest liver BA determine Treg function and should be considered as a therapeutic target to restore protective hepatic immune responses.

BACKGROUND:Undifferentiated embryonal sarcoma of the liver (UESL) is a rare tumor for which there are few evidence-based guidelines. The aim of this study was to define current management strategies and outcomes for these patients using a multi-institutional dataset curated by the Pediatric Surgical Oncology Research Collaborative.METHODS:Data were collected retrospectively for patients with UESL treated across 17 children's hospitals in North America from 1989 to 2019. Factors analyzed included patient and tumor characteristics, PRETEXT group, operative details, and neoadjuvant/adjuvant regimens. Event-free and overall survival (EFS, OS) were the primary and secondary outcomes, respectively.RESULTS:Seventy-eight patients were identified with a median age of 9.9 years [interquartile range [IQR): 7-12]. Twenty-seven patients underwent resection at diagnosis, and 47 patients underwent delayed resection, including eight liver transplants. Neoadjuvant chemotherapy led to a median change in maximum tumor diameter of 1.6 cm [IQR: 0.0-4.4] and greater than 90% tumor necrosis in 79% of the patients undergoing delayed resection. R0 resections were accomplished in 63 patients (81%). Univariate analysis found that metastatic disease impacted OS, and completeness of resection impacted both EFS and OS, while multivariate analysis revealed that R0 resection was associated with decreased expected hazards of experiencing an event [hazard ratio (HR): 0.14, 95% confidence interval (CI): 0.04-0.6]. At a median follow-up of 4 years [IQR: 2-8], the EFS was 70.0% [95% CI: 60%-82%] and OS was 83% [95% CI: 75%-93%].CONCLUSION:Complete resection is associated with improved survival for patients with UESL. Neoadjuvant chemotherapy causes minimal radiographic response, but significant tumor necrosis.

Liver histology in infants with cystic fibrosis (CF) and persistent cholestasis is seldom reported in detail. We extend previous observation of a distinctive intrahepatic cholangiopathy (ICCF) to 3 additional infants homozygous for CFTR pathological variants and a fourth infant with a heterozygous CFTR variant, summarizing our experience in 10 infants with CFTR variants and persistent cholestasis. Cholangiograms demonstrate abnormal extrahepatic ducts in 2 infants with CF, 1 with uniform dilatation interpreted as a choledochal cyst and the other with narrow patent ducts. Liver histology in 3 CF homozygotes had prominent ductular reaction with a focally destructive cholangiolitis (inflammation of small bile ducts). The CFTR heterozygote had generalized portal edema with ductular reaction and paucity but no cholangitis. Cholestasis slowly subsided in all infants. ICCF is characterized by severe ductular reaction, prominent cholangiocyte injury, and multifocal necrotizing cholangiolitis. Local aggregates of portal ceroid might suggest previous bile leakage from damaged ducts. ICCF in liver biopsies from infants with cystic fibrosis and persistent cholestasis is unrelated to the specific CFTR genotype. Liver biopsy findings and intraoperative cholangiogram help rule out biliary atresia. ICCF is an early manifestation of CF, a likely prototype for pathogenesis of cystic fibrosis liver disease later in life.