Etoposide and Cisplatin for Non-Small Cell Lung Cancer 

David B. Geffen, Sofia Man, Yoram Cohen*

Dept. of Oncology, Soroka-University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheba

Etoposide and cisplatin (EP) has been the standard therapy for non-small cell lung cancer (NSCLC) at many cancer centers for over a decade. We analyzed our experience with EP in NSCLC to provide a baseline for comparison with new drugs. From 1986 through 1994, 46 of our patients with NSCLC received EP as first-line chemotherapy. Radiation therapy was administered to 25 of them, including 20 who received it immediately before or concomitantly with chemotherapy. Toxicity was mild and included only 1 episode of neutropenic fever and 1 case of reversible renal failure.

Overall response was 22%. In 3, response was complete (pathologically documented in 2 of them) and in 7 partial. Median survival in locally advanced (stage III) and metastatic disease (stage IV and recurrent) were 12 months and 7 months, respectively. 2 patients are alive and free of disease more than 6 years after diagnosis.

Our results are consistent with other published studies of EP in NSCLC. EP provides modest benefit in locally advanced NSCLC, with minimal toxicity.

Jules E. Harris Chair in Oncology.

Alopecia Due to Seroxat 

Leonid Umansky, Abraham Dorevitch, Avner Sella

Psychiatry Chronic Dept., Eitanim Mental Health Center, Jerusalem

There are 2 stages of alopecia, anagen and telogen effluvium, both of which may be associated with medication- related alopecia. We describe massive hair loss in a 51-year-old woman during treatment with Seroxat (paroxetine), which remitted after it was discontinued. Pathological mechanisms of drug-associated alopecia are complex and have yet to be fully elucidated.

Carbamazepine Hypersensitivity 

Shimon Ivry, Doobi Shteinmintz, Hava Tabenkin

Dept. of Family Medicine, HaEmek Hospital, Afula and National Residency Institute, Ben-Gurion University of the Negev, Beer Sheba

Carbamazepine (C) can cause a characteristic hypersensitivity reaction (CHS}. This multisystem reaction typically presents as fever, mucocutaneous eruption and lymphadenopathy. The syndrome usually develops between 1 week and 3 months after starting therapy, with involvement of the liver, lung, kidney and inappropriate secretion of ADH. The incidence is less than 0.001% in those treated with C and it is diagnosed clinically. With onset of CHS, the drug must be stopped and if there is no improvement, cortico-steroids should be started. When the diagnosis is in doubt, the patch test, lymphocyte transformation test, macrophage migration inhibitor factor, and other tests can be helpful.

The pathogenesis is not known. Similar syndromes have been described with phenytoin and phenobarbital. There is clinical and in-vitro evidence of cross reactions between C and phenytoin. It is not known whether the CHS syndrome should be considered a premalignant state, with increased risk for the development of malignant lymphoma.

Elective Repair of Infra-Renal Aortic Aneurysm 

J.D. Cohen, P. Singer, M. Haddad, A. Zelikovski

Depts. of General Intensive Care and Vascular Surgery, Rabin Medical Center, Beilinson Campus; and Sackler Faculty of Medicine, Tel Aviv University

Age over 80 years is generally considered an independent risk factor in elective surgery for abdominal aortic aneurysm (AAA). As the general population increases in age, more elderly are likely to be candidates for such surgery.

We studied prospectively 100 consecutive patients undergoing elective AAA surgery between 1992-1995. All were operated on by the same team of anesthetists and surgeons and all were transferred to the general ICU for at least the first 24 hours. 16 were above the age of 80 (Group I) and 84 below (Group II).

We recorded preoperative factors (demographics, medical history, risk factor indices, EKG findings, as well as left ventricular ejection fraction (LVEF) and stress imaging when indicated); intraoperative factors (duration of surgery, size of aneurysm, complications and units of blood transfused); postoperative factors (length of ICU stay, duration of ventilation, APACHE II [Acute Physiological and Chronic Health Evaluation] and TISS [Therapeutic Intervention Scoring System] scores; complications in the ICU, need for readmission to the ICU, and mortality).

In Group I LVEF was greater (p=0.03) and aneurysm size significantly larger (p=0.036), but there were no other significant differences between the 2 groups with regard to pre- and intraoperative data. Group I patients were not ventilated as long (p=0.038), but there were no significant differences in outcome factors. Mortality for the whole group was 5% and was not significantly different in the 2 groups (1/16 in Group I and 4/84 in Group II).

We conclude that there is no excess morbidity or mortality in octogenarians undergoing AAA surgery. However risk of the aneurysms rupturing is significantly greater since they are larger. We suggest that age not be considered the sole criterion for aneurysm repair, or at least not in selected patients with normal LVEF.

Acute Ischemia of the Lesser Gastric Curvature 

D. Czeiger, A. Ariche, G. Shaked, N. Sion-Vardi, I. Levi

Trauma Service, Dept. of Surgery, and Pathology Institute, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer Sheba

The rich blood supply of the stomach protects it from ischemia and necrosis. Acute gastric ischemia, an emergency with high mortality, is rare. Atherosclerosis is the leading cause of acute ischemia, and the lesser curvature of the stomach is more vulnerable due to its relatively lesser blood supply. Reduction in gastric blood supply usually presents as chronic disease characterized by gastritis, gastric ulcer, or gastroparesis.

Gastroscopy can identify lesions of the gastric mucosa, and angiography demonstrates occluded vessels. Treatment of acute gastric ischemia is surgical, with total gastrectomy preferred over partial resection.

Non-Penetrating Deep Sclerectomy without Collagen Implantfor Glaucoma

Ben Zion Silverstone, Isaac Aizenman, Carmit Landau, Yaacov Rozenman

Ophthalmology Dept., Shaare Zedek Medical Center, Jerusalem

Deep sclerectomy (DS) can be used in glaucoma with increased intraocular pressure when medical treatment fails. It involves removing part of the ocular drainage apparatus. Resistance to intraocular fluid drainage is decreased, improving drainage and decreasing intraocular pressure. By avoiding anterior chamber penetration, DS diminishes frequency of the complications of filtering surgery.

24 eyes of 23 patients underwent DS for primary or secondary open angle glaucoma with elevated intraocular pressure not controlled medically. It included preparation of a 4.0 x 4.0 mm limbal-based external scleral flap, dissecting and removing most of an internal scleral flap (leaving it 1 mm smaller than the external flap), unroofing Schlemm's canal and removing fine endothelial tissue lining its inner walls. The external scleral flap was then repositioned and sutured. Collagen implants were not used. In some cases DS was combined with extracapsular cataract extraction and intra-ocular lens implantation.

Mean intraocular pressure decreased from 24.8‏3.9 mmHg initially to 12.8‏4.4 mmHg 6 months after operation (p<0.0001). There was no difference in postoperative intra-ocular pressure between DS as a single procedure or as part of a combined operation. Comations were mild and of short duration.

If long-term follow-up shows that lowered intraocular pressures are maintained, DS should be a surgical option in earlier stages of glaucoma.

Relationship Between Preterm Birth and Exertion During Pregnancy

S. Gazit-Nissim, E. Sheiner, M. Mazor, I. Shoham-Vardi

Depts. of Obstetrics and Gynecology, Epidemiology and of Health Services Evaluation, Soroka-University Medical Center, and Ben-Gurion University of the Negev, Beer Sheba

The relationship between physical activity at home and at work during pregnancy and preterm birth was studied. Using a case-control design, 99 women who delivered preterm were compared with 189 women who had term deliveries. The risk of preterm birth was tested in relation to characteristics of work in and outside the home. All women were interviewed post-partum before discharge.

There were no statistically significant differences between the groups in relation to sociodemographic and obstetrical factors, but level of education was significantly lower in the study group versus the control group (p=0.001).

Women who delivered preterm had devoted less time 3 months prior to delivery to household chores (mean of 3.7 hours vs. 4.8 hours in the control group, p=0.002). They also had spent less time walking around the home than the controls (1.2 vs. 1.5 hours, p=0.02). There were no differences between the groups in relation to physical activity outside the home, not during working hours, nor in duration of work. Significantly fewer women who delivered preterm were active in sports (odds ratio 0.22; 95% confidence interval 0.50-0.65; p=0.002).

A low level of education was significantly related to the risk of preterm birth, which may have resulted from lesser compliance with their physician's recommendations. It appears that in women not used to significant physical activity but who had access to adequate prenatal care, physical effort during pregnancy was not related to a higher risk of preterm birth.

Presurgical Neuropsychological assessment in Epilepsy: The Wada Test

Fani Andelman, Miri Neufeld, Irith Reider-Groswasser, Uri Kremer, Yoram Segev, Itzhak Fried

Functional Neurosurgery and EEG and Epilepsy Units, Section of Neuroradiology; and Pediatric Neurology Unit; Tel Aviv-Sourasky Medical Center, Tel Aviv

37 candidates for epilepsy surgery underwent the intra-carotid amytal procedure (IAP; also known as the Wada test) to determine hemispheric speech dominance and memory capacity. 31 demonstrated left hemisphere speech dominance, 2 showed evidence for bilateral language and 4 demonstrated right hemispheric language dominance.

Our study supports a correlational relationship between handedness, lesion laterality and age of onset of seizures, as reported in earlier studies. Left-handed patients with a left hemisphere lesion whose seizures began to an early age had a strong tendency for reversed language dominance.

Asymmetry of at least 20% in performing the memory test was taken as the cutoff score for demonstrating laterality of lesions. The asymmetry score correctly predicted laterality of lesions in all 28 patients; 6 did not have asymmetry scores and 3 were examined for language only. None of the patients who successfully passed the Wada memory test had any significant postsurgical memory deficits; 1 had transient reduction in verbal memory and 4 who did not pass the test were not operated on for this reason.

Our results demonstrate the importance of the Wada test in determining cerebral speech dominance, in predicting post-surgical amnesia, and support its usefulness in predicting laterality of seizure focus in candidates for temporal lobectomy.

Carbon Dioxide Gas Embolism during Laparascopic Cholecystectomy

Anat Laver-Segal, Miguel Iuchtman, Paltiel Weiner

Depts. of Anesthesiology, Surgery A and Medicine A, Hillel Yaffe Medical Center, Hadera and Rappaport Medical School, The Technion, Haifa

A case of carbon dioxide gas embolism during laparascopic cholecystetomy is presented. Prompt diagnosis and immediate treatment resulted in positive outcome. Laparascopic cholecystectomy is nowadays one of the most common operations for cholecystectomy and certainly the most frequent endoscopic surgical procedure. It is usually safe and effective. However, a number of serious complications have been reported during the procedure.

Gas embolism is one of the complications that may occur during the initial gas insufflation or during dissection of the gall bladder. Symptoms are mainly related to the speed and the amount of gas that reaches the venous system. Early recognition and prompt treatment are required to prevent severe morbidity or even fatal outcome.

Transesophageal echocardiography has detected many unsuspected cases of gas embolism. However, capnograph monitoring of end-tidal CO₂, routinely used in everyday anesthesia, is highly reliable in alerting to the possibility of gas embolism and also in confirming its occurrence.

In cases of suspected gas embolism close collaboration between anesthetist and surgeon is required.

High Dose Endobronchial Brachy - Therapy for Malignant Airway Obstruction

Alex Yarmolovsky, Alan Katz, Eyal Fenig, G. Fink, Daniel Bendayan, Aaron Sulkes, Mordechai R. Kramer

Institutes of Pulmonology and Oncology, Rabin Medical Center, Beilinson Campus, Petah Tikva, and Sackler Faculty of Medicine, Tel Aviv University

Brachytherapy is especially suitable for palliative treatment of endobronchial tumors adjacent to internal organs that might be damaged by intensive external beam radiation, but are easily accessed with a flexible bronchoscope. This treatment is mostly palliative.

30 patients underwent such palliative high-dose endobronchial brachytherapy to alleviate malignant airway obstruction. With the aid of a flexible fiberoptic bronchoscope an endobronchial catheter was inserted adjacent to the tumor and treatment delivered using a 192Ir remote afterloader for 5-10 min, in 2 or 3 sessions.

There was symptomatic improvement in 26 (86%) and objective improvement in 27 (90%). 1 patient died of hemoptysis.

Autologous Chondrocyte Transplantation - from Science Fiction to Routine Clinical Practice

Dror Robinson, Hana Ash, David Aviezer, Gabriel Agar, Nahum Halperin, Zvi Nevo

Dept. of Clinical Biochemistry, Sackler Medical School, Tel Aviv University, Ramat Aviv; Dept. of Orthopedic Surgery, Assaf Harofeh Medical Center, Zerifin; and CTI Ltd., Science Park, Kiriat Weizmann, Nes Ziona

Adult articular cartilage lacks the capacity for self-repair. The limiting factor appears to be the inability of chondrocytes to proliferate while embedded in the extracellular matrix typical of hyaline cartilage. Cartilage defects larger than 1 cm² change articular biomechanics and lead to eventual osteoarth-ritis and joint destruction.

During the past decade, several competing techniques have evolved to stimulate articular cartilage repair. Small lesions can be successfully treated by either micro-fracture or osteochondral cylinder grafting. The latter technique allows immediate weight bearing but leads to damage of previously uninvolved areas of articular cartilage, which limits its application to lesions of less than 2 cm².

When the damaged area is more extensive, grafting of autologous chondrocytes should be considered. First a diagnostic arthroscopy is performed to assess the damaged area and a small cartilage biopsy is taken. 6 weeks later, arthrotomy and chondrocyte transplantation are performed. In the interval, the antologous chondrocytes have expanded by 2 to 3 orders of magnitude. Our experience to date includes 10 cases with follow-up of 6 months to 5 years. Preoperative complaints of crepitation and locking disappear. There is functional improvement and pain reduction of approximately 50%. This procedure, currently limited to patients under 55 years of age with limited damage to an articular surface, for the first time allows reconstruction of damaged articular areas without resorting to allografts.

Pulmonary Involvement in Osler- Weber-Rendu Syndrome 

Efrat Bron-Harlev, Benjamin Zeevi, Ben-Zion Garty

Dept. of Medicine B and Cardiac Catheterization Unit, Schneider Children's Medical Center, Petah Tikva

Hereditary hemorrhagic telangiectasia (Osler-Weber-Ren-du syndrome) is a group of autosomal dominant diseases with variable penetration, characterized by vascular malformations. Recently hereditary hemorrhagic telangiectasia has been found to be a phenotypic expression of mutations in genes located on chromosomes 9 and 12, and possibly of other genes located on other chromosomes.

We describe 2 patients with hereditary hemorrhagic telangiectasia and pulmonary involvement who presented with repeated complaints of dyspnea and cyanosis and were diagnosed as having long-standing asthma. Both were treated with therapeutic catheterization and embolization with good clinical outcomes.

Favorable Outcome of Hyperacute Epidural Hematoma in an Octogenarian

A. Rakier, I. Orlovsky, M. Feinsod

Center for Applied Research in Head Injuries, Neurosurgery Dept. Rambam Medical Center, and B. Rappaport Faculty of Medicine, The Technion, Israel Institute of Technology, Haifa

Acute epidural hematoma is very rare in the elderly after head injury. It is usually associated with extremely high mortality or severe disability. In an 87-year-old woman a large, hyperacute, epidural hematoma was diagnosed. She was treated promptly and enjoyed an uneventful, complete recovery. This exceptional case should encourage an intensive approach even in seemingly minor head trauma in the elderly.

Unconventional Treatment of Severe Heart Failure in the Elderly

Z. Fidelman, Z. Korshun

Geriatric Medical Center, Natanya

In the elderly, congestive heart failure is common and associated with significant morbidity and mortality.

Comprehensive management of heart failure improves functional status and decreases mortality. Diuretics remain the mainstay in treating congestive heart failure. However, some patients are resistant to diuretics. This is a serious problem as it seems to represent a final manifestation of congestive heart failure.

In an 85-year-old woman diuretic resistance was recognized as the cause of failure of conventional diuretic therapy. When the dose of furosemide was rapidly increased from 120 mg per os to 1000 mg IV within 4 days, diuresis began and there was dramatic improvement in her condition. The dose was then gradually decreased until a conventional maintenance dose of 200 mg/day per os was reached. This dose was sufficient to keep her heart failure under control.

Family Physicians' Attitudes to Clinical Guidelines for Treatment of Diabetes 

Sasson Nakar, Shlomo Vinker, Tal Baro-Aloni, Eliezer Kitai

Dept. of Family Medicine, Rabin Medical Center and Sackler Faculty of Medicine, Tel Aviv University

Clinical guidelines are systematically developed statements designed to help practitioners and patients make decisions about appropriate health care for specific clinical states. Attitudes of family physicians to clinical guidelines for treating diabetes and guidelines in general were evaluated from anonymous questionnaires answered by physicians participating in continuous medical education throughout the country (May-June 1998). The questionnaire dealt with attitudes to the recently published specific guidelines for treating the diabetic patient and overall perception of the efficacy of clinical guidelines.

293 family physicians, aged 40.2‏7.0 responded (83%). 93.5% appreciated the guidelines and thought them applicable. Most (83.7%) reported the guidelines to be of help in their daily work; 31.4% said they were oversimplified; a quarter said they aimed main at containing costs. Most respondents preferred written guidelines of up to 5 pages.

In view of our results, attention can now be turned to developing ways to implement the guidelines. To improve adherence, they need to be short and the rate of publication of new clinical guidelines should be slowed.