Israel Medical Association Journal

Background: No specific clinical or histological factors are recognized to be associated with the development of pericardial effusion in non-small cell lung cancer (NSCLC) other than a metastatic disease.

Objectives: To assess whether specific clinical and histological features are associated with development of pericardial effusion in patients with NSCLC.

Methods: A consecutive cohort of patients with NSCLC who presented with symptomatic pericardial effusion 2014–2017 was compared to a control group of patients with advanced NSCLC without pericardial effusion.

Results: The 27 patients in the effusion group were generally younger, more often female, and with a higher percentage of never-smokers, compared to the 54 patients of the control group. Epidermal growth factor receptor/anaplastic lymphoma kinase (EGFR/ALK) mutation tumors were found in 48% of patients in the effusion group vs. 25% in the control group. In the multivariate analysis, the unadjusted odds ratio (OR) for the development of pericardial effusion in patients with somatic mutations was significantly higher compared to wild type tumors (OR 2.65, 95% confidence interval 1.00–7.00). However, a suspected association between pericardial effusion and mutation status was found to be confounded by age. While a high rate of recurrence was observed when pericardiocentesis was initially performed (9/17, 53%), no recurrence was documented when pericardial window procedure was performed (total of 17 patients).

Conclusions: Patients with EGFR/ALK mutations may be at higher risk for the development of pericardial effusion; therefore, attending physicians need to be aware and have a high index of clinical suspicion

Advances in Lymphoma management have resulted in significant improvements in patient outcomes over the last 50 years. Despite these developments, cardiotoxicity from lymphoma treatments remains an important cause of mortality and morbidity in this cohort of patients. We outlined the most common cardiotoxicities associated with lymphoma treatments and their respective investigation and management strategies, including the role of cardiac pre-assessment and late effects monitoring.

Increased life expectancy due to improved cancer prognosis, shared determinants (e.g., tobacco use), and cardiovascular toxicities related to cancer therapies, including the adverse cardiometabolic effects of androgen deprivation therapy for prostate cancer, make cardiovascular disease an frequent and important co-morbidity in patients with a genitourinary malignancy. Complex cardiovascular disease can pose significant challenges in the management of these patients given the uncertainties related to the best approach to reconcile ischemic and bleeding risks, and the role of invasive cardiovascular interventions in individuals with advanced cancer. In this review, we discuss the current evidence that informs decision-making in this clinical context.

Background: Progress in the treatment of breast cancer has led to substantial improvement in survival, but at the cost of increased side effects, with cardiotoxicity being the most significant one. The commonly used definition is cancer therapeutics-related cardiac dysfunction (CTRCD), defined as a left ventricular ejection fraction reduction of > 10%, to a value below 53%. Recent studies have implied that the incidence of CTRCD among patients with breast cancer is decreasing due to lower doses of anthracyclines and low association to trastuzumab and pertuzumab treatment.

Objectives: To evaluate the prevalence of CTRCD among patients with active breast cancer and to identify significant associates for its development.

Methods: Data were collected as part of the Israel Cardio-Oncology Registry, which enrolls all patients who are evaluated at the cardio-oncology clinic at our institution. Patients were divided to two groups: CTRCD and no-CTRCD.

Results: Among 103 consecutive patients, five (5%) developed CTRCD. There were no significant differences in the baseline cardiac risk factors between the groups. Significant correlations of CTRCD included treatment with trastuzumab (P = 0.001) or pertuzumab (P < 0.001), lower baseline global longitudinal strain (GLS) (P = 0.016), increased left ventricular end systolic diameter (P < 0.001), and lower e’ septal (P < 0.001).

Conclusions: CTRCD is an important concern among patients with active breast cancer, regardless of baseline risk factors, and is associated with trastuzumab and pertuzumab treatment. Early GLS evaluation may contribute to risk stratification and allow deployment of cardioprotective treatment

Background: Cardiac damage caused by oncological therapy may manifest early or many years after the exposure.

Objectives: To determine the differences between sub-acute and late-onset cardiotoxicity in left ventricular ejection fraction (LVEF) recovery as well as long-term prognosis.

Methods: We studied 91 patients diagnosed with impaired systolic function and previous exposure to oncological therapy. The study population was divided according to sub-acute (from 2 weeks to ≤ 1 year) and late-onset (> 1 year) presentation cardiotoxicity. Recovery of LVEF of at least 50% was defined as the primary end point and total mortality was the secondary end point.

Results: Fifty-three (58%) patients were classified as sub-acute, while 38 (42%) were defined as late-onset cardiotoxicity. Baseline clinical characteristics were similar in the two groups. The mean LVEF at presentation was significantly lower among patients in the late-onset vs. sub-acute group (28% vs. 37%, respectively, P < 0.001). Independent predictors of LVEF recovery were trastuzumab therapy and a higher baseline LVEF. Although long-term mortality rates were similar in the groups with sub-acute and late-onset cardiotoxicity, improvement of LVEF was independently associated with reduced mortality.

Conclusions: Our findings suggest that early detection and treatment of oncological cardiotoxicity play an important role in LVEF recovery and long-term prognosis.

Background: Type 2 diabetes mellitus is a multifactorial disease in which genetic susceptibility and environmental factors induce pancreatic β-cell dysfunction and insulin resistance. Additional factors such as hyperglycemia and hyperlipidemia have roles in β-cell dysfunction and disease progression. The phenomenon of lipid-induced pancreatic β-dysfunction, designated as lipotoxicity, has been observed in several in vitro and in vivo experiments; however, there is still no solid evidence for the occurrence of this event in humans. The toxic effect of high lipid levels on β-cell function consists of impaired insulin gene expression, apoptosis, and reduced glucose-stimulated insulin secretion.

Objectives: To demonstrate the importance of treating hypertriglyceridemia in reducing glucose intolerance and the need for insulin therapy in hospitalized diabetic patients.

Methods: We evaluated five clinical case reports and conducted a detailed literature review via the PubMed search engine.

Results: Reduction in elevated blood triglyceride and glucose levels in hospitalized diabetic patients resulted in a rapid decline in glucose levels and in the need for insulin therapy.

Conclusions: A decrease in high triglyceride levels in “lipotoxic” diabetic patients may improve insulin intolerance and glucose homeostasis and reduce the need for insulin therapy.

Background: Pulmonary infiltrates (PIs) detected in patients with non-Hodgkin lymphoma (NHL) may present a diagnostic challenge due to their wide differential diagnosis, including infection, pulmonary lymphoma and immunochemotherapy-associated pulmonary toxicity.

Objectives: To characterize therapy-associated PIs by positron emission tomography/computed tomography (PET/CT) imaging.

Methods: We conducted a historical analysis of fluorodeoxyglucose-PET/CT (¹⁸F-FDG-PET/CT) PIs in NHL patients treated with combined immunochemotherapy including rituximab. Incidence of PIs, radiological features, patients’ characteristics, underlying NHL type, rituximab/chemotherapy dosing schedules, and symptoms were recorded. Therapy-associated PIs were defined as new or worsening PIs appearing after treatment onset, without evidence of active pulmonary lymphoma or infection.

Results: Among 80 patients who met the pre-specified criteria, therapy-associated PIs were identified in 17 (21%), 6 of whom had accompanying symptoms. Increased FDG uptake was observed in nine, and PI resolution in six. The incidence of PIs was higher in females and in patients with aggressive lymphoma, at advanced stages, and in those who had received treatment consisting of a combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone every 14 days (R-CHOP-14).

Conclusions: This characterization of therapy-associated PIs may support the clinician managing NHL patients. Further prospective studies are needed to establish the role of each therapeutic component and the natural history of this phenomenon.

Background: Anal cancer is a relatively uncommon disease, accounting for only 4% of cancers of the lower gastrointestinal tract. 

Objectives: To summarize the single-center experience in the treatment of anal carcinoma using various radiation techniques.

Methods: We conducted a retrospective chart review of consecutive patients who were treated for anal cancer between the years 2002 and 2011. The data extracted included demographics, type of radiation technique, treatment-associated acute toxicity, and patterns of failure and survival. For statistical analysis purposes, the patients were divided into two groups according to radiotherapy technique: 2D (group A) and 3D (group B).

Results: A total of 42 patients – 25 (59.5%) females and 17 males (40.5%) – underwent definitive chemo-radiation treatment (CRT) for anal cancer. Group A comprised 26 patients and group B 14 patients. Toxicity did not differ significantly between the groups, only in grade 1-2 skin toxicity which was more common in group B. There were significant differences in the unplanned interruptions in treatment, in both the number of patients who needed a treatment break and the number of days needed (more in group A). There were no differences in treatment response and patterns of failure between these two techniques, or in overall survival between the two groups. 

Conclusions: Our study results are consistent with reported large randomized trials, indicating that current treatments for anal carcinomas are associated with high grade acute toxicity that may result in significant treatment interruptions. The 2D technique was associated with significantly more treatment interruptions, but did not differ from 3D with regard to treatment efficacy. 

 

Background: Due to increasing antimicrobial resistance, there has been renewed interest in old drugs that have fallen into disuse because of toxic side effects. One such drug is chloramphenicol. Data on the use and susceptibility patterns to chloramphenicol in developed countries in recent years are limited.

Objectives: To assess the susceptibility of bacteria to chloramphenicol, and evaluate the use of chloramphenicol in Israeli hospitals as influenced by infectious disease specialists’ attitudes with regard to its potential harms.

Methods: A national survey was conducted in all Israeli hospitals. Questionnaires were sent to the directors of infectious disease units and included items on chloramphenicol susceptibility in clinical isolates, use of chloramphenicol for the treatment of inpatients, local recommendations for use of chloramphenicol, and concerns regarding side effects.

Results: Chloramphenicol is used in 83.3% of hospitals, mostly for the treatment of aspiration pneumonia. While 22.2% of infectious disease unit directors believe that chloramphenicol should be avoided because of dangerous side effects, 88.9% believe there is a place for chloramphenicol in the treatment of patients in this era of increasing antibiotic resistance. Chloramphenicol susceptibility is routinely assessed in 44.4% of hospitals, with high susceptibility rates found among gram-positive, gram-negative and anaerobic bacteria.

Conclusions: In an era of increasing antibiotic resistance, many Israeli infectious disease unit directors believe that chloramphenicol has a role in the treatment of respiratory tract and other infections in hospitalized patients.