Israel Medical Association Journal

Background: The very long-term prognostic significance of ventricular late potentials (VLP) in patients post ST-elevation myocardial infarction (STEMI) is unclear.

Objective: To evaluate the long-term predictive value of VLP for mortality post-STEMI.

Methods: We conducted serial signal-averaged electrocardiography (SAECG) measurements in 63 patients on the 1st, 2nd and 3rd day pre-discharge, and 30 days after STEMI in patients admitted in 2001. We followed the patients for 10 years and correlated the presence of VLP with all-cause and cardiovascular mortality.

Results: The mean age was 59.9 ± 12.3 years. Thrombolysis was performed in 41 patients (65%). Percutaneous coronary intervention was performed pre-discharge in 40 patients (63%) and coronary artery bypass grafting in 7 (11%). Five consecutive measurements to define the presence of VLP were obtained in 52 patients (21 with VLP and 31 without). We found a higher prevalence of VLP in males compared to females (QRS segment > 114 msec, 51% vs. 12%, P = 0.02, duration of the low amplitude signal < 40 mV) in the terminal portion of the averaged QRS complex > 38 msec, 47% vs. 25%, P = 0.05). Over 10 years of follow-up, 14 (22%) patients died, 10 (70%) due to cardiovascular non-arrhythmic complications, 6 with VLP compared to only 3 without (28.6% vs. 9.7%, P = 0.125, hazard ratio = 2.96, confidence intervals = 0.74–11.84) (are these numbers meant to total 10?).

Conclusions: Over 10 years of follow-up, the presence of VLP in early post-STEMI is not predictive of arrhythmic or non-arrhythmic cardiovascular mortality.

Background: More than 90% of all thyroid cancers are differentiated thyroid carcinomas (DTC) with a 10 year survival rate greater than 90%. The commonly used risk stratification systems for DTC include: European Organization for Research and Treatment of Cancer (EORTC), AGES (Age, histologic Grade, Extent of tumor, Size), AMES (Metastasis) and MACIS (Completeness of resection, local Invasion). Other systems are also utilized. Several new factors that may be involved in DTC risk stratification have emerged in recent studies, with other "traditional" factors being challenged. 

Objectives: To present recent updates in the literature on new potential prognostic factors for DTC.

Methods: We conducted a literature review and analysis of publications regarding DTC prognostic factors or risk stratification published in the last 10 years. 

Results: Several new factors with potential prognostic implications for DTC were noted, including family history, lymph node involvement parameters, positive PET-CT findings, multifocal disease, thyroglobulin level and several molecular markers including BRAF. Increasing age is associated with poorer outcome in DTC; however, recent studies suggest that the cutoff point of 45 years may be contested. Furthermore, several studies have shown contradictory results regarding male gender as a negative prognostic factor, thus questioning its prognostic significance. 

Conclusions: A number of new factors with potential prognostic implications for DTC have emerged and should be addressed. However, their role and possible inclusion in new staging systems has yet to be determined.

 

Background: Radiotherapy to the prostate bed is used to eradicate residual microscopic disease following radical prostatectomy for prostate cancer. Recommendations are based on historical series. 

Objectives: To determine outcomes and toxicity of contemporary salvage radiation therapy (SRT) to the prostate bed. 

Methods: We reviewed a prospective ethics committee-approved database of 229 patients referred for SRT. Median pre-radiation prostate-specific antigen (PSA) was 0.5 ng/ml and median follow-up was 50.4 months (range 13.7–128). Treatment was planned and delivered using modern three-dimensional radiation techniques. Mean bioequivalent dose was 71 Gy (range 64–83 Gy). Progression was defined as two consecutive increases in PSA level > 0.2 ng/ml, metastases on follow-up imaging, commencement of anti-androgen treatment for any reason, or death from prostate cancer. Kaplan-Meier survival estimates and multivariate analysis was performed using STATA. 

Results: Five year progression-free survival was 68% (95%CI 59.8–74.8%), and stratified by PSA was 87%, 70% and 47% for PSA < 0.3, 0.3–0.7, and > 0.7 ng/ml (P < 0.001). Metastasis-free survival was 92.5%, prostate cancer-specific survival 96.4%, and overall survival 94.9%. Low pre-radiation PSA value was the most important predictor of progression-free survival (HR 2.76, P < 0.001). Daily image guidance was associated with reduced risk of gastrointestinal and genitourinary toxicity (P < 0.005). 

Conclusions: Contemporary SRT is associated with favorable outcomes. Early initiation of SRT at PSA < 0.3 ng/ml improves progression-free survival. Daily image guidance with online correction is associated with a decreased incidence of late toxicity.

 

Background: Several studies link the pathogenesis of nephrotic syndrome to tumor necrosis factor-alpha (TNFα). However, data on the serum TNFα level in children with nephrotic syndrome are sparse. 

Objective: To investigate serum TNFα levels and the effect of steroid therapy in children with nephrotic syndrome. 

Methods: A prospective cohort pilot study of children with nephrotic syndrome and controls was conducted during a 1 year period. Serum TNFα levels were measured at presentation and at remission, or after a minimum of 80 days if remission was not achieved.

Results: Thirteen patients aged 2–16 years with nephrotic syndrome were compared with 12 control subjects. Seven patients had steroid-sensitive and six had steroid-resistant nephrotic syndrome. Mean baseline serum TNFα level was significantly higher in the steroid-resistant nephrotic syndrome patients than the controls (6.13 pg/ml vs. 4.36 pg/ml, P = 0.0483). Mean post-treatment TNFα level was significantly higher in the steroid-resistant than in the steroid-sensitive nephrotic syndrome patients (5.67 pg/ml vs. 2.14 pg/ml, P = 0.001). In the steroid-resistant nephrotic syndrome patients, mean serum TNFα levels were similar before and after treatment.

Conclusions: Elevated serum TNFα levels are associated with a lack of response to corticosteroids. Further studies are needed to investigate the role of TNFα in the pathogenesis of nephrotic syndrome.

 

The identification and prompt diagnosis of Horner syndrome (HS) is essential for preventing permanent damage. HS may arise when a lesion presents anywhere along the three-neuron oculosympathetic pathway that begins at the posterior-lateral nuclei of the hypothalamus all the way through to the orbit. We present four cases and review the literature to familiarize the reader with the identification, diagnosis and treatment of Horner syndrome. The four patients, three adults and one child, were followed for at least 6 months following the initial diagnosis (range 6–18 months). There was partial resolution in three of the four cases, while the fourth resolved completely. There are numerous causes of HS, some of them iatrogenic. While iatrogenic cases of HR are rare in both adults and children, HS is seen more often following surgical procedures. Prompt recognition of the syndrome and correction of the offending agent may prevent permanent damage to the neuronal pathway. It is therefore recommended that practitioners be aware of the risks for development of iatrogenic HS and the signs for early detection.

Background: Stereotactic ablative radiation therapy (SABR) is the application of a very high radiation dose to a small treatment volume. It is the new standard of care in medically inoperable early-stage lung cancer. 

Objectives: To report the outcomes of SABR in stage I lung cancer at Sheba Medical Center since its introduction in 2009.

Methods: We conducted a retrospective chart review of patients with stage I lung cancer treated during the period 2009–2015. Survival status was retrieved from the electronic medical records and confirmed with the national registry. Local failure was defined as increased FDG uptake on PETCT scan within a 2 cm radius of the treated region. Toxicity was estimated from medical records and graded according to common toxicity criteria for adverse events (CTCAE) version 4.03. Overall survival and local control were estimated by the Kaplan-Meier method.

Results: During the study period 114 patients were treated for 122 stage I lung cancer lesions. Median follow-up time was 27 months (range 8.2–69.5 months), median age was 76 years. Eighty-two percent of the tumors were stage IA (size ≤ 3 cm). Median survival was 46 months; estimated 3 year overall survival was 59% (95%CI 47–69%) and local control was 88% (95%CI 78–94%). Toxicity included chest wall pain in 8.4% of patients, rib fracture in 0.9%, grade 1–2 pneumonitis in 12%, grade 3 in 12% and grade 5 (death) in 0.9%.

Conclusions: SABR has been successfully implemented at Sheba Medical Center for the treatment of stage I lung cancer in inoperable patients. It is associated with excellent local control, minor toxicity and an acceptable overall survival.

 

Background: Anti-BLyS treatment with the human belimumab monoclonal antibody was shown to be a safe and effective therapeutic modality in lupus patients with active disease (i.e., without significant neurological/renal involvement) despite standard treatment.

Objectives: To evaluate the “real-life” safety and efficacy of belimumab added to standard therapy in patents with active lupus in five Israeli medical centers.

Methods: We conducted a retrospective open-labeled study of 36 lupus patients who received belimumab monthly for at least 1 year in addition to standard treatment. Laboratory tests (C3/C4, anti dsDNA autoantibodies, chemistry, urinalysis and complete blood count) were done every 3–4 months. Adverse events were obtained from patients’ medical records. Efficacy assessment by the treating physicians was defined as excellent, good/partial, or no response.

Results: The study group comprised 36 lupus patients (8 males, 28 females) with a mean age of 41.6 } 12.2 years. Belimumab was given for a mean period of 2.3 } 1.7 years (range 1–7). None of the patients discontinued belimumab due to adverse events. Four patients (11.1%) had an infection related to belimumab. Only 5 patients (13.9%) stopped taking belimumab due to lack of efficacy. The response was excellent in 25 patients (69.5%) and good/partial in the other 6 (16.6%). Concomitantly, serological response (reduction of C3/C4 and anti-dsDNA autoantibodies) was also observed. Moreover, following belimumab treatment, there was a significant reduction in the usage of corticosteroids (from 100% to 27.7%) and immunosuppressive agents (from 83.3% to 8.3%).

Conclusions: Belimumab, in addition to standard therapy, is a safe and effective treatment for active lupus patients.

Background: Silicone breast augmentation is a common cosmetic surgery. Previous case reports demonstrated lymphadenopathy in the presence of implant ruptures.

Objectives: To investigate the association between enlarged axillary lymph nodes and silicone implant ruptures as seen on breast magnetic resonance imaging (MRI).

Methods: Two groups were derived retrospectively from breast MRI reports in our institution for the period December 2011–May 2014. A search of our hospital records for "silicone" and "lymph node" was performed (group A), and the relationship between the presence of enlarged nodes and ruptures was evaluated. The prevalence of ruptures in the presence of nodes was calculated and the association between MRI imaging features and ruptures evaluated. A search for "silicone" and "implant rupture" was performed (group B) and, as for group A, the relationship between the presence of ruptures and nodes was evaluated and the prevalence of enlarged nodes in the presence of ruptures calculated.

Results: Group A comprised 45 women with enlarged nodes. Intracapsular ruptures were associated with nodes (P = 0.005), while extracapsular ruptures showed a trend of association with nodes (P = 0.08). The prevalence of ruptures in the presence of nodes was 31.4%. Nodes associated with ruptures showed a strong silicone signal (P = 0.008) and absent enhancement (P = 0.005). Group B comprised 73 women with ruptures. Enlarged nodes were associated with both intra- and extracapsular ruptures (P < 0.001 and P = 0.002 respectively). The prevalence of nodes in the presence of ruptures was 22.2%.

Conclusions: Enlarged axillary nodes were associated with ruptures in two groups of patients. This finding can guide clinical decisions when either enlarged nodes or ruptures are encountered in patients with silicone implants. The association between silicone lymphadenopathy and implant rupture raises concerns regarding the role of rupture in silicone-induced systemic disease.