Daniel M. Green

Screening for Wilms tumor in children with Beckwith-Wiedemann syndrome or idiopathic hemihypertrophy.

BACKGROUNDnChildren with Beckwith-Wiedemann syndrome and idiopathic hemihypertrophy (BWS/HH) are at increased risk for developing Wilms tumor and screening with abdominal sonography is frequently recommended. However, there is a paucity of published data supporting this strategy. The purpose of this study was to determine whether sonographic screening at intervals of 4 months or less reduced the proportion of late-stage Wilms Tumor (WT) in children with BWS/HH.nnnPROCEDUREnA case series analysis was employed to compare the proportion of late-stage (stage III or IV) Wilms tumor in patients with BWS/HH who were screened with sonography (n = 15) to the proportion of late-stage Wilms tumor in unscreened patients with BWS/HH (n = 59). Patients were identified from the BWS Registry and from previously published studies. Screened patients had sonograms at intervals of 4 months or less.nnnRESULTSnNone of the 12 screened children with Wilms tumor had late-stage disease, whereas 25 of 59 (42%) of unscreened children had late-stage Wilms tumor, a difference that was statistically significant (P < 0.003). Three children had false positive screening studies. They were operated on for suspected Wilms tumor but the lesions proved to be complicated renal cysts (n = 2) or nephroblastomatosis (n = 1).nnnCONCLUSIONSnThis study suggests that children with BWS/HH may benefit from screening sonograms at intervals of 4 months or less. However, false positive screening exams may result in unnecessary surgery. Given the rarity of BWS/HH, a larger, prospective international screening study is necessary to determine if the benefits of screening outweigh the risks.

Secondary acute myelogenous leukemia in patients previously treated for childhood renal tumors : A report from the National Wilms Tumor Study group

Purpose This review characterized cases of secondary acute myelogenous leukemia (AML) occurring after treatment of renal neoplasms on protocols of the National Wilms Tumor Study Group (NWTSG) between October 1969 and December 1991. Patients and Methods The NWTSG database was reviewed for cases of secondary AML and for WT1 status of the affected patients. Referring institutions were contacted by a confidential letter requesting pathology reports, results of immunophenotyping, cytogenetic, and molecular analyses, and details concerning treatment of AML. Results Of the 5,278 patients treated during the study period, 43 had second malignant neoplasms, and 7 of these 43 had AML. At the time of diagnosis of Wilms tumor, the median age of the seven patients (4 boys) was 3.2 years. Five of the seven renal neoplasms had favorable histologic characteristics. The most common French-American-British morphology was M5. One patient had bilateral tumors, and two were treated for recurrent Wilms tumor. All patients received chemotherapy regimens that included doxorubicin (6) or etoposide (1), and six were treated with infradiaphragmatic irradiation. The median latency period from initial diagnosis of the renal neoplasm to development of secondary AML was 3 years (range, 1.2–4 yrs). One patient had the translocation t(9;11)(p22;q23);WT1 status was not noted for any of the seven patients. Conclusions The development of secondary AML in this subset of patients after treatment of renal neoplasms may reflect the interaction of the effects of treatment and possible genetic predisposition toward cancer.

Factors that influence the further survival of patients who survive five years after the diagnosis of cancer in childhood or adolescence

To evaluate the further survival, and to identify disease and treatment factors which influence the further survival, of five-year survivors of cancer diagnosed during childhood or adolescence, we reviewed the courses of 591 previously untreated patients who were less than 20 years of age at diagnosis and survived for five years after diagnosis. Fifty-three of 143 patients who experienced disease recurrence during the first five years after diagnosis died during the period of observation, compared to 18 of 448 patients who did not experience disease recurrence during the first five years after diagnosis. The sex-specific standardized mortality ratios for the group of patients who never relapsed or relapsed more than five years after diagnosis were not significantly different from those of the New York State population. Cox proportional hazards modelling of the subgroup of patients who relapsed during the first five years after diagnosis demonstrated that disease which was treated surgically, a diagnosis of Hodgkins disease or acute lymphoblastic leukemia, and older age at diagnosis were significantly associated with further survival in this group, whereas similar modelling of the patients who did not experience disease recurrence during the first five years after diagnosis failed to identify any variables which were associated with continued survival. The results of this study suggest that childhood and adolescent cancer patients who survive for five years without disease recurrence have a survival rate similar to that of the general population. Continued follow-up of this cohort is required to determine if the present findings can still be demonstrated as the majority of the cohort ages beyond 35 years of age.

Renal artery stenosis and hypertension after abdominal irradiation for Hodgkin disease. Successful treatment with nephrectomy.

Hypertension secondary to stenosis of the left renal artery developed in a thirteen-year-old male six years after completion of inverted Y irradiation (3,600 rad) for abdominal Hodgkin disease. Surgical treatment with nephrectomy resulted in control of the hypertension without the use of antihypertensive agents. We review the literature for this unusual complication of abdominal irradiation, and recommend that a 99mTc-DMSA renal scan, selective renal vein sampling for renin determinations, and renal arteriography be performed on any patient in whom hypertension develops following abdominal irradiation in childhood.

Renal failure does not preclude cure in children receiving chemotherapy for Wilms tumor: A report from the National Wilms Tumor Study Group

Children with Wilms tumor can develop renal failure during treatment. Since there are few published data concerning the appropriate chemotherapy for this situation, we reviewed the experience of children who developed renal failure while being treated on National Wilms Tumor Study Group (NWTSG) studies 1–4 (1969–1994).

Long-term complications of treatment of children and adolescents with cancer: gene polymorphisms and causes of excess mortality.

The therapy of children and adolescents with cancer has become increasingly successful; more than 70% of all those diagnosed now live 5 or more years after diagnosis, and most will never suffer a recurrence of the original cancer. As these survivors of childhood and adolescent cancer mature, they become aware of issues related to the original diagnosis and treatment of which they may have been unaware during the time of active therapy. These include wellknown quality-of-the-adult-life issues, such as normal reproduction, as well as less widely appreciated concerns; for example, the possible occurrence of second malignant tumors. The Ninth International Conference on the Long-Term Complications of Treatment of Children and Adolescents with Cancer was held in Niagara-on-the-Lake, Ontario, Canada from June 9 to 10, 2006. The conference attendees included over 250 professionals, including 106 MDs and PhDs from the United States, 15 from the United Kingdom, 15 from the Netherlands, 14 from Canada, 5 from Australia, 3 from Germany, 2 from Denmark, 2 from Israel, 2 from New Zealand, and 1 from Belgium, Brazil, Greece, Hong Kong, Italy, Japan, Romania, Slovenia, Switzerland. In addition, the conference was attended by 99 nurse practitioners, physician’s assistants, nurses, and other allied health professionals, including masters students, clinical research associates, social workers, etc. from 24 states (Arkansas, California, Colorado, Connecticut, Florida, Iowa, Illinois, Massachusetts, Michigan, Minnesota, Missouri, North Carolina, Nebraska, New Jersey, New York, Ohio, Oregon, Pennsylvania, Tennessee, Texas, Utah, Virginia, Washington, Wisconsin) and the District of Columbia, and from Australia, Canada, The Netherlands, New Zealand, and the United Kingdom. The conference included 10 invited presentations organized around the theme of the symposium. These talks encompassed the origin and identification of gene polymorphisms, the difference between association of gene polymorphisms with versus causation of diseases, the relationship of gene polymorphisms and drug toxicity, the causes of mortality in survivors of childhood cancer, the relationship between gene polymorphisms and susceptibility to coronary artery disease, leptin receptor gene polymorphisms and obesity, glutathione-S-transferase and XRCC1 polymorphisms and second malignant tumors, genetic polymorphisms and treatment related leukemia, gene polymorphisms and behavior, and the use of gene polymorphisms for disease prevention. The present issue includes all articles prepared by the invited speakers. The comprehensive and thoughtful articles prepared by the invited speakers provide an excellent review of these areas for all who provide care for long-term survivors of childhood and adolescent cancer.