Israel Medical Association Journal

Background: The marijuana plant cannabis is known to have therapeutic effects, including improvement of inflammatory processes. However, no report of patients using cannabis for Crohn’s disease (CD) was ever published.

Objectives: To describe the effects of cannabis use in patients suffering from CD.

Methods: In this retrospective observational study we examined disease activity, use of medication, need for surgery, and hospitalization before and after cannabis use in 30 patients (26 males) with CD. Disease activity was assessed by the Harvey Bradshaw index for Crohn’s disease.

Results: Of the 30 patients 21 improved significantly after treatment with cannabis. The average Harvey Bradshaw index improved from 14 ± 6.7 to 7 ± 4.7 (P < 0.001). The need for other medication was significantly reduced. Fifteen of the patients had 19 surgeries during an average period of 9 years before cannabis use, but only 2 required surgery during an average period of 3 years of cannabis use.

Conclusions: This is the first report of cannabis use in Crohn’s disease in humans. The results indicate that cannabis may have a positive effect on disease activity, as reflected by reduction in disease activity index, and in the need for other drugs and surgery. Prospective placebo-controlled studies are warranted to fully evaluate the efficacy and side effects of cannabis in CD.
 

 Background:  Pomegranate extract (POMx) consumption has been shown to reduce the incidence and severity of collagen-induced arthritis in mice.

Objectives:  To investigate whether pomegranate consumption affects disease activity in patients with rheumatoid arthritis (RA), in relation to their serum oxidative status.

Methods:  In this pilot 12 week open-labeled study eight patients with active RA consumed POMx (10 ml/day) for 12 weeks. Patients’ joint status and serum oxidative status (lipid peroxidation, total thiols group, paraoxonase 1 activity) were evaluated at baseline and at week 12.

Results:  Six patients completed the study. POMx consumption significantly (P < 0.02) reduced the composite Disease Activity Index (DAS28) by 17%, which could be related mostly to a significant (P < 0.005) reduction in the tender joint count (by 62%). These results were associated with a significant (P < 0.02) reduction in serum oxidative status and a moderate but significant (P < 0.02) increase in serum high density lipoprotein-associated paraoxonase 1 (PON1) activity. The addition of POMx to serum from RA patients reduced free radical-induced lipid peroxidation by up to 25%.

Conclusions:  The pomegranate consumption reduced DAS28 in RA patients, and this effect could be related to the antioxidative property of pomegranates. Dietary supplementation with pomegranates may be a useful complementary strategy to attenuate clinical symptoms in RA patients.

Background: Surgery is considered the mainstay of treatment for esophageal carcinoma. Transhiatal esophagectomy with cervical esophagogastric anastomosis is considered relatively safe with an oncological outcome comparable to that using the transthoracic approach.

Objectives: To review the results of the first 100 transhiatal esophagectomies performed in a single Israeli center.

Methods: The records of all patients who had undergone transhiatal esophagectomy during the period 2003–2009 were reviewed. The study group comprised the first 100 patients. All patients who had undergone colon or small bowel transposition were excluded. Indications for surgery included esophageal cancer, caustic injury and achalasia.

Results: The median follow-up period was 19.5 months. The anastomotic leakage rate was 15% and all were managed successfully with local wound care. The benign stricture rate was 10% and all were managed successfully with endoscopic balloon dilation. Anastomotic leakage was found to be a risk factor for stricture formation. Overall survival was 54%. Response to neoadjuvant therapy was associated with a favorable prognosis.

Conclusions: Transhiatal esophagectomy is a relatively safe approach with adequate oncological results, as long as it is performed in a high volume center.
 

Background: Anti-lipoprotein lipase antibodies have been described in rare cases of patients with hypertriglyceridemia. However, no systematic study evaluating these antibodies in patients with this lipid abnormality has been undertaken.

Objectives: To analyze the correlation of anti-lipoprotein lipase (anti-LPL) antibodies with other laboratory findings in patients with hypertriglyceridemia but no autoimmune disease.

Methods: We evaluated 44 hypertriglyceridemic patients without autoimmune disease. Clinical and laboratory evaluations included analyses of co-morbidities, fasting lipid profile and anti-LPL antibodies.

Results: Mean patient age was 55 ± 10 years; 46% of the patients were female and 64% were Caucasian. The mean disease duration was 94.4 months and mean body mass index 28.7 ± 3.6 kg/m²; 34.0% were diabetic, 25.0% were obese, 72.7% had systemic arterial hypertension, 75% were sedentary, 15.9% were smokers, 56.8% had a family history of dyslipidemia, 45.5% had a family history of coronary insufficiency, 20.5% had acute myocardial infarction, 9.0% had undergone revascularization and 11.0% angioplasty, 79.5% were being treated with statins and 43.2% were taking fibrates. Median triglyceride levels were 254 mg/dl (range 100-3781 mg/dl), and total cholesterol level was 233 ± 111 mg/dl. High-density lipoprotein was 42.6 ± 15.4 mg/dl, low-density lipoprotein 110.7 ± 42.4 mg/dl and very low-density lipoprotein 48 ± 15 mg/dl. Anti-LPL antibodies were identified in 2 patients (4.5%), both of whom had a family history of dyslipidemia, coronary insufficiency and acute myocardial infarction; one had undergone myocardial revascularization and percutaneous transluminal coronary angioplasty, and both were using fibrates and had normal triglyceride levels.

Conclusions: Our findings demonstrate a correlation between the immune response and dyslipoproteinemia in hypertriglyceridemic patients, suggesting that autoimmune disease contributes to the dyslipidemia process.
 

Background: Several murine models are susceptible to atherosclerosis, such as low density-lipoprotein receptor-deficient (LDLR^-/-) and apolipoprotein E-deficient (apoE^-/-) mice, and are used for studying pathophysiological mechanisms. Atherosclerotic lesions in the aortic valve and thoracic/abdominal aorta are commonly associated with hyperlipidemia. We recently demonstrated the development of large atherosclerotic plaques in Helicobacter pylori-infected heterozygous LDLR^+/- apoE^+/- mice.

Objectives: To measure novel biomarkers related to atherosclerosis, blood coagulation, and oxidative stress in order to investigate their possible pathogenic roles in atherosclerosis-prone mice.

Methods: Mice were fed with a normal chow diet or high-fat diet and sacrificed at different age intervals to measure aortic plaque size. Plasma cholesterol was enzymatically measured. Enzyme-linked immunosorbent assay was used to measure oxidized LDL (oxLDL)/beta-2-glycoprotein I (β2GPI) complexes, immunoglobulin M (IgM) antibodies against native LDL, oxLDL, or oxLDL/β2GPI, and urine 11-dehydro-thromboxane B₂ (11-dhTxB₂) or 8-hydroxy-deoxyguanosine.

Results: There was a parallel increase in plaque size, plasma cholesterol, and urinary 11-dhTxB₂ in atherosclerosis-prone mice. In contrast to atherosclerosis-prone strains, an elevation of urinary 11-dhTxB₂ with no significant plaque generation was observed in LDLR^+/- apoE^+/- mice. The atherogenic autoantigen oxLDL/β2GPI complex was detected only in LDLR^-/- mice. These levels seem to depend on plaque size. IgM antibodies against oxLDL in apoE^-/- mice were found, accompanied by atherosclerotic progression.

Conclusions: Progression of atherosclerotic lesions was associated not only with cholesterolemia but also with platelet activation and natural autoimmune-mediated regulatory mechanism(s) in murine models.
 

Background: Glioblastoma multiforme (GBM) is an ultimately fatal disease that affects patients of all ages. Elderly patients (65 years and older) constitute a special subgroup of patients characterized by a worse prognosis and frequent comorbidities.

Objectives: To assess the efficacy of different treatment modalities in terms of survival in elderly patients with GBM¹.

Methods: Using retrospective analysis, we extracted, anonymized and analyzed the files of 74 deceased patients (aged 65 or older) treated for GBM in a single institution.

Results: Mean survival time was 8.97 months and median survival time 7.68 months. Patients who underwent tumor resection had a mean survival of 11.83 months, as compared to patients who underwent no surgical intervention or only biopsy and had a mean survival of 5.22 months (P < 0.0001). Patients who underwent full radiation treatment had a mean survival of 11.31 months, compared to patients who received only partial radiotherapy or none at all and had a mean survival of 4.09 months (P < 0.0001). Patients who underwent chemotherapy had a mean survival 12.4 months, compared to patients who did not receive any chemotherapy and had a mean survival of 5.89 months (P < 0.001).

Conclusions: Age alone should not be a factor in the decision on which treatment should be given. Treatment should be individualized to match the patient’s overall condition and his or wishes, while taking into consideration the better overall prognosis expected with aggressive treatment.
 

Background: Major changes in the evaluation and treatment of curable colorectal cancer (CRC) have emerged in the last two decades. These changes have led to better patient outcome over time.

Objectives: To evaluate the impact of these changes as reflected in the difference in long-term outcome of a consecutive group of recently laparoscopically operated curable CRC[1] patients and a consecutive group of patients operated 20 years earlier in the same department.

Methods: Data of the new group were taken from our prospectively collected data of patients who underwent elective laparoscopic surgery for CRC in recent years. Data regarding patients operated on 20 years ago were retrieved from previous prospectively collected data on the long-term survival of CRC patients operated in the same department.

Results: The recently operated group comprised 203 patients and the previous group 199 patients. Perioperative mortality was 0.5% in the new group versus 1.5% in the old group (not significant). There were more early-stage and more proximal tumors in the recently operated group. A Kaplan-Meier 5-year survival analysis revealed no difference between stage I patients of the two groups. However, there was a significant increase in 5-year survival in the new group for stage II (85% vs. 63%, P = 0.004) and for stage III patients (57% vs. 39%, P = 0.01). This trend was maintained after removing the rectal cancer patients from the calculated data.

Conclusions: We have demonstrated improved survival for stage II and III CRC patients over a 20-year period in the same medical center. This change most likely reflects advances both in imaging techniques leading to more accurate staging and in adjuvant treatments.

Background: Intravitreal injections of the anti-vascular endothelial growth factor (VEGF) drugs bevacizumab (Avastin®) and ranibizumab (Lucentis®) became the mainstay of treatment for various retinal pathologies, but there is no consensus among ophthalmologists on the precise use of these drugs.

Objectives: To describe the current application of anti-VEGF[1] drugs among retinal specialists in Israel.

Methods: A questionnaire was sent via email to all 62 members of the Israeli Society of Retinal Specialists. The survey included 34 questions on various aspects of the use of anti-VEGF drugs: diagnosis, treatment, follow-up of different retinal pathologies, and the measures taken for ensuring sterile administration of the intravitreal injections.

Results: Fifty members (80%) completed the survey. Most of them (56%) offered both bevacizumab and ranibizumab to their patients for age-related macular degeneration, but 70% were influenced by the patient’s socioeconomic status. Three consecutive monthly injections were usually recommended (58%) for the first 3 months, and treatment was extended as long as subretinal or intraretinal fluids persisted (57%). Over two-thirds (68%) switched the drugs after the 3-monthly series if the first one yielded no improvement in fluid status. The routine practice for intravitreal injection (> 80%) involved the wearing of sterile gloves, using an eyelid speculum, and administering povidone-iodine pretreatment and topical antibiotics after treatment.

Conclusions: Intravitreal VEGF administration varies widely among Israeli retinal specialists. The current survey is intended to assist Israeli ophthalmologists in establishing their own treatment strategy for patients with retinal pathologies.