High-Dose Chemotherapy and Autologous Stem Cell Trans-Plantation for Refractory and Relapsing Hodgkin's Disease

A. Avigdor, I. Hardan, O. Shpilberg, P. Raanani, I. Grotto, I. Ben-Bassat

Hematology Institute and Hemato-oncology Unit, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University

High dose chemotherapy and autologous stem cell transplantation are widely used in relapsed and primary refractory Hodgkin's disease. We transplanted 42 patients with Hodgkin's disease between 1990-1998. Median follow-up was 31 months (range 1-102). 29 (69%) were transplanted after relapse and 13 (31%) were refractory to first line therapy. Median age at transplantation was 29 years (range 19-58) and 23 (55%) were males.

All were treated with the BEAM protocol (carmustine, etoposide, cytarabine and melphelan). 18 who were in remission received radiotherapy following transplantation. The source of the stem cells was bone marrow in 17% and peripheral blood in 83%. At initial diagnosis: 57% had stage III-IV disease and B symptoms were present in 52%. 75% were treated with MOPP, ABVD or with related versions. Radiotherapy followed in 52%. Prior to transplantation, 45% of the relapsed group were in the advanced stage. 33% and 12% of all patients had lung and bone involvement, respectively.

The complete remission rate was 86% for the 2 groups. 2 (5%) died from transplant-related complications and MDS/AML developed in 2 (5%) after transplantation. The 3-year overall survival (OS) and disease-free survival (DFS) were 68% and 60%, respectively. The 3-year OS for the relapsed group was 64% compared with 76% for the refractory group, and the 3-year DFS for the relapsed group was 60% vs. 42% for the refractory group (neither difference significant). Radiotherapy following transplantation did not have a beneficial effect on DFS. No prognostic factors for outcome of transplantation were found, most probably due to the limited number of patients and the high variability of disease characteristics.

We conclude that high dose chemotherapy and autologous stem cell transplantation are effective and relatively safe for relapsed or primary refractory Hodgkin's disease. The DFS at 3 years was longer for those transplanted after relapse than those with primary refractory disease, but not significantly. Patients with primary refractory disease can be salvaged with high dose chemotherapy.

Ent of Femoral Artery Pseudo-Aneurysms 

G. Szendro, A. Klimov, A. Lennox, B. Jonathan, L. Avrahami, B. Yechieli, M. Griffin, S. Yurfest, Y. Charach, L. Golcman, A.N. Nicolaides

Vascular Surgery Dept., Soroka Medical Center, Beer Sheba; Irvine Laboratory for Cardiovascular Investigation and Research, St. Mary's  Hospital, Imperial College Medical  School, London; Vascular Laboratory, Soroka Medical Center, Beer Sheba; and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheba

The femoral artery remains the most used peripheral site for radiological catheter access. With a greater number of both diagnostic and therapeutic procedures being performed by interventional radiologists and cardiologists, and with larger catheters being used for stenting and endovascular grafting, the incidence of iatrogenic pseudo-aneurysms reported has reached as high as 0.5-2%. Ideally, they should thrombose spontaneously. However, when this does not occur, management options include: observation, ultrasound-guided obliterative compression, direct thrombin injection, embolization, stent graft insertion, and very rarely- surgery.

During a 7-year period (1992-1999) we treated 131 cases of femoral artery false aneurysms. Until 1998 ultrasound-guided compression-obliteration, with a 95% success rate, was our method of choice. Since 1998, direct thrombin injection, with 100% success in 24 cases, has become our preferred method. It is pain-free, fully successful even in anticoagulated patients, and is currently our treatment of choice.

Noncontrast Spiral CT for Diagnosis of Acute Flank Pain

Alexander Tzivian, Igor Sherman, Yacov Yacobi,  Surin Elias, Ami Sidi, Jack Asherov

Depts. of Urology, Emergency Medicine, and of Radiology, Wolfson Medical Center, Holon

Acute flank pain is commonly encountered in the emergency department, and often requires imaging to establish its cause. For decades intravenous urography and sonography have been the primary media for evaluating flank pain.

Recently, noncontrast spiral CT (NCSCT) has been shown to be accurate and highly successful in diagnosing cause in such cases. We evaluated its use in the diagnosis of acute flank pain. During a 7-month period, 147 such cases had NCSCT imaging immediately after initial evaluation in the emergency department. Using a spiral CT scan without oral or IV contrast media, 109 of 147 cases were found to have ureteral stones, and 34 others to have other urological conditions unrelated to the cause of pain; 38 CT scans were negative for ureterolithiasis and in 14 non-urological disease was diagnosed.

NCSCT is a valuable diagnostic technique for patients in the emergency department with flank pain. It rapidly and accurately detects ureteral stones causing renal colic and also detects extra-urinary causes of acute flank pain.

Multiresistant Escherichia Coli from Elderly Patients

Ilana Slucky-Shraga, Moshe Wolk, Sofia Volis, Israel Vulikh, David Sompolinsky

Dept. of Medicine and Microbiology Laboratory, Mayanei Hayeshua Hospital, Bnei Brak; Central Laboratories, Ministry of Health, Jerusalem; and Faculty of Life Sciences, Bar Ilan University, Ramat Gan

We examined all ceftriaxone-resistant Escherichia coli isolates obtained from clinical samples during 16 months (1 Dec. '97 - 31 Mar. '99). A total of 97 resistant isolates from 36 patients were obtained, mostly from urine specimens. Of these patients, 35/36 were over 75 years old, most lived in nursing homes, were dependent on nursing in their daily lives, and were incontinent and/or had indwelling catheters.

All 97 isolates had similar susceptibility profiles: resistant to ciprofloxacin, gentamicin, ampicillin, amoxycillin/clavulanate, tricarcillin/clavulanate, aztreonam, and cefuroxime; decreased susceptibility to ceftazidime and cefepime; and susceptible to imipenem and meropenem. Double-disc tests indicated that all strains produced extended spectrum beta-lactamase(s). All the isolates belonged to 1 of 3 E. coli serotypes: 79 were 0153:H31, 13 were 0142:H10, and 5 were 0102:H6.

Videothorascopic Sympathectomy for Palmar Hyperhidriosis

Nahum Nesher, Ronen Galili, Ram Sharony, Gidon Uretzky, Milton Saute

Dept. of Cardiothoracic Surgery, Lady Davis - Carmel Medical Center and Rappaport Faculty of Medicine, Israel Institute of Technology, Haifa

Palmar hyperhidriosis is not a life-threatening disease but leads to loss in the quality of life. Conservative treatment is ineffective and major surgery involves perioperative complications and esthetic impairment.

From 1992 to 1998 we treated 156 patients with palmar hyperhidriosis using a single port, drainless videothoracoscopic procedure with almost no complications.

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.

Cilazapril for Essential Hypertension Treated in the Community 

Reuven Zimlichman

Dept. of Medicine and Hypertension Institute, Wolfson Medical Center and Sackler Faculty of Medicine, Tel Aviv University

In a multicenter study in community clinics, 413 patients with mild to moderate essential hypertension were treated with cilazapril (Vasocase), 2.5 mg daily. Patients had either been untreated or had developed side-effects from previous antihypertensive treatment. When response was inadequate the dose was either increased to 5 mg or another antihypertensive medication was added, or both.

Treatment significantly reduced systolic and diastolic blood pressures. Pulse rate decreased significantly from the second month of treatment onwards. At the end of the 3rd month of treatment blood pressure was normalized or had decreased by more than 10 mmHg in 91.9% of patients. Physicians' evaluations revealed improvement in 62%; patients' self-evaluations suggested improvement in 61%. Efficacy was equal in all age groups and in both obese and nonobese patients. Antihypertensive response was superior in those with normal renal function. Side-effects were rare and similar to those reported in the literature.

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.

Management of Compound High Energy Injuries of the Limbs 

A. Lerner, I. Weisz, G. Nierenberg, D. Horer, H. Stein

Dept. of Orthopedic Surgery A, Rambam Medical Center, and Technion Medical Faculty, Haifa

We treated 49 patients with high energy injuries of the limbs between 1.1.94-31.12.97. They had sustained 61 fractures, 50 of which were open; 14 had bilateral injuries, and 3 had lost a limb. All fractures were stabilized on arrival with an A-O tubular external fixator. Soft tissue loss was covered by a combination of split skin graft and tissue flaps following repeated surgical debridement.

After 10 days, or when all soft tissue defects were covered, the cantilever external fixation frame was exchanged for a hybrid ring which provided three-dimensional stability and allowed early full weight bearing and joint mobilization. The hybrid ring frame did not interfere with the care of soft tissue injuries. Furthermore, it kept the risk of developing deep infections to a bare minimum. At follow-up after a median of 20 months, 1 patient had developed osteomyelitis but all had returned to independent function.

Treatment of Hypertension with Losartan

R. Zimlichman

Dept. of Medicine and Hypertension, Wolfson Medical Center, Holon

The efficacy, safety and side-effects of treatment with losartan (Ocsaar) was studied for the first time in Israel in a large group of patients with mild to moderate hypertension in several community clinics. The 421 patients (51% men) aged 30-86 years (mean 58.6) received 50 mg of losartan daily, increased when necessary to 100 mg, and/or a second antihypertensive drug was given. After 4 weeks blood pressure was normalized in 344 and after 12 weeks in 363. Side-effects were minimal and treatment was effective in all age groups.

Treatment of Velopharyngeal Insufficiency

Abraham Amir, Ram Silfen, Daniel J. Hauben

Dept. of Plastic and Reconstructive Surgery, Rabin Medical Center, Beilinson Campus, Petah Tikvah

Weak and hypernasal speech, along with nasal escape of air, are the main characteristics of velo-pharyngeal incompetence (VPI). We describe 10 years of experience (1989-1998) with surgical treatment of VPI.

51 patients underwent pharyngeal flap elevation. 37 had cleft palate (8 of them submucous), 7 had neuromuscular disorders and another 7 were idiopathic. All underwent evaluation by a speech therapist before and after operation. 25 had further nasal endoscopy and/or videofluroscopy.

There was significant speech improvement in volume and clarity in 35 (73%), mild improvement in 13 (27%) and none in 3. The complication rate was 15% and included sleep apnea, wound infection and dehiscence, stridor and bleeding. Complications were correlated with advanced age.

VPI should be diagnosed as early as possible to achieve good results and to prevent social problems.

Listeria Monocytogenes Infections - Ten Years' Experience

Tova Rainis, Israel Potasman

Infectious Disease Unit, Bnai Zion Medical Center, and Faculty of Medicine, Technion, Haifa

7 cases of listeriosis were diagnosed here between 1988-1997 (6 in last 3 years), or 2.94/100,000 admissions. 2 elderly patients suffered from meningitis and 2 pregnant women presented with premature contractions, 1 of whom delivered a premature, infected baby. 2 other patients had fever and gastroenteritis.

Listeria monocytogenes was isolated from blood in 4, CSF in 2 and the placenta in 1. It was isolated from those with bacterial meningitis. All patients recovered. Both increased awareness for prevention and better diagnosis are essential to reduce morbidity from this unusual pathogen.

Computerization in a Community Health Service Provider

Boaz Porter

Maccabi Health Services, Beer Sheba

As the second largest health service provider organization in Israel, we have been progressively computerized. The process was begun in 1988, focusing on improving administrative and financial processes.

Today there is a single centralized database for 6,000 users. The system monitors member eligibility, accounting procedures and clinical processes, including diagnoses, laboratory tests, imaging procedures and drug-prescribing. The potential of the computer for physician support is now being realized through integration of clinical guidelines and reminder systems into the computerized clinical record. In addition, the centralized database is used for quality improvement, facilitating cost-effective drug-prescribing and efficient use of technology.

The establishment of a computerized working environment for 2,000 physicians and 4,000 other healthcare workers serving 1.3 million patients is a unique model for the development of community health services. Data regarding demographics, disease patterns, drug-prescribing, use of new technology and costs are now readily available to all, from senior management to the individual physician in independent practice.

The computer revolution has also presented a new set of problems such patient-record confidentiality and the effect of the computer on the physician-patient encounter.

Retroperitoneoscopic Lumbar Sympathectomy

D. Seror, O Zamir, D. Eimerl, H.R. Freund

Depts. of Surgery and Anesthesia, Hadassah University Hospital, Mount Scopus and Hebrew University-Hadassah Medical School, Jerusalem

We present our initial experience with retroperitoneoscopic lumbar sympathectomy in a series of 5 men aged 25-45 years. 3 suffered from ischemia of the lower limbs due to Buerger's disease, 1 had severe reflex sympathetic dystrophy and 1 had vasculitis with severe, non-healing lower leg ulcers.

The right retroperitoneal space was developed with a dissecting balloon-trocar introduced via a small lateral muscle- splitting flank incision. 2 additional 5 mm trocars were used for instrumentation and clipping. L2-L3 or L3-L4 ganglia were resected; mean operating time was 120 minutes. Only oral analgesics were needed for postoperative pain control and oral food intake was resumed the following morning. The procedure was successful in all and was without complications. Mean hospital stay was 2 days.

All patients reported significant relief of ischemia or dystrophic pain and/or improvement in trophic changes in the extremities. In the patient with leg ulcers, the largest was successfully covered with a skin graft. The retroperitoneoscopic approach to lumbar sympathectomy successfully combines the advantages of minimal invasive surgery and the reliability and effectiveness of well-established open sympathectomy.

Laparoscopic Donor Nephrectomy: Initial Experience

Amir Szold, Joseph M. Klausner, Richard Nakache

Advanced Endoscopic Surgery Unit, Transplantation Unit and Depts. of Surgery B-C, Tel Aviv-Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University

We present our initial experience in laparoscopic nephrectomy. 6 patients were operated for a kidney donation and 2 for treatment of a benign disease. All procedures were completed successfully, with no conversion to laparotomy or intra-operative complications. Mean operating time was 210 minutes, and in the donor kidneys the mean warm-ischemic time was 165 seconds. There were 3 postoperative complications, and mean hospitalization was 3.5 days. The transplanted kidneys are all functioning.

From our initial experience, laparoscopic nephrectomy appears to be both feasible and safe. Its implementation requires a combined team with experience in donor surgery and advanced laparoscopic skills. The procedure may increase the availability of living donor kidneys, due to the smaller impact on the donor compared to conventional donor nephrectomy.