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עמוד בית Wed, 26.06.19

December 2006

A. Duek, L. Shvidel, A. Braester and A. Berrebi
 Background: Autoimmune disorders often develop during the course of B chronic lymphocytic leukemia. The source of the autoantibodies is still uncertain: either uncontrolled production of the malignant B cells or disturbances of the residual normal B and T cells involved in the immune system.

Objectives: To evaluate immunologic parameters in B-CLL[1] associated with autoimmune disorders. As a hypothesis we postulated that in those cases, the malignant B cells might disclose an activated phenotype pattern leading to the production of autoantibodies.

Methods: In the Registry of the Israel Study Group on CLL that includes 964 patients, we found 115 cases showing a single or a complex of autoimmune disorders. We evaluated the lymphocyte morphology, immunoglobulin G and beta-2-microglobulin serum levels and positivity of the CD38 and FMC7 markers, and compared these values with those of a matched CLL population without autoimmune disorder. 

Results: The main autoimmune disorders encountered were autoimmune hemolytic anemia (55 patients), Evan's syndrome (n=7), Hashimoto's thyroiditis (n=15), vasculitis (n=5) and rheumatoid arthritis (n=4). We found atypical prolymphocytic morphology in 22%, high expression of the activation antigens CD38 and/or FMC7 in 30%, and high level of immunoglobulin G (> 1000 mg/dl) and beta-2-microglobulin in 57% and 78% respectively. When compared with a matched CLL population without an autoimmune disorder, these values were statistically significant.

Conclusions: Our data, which show activated lymphocyte morphology, high levels of IgG[2] and beta-2-microglobulin, and increased expression of CD38 and/or FMC7 in a significant number of cases, suggest that some degree of activation of B cells may lead to the occurrence of an autoimmune disorder in CLL.


[1] CLL = chronic lymphocytic leukemia

[2] Ig = immunoglobulin 

O. Bairey, R. Ruchlemer and O. Shpilberg

Background: Non-Hodgkin’s lymphoma of the colon is a rare and consequently poorly studied extranodal lymphoma. Most of the previous publications used old pathologic classifications and old diagnostic and treatment approaches.

Objective: To examine the clinical presentation, pathologic classification, treatment and outcome of patients with NHL[1] of the colon.

Methods: A retrospective study was performed of all patients with NHL and involvement of the colon in two medical centers. The patient group consisted of 17 patients over a 13 year period.

Results: Fourteen patients had primary involvement and 3 secondary. The ileocecal region and cecum were the most frequent sites of involvement, occurring in 76% of patients. Most patients had bulky disease: three had a diameter > 5 cm and eight a diameter > 10 cm. Aggressive histology was found in 12 patients: diffuse large B cell lymphoma in 11 and peripheral T cell lymphoma in 1. Three patients had mantle cell lymphoma and two had indolent lymphomas: mucosa-associated lymphoid tissue (n=1) and small lymphocytic (n=1). Eleven patients underwent hemicolectomy: right sided in 9 and left sided in 2, and 5 DLBCL[2] patients required emergency surgery for intestinal perforation. The median overall survival was 44 months (range 1–147). Disease stage influenced prognosis; six of seven patients with limited-stage DLBCL who received aggressive chemotherapy achieved complete remission and enjoyed prolonged survival, whereas patients with aggressive disseminated disease had resistant disease and poor survival (median 8 months).

Conclusions: Most colonic lymphomas are aggressive B cell lymphomas. Diagnosis is often delayed. Early diagnosis may prevent perforation. Those with limited-stage disease when treated with aggressive chemotherapy may enjoy prolonged survival. 

The role of elective hemicolectomy to prevent perforation should be examined in prospective trials.

[1] NHL = non-Hodgkin's lymphoma

[2] DLBCL = diffuse large B cell lymphoma  

A. Elis, J. Radnay, H. Shapiro, D. Itzhaky, Y. Manor and M. Lishner
 Background: Monoclonal gammopathy of undetermined significance is defined by the presence of: low serum and/or urine monoclonal protein level; less than 10% plasma cells in bone marrow; normal serum calcium, creatinine and hemoglobin levels; and no bone lesions on full skeletal X-ray survey.

Objectives: To study the necessity of bone marrow examination for the diagnosis and clinical course of MGUS[1].

Methods: We retrospectively screened the medical records of all patients in whom monoclonal protein was found in the serum during 2001–2002 in the medical laboratories of Sapir Medical Center. Asymptomatic patients who had serum monoclonal immunoglobulin G < 3.0 g/dl or IgA[2] < 2.0 g/dl or IgM < 1.0 g/dl without anemia, renal failure, hypercalcemia or any bone lesions on skeletal survey were eligible. Full records of patients who were evaluated in the hematology clinic were available (group 1). The remaining patients were followed by their family physicians; thus we had access only to their electronic files including laboratory results and new diagnoses (group 2). Demographic and clinical parameters as well as clinical course were evaluated.

Results: Both groups (57 and 255 patients, respectively) had similar demographic, laboratory and clinical characteristics. Bone marrow examination was performed in 30 of 57 patients (group 1): 16 were normal, 8 had an excess of normal plasma cells, and 6 had excess of pathologic plasma cells. However, only in two of the latter six could a diagnosis of multiple myeloma be established. All group 1 patients were followed for 22 ± 11 months and only two developed overt multiple myeloma. During the same period, 6 of 255 patients (group 2) were diagnosed as multiple myeloma and 3 as MGUS in other hospitals. The rest had a stable course with no change in their laboratory values.

Conclusions: Our findings suggest that bone marrow examination should not be performed routinely in patients who fulfill strict clinical and laboratory criteria of MGUS.


[1] MGUS = monoclonal gammopathy of undetermined significance

[2] Ig = immunoglobulin

A. Nemets, I. Isakov, M. Huerta, Y. Barshai, S. Oren and G. Lugassy
 Background: Thrombosis is a major cause of morbidity and mortality in polycythemia vera. Hypercoagulability is principally due to hyperviscosity of the whole blood, an exponential function of the hematocrit. PV[1] is also associated with endothelial dysfunction that can predispose to arterial disease. Reduction of the red cell mass to a safe level by phlebotomy is the first principle of therapy in PV. This therapy may have some effect on the arterial compliance in PV patients.

Objectives: To estimate the influence of phlebotomies on large artery (C1) and small artery compliance (C2) in PV patients by using non-invasive methods.

Methods: Short-term hemodynamic effects of phlebotomy were studied by pulse wave analysis using the HDI-Pulse Wave CR2000 (Minneapolis, MN, USA) before and immediately after venesection (300–500 ml of blood). We repeated the evaluation after 1 month to measure the long-term effects.

Results: Seventeen PV patients were included in the study and 47 measurements of arterial compliance were performed: 37 for short-term effects and 10 for long-term effects. The mean large artery compliance (C1) before phlebotomy was 12.0 ml/mmHg x 10 (range 4.5–28.6), and 12.6 ml/mmHg x 10 (range 5.2–20.1) immediately after phlebotomy (NS). The mean small artery compliance (C2) before and immediately after phlebotomy were 4.4 mg/mmHg x 10 (range 1.2–14.3) and 5.5 mg/mmHg x 10 (range 1.2–15.6) respectively (delta C2–1.1, P < 0.001). No difference in these parameters could be demonstrated in the long-term arm.

Conclusions: Phlebotomy immediately improves arterial compliance in small vessels of PV patients, but this effect is short lived.


[1] PV = polycythemia vera

A. Kolomansky, R. Hoffman, G. Sarig, B. Brenner and N. Haim
 Background: Little is known about the epidemiology of venous thromboembolism in hospitalized patients in Israel. Also, a direct comparison of the clinical and laboratory features between cancer and non-cancer patients has not yet been reported.

Objectives: To investigate and compare the epidemiologic, clinical and laboratory characteristics of cancer and non-cancer patients hospitalized with venous thromboembolism in a large referral medical center in Israel.

Methods: Between February 2002 and February 2003, patients diagnosed at the Rambam Medical Center as suffering from VTE[1] (deep vein thrombosis and/or pulmonary embolism), based on diagnostic findings on Doppler ultrasonography, spiral computed tomography scan or lung scan showing high probability for pulmonary embolism, were prospectively identified and evaluated. In addition, at the conclusion of the study period, the reports of spiral chest CT scans, performed during the aforementioned period in this hospital, were retrospectively reviewed to minimize the number of unidentified cases. Blood samples were drawn for evaluation of the coagulation profile.

Results: Altogether, 147 patients were identified and 153 VTE events diagnosed, accounting for 0.25% of all hospitalizations during the study period. The cancer group included 63 patients (43%), most of whom had advanced disease (63%). The most common malignancies were cancer of the lung (16%), breast (14%), colon (11%) and pancreas (10%). Of 121 venous thromboembolic events (with or without pulmonary embolism) there were 14 upper extremity thromboses (12%). The most common risk factors for VTE, except malignancy, were immobilization (33%), surgery/trauma (20%) and congestive heart failure (17%). There was no difference in prevalence of various risk factors between cancer and non-cancer patients. During an acute VTE event, D-dimer levels were higher in cancer patients than non-cancer patients (4.04 ± 4.27 vs. 2.58 ± 1.83 mg/L respectively, P = 0.0550). Relatively low values of activated protein C sensitivity ratio and normalized protein C activation time were observed in both cancer and non-cancer groups (2.05 ± 0.23 vs. 2.01 ± 0.33 and 0.75 ± 0.17vs. 0.71 ± 0.22, respectively). These values did not differ significantly between the groups.

Conclusion: The proportion of cancer patients among patients suffering from VTE was high. Their demographic, clinical and laboratory characteristics (during an acute event) were not different from those of non-cancer patients, except for higher D-dimer levels.


[1] VTE = venous thromboembolism

M. Tokar, D. Bobilev, S. Ariad and D.B. Geffen

Background: Disseminated intravascular coagulation associated with malignant bone marrow involvement has been described as a rare complication of gastric carcinoma and most patients die within 1–4 weeks. Effective chemotherapy of the underlying malignancy may be the only way to control acute DIC[1].

Objectives: To assess the benefit of infusional 5-fluorouracil as the primary treatment of metastatic gastric carcinoma and DIC at diagnosis.

Methods: From February 2001 to January 2005, six women (median age 48 years) with gastric carcinoma who presented with diffuse bone metastases and acute DIC were treated in our department. Diagnosis was based on primary gastric and bone marrow biopsies. DIC was confirmed by laboratory findings. Initial treatment consisted of infusional 5FU[2] 200 mg/m2/day. When the bleeding tendency stopped, cisplatin 60 mg/m2 and epirubicin 50 mg/m2 given every 3 weeks were added.

Results: Within one week of starting the treatment, the clinical and laboratory signs of acute DIC were resolved in five of six patients. Upon clinical improvement, five patients subsequently received epirubicin and cisplatin. Survival, however, was short (mean 15 weeks). All patients died with symptoms of bleeding, showing clinical and laboratory signs of DIC.

Conclusions: Based on our experience, infusional 5FU is an effective regimen with negligible myelosuppression; thus, it may be a good choice as initial therapy for this group of patients. The response induced by protracted 5FU was usually short and lasted for a few weeks only. Therefore, once DIC symptoms are controlled, the addition of newer cytotoxic drugs may be necessary to consolidate the remission.

[1] DIC = disseminated intravascular coagulation

[2] 5FU = 5-fluorouracil


U. Elchalal, E. Gabbay, M. Nadjari, D. Varon, O. Zelig and E. Ben-Chetrit
E.S. Kokia, R. Marom, V. Shalev, Y. Jan and J. Shemer
 Background: During war the health management organizations have tremendous difficulty monitoring members' needs according to geographic spread.

Objectives: To describe how an HMO[1] used its health information technology in a way that enables its management to receive updated online information on the demands of the insured, according to their distribution throughout the country during the time of the war in Lebanon in July-August 2006.

Methods: Data were derived from the computerized medical records of Maccabi Healthcare Services – the second largest HMO in Israel, providing care to more than 1.7 million members nationwide. Data on healthcare utilization by northern members were compared to the geographic distribution of clinics.

Results: The war was characterized by the massive evacuation of citizens southwards. During this period there was an abrupt decline in the utilization of medical services by northern members in the northern region. This decline returned to normal 10 days after the ceasefire. A reciprocal increase was noted in the use of health services by citizens from the north in other regions. This increase returned to normal after the war. No such pattern was noticed during the same period in 2005.

Conclusions: Real-time surveillance of trends in consumption of health services by citizens in times of regular daily living as well as during emergencies and wars is a vital management tool for medical directors responsible for providing health services.


[1] HMO = health management organization

Original Articles
E. Jaul, P. Singer and R. Calderon-Margalit
 Background: Despite the ongoing debate on tube feeding among severely demented patients, the current approach in western countries is to avoid feeding by tube.

Objectives: To assess the clinical course and outcome of demented elderly patients with severe disabilities by feeding mode.

Methods: The study was conducted in a skilled nursing department of a major psychogeriatric hospital in Israel. Eighty-eight patients aged 79 ± 9 years were followed for 17 months: 62 were fed by nasogastric tube and 26 were orally fed. The groups were compared for background characteristics, underlying medical condition, functional impairment, clinical and nutritional outcomes, and survival.

Results: Tube feeding had no beneficial effect on clinical and nutritional outcomes or on healing preexisting pressure ulcers, compared with oral feeding. Very few patients on tube feeding showed signs of discomfort, partly because of low cognitive function. Survival was significantly higher in the tube-fed patients (P < 0.001), which could be partly explained by the different case mix (i.e., the underlying diseases)

Conclusions: Tube feeding seems to have no nutritional advantage in severely demented elderly patients. Median survival was longer in tube-fed individuals who had no acute co-morbidity. However, since tube feeding does not add to patient pain and discomfort, it should not be contraindicated when it complies with the values and wishes of patients and their families.

A. Jotkowitz, A. Porath, A. Shotan, M. Mittelman, E. Grossman, R. Zimlichman, B.S. Lewis, A. Caspi, S. Gottlieb and M. Garty, for the Steering Committee of the Israeli Heart Failure National Survey 2003

Background: Despite significant advances in the therapy of heart failure, many patients still do not receive optimal treatment.

Objectives: To document the standard of care that patients hospitalized with HF[1] in Israel received during a 2 month period.

Methods: The Heart Failure Survey in Israel 2003 was a prospective 2 month survey of patients admitted to all 25 public hospitals in Israel with a diagnosis of HF.

Results: The mean age of the 4102 patients was 73 years and 43% were female. The use of angiotensin-converting enzyme/angiotensin receptor blockers and beta blockers both declined from NYHA class I to IV (68.8% to 50.6% for ACE[2]-inhibitor/ARB[3] and 64.1% to 52.9% for beta blockers, P < 0.001 for comparisons). The percentage of patients by NYHA class taking an ACE-inhibitor or ARB and a beta blocker at hospital discharge also declined from NYHA class I to IV (47.5% to 28.8%, P < 0.002 for comparisons). The strongest predictor of being discharged with an ACE-inhibitor or ARB was the use of these medications at hospital admission. Negative predictors for their usage were age, creatinine, disease severity class, and functional status.

Conclusions: Despite the dissemination of guidelines many patients did not receive optimal care for HF. Reasons for this discrepancy need to be identified and modified.

[1] HF = heart failure

[2] ACE = angiotensin-converting enzyme

[3] ARB = angiotensin receptor blocker

R. Avisar, R. Friling, M. Snir, I. Avisar and D. Weinberger

Background: The prevalence and incidence of blindness in Israel appear to be comparable to other western countries. Comparisons are difficult because of different definitions of blindness, and the uniqueness of the Israeli registry for the blind.

Objective: To characterize the population who were registered as Blind in Israel in the years 1998–2003 and estimate the prevalence and incidence of blindness by age and causes of blindness.

Methods: A retrospective review of the annual report of the National Registry for the Blind in Israel between 1998 and 2003 identified 21,585 blind persons who received a certificate for blindness. Blind persons are identified by ophthalmologists throughout Israel and referred to the Registry of the Blind if they have a visual acuity of 3/60 or worse, or a visual field loss of < 20 degrees in their better eye. This report includes prevalence data on 21,585 persons enrolled in this review still alive and living in Israel in 2003. We estimated the prevalence rate of blindness nationwide and the incidence rate for each cause of blindness for every year.

Results: The main leading causes of blindness in Israel in 1998 were (in percent of the total number of newly registered patients): age-related macular degeneration (20.1%), glaucoma (13.8%), myopic maculopathy (12%), cataract (10.4%), diabetic retinopathy and maculopathy (10.1%), and optic atrophy (7.9%), and in 2003, 28%, 11.8%, 7.4%, 6.5%, 14.4% and 6.5% respectively.

Conclusions: The results indicate that the incidence of age-related macular degeneration, diabetic retinopathy and maculopathy in Israel is increasing, while that of glaucoma, myopic maculopthy, optic atrophy and cataract is decreasing.

הבהרה משפטית: כל נושא המופיע באתר זה נועד להשכלה בלבד ואין לראות בו ייעוץ רפואי או משפטי. אין הר"י אחראית לתוכן המתפרסם באתר זה ולכל נזק שעלול להיגרם. כל הזכויות על המידע באתר שייכות להסתדרות הרפואית בישראל. מדיניות פרטיות
ז'בוטינסקי 35 רמת גן, בניין התאומים 2 קומות 10-11, ת.ד. 3566, מיקוד 5213604. טלפון: 03-6100444, פקס: 03-5753303