Neuroblastoma-associated Opsoclonous Myoclonous Ataxia Syndrome: Profile and Outcome Report on 15 Egyptian Patients.

Opsoclonous myoclonous ataxia syndrome (OMAS) is a rare primarily immune-mediated disease in children. The current study aim was to find out the patterns and outcome of OMAS associated with neuroblastoma (NBL) among Children's Cancer Hospital-Egypt patients. Data was reviewed for 15 eligible patients enrolled between 2007 and 2016. OMAS treatment included prednisolone and cyclophosphamide with/without intravenous immunoglobulin; NBL treatment was given according to risk-corresponding protocol. Patients' age ranged from 0.75 to 12 years at presentation with male/female: 1.1/1. Concurrent diagnosis of OMAS and NBL occurred in 6 patients (40%). OMAS preceded NBL within 0.25 to 2 years in 33%, while NBL preceded OMAS within 0.5 to 1.5 years in 27%. Full OMAS picture was present in 10/15 patients, while 20% presented with truncal ataxia and myoclonus, 1 with truncal ataxia and opsoclonus, and 1 had opsoclonus and myoclonus. Median time till improvement of manifestations was 5 months. The 5-year OMAS progression-free survival was 33.3%, where 10 patients needed second-line therapy due to relapse/progression of OMAS. The median time to progression was 28 months measured from OMAS diagnosis. All patients remained alive with NBL 5-year overall survival of 100% and event-free survival of 85.7% for. However, 73% of the patients showed late sequelae ranging from ocular to cognitive, behavioral and motor disorders; rarely seizures and hemolytic anemia.

Prognostic Factors and Treatment Outcome of Relapsing and Refractory Pediatric Mature B-cell Non-Hodgkin Lymphoma, Children's Cancer Hospital Egypt Experience.

BACKGROUND: Relapsed non-Hodgkin lymphoma treated by chemotherapy and hematopoietic stem cell transplantation (HSCT) has a dismal prognosis. PATIENTS: It is a retrospective study, including pediatric patients diagnosed as mature B-cell non-Hodgkin lymphoma who were primarily refractory or relapsed over 8 years at CCHE. The aim of the study was to analyze the prognostic factors and outcomes of this group of patients. Our result is, 53 of 750 (7%) patients were included. Thirty-four (64.2%) patients had Burkitt lymphoma. Forty-eight (90.6%) patients received LMB 96 protocol initially. The median delay of duration between chemotherapy cycles in first-line treatment was 37 days. Thirty-five (66%) patients relapsed, 23 (65.7%) of them relapsed early, whereas 18 (34%) had tumor progression. Thirty-one (58.5%) patients presented with stage IV at the time of relapse. rituximab, ifosfamide, carboplatin, etoposide was the second line of treatment in 42 (79.24%) patients, and complete second remission was achieved only in 13 (24.3%) patients. Allogeneic HSCT was done for 4 (7.5%) patients, and auto HSCT was done for 3 (5.7%) patients. Three years of overall survival for relapsed and progressed patients were 35.3% and 11.1%, respectively, with a P-value of 0.009. Three years overall survival for patients who underwent HSCT was 85.7% compared with 18.1% for no HSCT with a P-value of 0.007. CONCLUSIONS: The relapse rate is higher than literatures because of the delay of duration between chemotherapy cycles in first-line treatment and more advanced stage at time of relapse. Progression of the disease had a worse outcome than relapse. HSCT in patients with the second remission markedly improved the outcome.

Different 18 F-FDG PET parameters for the prediction of histological response to neoadjuvant chemotherapy in pediatric Ewing sarcoma family of tumors.

BACKGROUND: The histological response to neoadjuvant chemotherapy (NAC) in pediatric patients with Ewing sarcoma family of tumors (ESFT) can predict the disease-free survival. Therefore, a noninvasive method for response assessment is needed. Using the currently established imaging modalities, mass reduction does not always correlate with the percentage of necrosis. OBJECTIVE: To determine the potential role of 18 fluorine-labeled fluoro-2-deoxyglucose positron emission tomography (18 F-FDG PET) metabolic parameters in the prediction of poor histological response to NAC in pediatric patients with ESFT. METHODS: Thirty-six patients who were treated with NAC and surgery at the Children's Cancer Hospital, Egypt, were prospectively included in this study. All patients underwent two studies; a PET/CT study before NAC and another one after NAC completion. Metabolic PET parameters were measured in each study. The ability of each of these parameters, their pretreatment and pre-local control values, as well as the percentage reduction between their pretreatment and pre-local control values, were evaluated to differentiate between good and poor responders using the histological response as a standard reference. RESULTS: Neither the pretreatment value nor the percentage reduction of any of the measured PET parameters predicted poor histological response. After NACcompletion, metabolic tumor volume (MTV) at the threshold of an SUV of 2.5 isocontour (MTV(2.5)post ), MTV at the threshold of hepatic reference SUVmean (MTV(HR)post ), and total lesion glycolysis at the threshold of hepatic reference SUVmean (TLG(HR)post ) predicted poor histological response (P  = 0.006, 0.018, and 0.003, respectively). The cutoff values of 90% reduction of TLG(HR) and maximum standardized uptake value (SUVmax)post ≤2.5 could differentiate between good and poor responders. CONCLUSION: FDG PET parameters can predict poor histological response to NAC in ESFT patients. MTV and TLG at the thresholds of an SUV of 2.5 isocontour and hepatic reference SUVmean are the two most promising thresholds in predicting the response of patients. The cutoff value of SUVmaxpost ≤2.5 predicts poor histological response.

Management and outcome of pediatric Wilms tumor with malignant inferior Vena cava thrombus: largest cohort of single-center experience.

BACKGROUND: Wilms tumor (WT) with an inferior Vena cava (IVC) malignant thrombus comprises 4-10% of all WT cases. METHODS: This retrospective analysis included 51 pediatric patients presenting at Children Cancer Hospital Egypt-57357 from July 2007 to December 2016 with the diagnosis of WT with malignant IVC thrombus. RESULTS: Median age at presentation = 4.4 years and 28 cases (55%) were females. Twenty-five patients (49%) were metastatic and 4 patients (7.8%) had bilateral disease. Forty-seven cases (92.2%) had favorable histology with no evidence of anaplasia. Level of thrombus extension at presentation was classified as infra-hepatic, retro-hepatic, supra-hepatic and intra-cardiac in 33, 9, 6 and 3 patients, respectively. Fifty patients started neoadjuvant chemotherapy (CTH) with 16 patients showing complete resolution of thrombus after 6 weeks of CTH. None of the patients developed thrombus progression after neoadjuvant CTH; one patient had stationary intra-cardiac thrombus, while remaining patients showed partial regression of their thrombus and had nephrectomy with en-bloc thrombectomy. The mean cranio-caudal dimension of IVC thrombi at initial presentation was 6.5 cm, and 3.6 cm post 6th week of CTH. The 5-year OS and EFS were 75.9% and 71.1%, respectively. There was no significant correlation of initial levels of thrombus extension with survival. CONCLUSION: Neoadjuvant chemotherapy followed by radical nephrectomy with en-bloc thrombectomy and radiotherapy seems a successful approach for management of patients with WT and IVC tumor thrombus. Measurement of the cranio-caudal dimension of thrombus and its response to treatment should be considered in the surgical planning.

Watch and See Strategy in Selected Neuroblastoma Case Scenarios: Success and Limitations.

Neuroblastoma (NBL) in infants has the potential to regress/mature spontaneously. The literature showed some cases, subjected to initial observation, with reasonable outcome. Deferring/avoiding active treatment was investigated in selected favorable NBL cases. Patients enrolled on the watch and see strategy (W&S) had small primary tumor, localized stages 1 to 2, uncomplicated stage 4s, or stage 3. Tissue biopsy was not mandatory for infants below 6 months with localized mass. On progression, active intervention was indicated according to disease stage and risk after biological characterization. In total, 32 patients were enrolled on W&S strategy; male/female:2.6/1. Twelve had stages 1 to 2, 16 had stage 4s, and 4 were stage 3. Primary adrenal site was reported in 85% patients, and 65% patients had small mass (≤5 cm). Five-year overall and event-free survival were 100% and 80.9±7%, respectively, with a 43-month median follow-up duration. Spontaneous total/near total resolution of mass occurred in 50% patients. Median time to regression was 1.7 months, and 20.7 months until resolution. Only 19% patients witnessed progression; median time to progression was 4.8 months. W&S is a reasonable approach for localized and uncomplicated stages 3 and 4S NBL. Extended tumor size is a newly investigated entity in the present study. All progressive cases were safely rescued with 100% survival outcome.

Bilateral adrenal neuroblastoma: peculiar pattern of a rare pediatric presentation.

BACKGROUND: Bilateral suprarenal neuroblastoma (BSN) is a rare presentation. Few previously published literature showed BSN patients to have favorable pattern and prognosis. This study aim was to evaluate clinical and biological features in relation to outcome of Egyptian patients with BSN. METHODS: Included patients were diagnosed from 2007 to 2017, retrospectively. Tissue biopsy, imaging and bone marrow were evaluated at presentation. Clinical, demographic, biological variables and risk group were determined and analyzed in relation to overall (OS) and event-free-survival (EFS). RESULTS: BSN patients (n = 33) represented 2% of hospital patients with neuroblastoma during the 10-year study period, 17 were males and 16 were females. Twenty-four patients (72.7%) were infants, and 9 patients (27.3%) were above 1 year of age (range: 1 month to 3 years). Metachronous disease was present in only one patient. Amplified MYCN was found in 10 patients. Initially, most patients (n = 25) had distant metastasis, 6 had stage 3 versus 2 stage 2. Fifteen were high risk (HR), 15 intermediate (IR), 1 low risk (LR) and 2 were undetermined due to inadequate tissue biopsy. Three-year OS for HR and IR patients were 40.5% and 83.9% versus 23.2% and 56.6% EFS; respectively. CONCLUSION: BSN treatment is similar to unilateral disease. A more conservative surgical approach with adrenal tissue preservation on less extensive side should be considered. Biological variables and extent of disease are amongst the most important prognostic determinants. Future studies are warranted to further address the biologic profiling of BSN and highlight prognostic significance of size difference between both adrenal sides.

Nephrectomy for Pediatric Renal Tumors: A Modified Surgical Approach to Minimize Post-operative Intestinal Obstruction.

BACKGROUND: The authors present a modified surgical technique during tumor nephrectomy in children with a conservative approach towards small bowel manipulation and cutting of the peritoneal reflections. We aimed to evaluate this modified surgical approach regarding the incidence of post-operative small bowel obstruction (SBO), and its technical utility. METHODS: The study includes all children with unilateral renal tumors who underwent radical nephrectomy and lymph nodes sampling at our tertiary center from 2010 to 2022. The modified technique was performed via the usual transverse incision. We cut the peritoneal reflections short of the cecum or short of the sigmoid colon. The colon is reflected over SB packing it, proceeding to nephrectomy and lymph nodes sampling. Data included demographics, clinical characteristics, treatment strategy, operative details, post-operative SBO, and overall outcomes. RESULTS: The study included 890 patients with a median age of 3.2 years. The median tumor largest diameter was 13 cm (range: 9-18 cm). The modified surgical technique was adopted in 287 patients (32.3 %). Forty-three patients (43/890, 4.8 %) had post-operative SBO. Out of them, only 4 cases were operated on using the modified surgical technique (p-value<0.001). There were no significant differences between both techniques regarding timing of surgery, tumor rupture, lymph nodes sampling, and tumor size (p-value = 0.775, 0.328, 0.216, and 0.563, respectively). CONCLUSIONS: The modified surgical approach is significantly correlated with lower incidence of post-operative SBO with no increased risk of tumor rupture or incomplete lymph nodes sampling. The timing of surgery or tumor characteristics had no significant impact on the technical utility of the modified surgical approach. LEVEL OF EVIDENCE: Level IV.

Does Salvage Chemotherapy Regimen Intensity Embark on Clearance of Bone Marrow Neuroblastoma?

Introduction: Neuroblastoma (NBL) is the most common extracranial solid tumor in children. It accounts for 15% of the deaths from cancer in the pediatric age group. Approximately half of the newly diagnosed children are at "high risk" (HR) of treatment failure. This study aim was to evaluate the impact of salvage chemotherapy ICE (ifosfamide, carboplatin, and etoposide) versus TC (topotecan/cyclophosphamide) when administered to NBL HR patients having residual bone marrow disease after primary tumor control on the first line treatment regimen. Materials and Methods: The present retrospective study included two groups of eligible stage 4 NBL patients with persistent bone marrow disease. Group (1), 29 patients, received ICE whereas less intensive TC was administered to Group (2), 32 patients. Data analysis included epidemiological variables, pathology subtype, MYCN gene status, primary tumor response and their correlation with bone marrow disease clearance on each regimen. Results: A higher tendency of complete bone marrow clearance was reported in patients who received ICE compared to TC; 41.4% versus 25.0%, respectively. However, the difference was not statistically significant (p= 0.174). Conclusion: TC regimen appears to be a good alternative to ICE as salvage treatment in an attempt to clear NBL bone marrow residual, with the privilege of being less toxic and can be given on outpatient basis. Further randomized trials of larger study sample size with survival impact analysis are warranted.

Surgery in perforated pediatric intestinal lymphoma.

BACKGROUND: Perforation is the most common surgical complication in pediatric intestinal lymphoma. During operation, many surgical decisions are debatable. AIM: To assess the outcome of surgical management of perforated pediatric intestinal lymphoma. PATIENTS AND METHODS: This is a retrospective analysis of all pediatric patients (<18 years old) with intestinal lymphoma treated in our hospital between July 2007 and June 2017. Risk factors for perforation, type of management and outcome in cases of intestinal perforation were analyzed. RESULTS: The study included 240 patients with intestinal lymphoma. Perforation developed in 16 patients (6.7%) with a median age of 5.3 (range: 2.8-15.7) years. Most of the patients (92.5%) had Burkitt lymphoma. The ileum was the most common site of perforation (n = 10). Perforation occurred at presentation (n = 2), during induction (n = 10), during maintenance chemotherapy (n = 2), or at relapse (n = 2). Primary resection anastomosis was done in 12 patients. The resected specimen showed a viable tumor in ten patients. Wound infection (25%) and dehiscence (12.5%) were the most common postoperative complications. The 5-year overall and event-free survivals of patients with perforation were 78.6% and 71.4%, respectively, compared with 85.5% and 81.2% in non-perforated patients; the difference was not significant (p = 0.374 and p = 0.270, respectively). CONCLUSION: Perforation is not an adverse prognostic factor for survival in pediatric intestinal lymphoma patients. Primary resection anastomosis seems to be a safe option if complete tumor resection is feasible.

Role of surgery in localized initially unresectable neuroblastoma.

PURPOSE: Evaluating the role of surgery and the extent of tumor resection on the outcome of patients with localized initially unresectable neuroblastoma (NB). PATIENTS AND METHODS: This was a retrospective case review study including patients with localized initially unresectable NB. The primary tumor was considered unresectable according to imaging defined risk factors (IDRFs). Surgical resection was attempted after four to six courses of chemotherapy. The extent of resection was classified as follows: ≥90% resection, incomplete resection (50-90%) and cases with <50% resection or just a biopsy. Survival analysis was performed using an intention-to-treat approach. RESULTS: A total of 202 patients with NB were included. Surgical resection was done in 106 patients. It was ≥90% in 89 patients (83.9%). Surgical resection was not performed in 96 patients (47.5%). Fifty-five (57.2%) were in good response after primary chemotherapy and 41 patients (42.7%) had persisting IDRFs, nine of them had biopsy only, and a follow-up strategy was considered in the other 32 patients. The overall 5-year event-free survival (EFS) and overall survival (OS) were 89.1 ± 2.4% and 94.9 ± 1.7%, respectively, with significantly better OS and EFS for patients who had resection versus no resection (p = 0.003 and 0.04, respectively). There was no impact of extent of resection on EFS and OS in the whole group (p = 0.91, p = 0.9) and in subgroup analysis stratified by site, histology, and age of the patients. CONCLUSION: In children with localized initially unresectable NB, surgical resection was the only significant risk factor associated with better survival. The extent of tumor resection had no impact on EFS and OS. The concept of accepting incomplete resection to avoid serious complications was successful.

Survival outcome of intermediate risk neuroblastoma at Children Cancer Hospital Egypt.

AIM: The study aims to evaluate survival outcome in newly diagnosed pediatric intermediate risk neuroblastoma patients treated at the Children Cancer Hospital - Egypt and their relation to various clinical and pathological factors. METHODS: The study included stage 3 patients <1.5 years, children 1.5 years or older with stage 3 disease and favorable histopathological features, infants (<1 year) with International Neuroblastoma Staging System (INSS) stage 4 disease, stage 4 children 1-1.5 years with favorable biology, and infants stage 4 s (with unfavorable biologic features). Patients received systemic chemotherapy, in the form of etoposide and carboplatin alternating with cyclophosphamide, doxorubicin and vincristine, administered at 3-week intervals, with a total of 6 or 8 cycles guided by reaching objective overall response (complete/very good partial/partial response). RESULTS: The study included 136 patients, 67 males and 69 females. 101 patients had abdominal primary tumors, 28 had mediastinal masss and 7 with masses in the neck; 68% were stage 3 and the remaining (n = 44) had metastatic disease. The three-year overall survival (OS) and event-free survival (EFS) estimates were 94% ±â€¯2% and 90.9% ±â€¯2.5%, respectively. OS and EFS by gender, age, pathology and INPC were all statistically not significantly different. Moreover, OS for patients having surgery versus no surgery (inoperable residual only) was statistically significant (98.4% ±â€¯1.6% & 88.7% ±â€¯5.3%, respectively, p = .034). CONCLUSION: A very high rate of survival is currently achievable in patients with intermediate risk neuroblastoma by chemotherapy or chemotherapy and surgery. In addition to response, our plan is to adopt biologically-based treatment to reduce treatment-induced complications among survivors.

Prevalence of human papilloma virus (HPV) and its genotypes in cervical specimens of Egyptian women by linear array HPV genotyping test.

BACKGROUND: The association of human papillomavirus (HPV) with cervical cancer is well established. AIM: To investigate HPV genotype distribution and co-infection occurrence in cervical specimens from a group of Egyptian women. METHODS: A group of 152 women with and without cervical lesions were studied. All women had cervical cytology and HPV testing. They were classified according to cytology into those with normal cytology, with squamous intraepithelial lesions (SIL) and invasive squamous cell carcinoma (SCC). Cervical samples were analyzed to identify the presence of HPV by PCR, and all positive HPV-DNA samples underwent viral genotype analysis by means of LINEAR ARRAY HPV Genotyping assay. RESULTS: A total of 26 HPV types with a prevalence of 40.8 % were detected. This prevalence was distributed as follows: 17.7 % among cytologically normal females, 56.5, 3.2, and 22.6 % among those with LSIL, HSIL and invasive SCC respectively. Low-risk HPV types were detected in 81.8 % of the cytologically-normal women, in 5.7 % of those in LSIL women, and in 14.3 % of infections with invasive SCC, while no low-risk types were detected in HSIL. High-risk HPV types were detected in 18.2 % of infections in the cytologically normal women, 14.3 % of infections in LSIL, and in 21.4 % of invasive lesions. The probable and possible carcinogenic HPV were not detected as single infections. Mixed infection was present in 80 % of women with LSIL, in 100 % of those with HSIL, and in 64.3 % of those with invasive SCC. This difference was statistically significant. HPV 16, 18 and 31 were the most prevalent HR HPV types, constituting 41.9, 29.03 and 12.9 % respectively, and HPV 6, 62 and CP6108 were the most prevalent LR HPV types constituting 11.3, 9.7 and 9.7 % respectively. CONCLUSION: These data expand the knowledge concerning HPV prevalence and type distribution in Egypt which may help to create a national HPV prevention program. HPV testing using the LINEAR ARRAY HPV Genotyping assay is a useful tool when combined with cytology in the diagnosis of mixed and non-conventional HPV viral types.

Clinical significance of anaplasia in childhood rhabdomyosarcoma.

BACKGROUND: The presence of anaplastic features has been known to correlate with poor clinical outcome in various pediatric malignancies, including Wilms tumor and medulloblastoma but not in rhabdomyosarcoma. AIM: Aim was to study the frequency of anaplasia at presentation in childhood rhabdomyosarcoma and its relationship to clinical and pathological characteristics as well as to outcome. PATIENTS AND METHODS: Anaplasia was retrospectively assessed in 105 consecutive pediatric rhabdomyosarcoma patients who were registered at the Children's Cancer Hospital in Egypt (CCHE) during the period from July 2007 till the end of May 2010. RESULTS: Anaplasia was diagnosed in 18 patients (17.1%), focal in 10 (9.5%) and diffuse in 8 (7.6%). The distribution of anaplasia was found to be more common in older patients having age⩾10 years. Also it was more likely to occur in the high risk group and in tumors with unfavorable histology (alveolar subtype), and stage IV. The 3-year failure free survival rates for patients with and without anaplasia were 27.8±10.6% and 53.4±5.8%, respectively (p=0.014) and the 3-year overall survival rates were 35.3±11.6% and 61±6%, respectively (p=0.019). CONCLUSIONS: The frequency of anaplasia in pediatric patients with rhabdomyosarcoma in our study was 17.1%. The presence of anaplasia had statistically significant worse clinical outcome.