الفهرس 
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Abstract
Neu roblastoma is almost exclusively a disease of children. It is the third most common childhood cancer after leukaemia and brain tumours, and the most common solid extra-cranial tumour in children. More than 600 cases are diagnosed in the United States each year and about 100 in UK which accounts for approximately 15 percent of all paediatric cancer fatalities; The incidence of Neuroblastoma is greater among white than black infants (ratio of 1.7 and 1.9 to 1 for males and females, respectively), but little if any racial difference is apparent among older children In this study the impact of up-front 131 I-MIBG and preoperative chemotherapy on intra-operative surgical technique was accurately monitored. Recording of intra-operative data at different stages of surgical intervention including accessibility and respectability of the tumour, success in achieving a complete resection and frequency of presence of visible residuals after resection, intra-operative and immediate postoperative complications, disease free survival and prognosis was completed. Finally data were analysed to anticipate impact and best time for planning surgical resection. Out of all Neuroblastoma patients presented to our institute (2001 2006), 35 patients fulfilled the selection criteria of having no previous treatment received, primary tumour site of adrenal, non adrenal abdominal, thoracic, abdomin-othoracic, of any stage rather than stage I and finally eligible and fit to receive preoperative 131 I-MIBG up-front therapy, preoperative chemotherapy and surgical intervention at the proper planned time. Response to treatment was recorded and classified, defines different responses to treatment as classified; many investigators adopted the expression of objective response to denote a group of responders having a satisfactory treatment outcome in the form of CR to PR. Follow up was through complete reassessment for patients at the end of their treatment and during the scheduled follow up period (24 60 months), CT/MRI for the sites of previously known lesions and 1311-MIBG-scan were planned every 3 months during the first year and then every 6 months. Epidemiological review showed an increase of the male predominance with a ratio of 1:33:1 Male to Female, literature records stated the existence of a modest difference in incidence rates by sex (boy : girl rate ratio = 1.2). Age distribution expressed a different pattern: only 9% were less than 1 year, majority (67 %) were found five or less years old while 33 % were found more than five years old. Evaluation of age as a prognostic index has shown that impact on survival is insignificant. Primary sites of tumour varied greatly, this included abdominal cavity in 60%, 18% in paraspinal ganglia or involved other sites (6% thoracic, 6% pelvic, 3% cervical and 7% miscellaneous). 75% of patients were presented by abdominal distension, while 37% with dyspnoea that could be explained on base of presence of a mass causing airway obstruction or chronic cough (reported in 5%) , leading to a chest radiograph. Because more than 50% of patients present with advanced-stage disease, 201 usually to the bone and bone marrow, common presentation symptoms included bone pain and a limp (12% in this cohort), the presence of bone metastases can lead to pathologic fractures . However, patients may also present with weight loss (45%), fatigue (20%), unexplained fever (15%), irritability and headache (5%), other symptoms recorded in literature include periorbital ecchymosis secondary to metastatic disease to the orbits. On further clinical examinations and investigations, other signs could be observed, 46% of patients had anaemia while cyanosis, oedema, delayed milestone, hypertension, paresis and paralysis caused by tumour invading through neural foramina and compressing the spinal cord extradurally were reported by some authors. Our study has shown different secondary metastatic sites of the disease, LNs had the highest share among all in a percentage of 51% followed by bone and bone marrow metastasis at percentages of 31% and 29 %, this is of a unique value in managing and treating neuroblastoma as presence of metastasis should be taken in consideration on planning treatment protocols due to their impact on prognosis Diagnostic tools for this cohort of patients followed the International Neuroblastoma Staging System (INSS) by either characteristic histolopathologic evaluation of tumour tissue through tissue biopsy (77%), FNAC in 9%; or by the presence of tumour cells in a bone marrow aspirate/biopsy and elevated levels of urinary catecholamines in 14% of patients. Eventhough ferritin level in serum at diagnosis is useful for selecting appropriate therapy especially in Stage III of the disease we did not find it useful in anticipating prognosis. 66% of patients had elevated level of serum Ferritine suggestive of poor outcome and reflecting the possible requirement of a more aggressive therapy, while 34% had normal levels expected to have a good outcome yet on real evaluation of the impact on prognosis, the statistical significance found to be negative denying any impact on survival. Other authors as well denied the value of using Serum Ferritine as a sole indicator of tumour activity in neuroblastoma While Neorone Specific Enolase recorded among our patients expressed a significant impact on survival (p<0.05) and found useful to detect disease relapse and metastatic recurrence. On review of the treatment results, encouraging results have been reported with 131-IMIBG used alone in patients resistant to conventional therapy and at diagnosis and new protocol to use 131I-MIBG therapy in newly diagnosed patients instead of combination chemotherapy prior to surgery has been raisin. We have experienced a complete response to MIBG therapy in 2 patients (2.71%) and partial response in(37.14%), these patients had a fairly straight forward surgical intervention with relative easy surgical technique and complete resection of the residual tumour, and on evaluation of the impact of this objective response on surgical resectability, a (p<0.025) was estimated suggesting a significant impact of MIBG therapy response on surgical technique. 202 In our study 33 patients completed the initial four cycles of 1st line chemotherapy in the form of alternating cycles of OPEC / OJEC while only one patient died after the third cycle as a result of intracranial haemorrhage and coma. The Objective Response was 74% with tolerable toxicity and their surgical resection was relatively easy, successful and complete in the majority of cases who expressed objective response to treatment. Authors demonstrated the efficacy of that treatment recorded reassuring figures . While further analysis showed that cases which express good response to initial 4 cycles will continue to respond properly to the completion of 7 cycles, and surgical intervention is best employed either following the initial 4 cycles or better following completion of the 7 cycles depending on the volume of residual during reassessment following the 4th cycle of 1st line chemotherapy as statistical analysis of intra-operative data has shown maximum success in completion of resection of the primary among those who had their planned surgical interventions following completion of 7 cycles of 1st line Chemotherapy while cases that express minor response or even show evidence of progression of the disease should switch to another line of treatment possibly via offering early surgical exploration for possibility of debulking of the tumor to allow better response to further adjuvant therapy. The role of surgical intervention in the multimodality approach to neuroblastoma is undebatable, however there is still much controversy regarding the best surgical approach particularly for high-risk disease. The time of surgical intervention, extent of surgery to include primary and or secondary tumour sites, radicality and outcome of resection are yet still to be explores. Further analysis of our results challenging the operative results against response to initial pre-surgical multi-modality treatment has shown clearly that initial surgical intervention, was successful and complete in 14 out of 24 patients who had objective response to pre-surgical treatment while was neither successful nor complete in all patients who expressed minor response or progressive disease despite pre-surgical element of multimodality treatment (p<0.025) suggesting a significant correlation. On the other hand 2nd line chemotherapy expressed a non significant impact on surgical resectability, i.e. p<1. Though Second Look surgery implemented a great impact and had a significant role (p<0.01) in achieving complete clearance for those who had incomplete resection at the initial session, there was no significant impact of the initial response to pre operative treatment (p<1) on results of 2nd Look Surgery. Some authors used 2nd look surgery for assessing the effectiveness of treatment and for sampling of retroperitoneal lymph nodes as a prognostic indicator However this value is of less important now due to the prominent progress in radiological techniques and investigations. 7 of our patients had localized radiation to residuals following incomplete surgical resections, The value of External beam radiation therapy that appeared effective in high-intensive treatment of stage 4 neuroblastoma has been recorded, it seems to compensate the disadvantage of incomplete response to induction chemotherapy 203 In an over all evaluation for the treatment outcome, the overall survival after 6 month of treatment was 77% and after 12 months 60%, 2 years overall survival was 54%. In addition to the previously discussed impact of biochemical levels as prognostic factors , we experienced that disease Stage at time of presentation was a prominent prognostic indicator for survival, patients who presented at stage 2 of the disease had a far better survival than those who presented at stage 3 and 4 of the disease, (p <0.025), this is confirmed by other authors who have pointed to the fact that one with biggest prognostic efficacy is the stage of the disease at the time of presentation , suggesting a significant impact for the stage of the disease on survival and prognosis. And though primary site of the disease didn’t have a direct impact on prognosis (P<1 ) , it is still affects treatment outcome as many authors have reported the value of complete resection of the tumour on prognosis which in turn is affected by the primary tumour site Evaluation of the impact of the overall tumour clearance on survival, a significant impact was calculated, complete resection of the primary tumour and retroperitoneal lymphadenectomy provides excellent locoregional control for patients with abdominal neuroblastoma and produces a better survival rate. If there is any doubt in the primary possibility of complete tumour resection a reduction of the tumour mass can be achieved by chemotherapy. This allows radical surgery achievable in significantly more cases. On the other hand, the response to 2nd line chemotherapy on the overall all survival was limited and expressed a non significant relation. Finally, another important factor that has played a great role in providing our patients with a better survival was the level of family awareness and health education, children of parents who had a reasonable level of education had a better chance of having a better follow up, more close contact and early hospital admission and treatment on suspecting complication by parents during the follow up period. Teaching parents about the nature of the disease, symptoms and signs and possible complications is a cornerstone in fighting the disease.