A preclinical and clinical study of lithium in low-grade neuroendocrine tumors

Background.

Low-grade neuroendocrine tumors (NETs) respond poorly to chemotherapy; effective, less toxic therapies are needed. Glycogen synthase kinase (GSK)-3β has been shown to regulate growth and hormone production in NETs. Use of lithium chloride in murine models suppressed carcinoid cell growth, reduced GSK-3β levels, and reduced expression of chromogranin A. This study assessed the efficacy of lithium chloride in patients with NETs.

Design.

Eligible patients had low-grade NETs. A single-arm, open-label phase II design was used. Lithium was dosed at 300 mg orally three times daily, titrated to serum levels of 0.8–1.0 mmol/L. The primary endpoint was objective tumor response by the Response Evaluation Criteria in Solid Tumors. Secondary endpoints included overall survival, progression-free survival, GSK-3β phosphorylation, and toxicity.

Results.

Fifteen patients were enrolled between October 3, 2007 and July 17, 2008, six men and nine women. The median age was 58 years. Patient diagnoses were carcinoid tumor for eight patients, islet cell tumor for five patients, and two unknown primary sites. Eastern Cooperative Oncology Group performance status scores were 0 or 1. Two patients came off study because of side effects. The median progression-free survival interval was 4.50 months. There were no radiographic responses. Because of an early stopping rule requiring at least one objective response in the first 13 evaluable patients, the study was closed to further accrual. Patients had pre- and post-therapy biopsies.

Conclusions.

Lithium chloride was ineffective at obtaining radiographic responses in our 13 patients who were treated as part of this study. Based on the pre- and post-treatment tumor biopsies, lithium did not potently inhibit GSK-3β at serum levels used to treat bipolar disorders.     

Epilepsy in a cohort of Senegalese children

Epilepsy is a significant health public problem in Senegal with an estimated prevalence of 8 to 14%. The aim of this study was to determine the clinical and electroencephalographic features of epilepsy in a cohort of Senegalese infants, search for etiological factors and determine the impact of disease on school life. This retrospective study concerned 459 children who attended the neurological outpatients clinic at the Fann hospital, Dakar, Senegal, between July 2003 and December 2006. All were aged under 19 years. Among the 135 children with idiopathic epilepsy, 23.7% had parental consanguinity and 37.77 % familial epilepsy. Rolandic epilepsy and epilepsy with absences were more frequent but several infants with idiopathic epilepsy were not classified. Non-idiopathic epilepsy was noted in 312 children. In this group, estimates of parental consanguinity and familial epilepsy were of 21.79 and 17.94%, respectively. Etiological factors were predominantly pregnancy and birth abnormalities (28.84%) and central nervous system infection (20.19%). Twelve children had febrile seizures. Of patients with idiopathic epilepsy, 65.18% were attending school versus only 9.29 with non-idiopathic epilepsy.     

Therapeutic results and evolution of Black African patients with follicular lymphoma: Ivory Coast experience

We reported in this study a treatment results about 36 Africans patients with follicular lymphoma. The average age of patients was 18 to 73 years old with a median age at 50.83 years old and a sex ratio of 1. Clinical characteristics of patients are mainly represented by advance stage with 70% of stage III and IV of Ann Arbor classification. Histological, we mainly notified follicular lymphoma constituted of small cells 50%, followed by mixed follicular and large cells lymphomas with respectively 27.78 and 22.22%. Using varieties of therapeutics regiments, we obtained 41.67% of complete remission. There were significant correlations between complete remission and histology subtypes. Indeed, the follicular lymphomas constituted by large cells and mixed cells had higher rate of complete remission with respectively 46.67% and 40% in relation with those of small cells with a higher failure rate. Median follow-up was 24 months, the estimated 5-years overall survival and event-free survival were 22%. After a long period, 25 cases of death have been reported, 5 cases of losing sight and 6 patients are still alive and following treatment. Our results are lowers than the reported case in developing country. This none satisfying was in relation with the lower socio-economical level of the main part of the patients. The short survival delay time of our patients didn't permit time to observe transformation case in diffuse large cell lymphomas.     

The traffic elbow. A series of 9 cases

"Traffic elbow" is a condition occurring when high energy trauma involves a patient's elbow resting on the window of the car or completely outside it. This is a prospective study over 30 months of 9 patients with "traffic elbow" and therefore sufferring complex open trauma to the elbow. There were 8 men and 1 woman with a median delay of 4 hours before arrival in hospital. The dominant member was affected in 3 cases. The severity of the lesions, using the Mangled Extremity Severity Score (MESS), was more than 7, comprising lesions corresponding to type 1 of the complex trauma of the superior member (TCMS) in 2 patients and a MESS score of between 3 and 6 corresponding to types 2 or 3 of the TCMS for the other 7 patients. The therapeutic possibilities are limited considering the frequent context of polytrauma. In 4 cases we performed a debridement and external humero-ulnar fixation, in 3 cases a debridement and stabilization with Kirschner's wires completed by a fenestrated cast, and in 2 cases a lifesaving amputation. All patients, except those that had had amputation, developed deep sepsis that resolved after adequate treatment. Assessment of the non-amputee patients according to the Mayo Performance Score, yielded more than 70% of bad results. The authors stress the gravity of these lesions whose prognosis is guarded both concerning mobility of the elbow and the frequent neurovascular complications.     

The value of electromyographic studies in leprosy

In Dakar, during a definite period of time, all the new leprosy cases have been subjected to an electromyographic examination before treatment: a total of 37 patients and 518 examined nerves including all clinical forms: NCV: 33% of the examined nerves are found to be affected. The sensory nerves are frequently and early involved. In frequency order: sural (54%), posterior tibial (50%), sensory ulnar (35%), sensory median (29%), motor ulnar (28%), lateral popliteal (17%) and motor median (12%). The study of the SCV seems relatively more reliable than the sensory testing in the case of the ulnar and the median (75 comparisons): concordance in 69% of the cases; SCV only abnormal in 19%; sensory testing only abnormal in 12%. The EMG detection is superior to the motor testing and to the motor nerve conduction for the lateral popliteal (32 comparisons): 41% of concordant examination; 59% of differences among which 44% of anomalies revealed only by detection.