Pancreaticoduodenectomy for the treatment of pancreatic neoplasms in children: A Pediatric Surgical Oncology Research Collaborative study

BackgroundTo better characterize short- term and long- term outcomes in children with pancreatic tumors treated with pancreaticoduodenectomy (PD).MethodsPatients 21 years of age or younger who underwent PD at Pediatric Surgical Oncology Collaborative (PSORC) hospitals between 1990 and 2017 were identified. Demographic, clinical information, and outcomes (operative complications, long- term pancreatic function, recurrence, and survival) were collected.ResultsSixty- five patients from 18 institutions with a median age of 13 years (4 months- 22 years) and a median (IQR) follow- up of 2.8 (4.3) years were analyzed. Solid pseudopapillary tumor of the pancreas (SPN) was the most common histology. Postoperative complications included pancreatic leak in 14% (n = 9), delayed gastric emptying in 9% (n = 6), marginal ulcer in one patient, and perioperative (30- day) death due to hepatic failure in one patient. Pancreatic insufficiency was observed in 32% (n = 21) of patients, with 23%, 3%, and 6% with exocrine, or endocrine insufficiencies, or both, respectively. Children with SPN and benign neoplasms all survived. Overall, there were 14 (22%) recurrences and 11 deaths (17%). Univariate analysis revealed non- SPN malignant tumor diagnosis, preoperative vascular involvement, intraoperative transfusion requirement, pathologic vascular invasion, positive margins, and need for neoadjuvant chemotherapy as risk factors for recurrence and poor survival. Multivariate analysis only revealed pathologic vascular invasion as a risk factor for recurrence and poor survival.ConclusionThis is the largest series of pediatric PD patients. PD is curative for SPN and benign neoplasms. Pancreatic insufficiency is the most common postoperative complication. Outcome is primarily associated with histology.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156233/2/pbc28425.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156233/1/pbc28425_am.pd

Pancreaticoduodenectomy for the treatment of pancreatic neoplasms in children: A Pediatric Surgical Oncology Research Collaborative study

Background: To better characterize short-term and long-term outcomes in children with pancreatic tumors treated with pancreaticoduodenectomy (PD). Methods: Patients 21 years of age or younger who underwent PD at Pediatric Surgical Oncology Collaborative (PSORC) hospitals between 1990 and 2017 were identified. Demographic, clinical information, and outcomes (operative complications, long-term pancreatic function, recurrence, and survival) were collected. Results: Sixty-five patients from 18 institutions with a median age of 13 years (4 months-22 years) and a median (IQR) follow-up of 2.8 (4.3) years were analyzed. Solid pseudopapillary tumor of the pancreas (SPN) was the most common histology. Postoperative complications included pancreatic leak in 14% (n = 9), delayed gastric emptying in 9% (n = 6), marginal ulcer in one patient, and perioperative (30-day) death due to hepatic failure in one patient. Pancreatic insufficiency was observed in 32% (n = 21) of patients, with 23%, 3%, and 6% with exocrine, or endocrine insufficiencies, or both, respectively. Children with SPN and benign neoplasms all survived. Overall, there were 14 (22%) recurrences and 11 deaths (17%). Univariate analysis revealed non-SPN malignant tumor diagnosis, preoperative vascular involvement, intraoperative transfusion requirement, pathologic vascular invasion, positive margins, and need for neoadjuvant chemotherapy as risk factors for recurrence and poor survival. Multivariate analysis only revealed pathologic vascular invasion as a risk factor for recurrence and poor survival. Conclusion: This is the largest series of pediatric PD patients. PD is curative for SPN and benign neoplasms. Pancreatic insufficiency is the most common postoperative complication. Outcome is primarily associated with histology

Esophageal adenocarcinoma and squamous cell carcinoma in children and adolescents: Report of 3 cases and comprehensive literature review

Malignant esophageal tumors are exceedingly rare in children and adolescents. We present 3 cases of esophageal adenocarcinoma (AC) and squamous cell carcinoma (SSC) in patients ≤21 years of age who were treated at our institution between 1950 and 2015. We also undertook an analysis of those cases, combined with cases from a review of the literature, to examine patient demographics, disease characteristics, and outcomes. We identified one patient with AC and two patients with SCC treated at our institution, as well as 19 cases of AC (median age 16) and 23 cases of SCC (median age 15) reported in the literature. Male predominance was noted at a ratio of 2.2 to 1. Dysphagia, weight loss, and anemia were the most common presenting symptoms for both entities. Approximately 84% of AC tumors were located in the distal esophagus and gastroesophageal junction whereas SCC tumors were distributed evenly throughout esophagus. Metastatic disease at presentation was found in 68.4% of patients with AC compared to 30.4% of those with SCC. Survival was not significantly different between SCC and AC (P = 0.36), between genders (P = 0.13), and between patients treated with surgery vs. multimodality therapy (P = 0.15). Metastasis, however, predicted worse outcome (P = 0.0019). We found that adolescent AC and SCC show characteristics similar to such tumors when presenting in adults. Though extremely rare in the adolescent population, these malignant diseases should always be ruled out when young patients present with a short history of dysphagia with signs of clinical deterioration

Unicentric Castleman disease in the mediastinum

Castleman disease (CD) is a benign lymphoproliferative disorder that rarely occurs in the pediatric population. This entity arises as either unicentric CD or multicentric CD, and is histopathologically classified as hyaline vascular, plasma cell, or mixed variant. CD is frequently misdiagnosed because it is poorly understood and presents with a variety of symptoms. We present a case of a 15-year-old previously healthy girl with unicentric CD. She presented to an Emergency Department with acute onset of chest pain. Radiographic imaging demonstrated a large right-sided mediastinal mass. Biopsy of the mass demonstrated atypical lymphoid tissue with vascular proliferation and concentric layering of peripheral lymphocytes, consistent with CD, hyaline vascular variant. Following multidisciplinary team discussion, the patient underwent complete resection of the mass. She completely recovered with no evidence of residual or recurrent disease on postoperative imaging

Resection of hepatic tumors with central venous and right atrial extension using cardiopulmonary bypass

Background: Pediatric liver tumors occasionally present with vascular invasion. Standard anatomic resections usually result in complete resection when tumor is intra-hepatic; however, direct tumor extension into the inferior vena cava (IVC) and right atrium (RA) requires additional considerations. Here we present our surgical approach to resection of primary liver tumors directly extending into the IVC and RA. Methods: A retrospective analysis of patients undergoing hepatic resection of primary liver tumors with direct extension into the IVC and RA from 1/2013-4/2015 was performed. Results: Three patients were identified with tumors arising from the left hepatic lobe, extending into the suprahepatic IVC and RA. Two underwent in-situ parenchymal division, followed by cardiopulmonary bypass (CPB) for en-bloc resection of the intra-atrial tumor. The third had a congested right lobe due to venous obstruction by tumor, thereby requiring total hepatectomy, en-bloc intra-caval tumor excision, ex-situ left hemihepatectomy, and auto-transplantation of the right lobe. All patients required partial IVC or RA resection and reconstruction. Postoperatively, one patient died from metastatic disease at 5 months and two patients were alive after 50 months and 33 months. Conclusion: Cardiopulmonary bypass provides a safe, controlled approach for en-bloc resection of hepatic tumors extending into the IVC and RA. This minimizes the risk of tumor fracture or spillage, allowing for complete gross resection

A Human Organoid Model of Aggressive Hepatoblastoma for Disease Modeling and Drug Testing

Hepatoblastoma is the most common childhood liver cancer. Although survival has improved significantly over the past few decades, there remains a group of children with aggressive disease who do not respond to current treatment regimens. There is a critical need for novel models to study aggressive hepatoblastoma as research to find new treatments is hampered by the small number of laboratory models of the disease. Organoids have emerged as robust models for many diseases, including cancer. We have generated and characterized a novel organoid model of aggressive hepatoblastoma directly from freshly resected patient tumors as a proof of concept for this approach. Hepatoblastoma tumor organoids recapitulate the key elements of patient tumors, including tumor architecture, mutational profile, gene expression patterns, and features of Wnt/β-catenin signaling that are hallmarks of hepatoblastoma pathophysiology. Tumor organoids were successfully used alongside non-tumor liver organoids from the same patient to perform a drug screen using twelve candidate compounds. One drug, JQ1, demonstrated increased destruction of liver organoids from hepatoblastoma tumor tissue relative to organoids from the adjacent non-tumor liver. Our findings suggest that hepatoblastoma organoids could be used for a variety of applications and have the potential to improve treatment options for the subset of hepatoblastoma patients who do not respond to existing treatments

Button battery lodged in Meckel's diverticulum

Meckel's diverticulum is the most common congenital anomaly of the gastrointestinal tract. It is relatively uncommon, however, for patients to become symptomatic and rarer still for foreign bodies to become lodged within a Meckel's diverticulum. Here we present one such case in which a button battery was lodged in a Meckel's diverticulum, along with the patient's subsequent interdisciplinary management and review of the relevant literature. Keywords: Foreign body ingestion, Button battery, Meckel's diverticulu

YAP Subcellular Localization and Hippo Pathway Transcriptome Analysis in Pediatric Hepatocellular Carcinoma

Pediatric hepatocellular carcinoma (HCC) is a rare tumor which is associated with an extremely high mortality rate due to lack of effective chemotherapy. Recently, the Hippo pathway and its transcriptional co-activator Yes-associated protein (YAP) have been shown to play a role in hepatocyte proliferation and development of HCC in animal models. Therefore, we sought to examine the activity of YAP and the expression of Hippo pathway components in tumor and non-neoplastic liver tissue from 7 pediatric patients with moderately differentiated HCC. None of the patients had underlying cirrhosis or viral hepatitis, which is commonly seen in adults with HCC. This highlights a major difference in the pathogenesis of HCC between children and adults. We found a statistically significant increase in YAP nuclear localization in 100% of tumors. YAP target gene (CCNE1, CTGF, Cyr61) mRNA expression was also increased in the tumors that had the most significant increase in YAP nuclear localization. Based on Ki67 co-localization studies YAP nuclear localization was not simply a marker of proliferation. Our results demonstrate a clear increase in YAP activity in moderately differentiated pediatric HCC, providing evidence that it may play an important role in tumor survival and propagation

Myeloablative Chemotherapy with Autologous Stem Cell Transplant for Desmoplastic Small Round Cell Tumor

Desmoplastic small round cell tumor (DSRCT), a rare, aggressive neoplasm, has a poor prognosis. In this prospective study, we evaluated the role of myeloablative chemotherapy, followed by autologous stem cell transplant in improving survival in DSRCT. After high-dose induction chemotherapy and surgery, 19 patients with chemoresponsive DSRCT underwent autologous stem cell transplant. Myeloablative chemotherapy consisted of carboplatin (400–700 mg/m2/day for 3 days) + thiotepa (300 mg/m2/day for 3 days) ± topotecan (2 mg/m2/day for 5 days). All patients were engrafted and there was no treatment-related mortality. Seventeen patients received radiotherapy to sites of prior or residual disease at a median of 12 weeks after transplant. Five-year event-free and overall survival were 11 ± 7% and 16 ± 8%, respectively. Two patients survive disease-free 16 and 19 years after transplant (both in complete remission before transplant). 14 patients had progression and died of disease at a median of 18 months following autologous transplant. These data do not justify the use of myeloablative chemotherapy with carboplatin plus thiotepa in patients with DSRCT. Alternative therapies should be considered for this aggressive neoplasm