Durability of oncological outcomes of combination chemotherapy as a monotherapy for a select patient subset with non-metastatic non-alveolar bladder/prostate rhabdomyosarcoma.

INTRODUCTION AND OBJECTIVES: We aim to assess the long-term oncological outcomes of children with bladder/prostate rhabdomyosarcoma (B/P RMS) treated with multiagent chemotherapy as a monotherapy. We hypothesize that a highly select patient subset can be treated with multiagent chemotherapy as a monotherapy and spared the morbidity of local treatment with similar oncological outcomes. METHODS: Patients (≤21-year-old) treated for non-metastatic non-alveolar B/P RMS at a tertiary center and followed for>one year, were retrospectively reviewed. After pathological confirmation, patients received 12 weeks of induction VAC chemotherapy (IC) followed by second-look biopsies. Between 1996 and 2006 (group A), patients with>50% tumor size reduction and negative second-look biopsies following IC were spared local treatment and followed-up closely. Between 2007 and 2020 (group B), local treatment was routinely given at 12 weeks according to the COG protocols, irrespective of IC response. For all patients, consolidation chemotherapy was administered for additional 12-18 months. RESULTS: Between 1996 and 2020, 27 patients (10 stage II, 17 stage III) with a median age of 3(1-21) years were included. Median follow-up was 87.5(15.3-247.1) months. Among 15 patients in group A, 3 were ineligible for the monotherapy protocol and received local treatment. The remaining 12 patients [9 complete (CR) and 3 incomplete response (IR) to IC] were treated exclusively with chemotherapy, of whom 9 were alive free of relapse at last follow-up. Two patients with IR to IC had disease relapse: one had pulmonary relapse at 8.2 months and one had local relapse at 35 months. The 5-year OS and EFS of group A were 86.7% and 80%, respectively. Analyzing survival according to IC response, CR to IC was achieved in 10 patients (9 group A and one group B) and was associated with significantly better OS and EFS than IR(p = 0.026 and 0.004, respectively) (Summary figure). All patients with CR to IC were alive free of relapse at last follow-up. DISCUSSION: Treatment of RMS is traditionally multimodal. Local treatment of B/P RMS is associated with significant patient morbidity. In this study, CR to IC predicted better OS and EFS. Patients who achieved CR (radiological and pathological) to IC remained alive free of relapse irrespective of local treatment. CONCLUSIONS: Our results suggest that patients with non-metastatic non-alveolar B/P RMS who achieve CR to IC can be treated with combination chemotherapy as a monotherapy and spared the morbidity of local treatment with durable survival outcomes. Prospective validation in a larger patient cohort is needed to support our hypothesis.

Diffusion-weighted MR imaging of mediastinal lymphadenopathy in children.

PURPOSE: To assess mediastinal lymphadenopathy in children with diffusion-weighted MR imaging. MATERIALS AND METHODS: Retrospective analysis of 29 consecutive children (18 boys and 11 girls aged 2-15 years) with mediastinal lymphadenopathy. They underwent single-shot echo planar diffusion-weighted MR imaging of the mediastinum with b factors of 0, 300, and 600 s/mm(2). The ADC value of the mediastinal lymph nodes was calculated and correlated with biopsy results; statistical analysis was also performed. RESULTS: The mean ADC value for malignant mediastinal lymphadenopathy (n = 20) (0.99 ± 0.18 × 10(-3) mm(2)/s) was significantly lower (P = 0.001) than that for benign lymphadenopathy (n = 9) (1.35 ± 0.26 × 10(-3) mm(2)/s). There was significant difference between ADC values for non-Hodgkin lymphoma and metastatic nodes (P = 0.04). For differentiating malignant from benign mediastinal lymphadenopathy, the best result was obtained when an ADC value of 1.22 × 10(-3) mm(2)/s was used as a threshold value; area under the curve was 0.861, accuracy 93.1 %, sensitivity 100 %, specificity of 77.8 %, positive predictive value 90.9 %, and negative predictive value of 100 %. CONCLUSION: Diffusion-weighted MR imaging is a promising non-invasive imaging modality that can be used for differentiation of malignant from benign mediastinal lymphadenopathy in children.

Prognostic factors of germ cell and sex cord-stromal ovarian tumors in pediatric age: 5 years experience.

BACKGROUND: Ovarian tumors in the pediatric age group are not infrequent. Germ-cell tumors are the commonest ovarian neoplasm in the first two decades of life. Sex cord-stromal tumors are the most common ovarian tumors to cause precocious puberty in girls. PATIENTS AND METHODS: This retrospective study included all managed cases of malignant germ-cell and sex cord-stromal tumors in the pediatric age (less than 18 years). The medical records of the admitted cases from first of January, 2008 to 31 December, 2012 were reviewed and the following information was collected: patient age, clinical presentation, surgical stage, tumor histology, therapy, clinical course, and outcome. Serum alpha-fetoprotien on admission was studied. RESULTS: The study included 42 pediatric cases of germ-cell and granulosa cell tumors of the ovary. Mean age of the cases was 11.26 years (range: 7-15 years). Abdominal pain was the commonest presentation. Twenty-two cases (52.4%) were diagnosed as stage I disease. Twenty-eight cases (66.7%) were exposed to fertility sparing surgery. Age of the patient and site of tumor were significantly correlated to the survival (p value: 0.04 & 0.09 respectively). The correlations of stage of the disease, use of pre-operative chemotherapy, and type of surgical interference were highly significant (P value: 0.007, 0.001, and 0.001 respectively). Tumor size and histologic types were not significantly correlated to survival (P value: 0.19 & 0.67 respectively). CONCLUSION: The cumulative survival rate was 76.2%. The correlations of stage of the disease, use of pre-operative chemotherapy, and type of surgical interference were highly significant. Tumor size and histologic types were not significantly correlated to survival. Initial level of alpha-fetoprotein was not significantly correlated to survival or recurrence.

Bilateral Wilms' tumor: Mansoura multi-centers 15 years experience.

PURPOSE: Bilateral Wilms' tumor (WT) is a challenge. Aggressive surgical resection is needed to prevent recurrence. We revised the clinico-epidemiological criteria of bilateral WT patients in our locality and relation to outcome. SUBJECTS AND METHODS: 462 WT patients were registered in three medical centers at Mansoura, Egypt. Twenty five patients had bilateral WT whose medical records were revised for all clinico-epidemiologic data plus treatment details, toxicity, and outcome. RESULTS: The mean age was 34.5 months; 64% of cases were female. Abdominal mass was the commonest presentation (72%). Congenital anomalies were reported in two cases (one case showed hemihypertrophy and the other showed aniridia). About 60% had favorable pathology. Nineteen cases had synchronous bilateral WT (76%) and the remaining (six cases) had metachronous tumors. For the synchronous cases, the response rate to preoperative chemotherapy was 79% and nephron sparing surgery for the least involved kidney was possible in all. Survival rate was 74%. Metachronous tumor management included nephrectomy followed by chemotherapy for the initially diagnosed tumors. However, nephron sparing surgery of the contralateral tumors following preoperative chemotherapy was possible in two cases and the survival rate was 33%. No renal failure or any therapy-related complications were reported. CONCLUSIONS: Bilateral WT is predominantly synchronous with favorable histology, with female predilection and possibly congenital anomalies. Preoperative chemotherapy followed by nephron sparing surgery has a favorable outcome with preserved renal function especially in patients with synchronous WT. Response to preoperative chemotherapy had a statistically significant prognostic impact.

Descriptive epidemiology of hemophilia and other coagulation disorders in mansoura, egypt: retrospective analysis.

Hemophilia represent the most severe inherited bleeding disorder (INB), it's thought to affect inviduals from all geographical areas in equal frequency. In Egypt which has a population of approximately (80million) consanguineous marriage are frequent, therefore autosomal recessive coagulation disorders reach a higher prevalence than in many other countries.The primary aim of this study was to describe the epidemiological situation of hemophilia in Mansoura, Egypt, as based on retrospective analysis of clinical records Mansoura University Children Hospital between years 2000 and 2008. The second aim was to assess the orthopedic complications and occurrence of hepatitis C in those patients and relate this status to the type of replacement therapy received prior to the study.The study included 72 children with hematological disorders registered from 2000 to 2008 in MUCH. The hemophilic patient was defined as a person with physician-diagnosed hemophilia A or B and a measured factor VIII or IX activity level of 30% or less. Persons with acquired inhibitors of FVIII or FIX excluded. Severity level was categorized as mild if the factor activity level was 6-30%, moderate if 1-5% and severe if <1% of normal.The severe presentation represents the majority in 76.7% followed by moderate severity in 17.2%. The commonest IBDs was hemophilia A affecting 44 patients, followed by Hemophilia B affecting 15 patients. The rare types were Factor XI deficiency, Factor V deficiency, Factor VII deficiency and combined FVIII, FIX and FX deficiency. The commonest orthopedic manifestation needing therapy was found among hemophilia A representing 8.3%. Hepatitis C viremia detected by PCR was found in 11.1% of patients. The bleeding complications as hematoma or hemarthrosis were the common complications. Nevertheless, 44.4% of patients had no complications, From this study we can conclude that the most common IBDs in our locality is hemophilia A followed by hemophilia B. The common presenting symptom was bleeding following male circumcision. Hepatitis C infection and arthropathy represented the main complications. The discovery of IBDs in young age children with proper supportive therapy could prevent arthropathy. Proper screening of blood and blood products reduce the risk of viral hepatitis and HIV acquisition.

Expression of lung resistance protein and multidrug resistance-related protein (MRP1) in pediatric acute lymphoblastic leukemia.

Multidrug resistance (MDR) is a phenomenon by which cells become resistant to unrelated chemotherapeutic agents. The prognostic value that lung resistance protein (LRP) and multidrug resistance-related protein 1 (MRP1) have in the setting of pediatric acute lymphoblastic leukemia (ALL) is controversial. The aim of this study was to investigate the expression of LRP and MRP1 and effect on clinical outcome and prognosis. The mRNA expression of LRP and MRP1 were analyzed in leukemic blasts of 34 pediatric ALL patients. LRP and MRP1 mRNA expression were detected in 41.2% and 35.3%, respectively. Eleven (91.7%) of 12 patients without LRP achieved CR compared with 9 (50.0%) of 18 with LRP expression. Similarly, 11 (100%) of 11 patients without MRP1 expression achieved CR compared with 9 (47.4%) of 19 with MRP1 expression and higher LRP expression rate or MRP1 expression rate was present in patients with relapse than MDR genes negative patients. The expression of either of two genes was associated with poorer 2-year survival. Also, patients expressing both genes had poorer outcomes and had worse 2-year survival. We suggest that MDR expression affects complete remission and survival rates in ALL patients. Thus, diagnosis appears to provide prognostic information for pediatric ALL.