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Up to a third of children undergoing partial hepatectomy for primary hepatic malignancies experience at least one perioperative complication, with a presumed deleterious effect on both short- and long-term outcomes. We implemented a multidisciplinary treatment protocol in the management of these patients in order to improve complication rates following partial hepatectomy.A retrospective chart review was completed for all patients 18 years of age who underwent liver resection at our institution between 2002 and 2019 for primary hepatic cancer. Demographic, intraoperative, postoperative, pathologic, and outcome data were analyzed for perioperative complications using the CLASSIC and Clavien-Dindo (CD) scales, event-free survival (EFS) and overall survival (OS).A total of 73 patients were included in the analysis with 33 prior-to and 40 after dedicated provider protocol implementation. Perioperative complication rates decreased from 52% to 20% (p = 0.005) with major complications going from 18% to 10% (p = 0.31). On multivariable logistic regression, protocol implementation was associated with a reduction in any (OR 0.29 [95% CI 0.09 - 0.89]) but not major complications. On multivariate cox models, post protocol implementation was associated with improved event free survival (EFS) (HR 0.19 (0.036 - 0.195). Among patients with a diagnosis of hepatoblastoma (n = 62), the occurrence of a major perioperative complication was associated with a worse EFS (HR=5.45, p = 0.03) on multivariate analysis, however this did not translate into an impact on overall survival.Our results demonstrate that, for children with primary liver malignancies, a dedication of patients to high-volume surgeons can improve rates of complications of liver resections and may improve the oncological outcome of hepatoblastoma.

Purpose Hepatoblastoma (HB) and hepatocellular carcinoma (HCC) are the most common primary malignant tumors of childhood. Intraoperative indocyanine green (ICG) administration with near-infrared imaging (NIR) has emerged as a surgical technology that can be used to assist with localization of pulmonary metastases secondary to HB; however, there has been limited application as an adjunct for resection of the primary liver tumor and assessment of extrahepatic disease. Methods We present 14 patients treated for HB, HCC, and malignant rhabdoid tumor at our institution with the use of intraoperative NIR-ICG guidance. All patients were treated with 0.2–0.75 mg/kg IV ICG, 48–96 h prior to surgery. Intraoperative NIR-ICG guided imaging was performed with several commercial devices. Results Intraoperative NIR-ICG guidance allowed pulmonary metastasectomy in five patients using thoracoscopy or thoracotomy allowing for visualization of multiple nodules not seen on preoperative imaging most of which were positive for malignancy. NIR-ICG guidance allowed for assessment of extrahepatic extension in three patients; an HCC patient with extrahepatic lymph node extension of disease, an HB patient with extrapulmonary thoracic recurrence in the diaphragm and chest wall, and a patient with tumor rupture at diagnosis with peritoneal nodules at the time of surgery. This technique was used to guide partial hepatectomy in 11 patients for which the technique enabled successful identification of tumor and tumor margins. Three patients had nonspecific staining of the liver secondary to decreased timing from ICG injection to surgery or biliary obstruction. NIR-ICG enabled resection of satellite HB lesions in three multifocal patients and confirmed a benign satellite lesion in two additional patients. Conclusions Intraoperative use of NIR-ICG imaging during partial hepatectomy enabled enhanced identification and guidance for surgical resection of extrahepatic disease and multifocal liver tumors for the treatment of children with primary liver cancer.

This cohort study examines resident involvement in the care of US veterans who underwent noncardiac surgery.

Introduction The Nuss procedure is the most common and preferred operative correction of pectus excavatum. Surgeon preference and patient factors can result in variations in Nuss procedure technique. We hypothesize that certain techniques are associated with increased risk of complications. Materials and Methods We performed a single-center retrospective review of Nuss operations from 2016 to 2020. Variations in intraoperative techniques included sternal elevator (SE) use, number of bars placed, and usage of bilateral stabilizing sutures. Patient demographics, intraoperative data, and postoperative outcomes were reported as median with interquartile ranges or percentages. Statistical significance (p Results Two hundred and sixty-five patients were identified. Patients repaired with two bars were older with a larger Haller index (HI). Patient demographics were not significantly different for SE or stabilizing suture use. Placement of two bars was associated with significantly increased risk of readmission. Similarly, SE use was associated with increased risk of pleural effusion and readmission. Finally, the use of bilateral stabilizing sutures resulted in less frequent slipped bars without statistical significance. Conclusion Older patients with a larger HI were more likely to need two bars placed to repair pectus excavatum. Placement of multiple bars and SE use are associated with significantly higher odds of certain complications.

Sirolimus has demonstrated effectiveness as a treatment option for several types of vascular anomalies; however, it has a potential side effect of delayed surgical wound healing. The purpose of this study was to evaluate the association of sirolimus with postoperative complications in the pediatric vascular anomaly population.A retrospective cohort study was performed for children with a vascular anomaly who underwent excision or debulking of the anomaly from 2015 to 2020. Patient demographics, vascular anomaly characteristics, operative variables, sirolimus dosing information, and perioperative outcomes were collected. Univariate analysis was performed to compare outcomes based on the administration of sirolimus.Forty-seven patients with vascular anomalies underwent 57 surgical procedures (36 without perioperative sirolimus, 21 with perioperative sirolimus). The median age at the time of surgery was seven years (IQR 1.7-14.0). The most common anomalies were lymphatic and venolymphatic malformations. Of the patients administered perioperative sirolimus, the median preoperative and postoperative sirolimus levels were comparable (preoperative 6.9 ng/mL (IQR 4.9-10.1), postoperative 6.5 ng/mL (IQR 4.7-9.4)). The rate of postoperative complications (sirolimus 19%, without sirolimus 11%; p = 0.45) and wound complications (sirolimus 14%, without sirolimus 6%; p = 0.26) were comparable between the cohorts.Our results suggest sirolimus may not significantly increase perioperative complication rates in pediatric patients undergoing resection of their vascular anomaly.Level III.

Pancreatic angiosarcoma is an exceedingly rare malignancy accounting for

Background Children with unresectable hepatocellular carcinoma (HCC) have a poor prognosis and limited treatment options. Transarterial radioembolization (TARE) using Yttrium-90 (Y90) has emerged as a potential bridge therapy to hepatic resection or transplantation for HCC with very limited studies in children. Observations Here we present the clinical course of 2 children successfully treated with TARE Y90 for initially unresectable fibrolamellar HCC (FL-HCC) and bridged to partial hemihepatectomy with >1-year overall survival post-TARE. Conclusion Although there have been prior published reports of pediatric patients with HCC being treated with TARE Y90 and some being able to undergo subsequent orthotopic liver transplantation, this is the first report of pediatric HCC patients treated with TARE Y90 as a bridge to nontransplant resections and going on to have >1-year overall survival.

Crawford extent II repairs are the most extensive thoracoabdominal aortic aneurysm operations and pose the greatest risk of postoperative spinal cord deficit. We sought to examine spinal cord deficit after open extent II thoracoabdominal aortic aneurysm repair to identify predictors of the most serious type: persistent paraplegia or paraparesis.We included 1114 extent II thoracoabdominal aortic aneurysm repairs performed from 1991 to 2017. Intercostal/lumbar artery reattachment (n = 959, 86.1%) and cerebrospinal fluid drainage (n = 698, 62.7%) were used to mitigate the risk of postoperative spinal cord deficit. We used univariate and multivariable analyses to examine spinal cord deficit and identify predictors of persistent paraplegia or paraparesis, defined as paraplegia or paraparesis present at the time of early death or hospital discharge.Spinal cord deficit developed after 151 (13.6%) repairs: 86 (7.7%) cases of persistent paraplegia or paraparesis (51 paraplegia; 35 paraparesis) and 65 (6.1%) cases of transient paraplegia or paraparesis. Patients with spinal cord deficit were older (median 68 vs 65 years, P .001) and had more rupture (6.6% vs 2.2%, P = .002) and urgent/emergency repair (25.2% vs 16.9%, P = .01) than those without. Persistent paraplegia or paraparesis developed immediately in 47 patients (4.2%) and was delayed in 39 patients (3.5%). Urgent/emergency repair (relative risk ratio, 2.31; P = .002), coronary artery disease (relative risk ratio, 1.80, P = .01), and chronic symptoms (relative risk ratio, 1.76, P = .02) independently predicted persistent paraplegia or paraparesis. Reattaching intercostal/lumbar arteries (relative risk ratio, 0.38, P .001) and heritable disease (relative risk ratio, 0.36, P = .01) were protective. Early and late survival were poorer in those with persistent paraplegia or paraparesis than in those without.Spinal cord deficit after extent II thoracoabdominal aortic aneurysm repairs remains concerning; survival is worse in patients with persistent paraplegia or paraparesis. The complexity of spinal cord deficit and persistent paraplegia or paraparesis warrant further study.

Intercostal nerve cryoablation with the Nuss procedure has been shown to decrease opioid requirements and hospital length of stay; however, few studies have evaluated the impact on complications and hospital costs.A retrospective cohort study was performed for all Nuss procedures at our institution from 2016 through 2020. Outcomes were compared across 4 pain modalities: cryoablation with standardized pain regimen (n = 98), patient-controlled analgesia (PCA; n = 96), epidural (n = 36), and PCA with peripheral nerve block (PNB; n = 35). Outcomes collected included length of stay, opioid use, variable direct costs, and postoperative complications. Univariate and multivariate hierarchical regression analysis was used to compare outcomes between the pain modalities.Cryoablation was associated with increased total hospital cost compared with PCA (cryoablation, $11 145; PCA, $8975; P.01), but not when compared with epidural ($9678) or PCA with PNB ($10 303). The primary driver for increased costs was operating room supplies (PCA, $2741; epidural, $2767; PCA with PNB, $3157; and cryoablation, $5938; P.01). With multivariate analysis, cryoablation was associated with decreased length of stay (-1.94; 95% CI, -2.30 to -1.57), opioid use during hospitalization (-3.54; 95% CI, -4.81 to -2.28), and urinary retention (0.13; 95% CI, 0.05-0.35).Cryoablation significantly reduces opioid requirements and length of stay relative to alternative modalities, but it was associated with an increase in total hospital costs relative to PCA, but not epidural or PCA with PNB. Cryoablation was not associated with allodynia or slipped bars requiring reoperation.

Background: Thoracic inlet (TI) tumors are rare, and can be particularly challenging to resect due to proximity to mediastinal vessels and nerves. Traditional resection is typically performed throu...

Introduction: Hepatoblastoma (HB) is the most common pediatric primary liver tumor and has the fastest rising incidence of all pediatric solid tumors. Patients with high-risk, treatment refractory, or relapse disease have a survival rate of less than 50%. The development of clinically relevant models of these aggressive tumors will facilitate studies to identify drugs that target these cells.Methods: Fresh, whole primary tumor samples were implanted into the livers of immunocompromised mice. Tumor growth was monitored with MRI and ELISA to measure serum human Alpha-fetoprotein (AFP), which is detectable in the blood of tumor-bearing animals. Tumors were validated with immunohistochemistry (IHC) for HB markers Glypican-3 (GPC3) and Beta-catenin; short tandem repeat (STR) DNA validation; next generation sequencing-based mutation profiling of 124 genes involved in pediatric solid tumors; RNA sequencing (RNA-seq), and single cell RNA-seq (scRNA-seq). Lung metastasis was also detected in models with serial sectioning and H&E staining. Cells derived from tumors were grown in vitro in adherent and spheroid conditions and used for high throughput drug screening of candidate agents. Tumors were serially passaged in animals for further in vivo drug testing of novel targeted agents.Results: Nine patient-derived xenograft (PDX) models were generated that represent low- and high-risk tumors, treatment refractory cases, and relapsed tumors. Passaging of these models showed consistent implantation rates at or above 80% with tumors detectable in 2 to 4 weeks. Eight of nine models secrete human serum AFP. All models mimic gene expression and histological patterns of their primary tumor counterparts as well as identical STR DNA profiles. The models also show gene expression consistent with an HB2/high-risk profile according to the Sumazin HB expression signature. Interestingly, two models represent unique sub-clones of a very aggressive HB relapse with different AFP secretion and transcriptomic expression. scRNA-seq of these two models indicated outgrowth of disparate disease sub-clones. The nine models also demonstrate a range of DNA mutations with three or four mutations per tumor; all variants present in the original clinical samples were conserved in the PDX models. Lung metastasis was evident in six of nine models. Two stable patient-derived cell lines (PDCLs) were developed from models, and these cell lines show expression of HB markers and secrete AFP with growth in culture. Drug screening of adherent and spheroid tumor cells support the efficacy of novel targeted agents and indicate a spectrum of sensitivity to cisplatin, a frontline standard chemotherapy agent. Importantly, the models replicate the chemotherapy responses of the corresponding patients. Additional in vitro and in vivo work showed the efficacy of a histone deacetylase inhibitor, panobinostat.Conclusions: These novel orthotopic PDX models of HB fully recapitulate the primary tumors and represent a platform for clinically relevant drug screening and testing. Citation Format: Sarah E Woodfield, Roma H Patel, Andres F Espinoza, Richard S Whitlock, Jessica Epps, Andrew Badachhape, Samuel R Larson, Rohit K Srivastava, Aayushi P Shah, Saiabhiroop R Govindu, Barry Zorman, Brandon J Mistretta, Kevin E Fisher, Ilavarasi Gandhi, Jacquelyn Reuther, Martin Urbicain, Aryana M Ibarra, Sakuni Rankothgedera, Kimberly R Holloway, Stephen F Sarabia, Andras Heczey, Ketan B Ghaghada, Kalyani R Patel, Dolores Lopez-Terrada, Angshumoy Roy, Preethi H Gunaratne, Pavel Sumazin, Sanjeev A Vasudevan. Patient-derived xenograft mouse models of hepatoblastoma for a personalized medicine pipeline [abstract]. In: Proceedings of the AACR Special Conference: Advances in the Pathogenesis and Molecular Therapies of Liver Cancer; 2022 May 5-8; Boston, MA. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(17_Suppl):Abstract nr PO013.

Extrarenal malignant rhabdoid tumors (MRT) are highly aggressive tumors of childhood with a poor overall prognosis. While most commonly found within the kidney and central nervous system, MRT can also occur in other locations and present highly specific challenges for pediatric surgical providers in an effort to achieve a meaningful resection. Cervical rhabdoid tumors are extremely rare. We report the multidisciplinary management of a patient with a complex cervicothoracic malignant rhabdoid tumor who underwent successful surgical resection with a greater than one year survival.

Hepatoblastoma (HB) is the most common pediatric primary liver malignancy, and survival for high-risk disease approaches 50%. Mouse models of HB fail to recapitulate hallmarks of high-risk disease. The aim of this work was to generate murine models that show high-risk features including multifocal tumors, vascular invasion, metastasis, and circulating tumor cells (CTCs). HepT1 cells were injected into the livers or tail veins of mice, and tumor growth was monitored with magnetic resonance and bioluminescent imaging. Blood was analyzed with fluorescence-activated cell sorting to identify CTCs. Intra- and extra-hepatic tumor samples were harvested for immunohistochemistry and RNA and DNA sequencing. Cell lines were grown from tumor samples and profiled with RNA sequencing. With intrahepatic injection of HepT1 cells, 100% of animals grew liver tumors and showed vascular invasion, metastasis, and CTCs. Mutation profiling revealed genetic alterations in seven cancer-related genes, while transcriptomic analyses showed changes in gene expression with cells that invade vessels. Tail vein injection of HepT1 cells resulted in multifocal, metastatic disease. These unique models will facilitate further meaningful studies of high-risk HB. This article has an associated First Person interview with the first author of the paper.

Hepatoblastoma (HB) is the most common pediatric primary liver malignancy, and survival for high-risk disease approaches 50%. Mouse models of HB fail to recapitulate hallmarks of high-risk disease. The aim of this work was to generate murine models that show high-risk features including multifocal tumors, vascular invasion, metastasis, and circulating tumor cells (CTCs). HepT1 cells were injected into the livers or tail veins of mice, and tumor growth was monitored with magnetic resonance and bioluminescent imaging. Blood was analyzed with fluorescence activated cell sorting to identify CTCs. Intra- and extra-hepatic tumor samples were harvested for immunohistochemistry and RNA and DNA sequencing. Cell lines were grown from tumor samples and profiled with RNA sequencing. With intrahepatic injection of HepT1 cells, 100% of animals grew liver tumors and showed vascular invasion, metastasis, and CTCs. Mutation profiling revealed genetic alterations in seven cancer-related genes, while transcriptomic analyses showed changes in gene expression with cells that invade vessels. Tail vein injection of HepT1 cells resulted in multifocal, metastatic disease. These unique models will facilitate further meaningful studies of high-risk HB.Summary StatementIn this work, we developed and thoroughly characterized several unique models of hepatoblastoma derived from the HepT1 cell line that show high-risk features.

Introduction: Hepatoblastoma (HB) is the most frequent liver malignancy of childhood with an annual incidence of 1.5 per million and a survival rate less than 50%. Due to significant side effects and ineffectiveness of standard chemotherapy for relapse refractory disease, the treatment options are now shifting towards targeted therapies. Cyclin-dependent kinases (CDKs) are potential cancer therapeutic targets because of their critical role in promoting cell growth and regulating transcriptional processes. This study aims to assess the therapeutic efficacy of dinaciclib, cyclin-dependent kinase inhibitor, with HB in preclinical in vitroand in vivo models. Method: Dinaciclib was tested in patient derived cell lines (PDCL) from different patient derived xenograft (PDX) models using CellTiter-Glo Luminescent Viability assays. Dinaciclib was also assayed in vitro for cytotoxicity (MTT assay) and proliferation (CCK-8 assay). Differential expression of CDKs was checked by microarray analysis between normal liver and HB patients. Results were confirmed by immunoblotting assays. Immunoblotting assays were also used to see the effect of dinaciclib on CDK 1/2/5/9 and to assess the induction of apoptosis (PARP cleavage) in vitro. Dinaciclib was also tested in our orthotopic PDX models of high-risk HB. MRI and alpha-fetoprotein (AFP) ELISA were done to evaluate tumor growth. Tumor weights and volumes, as well as, immunohistochemistry were also used to assess effects of dinaciclib in vivo. Result: Dinaciclib suppressed cell proliferation and viability in a dose-dependent manner in all HB cell lines tested with IC50 in the low micromolar range (HepG2- 3.75; HepT1- 0.007; Huh6- 1.42; HB17- 0.72). Microarray analysis showed significant upregulation of CDK1 (p=0.0003), CDK2 (p=0.00023) and CDK9 (p=0.015) in HB patient samples, however, immunoblotting with dinaciclib-treated cells showed decreased expression of CDKs 1/2/5/9 as well as induction of apoptosis. Dinaciclib also showed in vivo inhibition of tumor growth compared to placebo in both PDX models (HB47: relative tumor volume p = 0.03, T/C ratio= 0.36, tumor weight p = 0.02; HB52: relative tumor volume p = 0.06, T/C ratio= 0.16, tumor weight p = 0.07). Conclusion: Dinaciclib treatment showed promising effects with preclinical HB cell lines and PDX models. Citation Format: Rohit K. Srivastava, Roma Patel, Andres F. Espinoza, Yang Yu, Richard S. Whitlock, Samuel Larson, Andrew Badachhape, Jianhua Yang, Sarah E. Woodfield, Sanjeev A. Vasudevan. Efficacy of dinaciclib in hepatoblastoma through inhibition of cyclin dependent kinases [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3891.

Open repair of a thoracoabdominal aortic aneurysm (TAAA) is an extensive operation and associated with significant perioperative morbidities and mortality, in large part due to distal aortic ischemia secondary to aortic cross-clamping that is necessitated during repair. Distal aortic ischemia may manifest as complications of the kidneys and viscera. Postoperative renal complications range from temporarily elevated levels of creatinine resulting from impaired kidney function to acute renal failure necessitating dialysis that may persist after hospital discharge. Continued advances in the management and adjuncts associated with TAAA repair since the groundbreaking era of E.S. Crawford have led to improved postoperative outcomes following surgery, but the dramatic improvements seen in reducing rates of spinal cord deficits, mesenteric ischemia and other serious postoperative complications have not been seen in contemporary rates of postoperative renal failure. We provide an overview of the various surgical techniques and adjuncts as they relate to the management of visceral and renal ischemia.

Purpose Ganglioneuroma (GN) and ganglioneuroblastoma-intermixed (GNB-I) represent benign variants of neuroblastic tumors in children; however, differentiating from more aggressive histological variants of GNB including the nodular subtype (GNB-N) prior to resection can be challenging, even with biopsy. Currently, no standard treatment guidelines exist. The purpose of this study was to identify pre-operative characteristics of benign neuroblastic tumors and evaluate outcomes for patients who underwent surgical resection or observation. Methods Retrospective chart review of children treated at a single institution between 2009 and 2019 for non-metastatic tumor with a tissue diagnosis of GN, GNB-N or GNB-I. Demographics, imaging, labs, operative details and outcomes were recorded and analyzed. Results Of 53 patients, 45% were male. The most common tumor location was abdomen (49%), followed by thorax (34%). Forty-five percent had at least one image defined risk factor. Biopsy was performed in 32% (17/53) and upfront surgery in 68% (36/53). Three patients (3/53, 5.6%) with biopsy demonstrating GN tumors were observed due to high surgical risk. Pathology of resected specimens demonstrated GN in 52% (26/50) and GNB-I or GNB-N in 48% (24/50). The majority of GNB tumors (75% (18/24) were GNB-I and 25% (6/24) were GNB-N. Therefore, 88% of the resected tumors were benign spectrum neuroblastic tumors (GN & GNB-I). Seven (7/50, 14%) patients experienced perioperative complication (temporary paralysis, Horner's syndrome, chylothorax, vocal cord paralysis). Recurrence was noted in 1 patient with GN (1/50, 2%) and 3 with GNB-N (3/50, 6%). There were no tumor-related deaths. Patients with GN were older than those with GNB (8.8 years (IQR 6–11.25) vs 5.6 years for GN (IQR 3–7); p = 0.01). GNB tumors were also more likely to have calcifications on imaging (63% vs. 38%, p = .01) and more commonly had MIBG avidity (88% vs 66%, p = .04). There were no significant differences in tumor size or symptoms at presentation. Conclusions In children with neuroblastic tumors, older age, CT without tumor calcifications, lack of MIBG avidity, and/or normal urine catecholamines may indicate benign GN. Close observation could be considered for asymptomatic patients meeting these criteria with biopsy-proven GN, with resection reserved for progressive growth or symptom development. However, larger, multicenter studies are needed for further validation. Level of evidence IV.

Hepatoblastoma (HB) is the most common pediatric liver malignancy. High-risk patients have poor survival, and current chemotherapies are associated with significant toxicities. Targeted therapies are needed to improve outcomes and patient quality of life. Most HB cases are TP53 wild-type; therefore, we hypothesized that targeting the p53 regulator Murine double minute 4 (MDM4) to reactivate p53 signaling may show efficacy. MDM4 expression was elevated in HB patient samples, and increased expression was strongly correlated with decreased expression of p53 target genes. Treatment with NSC207895 (XI-006), which inhibits MDM4 expression, or ATSP-7041, a stapled peptide dual inhibitor of MDM2 and MDM4, showed significant cytotoxic and antiproliferative effects in HB cells. Similar phenotypes were seen with short hairpin RNA (shRNA)-mediated inhibition of MDM4. Both NSC207895 and ATSP-7041 caused significant upregulation of p53 targets in HB cells. Knocking-down TP53 with shRNA or overexpressing MDM4 led to resistance to NSC207895-mediated cytotoxicity, suggesting that this phenotype is dependent on the MDM4-p53 axis. MDM4 inhibition also showed efficacy in a murine model of HB with significantly decreased tumor weight and increased apoptosis observed in the treatment group. This study demonstrates that inhibition of MDM4 is efficacious in HB by upregulating p53 tumor suppressor signaling.

Background Recent studies have shown intercostal cryoablation(IC) during the Nuss procedure decreases hospital length of stay(LOS) and opioid administration. However, few studies have also evaluated the risk of postoperative complications related to IC. Methods We performed a single center retrospective analysis of all patients who underwent Nuss procedure by one surgeon from 2/2016 to 2/2020, comparing intraoperative IC to other pain management modalities(non-IC). Primary outcomes were postoperative complications, hospital LOS, and opioid administration. Multivariate analysis was performed with outcomes reported as regression coefficients(RC) or odds ratios(OR) with 95% confidence interval. Results IC was associated with decreased hospital LOS (RC −1.91[−2.29 to −1.54], less hospital opioid administration (RC −4.28[−5.13 to −3.43]), and less discharge opioid administration (RC −3.82[−5.23 to −2.41]). With respect to postoperative complications, IC decreased the odds of urinary retention (OR 0.16[0.06 to 0.44]); however, increased the odds of slipped bars requiring reoperation (OR 36.65[5.04–266.39]). Conclusions Our single surgeon experience controls for surgeon variability and demonstrates intraoperative IC for the Nuss procedure is an effective pain management modality that decreases hospital LOS and opioid use during hospitalization and at discharge; however, it is associated with increased odds of slipped bars requiring reoperation. Level of evidence III

Background Sclerosing encapsulating peritonitis (SEP) is a rare chronic inflammatory condition characterized by small bowel encapsulation by a thick fibrocollagenous membrane. Patients with SEP often present with nonspecific symptoms, such as abdominal pain and distension, however some patients may present with symptoms suggestive of intestinal obstruction. Secondary SEP has been reported in patients undergoing peritoneal dialysis and has been recently described in adults following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Observations We report a clinical case of a 13-year-old female who presented with worsening abdominal pain and distension and persistent emesis who was found to have SEP 13 months following CRS and HIPEC for management of desmoplastic small round cell tumor and subsequently required operative intervention. Conclusion Although there have been published reports of adult patients experiencing cases of SEP following CRS/HIPEC, this is the first published case of secondary SEP occurring in a pediatric oncology patient.

Hepatoblastoma (HB) is the most common pediatric liver malignancy. Management of HB requires multidisciplinary efforts. The 5-year overall survival of this disease is about 80% in developed countries. Despite advances in the care of these patients, survival in recurrent or treatment-refractory disease is lower than 50%. This is due to more complex tumor biology, including hepatocellular carcinoma (HCC)-like mutations and expression of aggressive gene signatures leading to chemoresistance, vascular invasion, and metastatic spread. The current treatment protocols for pediatric liver cancer do not incorporate targeted therapies, and the ability to test these therapies is limited due to the inaccessibility of cell lines and mouse models. In this review, we discuss the current status of preclinical animal modeling in pediatric liver cancer, primarily HB. Although HB is a rare cancer, the research community has worked together to develop a range of interesting and relevant mouse models for diverse preclinical studies.

Introduction: Hepatoblastoma (HB) is the most frequent liver malignancy of childhood with an annual incidence of 1.5 per million and a survival rate less than 50% for high-risk, relapse, and treatment refractory patients. The overall goal of this study is to assess the therapeutic efficacies and anti-cancer mechanisms of novel drugs with HB through a drug sensitivity testing pipeline utilizing multiple novel, clinically relevant preclinical patient-derived cell line (PDCL) and patient-derived xenograft (PDX) models. Methods: A patient derived xenograft (PDX) mouse model was generated with intrahepatic implantation of tumor thrombus from a non-metastatic stage 3 patient who recurred after transplantation. A stable PDCL was grown from the murine tumor, and 60 targeted agents were tested for efficacy with the PDCL by using CellTiter-Glo Luminescent Viability assays. Anti-oncogenic effects of the most efficacious agent, dinaciclib (cyclin-dependent kinase (CDK) inhibitor), were further assayed in vitro with HB cell lines (HepG2, HepT1, Huh6, HB17) with phenotypic assays for cell toxicity (MTT assay), proliferation (CCK-8 assay), and anchorage independent colony formation (soft agar assay). Immunoblotting assays were used to assess changes in drug targets and induction of apoptosis (PARP cleavage) with cell lines. Dinaciclib was also tested in vivo in our orthotopic PDX models of high-risk HB. The drug was administered three times a week by intraperitoneal injection (20 mg/kg, 100 µL) for 3 weeks. Magnetic resonance imaging (MRI) and Alpha-fetoprotein (AFP) ELISA were done to evaluate tumor growth throughout the study as tumor-bearing animals show expression of human serum AFP. Tumor weights and volumes, as well as immunohistochemistry for H&E, Ki-67, and TUNEL, were also used to assess effects of drug in vivo. Results: The agent that showed the lowest IC50 value out of 60 tested agents was the CDK inhibitor, dinaciclib (0.7 µM). Dinaciclib suppressed cell proliferation and viability in a dose-dependent manner in all HB cell lines tested with IC50 values in the low micromolar range (HepG2 3.75 µM; HepT1 0.007 µM; Huh-6 1.42 µM; HB17 0.72 µM). Immunoblotting with dinaciclib-treated cells showed induction of PARP cleavage, indicating apoptosis, along with decreased protein expression of CDK1, 2, 5, and 9. Dinaciclib also showed significant in vivo inhibition of tumor growth compared to placebo (relative tumor volume p = 0.03, tumor weight p = 0.02). Conclusions: Drug screening of a novel HB PDCL identified an agent, dinaciclib, that shows preclinical efficacy with refractory disease. Further in vitro and in vivo validation confirmed that dinaciclib is a promising therapeutic agent for the treatment of HB. Such a personalized medicine pipeline of development of PDCLs and testing them with targeted agents will lead to the identification of new drugs that can be used with patients that do not respond to standard therapies. Citation Format: Rohit Kumar Srivastava, Roma Patel, Richard S. Whitlock, Samuel R. Larson, Andrew Badachhape, Sarah E. Woodfield, Sanjeev A. Vasudevan. Avenue to personalized targeted therapy for hepatoblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1174.

Introduction: Hepatoblastoma (HB) is the most common pediatric primary liver tumor and has the fastest rising incidence of all pediatric solid tumors. Patients with high-risk, treatment refractory, or relapse disease have a survival rate of less than 50%. The development of clinically relevant models of these aggressive tumors will facilitate studies to identify drugs that target these cells. Methods: Fresh, whole primary tumor samples were implanted into the livers of immunocompromised mice. Tumor growth was monitored with MRI and ELISA to measure serum human Alpha-fetoprotein (AFP), which is detectable in the blood of tumor-bearing animals. Tumors were validated with immunohistochemistry (IHC) for HB markers Glypican-3 (GPC3) and Beta-catenin; short tandem repeat (STR) DNA validation; next generation sequencing-based mutation profiling of 124 genes involved in pediatric solid tumors; and RNA sequencing (RNA-seq). Cells derived from tumors were grown in vitro and used for high throughput drug screening of candidate agents. Tumors were serially passaged in animals for further in vivo drug testing of novel targeted agents. Results: Nine patient-derived xenograft (PDX) models were generated that represent low- and high-risk tumors, treatment refractory cases, and relapsed tumors. Passaging of these models showed consistent implantation rates at or above 80% with tumors detectable in 2 to 4 weeks. Eight of nine models secrete human serum AFP. All models mimic gene expression and histological patterns of their primary tumor counterparts as well as identical STR DNA profiles. The models also show gene expression consistent with an HB2/high-risk profile according to the Sumazin HB expression signature. Interestingly, two models represent unique sub-clones of a very aggressive HB relapse with different AFP secretion and transcriptomic expression. The nine models also demonstrate a range of DNA mutations with three or four mutations per tumor; all variants present in the original clinical samples were conserved in the PDX models. Drug screening of tumor cells support the efficacy of novel targeted agents and indicate that these tumors are resistant to frontline standard chemotherapy, cisplatin and doxorubicin. More extensive in vivo testing showed the efficacy of a dual MDM2/MDM4 inhibitor (ALRN-6924), a cyclin dependent kinase inhibitor (dinaciclib), and a histone deacetylase inhibitor (panobinostat), and use of an orthotopic animal model also revealed drug toxicities associated with compromised liver function. Conclusions: These novel orthotopic PDX models of HB fully recapitulate the primary tumors and represent a platform for clinically relevant drug screening and testing. Further studies of the sub-clones of disease that grow in the animals will yield information about particularly aggressive HBs. Citation Format: Sarah Elizabeth Woodfield, Roma H. Patel, Samuel R. Larson, Andrew Badachhape, Rohit K. Srivastava, Aayushi P. Shah, Brandon Mistretta, Barry Zorman, Kevin Fisher, Ilavarasi Gandhi, Jacquelyn Reuther, Richard S. Whitlock, Aryana M. Ibarra, Sakuni Rankothgedera, Kimberly R. Holloway, Stephen F. Sarabia, Martin Urbicain, Andras Heczey, Dolores Lopez-Terrada, Angshumoy Roy, Preethi Gunaratne, Pavel Sumazin, Sanjeev A. Vasudevan. Novel orthotopic patient-derived xenograft mouse models of hepatoblastoma that replicate tumor heterogeneity, chemoresistance, and refractory disease [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2997.

Early hospital readmissions after kidney transplantation pose a significant financial burden and hardship for patients and health-care institutions alike. We sought to identify the risk factors associated with increased likelihood of readmission after transplantation, and examined to determine whether patient socioeconomic demographics impacted the likelihood of perioperative readmissions. We evaluated all deceased donor renal transplants performed at our institution between August 2011 and December 2015. In a cohort of 325 transplant operations that met our inclusion criteria, 117 (36%) were readmitted to the hospital within 90 days of discharge. In univariable analyses, length of stay and pretransplant disabled status were associated with increased likelihood of readmission within 90 days of transplant. When placed into multivariable models, there was a suggestion association with length of stay and disability status. Kidney donor profile index, estimated posttransplant survival, employment, race, age, and payor status were not associated with readmission. In conclusion, the factors associated with posttransplant readmission are not necessarily influenced by socioeconomic factors in our study population. The data collected in this single center study indicate that the factors associated with increased rates of readmission are likely clinical in nature.

We report an infant with COVID-19 who presented with bloody stools, lethargy and imaging findings significant for pneumatosis intestinalis. The infant was treated with conservative therapy, including resuscitation, bowel rest and intravenous antibiotics, successfully avoiding surgical intervention.

Hepatoblastoma is the most common childhood liver malignancy. The management of hepatoblastoma requires multidisciplinary efforts. The five-year overall survival is approximately 80% in developed countries. Surgery remains the mainstay of treatment for hepatoblastoma, and meticulous techniques must be employed to ensure safe and effective local control surgeries. Additionally, there have been several advances from both pediatric and adult literature in the way liver tumor surgery is performed. In this review, we highlight important aspects of liver surgery for hepatoblastoma, the management of metastatic disease, and the most current technical advances in performing these procedures in a safe and effective manner.

Aortic root aneurysm is the most common cardiovascular manifestation requiring surgical intervention in patients with Marfan syndrome (MFS), a heritable thoracic aortic disease. Elective replacement of the aortic root is the treatment of choice for patients with aneurysmal complications of the aortic root and ascending aorta. There are two basic approaches to aortic root replacement: valve-sparing (VS) and valve-replacing (VR) techniques. After successful aortic root replacement surgery, several patients with MFS may develop a late complication related to their aortic disease process, such as developing a pseudoaneurysm of the coronary artery reattachment buttons, aneurysmal expansion, or aortic dissection in the remaining native aorta. These patients may also develop other late complications that are not specifically related to the heritable thoracic aortic disease, such as infections that can lead to dehiscence of some or all of the distal or proximal anastomosis. Because these complications are rare, the clinical volume of reoperations of the aortic root in patients with MFS is low, making it difficult to assess contemporary experiences with these procedures. Only a few published reports have examined reoperative aortic root surgery in patients with MFS, each of which had only a small series of patients. Herein, we describe our contemporary experience with reoperative aortic root replacement in patients with MFS and provide our operative approach for these uncommon procedures.