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Purpose While pancreaticoduodenectomy (PD) has been extensively studied in adults, there are few data pertaining specifically to pediatric patients. We retrospectively analyzed PD-associated morbidity and mortality in pediatric patients. Methods Our analytic cohort included all consecutive patients ≤18years of age treated at our institution from 1993 to 2015 who underwent PD. Patient data (demographics, disease characteristics, surgical and adjuvant treatment, length of hospital stay, and postoperative course) were extracted from the medical records. Results We identified 12 children with a median age of 9years (7 female, 5 male). Final diagnoses were pancreatoblastoma (n=3), solid pseudopapillary tumor (n=3), neuroblastoma (n=2), rhabdomyosarcoma (n=2), and neuroendocrine carcinoma (n=2). Four patients underwent PD for resection of recurrent disease. 75% (9/12 patients) received neoadjuvant therapy. The median operative time was approximately 7hours with a mean blood loss of 590cm 3 . The distal pancreas was invaginated into the posterior stomach (n=3) or into the jejunum (n=5) or was directly sewn to the jejunal mucosa (n=4). There were no operative deaths. There were 4 patients (34%) with grade II complications, 1 with a grade IIIb complication (chest tube), and 1 with a grade IV complication (reexploration). The most common long-term morbidity was pancreas exocrine supplementation (n=10; 83%). Five patients (42%) diagnosed with either solid pseudopapillary tumor or rhabdomyosarcoma are currently alive with a mean survival of 77.4months. Conclusion Pancreaticoduodenectomy is a feasible management strategy for pediatric pancreatic malignancies and is associated with acceptable morbidity and overall survival. Long-term outcome is mostly dependent on histology of the tumor. Level of evidence Level IV; retrospective study with no comparison group.

Background Although nephrectomy rates are higher in children with neuroblastoma who have image-defined risk factors and/or high-risk disease who undergo resection prior to chemotherapy, no published data outline the key radiographic and clinical characteristics associated with nephrectomy. Methods With IRB approval, imaging studies of children undergoing primary resection of intraabdominal neuroblastoma between 2000 and 2014 were retrospectively reviewed. Fisher's exact and Wilcoxon rank-sum tests were used to compare categorical and continuous variables, respectively, with p-values adjusted for multiple testing using the false discovery rate approach. Results Twenty-seven of 380 consecutive patients with CT imaging obtained prior to primary neuroblastoma resection underwent partial or total nephrectomy. On preoperative imaging, renal vessel narrowing and encasement and tumor invasion of the renal hilum, pelvis, and/or parenchyma were present significantly more frequently among patients undergoing nephrectomy. Delayed renal excretion of contrast, hydronephrosis, and tumors with MYCN amplification were also more prevalent in the nephrectomy group. Conclusion Encasement and narrowing of renal vessels, delayed excretion, and tumor invasion into the kidney, particularly pelvis and capsule invasion, are significantly associated with partial or total nephrectomy at initial neuroblastoma resection. These observations provide valuable information for surgical planning as well as presurgical discussions with families prior to neuroblastoma resection.

Introduction Retroperitoneal partial nephrectomy has not been studied as a surgical approach for children with bilateral Wilms tumor. There are advantages to this technique, including isolation of urine leaks to the retroperitoneum, decreased risk of bowel injury, and decreased time to resuming a diet. Presently, all bilateral Wilms tumors are treated with neoadjuvant chemotherapy and attempted nephron-sparing surgery. In this study, we compare the outcomes of the retroperitoneal and transabdominal approaches in doing partial nephrectomy for bilateral Wilms tumor. Methods With the institutional review board approval, we reviewed records of 14 pediatric patients with metachronous or synchronous bilateral Wilms tumors who underwent surgery after chemotherapy between 1994 and 2014. Only operative procedures with the intent to cure were included (n = 15) and of these, 5 procedures were retroperitoneal and 10 were transabdominal in approach. Individual kidneys operated upon (n = 26) were analyzed using the preoperative radius exophytic/endophytic nearness anterior/posterior location nephrometry score to ensure that resected tumors were comparable between the two surgical groups. Charts were retrospectively analyzed for intraoperative parameters and postoperative course. Differences between parameters were evaluated using Mann-Whitney and chi-square tests. Results Resected tumors in both surgical treatment groups had comparable sizes, nephrometry scores, and rates of anaplasia. Operative time, blood loss, and transfusion requirement were similar between the two groups. The extent of lymph node sampling and rates of R0 resection were equivalent. One adverse intraoperative event, a bowel enterotomy, was seen in the transabdominal group. Patients after retroperitoneal partial nephrectomy required half the time to return to an oral diet as compared with those after a transabdominal surgery, approaching statistical significance (p = 0.08). Rates of the postoperative urine leak were similar, though two in the transabdominal group required reoperation for drainage. There were four recurrences, all in the transabdominal group. Conclusion Our experience demonstrates that the retroperitoneal approach is equivalent to the transabdominal technique with regards to intraoperative complications, lymph node dissection, and R0 resection. Advantages include less time to resumption of oral feeding, decreased risk of bowel injury, and isolation of urine leaks to the retroperitoneum. It should be considered a viable surgical option in the treatment of bilateral Wilms tumors.

PurposeTo determine if selected computed tomography (CT) characteristics of pulmonary nodules in pediatric patients with osteosarcoma can help distinguish the nodules as benign or malignant.MethodsThe institutional review board approved this HIPAA (Health Insurance Portability and Accountability Act-compliant, retrospective study of 30 pediatric osteosarcoma patients (median age 14 years, range 8-22) who underwent chest CT with resection of 117 pulmonary nodules from January 2001 to December 2006. Two pediatric radiologists and one chest radiologist independently and retrospectively reviewed the CT scans and classified nodules as benign, malignant, or indeterminate on the basis of nodule size, laterality, number, location, growth, density, margin appearance, and calcification. Generalized estimating equations were used to examine which characteristics were independent predictors of nodule malignancy.ResultsOf the 117 nodules, 80 (68%) were malignant and 37 (32%) were benign by pathologic review. The readers correctly classified 93% to 94% of the malignant nodules. For benign lesions, the results were not as accurate, with the readers correctly classifying only 11% to 30% of lesions. Most of the benign lesions were classified as indeterminate by the readers (54%-65%). Nodule size (≥5 mm) and the presence of calcifications were associated with an increased probability of malignancy (P < .05).ConclusionOn chest CT, nodule size 5 mm or greater and the presence of calcifications are associated with an increased probability of malignant nodule histology in pediatric patients with osteosarcoma. However, nodule characteristics, apart from size and calcification, at chest CT cannot reliably distinguish benign from malignant pulmonary nodules in these patients.

BACKGROUND: This study evaluated the safety and feasibility of the addition of pamidronate to chemotherapy for treatment of osteosarcoma. METHODS: The authors treated 40 patients with osteosarcoma with cisplatin, doxorubicin, and methotrexate with the addition of pamidronate 2 mg/kg/dose (max dose 90 mg) monthly for 12 doses. Survival, event-free survival (EFS), and durability of orthopedic reconstruction were evaluated. RESULTS: For patients with localized disease, event-free survival (EFS) at 5 years was 72% and overall survival 93%. For patients with metastatic disease, EFS at 5 years was 45% and overall survival 64%. Toxicity was similar to patients treated with chemotherapy alone. Thirteen of 14 uncemented implants demonstrated successful osteointegration. Among allograft reconstructions, there were 2 graft failures, 4 delayed unions, and 6 successful grafts. Overall, 5 of 33 reconstructions failed. There were no stress fractures or growth disturbances. CONCLUSIONS: Pamidronate can be safely incorporated with chemotherapy for the treatment of osteosarcoma. It does not impair the efficacy of chemotherapy. Pamidronate may improve the durability of limb reconstruction. Cancer 2011. © 2010 American Cancer Society.

Purpose: To evaluate the efficacy of 21 Gy hyperfractionated radiotherapy for local control in conjunction with surgery and intensive systemic therapy for patients with Stage 4 neuroblastoma. Methods and Materials: After achieving a partial or complete remission, 47 children, ages 1–10 years, with Stage 4 neuroblastoma were treated on four consecutive institutional protocols (N4–N7) with dose-intensive multi-agent chemotherapy, maximal surgical debulking, and hyperfractionated radiotherapy (1.5 Gy twice a day to 21 Gy). Radiotherapy fields encompassed the initial tumor volume and regional lymph nodes plus a 3-cm margin. This was followed by consolidation with either autologous bone marrow transplantation (N4 and N5) or immunotherapy (N6 and N7). Results: Forty-five of 47 patients had a complete response to surgery and chemotherapy prior to radiotherapy. Five-year actuarial rates of local control, progression-free survival, and overall survival were 84%, 40%, and 45%, respectively. Among 26 patients who relapsed, 1 failed only at the primary site, 22 developed distant metastases exclusively, and 3 had both local and distant failures. There were no acute complications of radiotherapy. Conclusion: Hyperfractionated radiotherapy to 21 Gy, in conjunction with dose-intensive systemic therapy and aggressive surgical resection, is well tolerated and is associated with durable local control for most patients with Stage 4 neuroblastoma.

We evaluated HLA-compatible donor leukocyte infusions (DLIs) and HLA-compatible or HLA-disparate EBV-specific T cells (EBV-CTLs) in 49 hematopoietic cell transplantation recipients with biopsy-proven EBV-lymphoproliferative disease (EBV-LPD). DLIs and EBV-CTLs each induced durable complete or partial remissions in 73% and 68% of treated patients including 74% and 72% of patients surviving ≥ 8 days after infusion, respectively. Reversible acute GVHD occurred in recipients of DLIs (17%) but not EBV-CTLs. The probability of complete response was significantly lower among patients with multiorgan involvement. In responders, DLIs and EBV-CTLs regularly induced exponential increases in EBV-specific CTL precursor (EBV-CTLp) frequencies within 7-14 days, with subsequent clearance of EBV viremia and resolution of disease. In nonresponders, EBV-CTLps did not increase and EBV viremia persisted. Treatment failures were correlated with impaired T-cell recognition of tumor targets. Either donor-derived EBV-CTLs that had been sensitized with autologous BLCLs transformed by EBV strain B95.8 could not lyse spontaneous donor-derived EBV-transformed BLCLs expanded from the patient's blood or biopsied tumor or they failed to lyse their targets because they were selectively restricted by HLA alleles not shared by the EBV-LPD. Therefore, either unselected DLIs or EBV-specific CTLs can eradicate both untreated and Rituxan-resistant lymphomatous EBV-LPD, with failures ascribable to impaired T-cell recognition of tumor-associated viral antigens or their presenting HLA alleles.

Purpose. This paper describes the clinical history and radiographic appearance of second malignancies in patients with bilateral retinoblastoma. Subjects/methods. The imaging studies and clinical data of 14 patients with a history of bilateral retinoblastoma who were treated for second malignancies were reviewed. Results. A total of 17 tumors were identified in 14 patients during the period 1978–1996. The median age of occurrence of the second malignancy was 17 years (range 10–32 years). Fourteen of the 17 malignancies occurred in the facial structures and three developed in the lower extremities. The histologies included osteosarcoma (n = 5), malignant fibrous histiocytoma (n = 3), high-grade spindle cell sarcoma (n = 3), malignant mesenchymoma (n = 1), leiomyosarcoma (n = 4) and angiosarcoma (n = 1). The tumors were locally aggressive and had a similar appearance to those found in nonretinoblastoma patients. Six of the 14 patients are alive and disease free. Discussion. Most of the adolescent and young adult retinoblastoma survivors developed second malignancies in the irradiated facial structures but some occurred in distal sites. Radiologically, these tumors do not differ in appearance from those seen in non-retinoblastoma patients with the exception of their location.

Epstein-Barr virus (EBV)-associated smooth muscle tumors or leiomyosarcomas (EBV LMS) are extremely rare. These tumors develop in patients with acquired or underlying immune deficiency including those after solid organ transplant (SOT) and exhibit a latency type II phenotype. EBV LMSs are typically aggressive and respond poorly to conventional therapy. As part of an on-going trial of EBV specific cytotoxic T lymphocytes for the treatment of EBV related malignancies we have treated 5 patients with EBV LMS with cytotoxic T cell lines generated from normal donors. Five patients, three after SOT (kidney N=1, small bowel N=2), one after solid organ (kidney) and hematopoetic stem cell transplant, and one with a poorly defined underlying immune deficiency syndrome developed EBV LMS. Two patients were successfully treated for EBV lymphoproliferative disease prior to developing EBV LMS. EBV LMS was diagnosed 18 – 46 months after SOT in 4 patients, at 9 years old in the fifth and were multifocal at diagnosis in all 5 patients. All four patients who had undergone SOT failed to respond to decreased immune suppression, one had failed treatment with autologous EBV CTLs and two had failed cytotoxic chemotherapy. The EBV LMS was of host origin in 4/5 patients and of mixed donor and host origin in one. Lines of EBV CTLs were generated as previously described by co-culture of donor peripheral blood T lymphocytes with autologous EBV transformed BLCLs. Lines are tested for EBV specific cytotoxicity, sterility and absence of alloreactivity. Patients with EBV LMS were treated with cell lines generated from unrelated as well as related donors. Three patients received EBV CTLs generated from related haplo-identical parent donors including one whose parental donor was also the donor of her transplanted kidney. One patient received EBV CTLs from an HLA identical related donor. All other lines were generated from 3rd parties. Lines from unrelated third party donors were matched at 2 – 4/8 HLA alleles. In all instances EBV directed cytotoxicity of infused lines was restricted by HLA alleles shared by the patient and the EBV LMS. Three patients achieved partial remissions (PR) lasting 18 – 122 months and one patient has had stable disease for >80 months. One patient had stable disease for 14 months before progression. Expansion of EBV CTLp was demonstrated in all patients after infusion of EBV CTLs lasting from 0.5 to 4 months. Based on the prediction that 3rd party partially matched EBV CTLs are unlikely to persist long term in vivo four of the patients have received multiple cycles of EBV CTLs in an effort to maintain these responses. EBV directed cytotoxic T cell therapy is a novel treatment strategy for EBV LMS, a malignancy that is typically associated with a very poor prognosis. EBV CTLs from immunologically normal, partially HLA-matched third party donors, appropriately specific and HLA restricted can induce significant and durable responses to EBV LMS. Approaches designed to selectively expand T-cells specific for EBV antigens expressed by these malignancies may further improve responses. Disclosures: No relevant conflicts of interest to declare.