Technical advances in the surgical management of Wilms tumors in children.

Surgery is one of the cornerstones of Wilms tumor treatment. In this article, we present technical advancements that are finding their way into the armamentarium of pediatric cancer surgeons. We discuss the current approaches, challenges, opportunities, and future directions of minimally invasive surgery (laparoscopic and robotics), image-guided surgery, and fluorescence-guided surgery. Furthermore, we discuss the use of intraoperative ultrasonography, as well as the use of new techniques to improve the quality of lymph node sampling.

Outcomes of Pediatric Patients With Metastatic Ewing Sarcoma Treated With Interval Compression.

BACKGROUND: Interval compression (IC), a regimen of alternating vincristine/doxorubicin/cyclophosphamide and ifosfamide/etoposide every 2 weeks, improves survival for localized Ewing sarcoma (ES), with uncertain effect on metastatic disease. MATERIALS AND METHODS: We reviewed the charts of pediatric patients with metastatic ES treated with IC at our center between January 2013 and March 2020. We calculated event-free survival and overall survival (OS) and used log-rank tests for univariate comparisons. RESULTS: We identified 34 patients 2.7 to 17.1 years of age (median: 11.6 y). Twenty-six patients (76%) had pulmonary metastases, and 14 (41%) had extrapulmonary metastases. All patients received local control therapy: surgery only (n=7, 21%), radiotherapy only (n=18, 53%), or both (n=9, 26%). The estimated 3-year OS and event-free survival were 62%±9% and 39%±9%, respectively. Patients with pulmonary-only and extrapulmonary metastasis had a 3-year OS of 88%±8% and 27%±13%, respectively ( P =0.0074). Age group (above vs. below 12 y), or primary tumor site did not affect survival, but local control therapy did (surgery only, 83%±15%; combined surgery and radiation, 30%±18%; radiation only, 15%±10%; P =0.048). CONCLUSION: IC yielded similar outcomes for patients with metastatic ES to other reported regimens. We suggest including this approach to other blocks of therapy.

Evidence-based surgical guidelines for treating children with Wilms tumor in low-resource settings.

BACKGROUND: Survival of Wilms tumor (WT) is > 90% in high-resource settings but < 30% in low-resource settings. Adapting a standardized surgical approach to WT is challenging in low-resource settings, but a local control strategy is crucial to improving outcomes. OBJECTIVE: Provide resource-sensitive recommendations for the surgical management of WT. METHODS: We performed a systematic review of PubMed and EMBASE through July 7, 2020, and used the GRADE approach to assess evidence and recommendations. RECOMMENDATIONS: Initiation of treatment should be expedited, and surgery should be done in a high-volume setting. Cross-sectional imaging should be done to optimize preoperative planning. For patients with typical clinical features of WT, biopsy should not be done before chemotherapy, and neoadjuvant chemotherapy should precede surgical resection. Also, resection should include a large transperitoneal laparotomy, adequate lymph node sampling, and documentation of staging findings. For WT with tumor thrombus in the inferior vena cava, neoadjuvant chemotherapy should be given before en bloc resection of the tumor and thrombus and evaluation for viable tumor thrombus. For those with bilateral WT, neoadjuvant chemotherapy should be given for 6-12 weeks. Neither routine use of complex hilar control techniques during nephron-sparing surgery nor nephron-sparing resection for unilateral WT with a normal contralateral kidney is recommended. When indicated, postoperative radiotherapy should be administered within 14 days of surgery. Post-chemotherapy pulmonary oligometastasis should be resected when feasible, if local protocols allow omission of whole-lung irradiation in patients with nonanaplastic histology stage IV WT with pulmonary metastasis without evidence of extrapulmonary metastasis. CONCLUSION: We provide evidence-based recommendations for the surgical management of WT, considering the benefits/risks associated with limited-resource settings.

Global Neuroblastoma Network: An international multidisciplinary neuroblastoma tumor board for resource-limited countries.

BACKGROUND: Tumor boards are part of standard care of patients with complex cancers, but appropriate multidisciplinary expertise and infrastructure are often not available in low- and middle-income countries (LMIC) for pediatric cancers, such as neuroblastoma. Our goal was to review results of a Global Neuroblastoma Network (GNN) tumor board accessible to LMIC. METHODS: De-identified clinical cases presented via internet conference during a weekly GNN virtual tumor board from 2010 through 2020 were evaluated in a standardized format, including diagnostic imaging, pathology, therapy information, resource limitations, and questions for discussion. Information summarized included the presentations, a survey of the impact on care, and a resource questionnaire. RESULTS: Registered GNN participants included 575 individuals from 77 countries, with a median of 39 participants per session. Total 412 cases were presented from 32 countries, including 351 unique neuroblastoma patients, 52 follow-up cases, and nine non-neuroblastoma diagnoses. Twenty-eight educational sessions were presented. Limited critical resources for diagnostics and staging of cases included MYCN analysis (54.7%), metaiodobenzylguanidine (MIBG) scans (38.7%), and International Neuroblastoma Pathology Classification (49%). Therapies were also limited, with markedly decreased use of radiation and autologous stem cell transplant for high-risk cases, and no availability of anti-GD2 antibody in LMIC. Limited sampling with a post-presentation survey showed that 100% found the GNN helpful, and 70% altered the care plan based on the discussion. CONCLUSION: This report shows the utility of an international tumor board for LMIC focused on a challenging solid tumor where local expertise may be limited, with international multidisciplinary expert participation and educational sessions.

Inferior vena cava involvement in children with Wilms tumor.

OBJECTIVES: Retrospective review of children with WT thrombus involving the IVC. METHODS: We reviewed the charts of 123 patients with WT diagnosed between January 2006 and December 2015. Patients with caval tumor thrombus were identified, demographic data, radiological images, extent of thrombus, chemo- and radiotherapy, surgical approach, pathology reports and outcomes were analyzed. RESULTS: IVC involvement was identified in 11 patients (9%). Left-sided tumors were more common (55%). Sensitivity of CT scan in thrombus identification was 64%. Neoadjuvant chemotherapy was the primary mode of treatment with 19% reduction of primary tumor size, thrombus resolution in four and regression in six patients. No thrombus progression was observed. Delayed surgical treatment was either nephro-ureterectomy (nine patients) or partial nephrectomy in patients with bilateral WT (two patients). During surgery, thrombectomy and intimal stripping achieved local control in patients with persistent caval tumor. Cardiopulmonary bypass was not needed in patients with initial atrial involvement (five patients). Despite adherence and invasion of tumor thrombus to IVC wall, only one patient required segmental vein resection. All patients eventually achieved CR, none had local relapse. One patient had lung relapse treated to complete remission. The 3-year EFS is 85.7 ± 13.2% and the 3-year OS is 100%. CONCLUSION: IVC tumor thrombus in patients with WT was managed successfully using preoperative chemotherapy followed by surgery with minimal aggressive approach. Luminal thrombus removal and intimal stripping supplanted by local radio boost when indicated seem to be adequate tools for local control with documented good overall outcomes.

Improved care of rhabdomyosarcoma in Jordan using less intensive therapy.

BACKGROUND: The care of rhabdomyosarcoma (RMS) is complex due to its multimodal nature. By following standard protocols with acceptable toxicity and building local expertise, better outcome should be achievable. PROCEDURE: A retrospective study was conducted of records of patients (n = 45; 31 males; median age 26 months) with RMS treated at King Hussein Cancer Center in Jordan from January 2004 to December 2008. Patient demographics, tumor characteristics, risk stratification, treatment plan, and outcomes were studied. In June 2006, the cyclophosphamide dose was lowered from 2.2 g/m(2) to 1.2 g/m(2) per cycle because of the significant toxicity with higher dose. Survival rates, hematological toxicities, period of hospitalization due to febrile neutropenia (FN), and response rate at week 12 of treatment were compared between low- and high-dose cyclophosphamide groups. RESULTS: Four-year progression-free survival (PFS) and overall survival (OS) rates were 61% ± 7.5% and 72% ± 6.9%, respectively. There was a significant difference in outcome by risk group in 4-year PFS (low-risk, 88% ± 12%; intermediate-risk 63% ± 9.3%; high-risk, 14% ± 13%; P = 0.0001) and OS (low-risk, 88% ± 12%; intermediate-risk 79% ± 7.5%; high-risk, 17% ± 15%; P = 0.0011). There was significant reduction in hematological toxicities, incidence of FN, and period of hospitalization for FN in patients given low-dose cyclophosphamide but no significant difference in PFS between low- and high-dose cyclophosphamide groups. CONCLUSIONS: Survival rates of patients with RMS in some developing countries can be improved by following or modifying evidence-based approaches successful in developed countries and establishing multidisciplinary strategies. Therapy intensity should be increased in developing countries only when evidence supports its utility.

Inflammatory myofibroblastic tumor causing unexplained anemia in a toddler: a case report.

INTRODUCTION: Inflammatory myofibroblastic tumor is a very rare benign tumor in children that mimics malignant tumors in its aggressiveness locally and by the possibility of recurrence after surgical resection, and causing anemia of chronic disease, which is a decrease in hemoglobin 1 to 2 g/dL below normal level in a patient with chronic illness. CASE PRESENTATION: A 32-month-old boy from Libya presented with microcytic hypochromic anemia. He had been treated in three countries and five centers without response to medical therapy. He was investigated at our center and found to have a mass in the colon causing intermittent intussusception and bleeding. He was treated surgically, and his condition improved dramatically. The pathology report proved a diagnosis of inflammatory myofibroblastic tumor. CONCLUSION: We report a case of an unusual tumor of the gastrointestinal tract causing chronic anemia not responding to medical treatment, and discuss the characteristics of inflammatory myofibroblastic tumor. In our case, we stress the involvement of a multidisciplinary team in treating such a patient who presents with common symptoms and signs but in whom there has been no response to any of the measures and treatment protocols.

Distinct features of teratoid Wilms tumor.

Teratoid Wilms tumor is an unusual variant of nephroblastoma in which heterologous tissue predominates. Typically, histopathologic examination shows a mixture of mature squamous and mucus-producing columnar epithelium and a prominent component of mature adipose tissue. The treatment of this tumor has not been established because of its rarity with some reports doubting the value of chemotherapy. We report 3 new cases and review the 23 previously reported cases that we were able to identify. The first case was a 2-year-old boy with a huge tumor that occupied most of the abdominal cavity. The second case was a 5-year-old girl with a metastatic tumor in association with horseshoe kidney and is the first case of teratoid Wilms tumor with brain metastasis. The third case was an 11-month-old girl with bilateral involvement. Imaging studies of our patients were similar to those reported in the literature with areas of fat attenuation and calcification. Failure to respond to preoperative chemotherapy was seen in our patients and in most previously reported cases that were treated with preoperative chemotherapy. We recommend treating this entity with protocols designed for Wilms tumor and to conduct further basic research to understand its biologic nature.

INI1 (BAF 47) immunohistochemistry is an essential diagnostic tool for children with hepatic tumors and low alpha fetoprotein.

Malignant rhabdoid tumor (MRT) of the liver is a rare malignancy with grave prognosis. This entity should be considered in the differential diagnosis of any aggressive liver tumor with low levels of alpha fetoprotein. We report 2 cases of hepatic MRT presenting in infancy. In these 2 cases, we show that loss of INI1 facilitates making the correct diagnosis of primary hepatic MRT utilizing BAF 47 (INI1 gene product) immunostains. Difficulty encountered in making this rare diagnosis, including the need for repeated biopsies, can be avoided if MRT is considered in the differential diagnosis early on and BAF 47 immunohistochemistry is ordered.

Age, stage, and radiotherapy, but not primary tumor site, affects the outcome of patients with malignant rhabdoid tumors.

BACKGROUND: Malignant rhabdoid tumors (MRTs) are aggressive and often fatal; the Surveillance, Epidemiology, and End Results (SEER) database offers an opportunity to study this rare malignancy. METHODS: From the SEER database, we extracted records of patients with a reported diagnosis of MRT and analyzed them for clinical features and survival rates by univariate and multivariate analyses. RESULTS: For the 229 patients included in our data, who were diagnosed from 1986 to 2005, primary tumors were located in the central nervous system (CNS) (35%), kidneys (20%), and extra-renal non-cranial sites (ERNC-MRTs) (45%). Most patients with renal and CNS tumors were less than 18 years old (87% and 96%, respectively) while more than half of the patients with ERNC-MRTs (61%) were adults. Among staged tumors, 23% were localized, 34% regional, and 43% distant. Renal tumors had significantly more metastatic disease (47%; P = 0.006) than ERNC-MRTs. The estimated 5-year survival for the entire group was 33 +/- 3.4% (SE). Univariate and multivariate analyses showed that age at diagnosis (2-18 years), localized stage of tumors, and use of radiotherapy were significantly associated with improved survival. Adults had a better outcome than young children (<2 years old) but a poorer outcome than older children (2-18 years old); tumor stage, but not radiotherapy use, affected outcome in adults. The survival and prognostic factors of children diagnosed before and after 2000 did not differ significantly. CONCLUSION: Our population-based study indicates that age at diagnosis, tumor stage, and use of radiotherapy favorably impact survival rates of patients with MRTs.

From upfront nephrectomy to preoperative chemotherapy and back: a single institution experience in the treatment of Wilms tumor.

BACKGROUND: Over the past decades, 2 different approaches for the treatment of Wilms tumor have emerged: upfront nephrectomy (UN) and preoperative chemotherapy (PC), with adjuvant treatment adjusted to stage, histology, and chemotherapy response. METHODS: In July 2005, we switched our strategy from UN to PC. This study is a retrospective review of patients treated at our institution between January 2003 and October 2007. RESULTS: Thirty-six children (20 males) with Wilms tumor were studied. Median age was 3.45 years (range: 0.3 to 15.8 y). Nineteen patients (53%) were treated according to the International Society of Paediatric Oncology 93-01/German Pediatric Oncology Hematology, Group protocol (PC group) and 17 (47%) according to the National Wilms' Tumor Study-5 (UN group). UN group received more radiation dose and less cumulative doses of doxorubicin. The 3-year event-free survival and overall survival estimates for the whole group were 86% and 89%, respectively. Survival estimates were similar in both groups. CONCLUSIONS: The use of PC reduced the use of radiation; however, patients treated using the SIOP 93-01/German Pediatric Oncology Hematology Group protocol received higher cumulative doses of doxorubicin; these doses were believed to be high in this young group of patients with potential for long-term toxicity. Although selecting a specific protocol for Wilms tumor is important, the development of surgical expertise and referral to specialized centers takes priority.

Local control of the primary tumour in metastatic neuroblastoma.

The previous studies have stressed on the importance of loco-regional control in the management of high-risk neuroblastoma. We searched the Surveillance, Epidemiology and End-Results (SEER) database for patients older than 2years with metastatic neuroblastoma who were diagnosed from 1998 to 2005. We identified 291 patients (mean age, 4.35years). The 5-year survival estimate was 53.2%+/-6.4% for patients who had complete resection of their primary tumours (n=116) and 35.7%+/-4.7% for patients who did not have complete resection (p=0.003). External-beam radiotherapy did not affect survival (p=0.79); this finding has to be taken with caution due to the study limitations.