Israel Medical Association Journal

Background: Thymectomy is a reliable surgical method for treating patients with myasthenia gravis (MG) and benign tumors of the thymus. Despite the advantages of minimally invasive surgical approaches for resection of thymic neoplasms, there are still controversies regarding the superiority of one type of surgery over another.

Objectives: To report the results of our initial Israeli experience with robotic thymectomy in 22 patients with MG and suspected benign thymic tumors.

Methods: We retrospectively analyzed 22 patients (10 men, 12 women) who underwent robotic thymectomy by a left-sided (16) or right-sided approach (6) using the da Vinci robotic system at Assaf Harofeh Medical Center. Seven patients were diagnosed with MG before surgery and 14 had suspected benign thymic neoplasms.

Results: Average operative time was 90 minutes. There were no deaths or intraoperative complications. Postoperative complications occurred in two patients (dyspnea and pleural effusion). Median blood loss was 12.3 cc (range 5–35 cc), median hospital stay 2.9 days (range 2–5 days), and mean weight of resected thymus 32.1 grams. Seven patients had thymic hyperplasia, six a lipothymoma, one a thymic cyst. Seven each had thymomas in different stages and one had a cavernous hemangioma.

Conclusions: Robotic thymectomy is a safe, technically effective surgical method for resection of thymic neoplasms. The advantages of this technique are safety, short hospitalization period, little blood loss, and low complications. We have included this surgical procedure in our thoracic surgery residency program and recommend a learning curve program of 10 to 12 procedures during residency.

Background: The VEGFR/PDGFR inhibitor sunitinib was approved in Israel in 2008 for the treatment of metastatic renal cell carcinoma (mRCC), based on an international trial. However, the efficacy of sunitinib treatment in Israeli mRCC patients has not been previously reported.

Objectives: To report the outcome and associated factors of sunitinib treatment in a large cohort of Israeli mRCC patients.

Methods: We conducted a retrospective study of an unselected cohort of mRCC patients who were treated with sunitinib during the period 2006–2013 in six Israeli hospitals. Univariate and multivariate analyses were performed to determine the association between treatment outcome and clinicopathologic factors.

Results: We identified 145 patients; the median age was 65 years, 63% were male, 80% had a nephrectomy, and 28% had prior systemic treatment. Seventy-nine percent (n=115) had clinical benefit (complete response 5%, n=7; partial response 33%, n= 48; stable disease 41%, n=60); 21% (n=30) were refractory to treatment. Median progression-free survival (PFS) was 12 months and median overall survival 21 months. Factors associated with clinical benefit were sunitinib-induced hypertension: [odds ratio (OR) 3.6, P = 0.042] and sunitinib dose reduction or treatment interruption (OR 2.4, P = 0.049). Factors associated with PFS were female gender [hazard ratio (HR) 2, P = 0.004], pre-sunitinib treatment neutrophil to lymphocyte ratio ≤ 3 (HR 2.19, P = 0.002), and active smoking (HR 0.19, P < 0.0001). Factors associated with overall survival were active smoking (HR 0.25, P < 0.0001) and sunitinib-induced hypertension (HR 0.48, P = 0.005). To minimize toxicity, the dose was reduced or the treatment interrupted in 39% (n=57). 

Conclusions: The efficacy of sunitinib treatment for mRCC among Israeli patients is similar to that of international data.

 Background: Vitamin D status is not evaluated routinely in cancer patients with bone metastasis who are treated with bisphosphonates.

Objectives: To assess the effect of vitamin D status on risk of hypocalcemia and quality of life in these patients.

Methods: We performed laboratory tests for routine serum biochemistry, 25(OH)D, plasma parathyroid hormone (PTH) and bone turnover markers (CTX, P1NP) in 54 patients aged 57.5 ± 13 years treated with intravenous bisphosphonates.

Results: Most of the patients (n=44, 77.8%) did not receive calcium and vitamin D supplementation. Their mean serum 25(OH)D levels (12.83 ± 6.86 ng/ml) correlated with vitamin D daily intake (P = 0.002). In 53 patients (98.1%) 25(OH)D levels were suboptimal (< 30 ng/ml). Albumin-corrected calcium levels correlated with plasma PTH (P = 0.001). No correlation was observed between daily calcium intake and serum calcium (P = 0.45). Hypocalcemia was observed in one patient. Mean plasma PTH was 88.5 ± 65 ng/L. Plasma PTH correlated negatively with 25(OH)D serum levels (P = 0.003) and positively with P1NP (P = 0.004). Albumin-corrected calcium correlated negatively with P1NP (mean 126.9 ± 191 ng/ml) but not with CTX levels (mean 0.265 ± 0.1 ng/ml) (P < 0.001). There was no correlation among quality of life parameters, yearly sun exposure and 25(OH)D levels (P = 0.99).

Conclusions: Vitamin D deficiency is frequent in oncology patients with bone metastasis treated with bisphosphonates and might increase bone damage. Our results indicate a minor risk for the development of severe hypocalcemia in vitamin D-deficient patients receiving bisphosphonate therapy. Although vitamin D deficiency might have some effect on the quality of life in these patients, it was not proven significant.
 

Background: Uveal melanoma is the most common primary intraocular tumor in adults. In the last two decades the Hadassah-Hebrew University ocular oncology clinic has become a referral center for uveal melanoma patients.

Objectives: To describe the characteristics of uveal melanoma patients in Israel, their treatment modalities and outcomes during the years 1988–2007.

Methods: Data were collected from the files of uveal melanoma patients in the departments of ophthalmology and oncology in our facility. Statistical analysis was performed using JMP statistical software.

Results: Data were available for 558 patients. The annual incidence of uveal melanoma in the last 5 years was 47.2 ± 7.1 new cases per year (mean ± standard error). There were 309 women (55.4%). The age at diagnosis was 60.8 ± 16.5 years (range 5–95). Overall, 6.6%, 16.8% and 86.9% involved the iris, ciliary-body and choroid, respectively. Tumors were classified as small, medium and large (9.0%, 64.5% and 17.9%, respectively) according to the COMS grouping criteria. The most common primary treatment was brachytherapy (74%), followed by enucleation (17.9%). Local recurrence was noted in 11.1% of patients, while metastases developed in 13.3%. The 5, 10 and 15 year melanoma-related mortality rate was 11.4%, 17.0% and 23.3%, respectively. Of the overall study population 9.3% died of metastatic uveal melanoma.

Conclusions: Uveal melanoma patients in Israel have tumors with characteristics similar to those in other countries. Brachytherapy is the predominant treatment, the local recurrence rate is low, and survival is comparable to that reported in the medical literature.

Background: Carotid artery stenting is used as an alternative to surgical endarterectomy.

Objectives: To determine the outcome of CAS[1] in a retrospective cohort of patients.

Methods: Between July 1999 and March 2003, 56 consecutive patients with carotid artery stenosis who were considered ineligible for surgery were treated (45 male, 11 female, mean age 69). All cases were performed prior to the introduction of distal protective devices in Israel.

Results: Intraprocedural complications included transient neurological findings in 5 patients (8%), cerebrovascular accident in 2 (3%), hemodynamic changes in 11 (18%), and 4 procedural failures. Post-procedural complications included transient ischemic attack in 3 patients and cardiovascular accident in 6 (10%). At 30 days follow-up, three patients (5%) remained with signs of CVA[2]. Two patients (3%) died during the post-procedural period and 16 (28%) during the 5 year follow-up, one due to recurrent CVA and the remainder to non-neurological causes. Five-year carotid Doppler follow-up was performed in 25 patients (45%), which revealed normal stent flow in 21 (84%), 50–60% restenosis in 3 patients (12%) and > 70% restenosis in one patient (4%).

Conclusions: This study confirms that stent procedures are beneficial for symptomatic carotid stenosis in patients not eligible for surgery.

Although the airway granulomata in Wegener's granulomatosis were stressed initially by Friedrich Wegener himself, in the last few decades systemic lesions mainly caused by acute vasculitis have received the most attention. However, recently, the implication of granulomatous manifestations in WG[1] has raised much interest. The present data suggest that an aberrant Th1-type response might play a role in the initiation of WG, clinico-pathologically characterized by granulomatous inflammation rather than vasculitis. Disease progression to generalized WG with the predominance of vasculitic manifestations is associated with a “switch” or further complexity of the collective T cell response with the appearance of another subset of Th2-type cells and a less prominent Th1-type cytokine production in the granulomatous lesions of the upper respiratory tract. However, the clinical significance of the granulomatous inflammation is not yet completely understood. Further research will also have to focus on the role of the granulomata during relapsing disease. We review present knowledge of granulomatous inflammation in WG. Morphologic aspects, the scale of cytokine alterations as well as the variety of clinical manifestations are discussed.