Israel Medical Association Journal

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.

Objectives: To assess the role of electrocardiography-gated CT-angiography (ECG-CTA) in the routine evaluation of CHD in neonates and infants particularly for the assessment of extracardiac findings.

Methods: The study cohort comprised 40 consecutive patients who underwent trans-thoracic echocardiography (TTE) and ECG-CTA. TTE and ECG-gated CTA findings regarding extracardiac vascular structures, coronary arteries and airways were compared with surgical or cardiac catheterization findings. Scans were evaluated for image quality using a subjective visual scale (from 1 to 4). Effective radiation dose was calculated for each scan.

Results: Median age was 28 ± 88 days and mean weight 3.7 ± 1.5 kg. Diagnostic quality was good or excellent (visual image score 3–4) in 39 of 40 scans (97.5%). ECG-CTA provided important additional information regarding extracardiac vascular structures and airway anatomy, complementing TTE in 75.6% of scans. Overall sensitivity of ECG-gated CTA for detecting extracardiac findings as compared with operative and cardiac catheterization findings was 97.6%. The calculated mean effective radiation dose was 1.4 ± 0.07 mSv (range 1.014–2.3 mSv).

Conclusions: ECG-CTA is an accurate modality for demonstrating extracardiac structures in complex CHD. It provides important complementary information to TTE regarding extracardiac vascular structures and coronary artery anatomy. This modality may obviate the need for invasive cardiac catheterization, thus exposing the patient to a much lower radiation dose. 

Objectives: To investigate whether young patients, i.e., under age 50, complain of symptoms for longer than older patients until the diagnosis of colon cancer is established.

Methods: In this retrospective cohort study, patients were divided into two groups: < 50 years old (group 1) and ≥ 50 (group 2). All had undergone surgery for left or right colon cancer during the 1 year period January 2000 through December 2009 at one medical center. Rectal and sigmoid cancers were excluded. Data collected included age, gender, quantity and quality of complaints, duration of complaints, in-hospital versus community diagnosis, pathological staging, the side of colon involved, and overall mortality. The main aim was the quality and duration of complaints. Secondary outcomes were the pathological stage at presentation and the mortality rate.

Results: The study group comprised 236 patients: 31 (13.1%) were < 50 years old and 205 (86.9%) were ≥ 50 years. No significant difference was found in the quantity and quality of complaints between the two groups. Patients in group 1 (< 50 years) complained for a longer period, 5.3 vs. 2.4 months (P = 0.002). More younger patients were diagnosed with stage IV disease (38.7% vs. 21.5%, P = 0.035) and fewer had stage I disease (3.2% vs. 15.6%, P = 0.06); the mortality rates were similar (41.9% vs. 39%). Applying a stepwise logistic regression model, the duration of complaints was found to be an independent predictor of mortality (P = 0.03, OR 1.6, 95% CI 1–3.6), independently of age (P = 0.003) and stage (P < 0.001).

Conclusions: Younger patients are more often diagnosed with colon cancer later, at a more advanced stage. Alertness to patients’ complaints, together with evaluation regardless of age but according to symptoms and clinical presentation are crucial. Large-scale population-based studies are needed to confirm this trend. 

Objectives: To present the feasibility and safety of DSMR in Israel.

Methods: Thirty patients with suspected or known CAD were studied. DSMR images were acquired during short breath-holds in three short axis views and four-, two-, and three-chamber views. Patients were examined at rest and during a standard dobutamine-atropine protocol. Regional wall motion was assessed in a 16-segment model and the image quality was evaluated using a four-point scale for the visibility of the endocardial border.

Results: In 28 patients (93.4%) DSMR was successfully performed and completed within an average of 55 ± 6 minutes. One patient could not be examined because of claustrophobia and another patient, who was on beta-blockers, did not reach the target heart rate. Image quality was excellent and there was no difference between the rest and stress images in short axis (3.91 ± 0.29 vs. 3.88 ± 0.34, P = 0.13, respectively) and long axis (3.83 ± 0.38 vs. 3.70 ± 0.49, P = 0.09, respectively) views. Segmental intra-observer agreement for wall motion contractility at rest and stress cine images was almost perfect (κ = 0.88, 95% confidence interval = 0.93–0.84, and κ = 0.82, 95% CI = 0.88–0.76) respectively. No serious side effects were observed during DSMR.

Conclusion: The present study confirms the feasibility, safety and excellent image quality of DSMR for the diagnosis of coronary artery diseases.

 Background: Hemorrhagic radiation cystitis (HRC) is a significant clinical problem that occurs after pelvic radiation therapy and is often refractory.

Objectives: To evaluate the efficacy and safety of hyperbaric oxygen therapy (HBO) for HRC.

Methods: Daily 90 minute sessions of HBO at 2 ATM 100% oxygen were given to 32 HRC patients with American Society of Therapeutic Radiology and Oncology (ASTRO) grades 3-4 hematuria.

Results: The median age was 72.5 (48–88 years). The median time interval between radiation therapy and HBO was 4 years (1–26 years). The patients received a median of 30 HBO sessions (3–53). Hematuria resolved in 27 patients (84%) and persisted in 5. Cystectomy was required in two, and ileal-conduit and bilateral percutaneous nephrostomies were performed in one and two patients, respectively. With a median follow-up of 12 months (5–74 months), the hematuria cleared completely in 16 patients (59%) and mild hematuria requiring no further treatment recurred in 10 others. Another patient with ASTRO grade 4 hematuria needed bladder irrigation and blood transfusions. Complications included eardrum perforation in four patients and transient vertigo and mild hemoptysis in one case each. None of them required HBO discontinuation.

Conclusions: HBO controlled bleeding in 84% of the patients. A durable freedom from significant hematuria was achieved in 96% of the patients. HBO seems to be an effective and safe modality in patients with HRC.

Background: In infants, small volume nebulizers with a face mask are commonly used to facilitate aerosol therapy. However, infants may be disturbed by mask application, causing poor mask-to-face seal and thus reducing the dose delivered.

Objectives: To compare lung function response to bronchodilator nebulization via two delivery devices: hood versus mask.

Methods: We studied 26 recurrently wheezy infants aged 45.8 weeks (95% confidence interval 39.6–52.0). Inhalations of 0.30 mg/kg salbutamol were administered in two alliqots 30 minutes apart using mask and hood in alternating order (M+H or H+M). Response to inhalations was measured by maximal expiratory flows at functional residual capacity at 5 minute intervals after each dose, and area under the VmaxFRC[1] curve was documented.

Results: A small but significant response to salbutamol was observed following the second inhalation with VmaxFRC, improving by 31.7% (7.2–56.2, P < 0.02) and AUC[2] by 425 %•min (-154, 1004; P < 0.02). The improvement following salbutamol was similar by both delivery modalities but with a small but significantly better response when H was used after M (P < 0.01).

Conclusions: Nebulized salbutamol induced a variable but positive response in wheezy infants. Salbutamol via hood was as effective as conventional face mask delivery. Since it is simple and patient-friendly, it could replace the face mask method particularly with uncooperative infants.

Background: Tight glucose control has been shown to improve the outcome of patients with severe acute illnesses who are hospitalized in intensive care units and on intravenous insulin-based regimens.

Objectives: To clarify the attitudes of internists towards tight control of glucose levels in acutely ill patients hospitalized in general medical wards.

Methods: A questionnaire on intensive glucose control in acutely ill patients hospitalized in medical wards was mailed to each of the 100 heads of internal medicine departments in Israel.

Results: Fifty physicians responded. Of these, 80% considered tight glucose control to be a major treatment target, but only two-thirds had defined it as a goal in their ward. Furthermore, only about half had a defined protocol for such an intervention. Most physicians considered patients with acute coronary syndrome, stroke and infectious diseases as candidates for a tight glucose control protocol. The most frequently used modalities were multiple blood glucose measurements and repeated injections of short-acting subcutaneous insulin. The main reasons given for not having a defined protocol were lack of guidelines, no evidence of a clear benefit during hospitalization on a medical ward, and a shortage of adequately trained staff.

Conclusions: Inconsistencies in physicians’ attitudes and in treatment protocols regarding tight control of glucose levels in acutely ill patients hospitalized on a medical ward need to be addressed. Evaluation of the feasibility, effectiveness and side effects of a defined protocol is needed before any regimen can be approved by the heads of the internal medicine departments.