Israel Medical Association Journal

Background: Intravenous recombinant tissue plasminogen activator therapy within 3 hours of stroke onset is a proven effective treatment for acute ischemic stroke.

Objectives: To assess the feasibility and safety of rt-PA[1] therapy for reperfusion in routine clinical practice in Israel, in a setting of a dedicated stroke unit.

Methods: Consecutive patients presenting within less than 3 hours of stroke onset were evaluated by an emergency physician and the neurology stroke team. After brain computerized tomography eligible patients were treated with intravenous rt-PA (0.9 mg/kg; maximum dose 90 mg) according to an in-hospital protocol corresponding to recommended criteria. Patients were admitted to the acute stroke unit. Safety and clinical outcome were routinely assessed. Re-canalization was assessed by serial transcranial Doppler.

Results: The study group comprised 16 patients, mean age 61 years (range 47–80 years), male to female ratio 10:6, whose median baseline National Institutes of Health stroke scale was 13 (range 6–24). They were treated within a mean door-to-CT time of 39 minutes (range 17–62 min), door-to-drug time 101 minutes (range 72–150), and stroke onset-to-drug time 151 minutes (range 90–180). There was an early improvement within 24 hours (of ≥ 4 points in the NIHSS[2] score) in 7 patients (44%) and no early deteriorations. There were no protocol deviations, no symptomatic intracranial hemorrhages, and no major systemic hemorrhage within 36 hours of rt-PA treatment. Three asymptomatic hemorrhagic transformations of the infarct were noted on routine follow-up brain CT associated with neurologic improvement. Outcome data were comparable to the National Institute of Neurological Disorders and Stroke rt-PA Stroke Study.

Conclusion: Intravenous rt-PA treatment within 3 hours of stroke onset in routine clinical practice in Israel is feasible and appears safe in the setting of a neurology stroke unit and team. Careful implementation of rt-PA therapy for selected patients in Israel is encouraged.

Background: Screening for celiac disease is based on the sequential evaluation of serologic tests and intestinal biopsy; an optimal screening protocol is still under investigation. The screening policy of one of the main healthcare providers in Israel (Maccabi) consists of measuring total immunoglobulin A and tissue transglutaminase IgA[1] antibodies and confirming positive results by endomysial antibodies. For IgA-deficient patients antigliadin IgG is measured.

Objectives: To evaluate the use of tTGA[2] as a first-level screening test in patients suspected of having celiac disease

Methods: The results of tTGA and EMA[3] tests over a 3 month period were obtained from the laboratory computer. Letters were sent to the referring physicians of patients with positive tests, requesting clinical information and small intestinal biopsy results. tTGA was performed using an anti-guinea pig tTG-IgA enzyme-linked immunosorbent assay kit.

Results: Overall, 2,505 tTGA tests were performed: 216 (8.6%) were tTGA-positive of which 162 (75%) were EMA-negative (group 1) and 54 (25%) EMA-positive (group 2). Clinical information was obtained for 91 patients in group 1 and 32 in group 2. Small intestinal biopsy was performed in 33 (36%) and 27 patients (84%) in groups 1 and 2, respectively. Celiac disease was diagnosed in 4 biopsies (12%) in group 1 and 23 (85%) in group 2 (P < 0.0001). The positive predictive value was 45% for tTGA and 85% for EMA.

Conclusions: Symptomatic patients with positive tTGA and negative EMA have a low rate of celiac disease compared to those who are tTGA-positive and EMA-positive. Confirmation with EMA is advised when tTGA is performed as a first-level screening for suspected celiac disease.

Background: There are radiobiologic and technical advantages to the use of interstitial brachytherapy alone or as an adjunct to external beam radiotherapy in the postoperative treatment of soft tissue sarcomas.

Objectives: To review the experience of the Rambam Medical Center in implementing interstitial brachytherapy in the treatment of 32 patients with soft tissue sarcomas.

Methods: Thirty-two patients with variously located soft tissue sarcomas were managed with a combination of surgery and brachytherapy of the tumor bed, with or without EBRT[1]. In 27 of 32 patients, brachytherapy catheters were placed intraoperatively, while in 5 patients the implant was performed as a separate postoperative procedure. Twenty-seven patients received low dose-rate brachytherapy with iridium-192 seeds. Five patients received fractionated high dose-rate brachytherapy using the microSelectron machine.

Results: With a median follow-up of 36 months, the overall local control rate was 87.5%. Four of 32 patients (13%) failed locally at the implant site, and 6 (19%) developed lung metastasis. Two of the five patients with lung metastasis had a local recurrence as well. At the time of analysis, eight patients had died of sarcoma (disease-specific mortality rate was 25%), while three had died of intercurrent causes. The 5 year actuarial disease-free survival rate was 56%, and the 5 year actuarial overall survival was 70%. Five patients (16%) developed severe wound complications following surgery/brachytherapy, and six patients (19%) developed late local toxicity (fibrosis and telangiectasia).

Conclusions: Wide local excision followed by interstitial brachytherapy has resulted in an 87.5% local control rate with a 17% local complication rate.

__________________________________________

Background: Imaging-guided core needle biopsy is a well-established technique for the diagnosis of bone and soft tissue tumors and tumor-like lesions in specialized orthopedic oncology centers.

Objective: To present our results of computed tomography-guided core needle biopsy with assessment of the accuracy of the technique.

Methods: Between July 1998 and October 2000, 215 CT-guided core needle biopies were performed and histologically examined in the Unit of Bone and Soft Tissue Pathology, Tel Aviv Sourasky Medical Center. There were 80 soft tissue and 135 bony lesions. All biopsies were performed by the same radiologist and the histologic examination by the same pathologist.  To assess the accuracy of the procedure, we compared the diagnosis at biopsy with the diagnosis after definitive surgery (when available).

Results: Bone core needle biopsy (n = 135) showed malignancy in 89 cases (primary or recurrent bone sarcoma, lymphoma, myeloma, metastatic carcinoma or melanoma). There were 29 benign lesions. In 17 cases the result was inconclusive and an open incisional biopsy was performed. Of the 80 soft tissue biopsies, 35 were malignant (25 soft tissue sarcomas, 6 lymphomas, 4 metastatic carcinomas); 40 were benign (myositis ossificans, neurofibroma, desmoid tumor, schwannoma, hematoma and others), and 5 were inconclusive and followed by an open incisional biopsy. The core needle biopsy histologic diagnosis was compared with that of the definitive surgery and the diagnostic accuracy was 90%. Only three samples initially diagnosed as benign turned out to be malignant. No significant complications occurred during the procedures.

Conclusions: CT-guided CNB[1] of musculoskeletal lesions is a safe and effective procedure that assures sufficient and proper material for histologic examination. The accuracy of this method in our center was 90%. Tumor sampling is extremely important, especially in soft tissue sarcomas, and cores should be taken in different directions, including areas of necrosis. The processing is quick, especially for bone CNB, and diagnosis can be achieved within 24 hours. The material undergoes excellent fixation and the immunostains are reliable.

Background: Celiac disease is common in both children and adults. Small intestinal biopsy is mandatory for establishing a diagnosis. Anti-endomysial antibodies, detected by immunofluorescence, have a sensitivity and specificity close to 100% in the diagnosis of CD[1]. Recently, tissue transglutaminase has been identified as the target autoantigen of antibodies against endomysium, and TTG[2] antibodies are comparable to EMA-IMF[3] in the diagnosis of CD.

Objective: To evaluate a new enzyme-linked immunosorbent assay kit for EMA, compared to EMA-IMF and TTG antibodies in the diagnosis of CD.

Methods: Our study population included all subjects with positive EMA-IMF who underwent intestinal biopsy (n=21). From the same sera, TTG antibodies and EMA-ELISA[4] were determined, and all antibody results were compared to the biopsy findings.

Results: EMA-IMF was able to predict biopsy findings of CD in 19 of 21 cases (90.5%). When patients with biopsy findings compatible with CD and positive EMA-IMF (n=19) were tested for EMA-ELISA and TTG antibodies, 18 of the 19 were positive for both EMA-ELISA and TTG antibodies. A significant correlation was found between EMA-ELISA and TTG antibody titers (r = 0.74, P < 0.001).

Conclusions: Our study demonstrates that EMA-ELISA is comparable to TTG antibodies in the diagnosis of CD, and supports the use of EMA-ELISA as a serologic marker for this disease.

Background: Matrix metalloproteinases are proteolytic enzymes that degrade extracellular matrix components. Numerous studies have demonstrated that individual MMPs[1] play a crucial role in tumor invasion and metastasis.

Objective: To examine the expression of MMPs and their inhibitor TIMP-2 in neoplastic and normal thyroid tissues.

Methods: We examined 33 cases of thyroid tumor (papillary, follicular and medullary carcinoma, follicular adenoma and multinodular goiter). MMP protein content and activity were measured by enzyme-linked immunosorbent assay and gel zymography. Immunohistochemistry was also performed.

Results: The thyroid tissues examined secreted MMP-2 and 9 as well as TIMP-2, but only MMP-2 was significantly higher in papillary carcinoma cases compared to the adjacent normal tissue or to the other tumor entities. Increased MMP-2 immunohistochemical staining was demonstrated in the neoplastic papillary epithelial component. No significant difference was seen between papillary carcinomas with lymph node metastases and those without.

Conclusions: Increased MMP-2 expression may be useful as a diagnostic marker to differentiate papillary carcinoma from other thyroid neoplasms, but it cannot serve as a useful prognostic marker.

Background: Foreign bodies are sometimes overlooked in the initial evaluation of soft tissue wounds in the emergency room setting. The physical examination identifies foreign bodies that are superficial enough to be seen or palpated, while radiographs reveal those that are radio-opaque. If these two criteria are not met, however, the foreign body may remain undetected. These patients present later with long-standing pain in the area of penetration sometimes associated with localized tenderness.

Objectives: To assess the role of ultrasonography in the diagnosis and management of patients with a suspected retained foreign body.

Methods: Ultrasound was used in 21 patients with suspected retained foreign bodies and the diagnosis was positive in 19. Fifteen underwent a surgical exploration in which the ultrasound was used as an adjunctive modality either pre- or intraoperatively to assist in the localization of the foreign body.

Results: All procedures were successful. No postoperative complications were recorded at an average follow-up of 2 years. Three patients gradually became asymptomatic and were left untreated. One patient was lost to follow-up.

Conclusion: Sonography is an extremely effective tool for the late diagnosis of retained foreign bodies in the soft tissues. We suggest that its availability in the emergency room may decrease the rate of misdiagnosis and avoid these unfortunate cases, although this remains tc be proven.
 

Sex steroid hormones (estrogens, progestagens and androgens) have been associated with healthy and neoplastic pancreatic biology, although the precise significance of the findings has not been well established. Receptors for the three different types of SSH are expressed in normal and tumoral pancreatic tissue with varying profiles related to cell origin (exocrine or endocrine), to type of neoplasm. and probably even to tumoral behavior. The activity of specific enzymes involved in the synthesis and transformation of SSH are increased in some neoplastic pancreatic tissues, which may influence the circulating concentrations of these hormones, such as the low serum testosterone: dihydrotestosterone ratio described in male patients with pancreatic carcinoma. Different patterns of age and gender-related incidence and growth of neoplasms have been identified. Experimental studies have shown that pancreatic carcinogenesis is promoted or inhibited by SSH. At present, the data supporting hormonal manipula­tion for the treatment of these tumors are non-conclusive. Normal and tumoral pancreatic tissues may be regarded as a target for SSH and an additional site of biosynthesis. The influence of these hormones on physiological activities is not well known but should be further explored. The study of SSH in pancreatic neoplasms will provide clues about its origin, development, tumoral behavior, prognosis and more specific hormonal therapy. We review here the evidence favoring the role of SSH and their possible clinical implications in pancreatic function.

Background: Tumor necrosis factor is associated with various local and systemic inflammatory sequelae following snakebite. Xanthine oxidase is a principal mediator of remote tissue injury (e.g., lungs, heart, liver).

Objective: To investigate in a snakebite-like animal model the as yet unexplored role of TNF and XO in mediating organ damage following snakebite.

Methods: Sprague-Dawley rats were injected intramuscularly with a non-lethal 500 g/kg dose of Vipera aspis venom (n=10) or saline (n=10). Blood pressure and heart rate were continuously monitored, TNF- was measured in the blood, and total XO + xanthine dehydrogenase activity was assessed in various tissues. Lung histology and permeability indices were analyzed.

Results: Venom injection caused a significant (P0.05) reduction in both heart rate and invasive arterial pressure. The blood circulating TNF levels were significantly higher in the intoxicated group (P0.05 vs. saline group), with changes seen at 30 minutes from intoxication in both groups. Total XO + XDH activity in the kidney, lung and liver of the venom-injected group was significantly (P0.05) higher than in the saline group, while the activity in the heart was similar.

Conclusions: The mediation of remote organ and hemodynamic changes following intramuscular injection of a non-lethal dose of Vipera aspis venom can be attributed partly to TNF and partly to XO. More research is needed to better understand the role of either compound and the time frame of their activity before specific antagonists can be introduced for snakebite management.