Israel Medical Association Journal

Background: Meningiomas are frequently detected incidentally. Their natural history has not yet been established because it is difficult to predict the growth pattern. Therefore, the management, after the radiological diagnosis, is still controversial.

Objectives: To evaluate the clinical outcome and growth rate of conservatively treated meningiomas at our tertiary center, identify prognostic factors of tumor growth, and suggest guidelines based on the available data and our experience.

Methods: We reviewed the clinical records of 56 patients with 63 untreated meningiomas. Most were diagnosed incidentally. Clinical features and imaging findings at diagnosis and during follow-up were compared between growing and non-growing tumors. Potential patient- and tumor-related predictive factors for growth were analyzed.

Results: The study group included 46 women (52 meningiomas) and 10 men (11 meningiomas) aged 39–83 years. Mean tumor size was 18 ± 11 mm (range 3–70 mm) at diagnosis and 22 ± 11 mm (range 8–70 mm) at last follow-up; mean follow-up time was 65 ± 34 months (range 15–152 months). During follow-up 24 tumors (38%) grew at a rate of 4 mm per year; none became symptomatic. Only two prognostic factors were statistically significantly associated with low growth rate: older age and tumor calcifications.

Conclusions: Given our finding of a low growth incidence of meningiomas in the elderly, we support conservative management in patients aged 70 years or older. Calcifications into the meningioma are also indicative of slow growth, suggesting a conservative strategy. Surgery is recommended in younger patients in whom tumor growth occurs more often and a longer follow-up is necessary.
 

Background: Uterine sarcoma constitutes a highly malignant group of uterine tumors. It accounts for 2–6% of uterine malignancies and its incidence is 1.7 in 100,000 women. The three most common variants of uterine sarcoma are endometrial stromal sarcoma, leiomyosarcoma and carcinosarcoma. Based on relatively small case series, the literature provides little information on the risk factors, the natural course of the disease and the preferred treatment.

Objectives: To evaluate uterine sarcoma patients treated in a tertiary referral center in Israel over a 20 year period (1980–2005).

Methods: We conducted a retrospective review of the charts of 40 uterine sarcoma patients, including their tumor characteristics, stage at diagnosis, treatment modalities, follow-up and survival.

Results: The patients’ mean age was 53 years (range 32–76); 30% of the patients had carcinosarcoma, 55% had leiomyosarcoma and 15% had ESS[1]. Half of the patients presented with stage I disease, 23% stage II, 10% stage III and 15% stage IV. Thirty-nine patients were treated by surgery. Adjuvant radiotherapy was administered to 39% of the patients, adjuvant chemotherapy to 21% and combined radiotherapy and chemotherapy to 9%. The mean follow-up period was 44 months, at which time disease had recurred in 44% of the patients. The disease stage was correlated with the 5-year survival rate, which was 73.1% for stages I-II and 22.2% for stages III- IV.

Conclusions: In accordance with other larger studies our data show that the only prognostic factor that was significantly correlated with prognosis was the stage of the disease at diagnosis. Despite advances in diagnosis and treatment, survival has not improved over the last 25 years.

The introduction of novel targeted therapies into the clinic in recent years has had a considerable impact on the management of several neoplastic diseases – such as gastrointestinal stromal tumors, hepatocellular carcinomas and renal cell carcinomas – considered until recently refractory to systemic therapies. We describe here two such novel biological agents, sunitinib and sorafenib, as a paradigm of the successful clinical application of new concepts. Sunitinib and sorafenib are small molecule tyrosine kinase inhibitors that target vascular endothelial growth factor receptor, platelet-derived growth factor receptor, C-Kit and others. Both agents are administered orally; sunitinib is typically given in cycles for 4 consecutive weeks with 2 weeks off, while sorafenib is given continually. Side effects occur in most patients, similar for both agents; they may affect several systems and organs but are mostly mild and easily manageable, rarely requiring discontinuation of the drug. However, these toxicities require prompt attention and intervention. The most frequently observed effects are hypertension, nausea, anorexia, asthenia and cutaneous manifestations; cardiac abnormalities may include congestive failure. Sunitinib, and markedly less frequently sorafenib, may cause thyroid gland dysfunction, mainly hypothyroidism. Antitumor activity has been shown for renal cell carcinoma in pivotal trials, for sunitinib as first-line treatment and for sorafenib in previously treated patients as second-line. Sunitinib is now approved as second-line therapy for patients with GIST[1] refractory to imatinib; sorafenib has resulted in a significant prolongation in median survival in patients with hepatocellular carcinoma. Ongoing clinical trials will further define the spectrum of these agents' antitumor activity, their role in combination with other drugs, as well as their optimal dose and schedule of administration.

Background: Interleukin-10 is an anti-inflammatory cytokine and consequently is considered by many to have a protective role in heart failure, as opposed to the notorious tumor necrosis factor-alpha.

Objectives: To test the hypothesis of the possible beneficial impact of IL-10[1] on mortality in systolic heart failure patients in relation to their circulating TNFα[2] levels.

Methods: We measured circulating levels of IL-10 and TNFα in 67 ambulatory systolic heart failure patients (age 65 ± 13 years).

Results: Mortality was or tended to be higher in patients with higher levels (above median level) of circulating TNFα (9/23, 39% vs. 6/44, 14%; P = 0.02) or IL-10 (10/34, 30% vs. 5/33, 15%; P = 0.10). However, mortality was highest in the subset of patients with elevation of both markers above median (7/16, 44% vs. 8/51, 16%; P = 0.019). Elevation of both markers was associated with more than a threefold hazard ratio for mortality (HR[3] 3.67, 95% confidence interval 1.14–11.78).

Conclusions: Elevated circulating IL-10 levels in systolic heart failure patients do not have a protective counterbalance effect on mortality. Moreover, patients with elevated IL-10 and TNFα had significantly higher mortality, suggesting that the possible interaction in the complex inflammatory and anti-inflammatory network may need further study.