Do longer formula feeding and later introduction of solids increase risk for pediatric acute lymphoblastic leukemia?

Milk formula feeding can elevate insulin-like growth factor-1 levels, possibly impacting leukemogenesis. The intent of the current study is to examine the associations between infant feeding practices and age at introduction of solids on risk of childhood acute lymphoblastic leukemia (ALL). Incident cases of infant and childhood (aged ≤14 years) ALL (n = 142) were enrolled in a case–control study. Cases were frequency matched on age, sex, race, and ethnicity to two sets of controls (n = 284 total). Multivariable logistic regression was used to determine the association between infant feeding practices and age at the introduction of solids and the odds ratio of ALL. In adjusted multivariable analyses, each additional month of formula feeding was associated with a 1.17 (1.09–1.25) odds ratio; each additional month of age at introduction of solids was associated with a 1.18 (1.07–1.30) odds ratio. In this study, longer duration of formula feeding and later age at the introduction of solid foods were independently associated with increased risk of ALL. Additional studies are needed to address the factors influencing duration of formula feeding and delayed introduction of solids. The results support the potential role of energy balance in early life as a contributor to risk for pediatric acute lymphoblastic leukemia.     

Increased pulmonary artery pressures among adolescents with sickle cell disease

The prevalence of pulmonary hypertension (PHT) among adolescents with sickle cell disease (SCD) is unknown. A tricuspid regurgitant (TR) jet peak velocity of 2.5 m/s or more is a screening test for PHT. The authors retrospectively reviewed echocardiograms and clinical data of adolescents followed at the Texas Children's Sickle Cell Center. Of 80 evaluable adolescents with SCD and echocardiogram data, 21 (26%) had a TR jet velocity of 2.5 m/s or more. Of these 21 patients with PHT, 12 (57%) had an echocardiogram performed during an inpatient stay for vaso-occlusive crisis (n = 6), acute chest syndrome (n = 4), fever (n = 1), or seizures (n = 1), and 9 (43%) had an echocardiogram performed as an outpatient in a baseline state of health. Elevation of pulmonary artery pressures was common in this adolescent cohort, but clinical symptoms were rare. Prospective study is warranted to determine the prevalence and course of elevated pulmonary artery pressures in this age group.     

CXCR4 expression in neuroblastoma primary tumors is associated with clinical presentation of bone and bone marrow metastases

Background/Purpose

The chemokine receptor, CXCR4, has been implicated in the mechanism of tumor cell metastasis to bone and bone marrow. Neuroblastoma, a cancer of children, is well known for its potential to metastasize to these sites. The goal of this study was to investigate whether the degree of expression of CXCR4 on cells from neuroblastoma primary tumors was related to the pattern of metastatic involvement.

Methods

Archived neuroblastoma primary tumor samples and clinical data were collected from 26 patients with newly diagnosed neuroblastoma. Expression of CXCR4 (12g5 antibody) was evaluated on formalin-fixed paraffin-embedded tumor tissues using standard immunohistochemical techniques. Each tumor was graded (grade 1 through 4) based on the proportion of cells that were positive for the 12g5 antibody. Tumor grades for CXCR4 expression were compared with clinical data from each patient.

Results

Higher grades of expression (grade 3 and 4) were found in tumors from patients with high-stage disease (P < .01) and in patients with bone and bone marrow metastases (P ≤ .01). Clinical outcome in patients with tumors highly expressing CXCR4 was significantly worse (P < .01) than in those patients with low-grade CXCR4.

Conclusions

CXCR4 expression in neuroblastoma primary tumors is significantly correlated with the pattern of metastatic spread.     

Malignant transformation within benign adnexal skin tumours

AIMS: To report five malignant trichogenic tumours arising in longstanding, previously benign adnexal neoplasms through malignant transformation. Malignant trichogenic adnexal tumours are extremely rare neoplasms. METHODS AND RESULTS: The patients were between 55 years and 79 years of age. Three of the tumours were located on the arms, two on the face. Three of our patients had a history of chronic lymphocytic leukaemia, one patient had a history of colonic adenocarcinoma. The duration of the tumour nodules was reported as between 20 and 40 years before sudden changes occurred. These changes included rapid growth, pain, itching, ulceration and bleeding. Histologically, all tumours were well circumscribed and encapsulated. There was a residual benign tumour component and morphological signs such as bone formation, dystrophic calcification and sclerosis suggesting long duration of the lesions. All patients except for one, who refused further clinical investigation due to her advanced age of 79 years, had an underlying systemic malignancy. CONCLUSIONS: The growth stimulus in these benign adnexal neoplasms resulting in malignant transformation may be attributed to the acquisition of additional genetic events or to immunosuppression due to an underlying neoplastic disease. Therefore, patients with systemic diseases or malignancy should be carefully examined and followed for sudden changes in pre-existing benign cutaneous tumours.     

Antegrade nailing of femoral shaft fractures combined with neck or distal femur fractures

Introduction Complex femoral fractures pose considerable therapeutic challenges to orthopedic surgeons. We present a retrospective review of 25 patients with complex femoral fractures treated with intramedullary locked nailing and supplemental screw fixation.Materials and methods Fifteen patients with ipsilateral femoral neck and shaft fractures (group 1) and 10 patients with ipsilateral femoral shaft and distal femur fractures (group 2) were treated from 1990 to 1998. High-energy injuries occurred in all patients. There were 4 open fractures. Antegrade, locked nailing of diaphyseal fractures was performed in all cases. Supplemental screws for the neck were used in all patients in group 1 and in 3 patients in group 2.Results All of the fractures united during the follow-up. Five patients in group 1 underwent reoperation (33.3%): one due to a delayed union, the second due to an implant failure, the third due to a nonunion of a neck fracture, and the last two because of an initially missed femoral neck fracture. None of the patients in group 2 underwent reoperation. Angular malalignment of the shaft was found in 6 fractures in group 1 (average 4.8^o, range 3^o–11^o) and in 4 fractures in group 2 (average 6^o, range 3^o–12^o). Shortening of the limb occurred in 3 patients in group 1 (average 1.4 cm, range 1–1.8) and in 1 patient in group 2 (2 cm). Loss of fixation was seen in 1 patient in each group. Avascular necrosis and infection were not seen in any case in both groups.Conclusion Femoral intramedullary nails with antegrade or retrograde options for insertion and different locking possibilities have extended the indications to include both diaphyseal and metaphyseal fractures. New nail designs, usually more expensive than the conventional nails, have been introduced into the market for this purpose. One has to keep in mind that antegrade, locked nailing of femoral shaft fractures combined with neck or distal femur fractures is a technically demanding but efficacious procedure. The success rate is high when the technique is meticulously implemented.     

Pseudoaneurysms of the popliteal and tibioperoneal arteries after gunshot injuries

BACKGROUND: Pseudoaneurysms (PsAns) of the popliteal and tibioperoneal arteries are very rare and occur as a late complication after arterial injury. This study was undertaken to describe the management of PsAns of the popliteal and tibioperoneal arteries after gunshot injuries in a civilian vascular surgical unit with a large trauma workload. METHODS: A retrospective review of the records of nine patients treated between January 1998 and November 2001 at the Thoracic and Cardiovascular Surgery Department of Numune Education and Research Hospital was undertaken. RESULTS: Nine PsAns of the popliteal and tibioperoneal arteries after gunshot injuries were treated. The delay in diagnosis from the time of injury ranged from 15 days to 14 months, with a median delay of 75 days. One case with graft occlusion was noticed in a patient with a popliteal artery PsAn. In these cases, the early and late patency rate and limb salvage were 100%. CONCLUSION: Early diagnosis of popliteal and tibioperoneal PsAns is an important factor in successful surgical reconstruction. The operative procedures will be simple if the interval between injury and operation is short, and surgical treatment for PsAns includes reconstruction of both arterial and venous arteries.     

Risk analysis of severe myelotoxicity with temozolomide: The effects of clinical and genetic factors

A benefit of temozolomide (TMZ) is that myelotoxicity is uncommon. Recently, several small series have reported significant myelotoxicity resulting in treatment delays or death. The ability to predict risk of myelotoxicity may influence patient care. We retrospectively reviewed 680 malignant glioma patients and developed a clinical risk formula for myelotoxicity for each gender by logistic regression. The variables that remained were assigned a score of 1 and added together for a final risk score. Women experienced more myelotoxicity than did men (p = 0.015). For males, risk factors included body surface area (BSA) ≥ 2 m² (odds ratio [OR] = 2.712, p = 0.04), not on steroids (OR = 2.214, p = 0.06), and on bowel medication (OR = 3.955, p = 0.008). For females, final factors included no prior chemotherapy (OR = 3.727, p = 0.001), creatinine ≥ 1 mg/dl (OR = 6.08, p = 0.002), platelets < 270,000/mm³ (OR = 2.438, p = 0.03), BSA < 2 m² (OR = 4.178, p = 0.04), not on medication for gastroesophageal reflux disease (OR = 2.942, p = 0.01), and on analgesics (OR = 2.169, p = 0.05). Age was included because of observable trends. Risk of developing myelotoxicity ranged from 0% to 33% (male) and from 0% to 100% (females). Polymorphisms in NQO1 (NAD(P)H dehydrogenase, quinone 1), MGMT (O⁶-methylguanine-DNA methyltransferase), and GSTP1 (glutathione S-transferase pi 1) were related to risk of developing myelotoxicity in a subset of patients. Myelotoxicity with TMZ is a significant clinical issue for those at risk. Use of a clinical model to predict risk and evaluation of identified genetic polymorphisms related to myelotoxicity may allow for individualized dosing, optimizing patient management.