Did salvage ICE chemotherapy improve the outcome in primary resistant/relapsing stage III/IV neuroblastoma?

Background and purposeNeuroblastoma is the most common extracranial and deadly 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” of treatment failure.The aim of this study is to evaluate the response rate of salvage chemotherapy by the ICE (Ifosfamide, Carboplatin, and Etoposide) regimen when administered to previously treated primary refractory or progressive high risk neuroblastoma patients.Patients and methodsSixty-six patients from the National Cancer Institute (NCI), Cairo University and the Children Cancer Hospital Egypt (CCHE) received salvage chemotherapy (ICE) either due to primary resistance in 51/66 (77.2%) or due to disease progression on primary chemotherapy in 15/66 (22.8%).ResultsThey were 40 males (60.6%) and 26 females (39.4%). Patients’ age ranged between 3 months and 12.5 years. The most common tumor site was suprarenal, followed by retroperitoneal mass. Two patients (3%) died from chemotherapy toxicity during ICE administration. Evaluation of tumor response in the remaining 64 patients showed the following: CR/PR in 24 patients (36.5%), SD in 11 patients (16.6%), and PD in 29 patients (43.9%).Fourteen patients (21.2%) were considered eligible for auto BMT, while 50/64 patients (78.8%) failed this second line (salvage) chemotherapy and had palliative lines of therapy.By the end of the study (May 2010), 47/66 (71.2%) of the patients were still alive, while 19/66 (28.8%) were dead. Two out of 14 patients (14.2%) who underwent HSCT died from post transplantation disease progression, while 12/14 (85.8%) were in CCR.ConclusionChemotherapy by ICE for primary resistant or progressive stage III/IV NB seems well tolerated. With a 36.6% response rate, 18% CCR, and 3% treatment mortality rate, it could be considered a good salvage therapy in the category of patients who are condemned for palliation.     

Therapeutic role of low-carbohydrate ketogenic diet in diabetes

IntroductionChanges in dietary habits influence the glycemic level. Preliminary studies using the low-carbohydrate ketogenic diet (LCKD) were found to be quite promising in controlling diabetes mellitus. Therefore, the objectives of this study are to investigate the therapeutic effects of LCKD in experimental diabetic rats following the administration of streptozotocin (STZ).Materials and methodsAdult rats were divided into three groups: normal diet, LCKD, and high-carbohydrate diet. Each group was subdivided into normal, sham, and diabetic groups. Diabetes was induced by a single intraperitoneal injection of STZ (55 mg/kg). Specific diets were given to each group of animals for a period of 8 wk and then the animals were sacrificed. The rats were monitored daily for food and water intake, whereas body weight, urine output, and blood glucose levels were monitored weekly. The histology of the islets of Langerhans was studied by histochemical methods.ResultsThe results showed that LCKD was effective in bringing blood glucose level close to normal (P < 0.01). Food and water intake and urine output were increased in all groups except the LCKD group (P < 0.01). The body weight was significantly reduced in all diabetic animals except in the LCKD group (P < 0.01). Histologic studies showed significant decrease in the islet size and number of β cells in all the diabetic groups.ConclusionThis study indicates that LCKD has a significant beneficial effect in ameliorating the diabetic state and helping to stabilize hyperglycemia.     

Methylene blue dye--a safe and effective alternative for sentinel lymph node localization

Abstract:  Sentinel lymph node (SLN) biopsy has emerged as an effective diagnostic tool in axillary staging in breast cancer. The commonly used technique employs isosulfan blue/patent blue V combined with radioactive colloid tracer. Methylene blue (MB) is a less expensive and readily available alternative dye. The study evaluated the safety and efficacy of MB in SLN localization. A retrospective study of 329 patients with early breast cancer who had SLN localization as part of an ethically approved prospective evaluation study of SLN localization technique was carried out. Lymph node positive, tumors >2 cm on clinical and radiological evaluation, those with previous breast and axillary surgery, neo-adjuvant chemotherapy were excluded from the study. One hundred seventy three patients underwent SLN localization using 1 mL of 1% MB, and a combined MB-radio colloid tracer technique was used in the other 156 patients. Allocation to the groups was by simple randomization. Injection of the dye and radioisotope was into the subdermal plane in the sub-areolar region. Patients underwent breast conservation surgery or mastectomy with SLN directed four node axillary sampling ± axillary clearance. The lymph node was examined by standard microscopy. There were no reported complications with the use of MB aside from temporary tattooing. The technique failed in eight patients giving an identification rate of 97.6%. Ten of the 258 (3.9%) patients had false-negative SLN, with negative predictive value of 96.1%, sensitivity of predicting further axillary disease of 73%, specificity of 87.3%, and overall accuracy of 85.7%. Reported adverse reaction to isosulfan blue/patent blue V varied from minor to severe anaphylactic reactions (1–3%) requiring vigorous resuscitation. Subdermal sub-areolar injection of MB is safe and effective readily available dye for SLN localization in axillary staging of breast cancer with no major adverse reaction.     

Differential expression of cyclin-dependent kinase inhibitors and apoptosis-related proteins in endocervical lesions

The development of neoplasia is associated with abnormalities of cell cycle control and apoptosis. In this study, a panel of cyclin-dependent kinase inhibitors (CDKIs) and apoptosis-related proteins (p16, p21, p53, Bcl2 and hsp27) was analysed by immunohistochemistry in 91 glandular cervical lesions. A significant increase in p21 and p53 expression occurred from normal cervix (n=11) through endometriosis/tubo-endometrioid metaplasia (TEM) (n=19) and cervical glandular intraepithelial neoplasia (CGIN)/adenocarcinoma in situ (AIS) (n=33) to invasive adenocarcinoma (n=28). p16 showed diffuse strong expression in CGIN/AIS and invasive adenocarcinoma compared with focal expression in some TEM/endometriosis lesions and no expression in normal cervix. Bcl2 was highly expressed in TEM/endometriosis compared with CGIN/AIS and adenocarcinoma. p16 immunostaining discriminated accurately between neoplastic and non-neoplastic cervical lesions, provided that diffuse strong positivity was present. Similarly, diffuse expression of Bcl2 distinguished endometriosis/TEM from CGIN/AIS. These data demonstrate that analysis of CDKIs and apoptosis-related proteins provides useful information in the diagnostic assessment of glandular lesions of the cervix.     

Recent advances in pharmacokinetic modeling

A major part of the science of pharmacokinetics is the modeling of the underlying processes that contribute to drug disposition. The purpose of pharmacokinetic models is to summarize the knowledge gained in preclinical and clinical studies at various stages in drug development and to rationally guide future studies with the use of adequately predictive models. This review highlights a variety of recent advances in mechanistic pharmacokinetic modeling. It is aimed at a broad audience, and hence, an attempt was made to maintain a balance between technical information and practical applications of pharmacokinetic modeling. It is hoped that drug researchers from all disciplines would be able to get a flavor of the function and capacity of pharmacokinetic modelers and their contribution to drug development. While this review is not intended to be a technical reference on modeling approaches, the roles of statistical applications and population methodologies are discussed where appropriate.     

Ketamine–propofol versus ketamine fentanyl for anesthesia in pediatric patients undergoing cardiac catheterization: A prospective randomized study

ObjectiveThe aim of the study was to assess, compare the safety and efficacy of continuous IV administration of a combination of ketamine–propofol versus ketamine fentanyl for anesthesia in children undergoing cardiac catheterization procedures with RT to Lt Shunt.MethodsThirty-six children aged from 1 to 8 years, with RT to Lt Shunt scheduled for Cardiac catheterization in Mansoura Children Hospital were included in this study. Patients in group KP (n = 18) received ketamine (1 mg/kg) and propofol (2 mg/kg) as induction agents followed by combination of ketamine (25 μg/kg/min) and propofol (25 μg/kg/min) for maintenance of anesthesia. On other hand, patients in group KF (n = 18) received ketamine (1 mg/kg) and fentanyl (1 μg/kg) as induction agents followed by combination of ketamine (25 μg/kg/min) and fentanyl (0.75 μg/kg/min) for maintenance of anesthesia. Hemodynamic, oxygenation, recovery variables and side effects were recorded.ResultsThere were no statistical significant differences with age, sex, duration of anesthesia. There were statistical significant decreases in mean arterial blood pressure (MAP), systemic vascular resistance (SVR), pulmonary to systemic vascular resistance ratio in KP group. Additionally, Sao₂ and Pao₂ after anesthesia in KF group were statistically significant higher than the other group. Also there was significant prolongation of time to full recovery in KF group compared with KP group.ConclusionWe concluded that a combination of ketamine–fentanyl is safer and more efficacious than ketamine–propofol for pediatric cardiac catheterization although it was associated with prolonged recovery time.     

Pulsating Suprasternal Lump: A Diagnostic and Management Dilemma

We report a 70-year-old female who complained of shortness of breath and a pulsating suprasternal lump. CT scan showed innominate artery dilatation. In addition, operative exposure showed tortuous arteries and a common origin of the left common carotid and innominate arteries. Surgical correction by innominate artery division and reimplantation at the ascending aorta was performed, and the patient’s symptoms completely disappeared after the procedure.