Photodynamic Therapy of Nasal Basal Cell Carcinoma

R. Haddad, M. Cohen, O. Kaplan, R. Greenberg, H. Kashtan

Dept. of Surgery, Tel Aviv-Sourasky Medical Center

Photodynamic therapy (PDT) is a noninvasive modality used topically for several skin cancers. We evaluated the effects of PDT on basal cell carcinoma (BCC) of the nose, using aminolevulinic acid (ALA) as a photosensitizer and a non-laser light source (Versa-LightTM). The advantages of this light source are synergistic, hyperthermia and fewer side effects.

A paste of 20% ALA was applied topically to biopsy-proven BCC of the nose. Lesions were covered with occlusive light-shielding dressing and after 18 hours they were submitted to 10 minutes of exposure to the light. Initial evaluation was made after 21 days and every 3 months thereafter. Patients who did not respond after 2 treatments were referred for surgery.

Mean follow-up in 31 patients was 19 months (range 6-36). There were no significant side-effects. There was complete response in 24/27 (88.9%), in whom there was recurrence in 2/27 (7.4%).
 

Dermatitis from Contact with Agave Americana

Haim Golan, Marina Landau, Ilan Goldberg, Sara Brenner

Dermatology Dept., Tel Aviv-Sourasky Medical Center

Various plants induce dermatitis in man. There have been only a few published cases of contact dermatitis caused by Agave americana (AA).

We report intentional exposure to AA in a soldier seeking sick leave, and review our previously reported cases. Treatment with oral antihistamines and topical saline compresses resulted in subsidence of the systemic symptoms within 24h and regression of cutaneous manifestations in 7-10 days.

Physicians should be alert to the possibility of self-inflicted contact dermatitis induced by exposure to plants, especially to A. americana. Systemic signs may accompany the cutaneous lesions.

Acute Lymphoblastic Leukemia in Adults Treated with German Multicenter Study Group Protocols

G. Goldstein, O. Shpilberg, P. Raanani, A. Chetrit, I. Ben-Bassat

Institutes of Hematology and of Clinical Epidemiology, Sheba Medical Center and Sackler Faculty of Medicine, Tel Aviv University

Acute lymphoblastic leukemia (ALL) is a malignant disease whose incidence is relatively low among adults, unlike in children. Adults with ALL have a lower rate of long-term disease-free survival. During the last 20 years, a German multicenter group has shown that their protocol have achieved good results in adult ALL.

We reviewed the medical records of 35 ALL patients, aged 19-63 years, whome we treated with these protocol (1988-1997). The remission rate was 94%. At a median follow-up of 46 months the 2-year overall survival was 54% and the disease-free survival was 94%. Although 2 patients died of bone marrow transplant complications, no death was directly associated with drug toxicity. The main grade 3 or 4 side effects (WHO classification) were neutropenia (91%), thrombocytopenia (71%) and anemia (71%).

With there protocols we achieved high overall and disease-free survival rates, especially in comparison with other reports. Despite the high rate of severe treatment toxicity, there were no fatalities directly related to treatment. These results emphasize the need to concentrate treatment of adult ALL patients in large medical centers with expertise in the use of the complicated treatment protocols required.

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.

What Primary Care Physicians Think of Israel's Health Policy Reform

Revital Gross, Hava Tabenkin, Shuli Brammli-Greenberg

JDC Brookdale Institute, Jerusalem, HaEmek Hospital, Afula; and Ben-Gurion University of the Negev, Beer Sheba

Opinions of the National Health Insurance (NHI) Law held by primary care physicians were surveyed. A questionnaire was submitted (April-July 1997) to 930 primary care physicians employed by sick funds, including general practitioners, family physicians, pediatricians and internists. Response rate was 86%.

They supported the main components of the NHI law. It was considered desirable "to a great" or "very great extent" to allocate funds to sick funds based on age and number of members (76%), to require them to accept all applicants (72%), to designate a uniform basket of services (65%), to allow members to transfer freely between funds (63%), and to allow sick funds to sell supplemental insurance (59%). However, only 41% were satisfied with the implementation of the law.

Multivariate analysis showed that employment by Maccabi, Meuhedet, or Leumit sick funds had an independent effect on low satisfaction with the law as implemented, and on negative opinions about the uniform basket of services, the accepting of all applicants, and allocation of funding based on age and number of members. Those employed by the Maccabi and Meuhedet funds were in favor of allowing sick funds to sell supplemental insurance.

The findings of the study have implications for policy-makers interested in increasing support for national health reform by physicians. It is important to examine possibilities of developing direct channels of communication between national policy-makers and physicians, as well as institutionalizing mechanisms that involve physicians directly in formulation of national policy.

Diabetes and Premature Delivery: Etiology and Risk Factors 

Avi Beigelman, Arnon Wiznitzer, Ilana Shoham-Vardi, Hilel Vardi, Gershon Holtcberg, Moshe Mazor

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

Preterm birth is the leading cause of perinatal morbidity and mortality, while preterm labor and delivery in diabetes mellitus (DM) carries an increased risk of perinatal complications. We investigated the hypothesis that DM (gestational and pregestational) is an independent risk factor for preterm birth and evaluated the hypothesis that the risk factors for preterm birth in diabetics are different from those in non-diabetics.

The study population consisted of all singleton deliveries at this hospital between 1990-1997. Excluded were those of mothers who had not had prenatal care, or who had only partial care or multiple gestations. There were 3 subgroups: 834 women with pregestational DM, 3,841 with gestational DM, and 66,253 non-diabetics.

The combined spontaneous and induced preterm delivery rate was determined in each subgroup. Potential risk factors for spontaneous preterm deliveries were assessed by a univariate model. A logistic regression model was used to assess the unique contribution of DM (gestational and pregestational) to preterm delivery in the presence of the other risk factors, and to compare risk factors for preterm delivery between subgroups.

The prevalence of spontaneous preterm delivery was: 7.1% in non-diabetics, 10.0% in those with gestational DM and 25.5% in those with pregestational DM. When adjusted by a multivariate model for other risk factors for preterm delivery, DM still remained an independent risk factor for spontaneous preterm delivery (gestational DM: odds ratio 1.28, 95% CI: 1.1-1.48; pregestational diabetes: odds ratio 3.4, 95% CI: 2.65-4.36).

The main difference in risk factors for preterm birth between the 3 subgroups was the amount of amniotic fluid. Polyhydramnios was an independent risk factor for preterm delivery in non-diabetics and in pregestational DM, but not in gestational DM. On the other hand, oligohydramnios was associated with a higher risk for preterm delivery only in gestational DM compared to non-diabetics.

DM (gestational and pregestational) is an independent risk factor for spontaneous preterm delivery. Polyhydramnios is an independent risk factor for preterm delivery in pregestational but not in gestational DM. Oligohydramnios is a greater risk factor for preterm delivery in gestational DM compared to non-diabetics.

Development of Molecular Tests for Rapid Detection of Enteropathogens 

Miri Yavzori, Nir Uriel, Nurith Porat, Ron Dagan, Ruhama Ambar, Ofer Shpilberg, Dani Cohen

Army Health Branch Research Unit, Medical Corps, Israel Defense Forces; Pediatric Infectious Disease Unit, Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheba; and Sackler Faculty of Medicine, Tel Aviv University

Amplification of specific DNA sequences by polymerase chain reaction (PCR), enables rapid, sensitive and direct, specific identification of pathogens at very low concentrations in clinical samples. Studies in recent years have reported identification of several enteropathogens directly from stool samples by PCR. The amplification process includes the use of primers complementary to the DNA sequences specific to the pathogen, thus relying on the pathogen's genotype, rather than its phenotype on which identification by the methods of classical microbiology were based.

We have developed PCR protocols for the differential identification of enteropathogens resembling the normal flora (enterotoxigenic E. coli (ETEC), E. coli O-157), Shigella spp, and the detection of enteropathogens that can not be grown on classic growth media (Norwalk virus). The amplification process is inhibited by several substrates present in fecal material (phenol, hemoglobin), limiting DNA extraction by phenol. The protocols we have developed for direct detection of Shigella spp and ETEC in stools circumvent inhibition of PCR by the use of a 4-hour pre-enrichment step in brain-heart infusion broth.

Rapid and accurate identification of enteropathogens is important for prompt and focused intervention to stop the chain of transmission in outbreaks of gastroenteritis in military and civilian populations.

Trends in Epidemiology of Hepatitis in the Israel Defense Forces 

Michael Gdalevich, David Gillis, Daniel Mimouni, Itamar Grotto, Ofer Shpilberg

Institute of Military Medicine, Medical Corps, Israel Defense Forces

During the 50's and 60's there were large scale epidemics of hepatitis A every 3-4 years in the Israel Defense Forces. During these epidemics the annual incidence exceeded 10/1000 soldiers at risk. There has been a highly significant decrease in rates during the past 30 years. The average annual incidence of clinically identified viral hepatitis A decreased from an average of 6/1000 during the 60's to 2.5/1000 during the 70's. The decrease coincided with the introduction in the 1970's of wide-scale post-exposure prophylaxis with immune serum globulin (ISG). The incidence was further significantly reduced to 0.5-1.0/1000 with the introduction of pre-exposure prophylaxis with ISG, starting in 1978 (p<0.001).

Other factors probably played a role in accelerating the decline in morbidity, such as improvement in personal hygiene and sanitation facilities, and in waste disposal and other aspects of military environmental health.

These improvements were probably more pronounced in the civilian sector, leading to decreased exposure of children to the virus and consequently a higher proportion of seronegatives at induction. Increase in the proportion of recruits without natural immunity to the virus poses greater risk, both in terms of personal morbidity as well as military operational ability. This risk, combined with problems of ISG use and availability, has propelled hepatitis A prevention policy towards the use of the new inactivated vaccines.

Tracheoesophageal Puncture after Total Laryngectomy

Roy Landsberg, Frida Korenbrot, Dov Ophir

Depts. of Otolaryngology and of Head and Neck Surgery, Meir Hospital, Kfar Saba and Sackler Faculty of Medicine, Tel Aviv University; and the Israel Cancer Association Voice Rehabilitation Program

Total laryngectomy due to malignant laryngeal tumors is followed by loss of speaking ability. Voice restoration in laryngectomized patients is the main target in their rehabilitation. Until the late 70's, esophageal speech was considered the most effective rehabilitation method. In 1980 Singer and Blom introduced a prosthesis for tracheoesophageal speech which has been gaining popularity. Tracheoesophageal puncture (TEP) can be performed either at the time of total laryngectomy, or later.

30 of our patients underwent TEP between 1991 and 1999, 15 at the time of total laryngectomy and 15 as a delayed secondary procedure. Mean follow-up was 36 months (range 6 months to 8 years) during which all regained speaking ability.

Over the long range, speech rehabilitation with the prosthesis was successful in 24 (80%). In only 1 in the primary TEP group did treatment fail, as the prosthesis had to be removed due to local recurrence of the tumor. Long range failure in 5/15 patients after secondary TEP stemmed from difficulties some patients had in handling the prosthesis and from psychological difficulties in adapting to the new speech device. Complications were mostly minor and occurred mainly in the secondary TEP group.

TEP performed at the time of total laryngectomy, or later as a secondary procedure, is effective for speech rehabilitation after laryngectomy.

Preflight Assessment by Hypoxic Inhalation Test in Cardio-Pulmonary Patients 

J. Lebzelter, G. Fink, E. Kleinman, I. Rosenberg, M.R. Kramer

Pulmonology Institute, Rabin Medical Center, Beilinson Campus, Petah Tikva

Flying may expose passengers to hypoxic conditions, which may induce hypoxemia, particularly in those with chronic heart and/or lung disease. Onset of dyspnea, wheezing, chest pain, cyanosis and right heart failure can lead to urgent need for oxygen during flight. The hypoxia inhalation test (HIT) provides a safe and simple means of identifying those who may develop hypoxemia during flight.

We report our experience with 48 self-reporting patients who underwent HIT prior to pre-planned air travel. They inhaled for 15-minute periods a reduced oxygen concentration (F₁O₂ 15%) under normobaric conditions, during which O₂ saturation was monitored by pulse oximeter; electrocardiogram, blood pressure and symptoms were also monitored. O₂ saturation of 85% (PaO₂ 50 mm Hg) was considered a positive test. In the 8 cases (17%) with a positive test, 5 had chronic obstructive pulmonary disease and 3 had cardiovascular and/or combined heart-lung disease.

We calculated predicted O₂ partial pressure in altitude (PaO₂ ALT) and compared it to actual results in the 8 patients with a positive HIT. In 5, use of the predicted formula would have under-diagnosed the hypoxemia that developed during the HIT. Thus, the results of the HIT changed treatment strategy in these patients. We recommend that patients with positive tests use O₂ (2LPM or 4LPM) during flight.

HIT is practical and of potential benefit in the objective assessment of patients with various degrees of heart, lung or combined heart-lung disease. Clinicians should be aware of the relative risk of hypoxia during flight in such patients, and of the value of HIT in identifying them, leading to increase in its use.

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.

Cortical Blindness Following Coronary Angiography 

Addie Ron, Simcha Meisel, Myra Shapiro-Feinberg,Herman O. Klein

Depts. of Medicine, Cardiology and Diagnostic Imaging,Meir Medical Center, Kfar Saba

Cortical blindness has been occasionally reported as a complication after cerebral angiography, but is rare after coronary angiography. The contrast agent is believed to be responsible for the sudden development of blindness. Although the exact mechanism is unknown, it appears that the contrast agent disrupts the blood brain barrier, mostly in the occipital areas.

We report a 77-year-old man who suddenly developed transient, bilateral cortical blindness 4 hours after coronary angiography. Using contrast enhancement, the CT scan showed typical, symmetrical involvement of both occipital lobes. There were no other neurological deficits. Vision and CT findings returned to normal within 48 hours.

Anaphylactic Shock after Diclofenac Sodium 

Amnon Hadar, Gershon Holcberg, Moshe Mazor

Division of Obstetrics and Gynecology, Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheba

Anaphylaxis due to diclofenac sodium (Voltaren) is rare. We describe a 39-year-old woman who received a suppository of diclofenac for analgesia 6-hours after cesarean section. She developed severe angioedema and profound hemodynamic shock 10 minutes after the diclofenac, to which she had been exposed in the past without any side-effects. There are few reports of such an acute, life-threatening, multisystem reaction to this drug in the English literature.

Botulin Toxin for Spasticity in Spinal Cord Damage

Ofer Keren, Flabia Shinberg, Amiram Catz, Neer Giladi

Loewenstein Rehabilitation Hospital, Ra'anana; Movement Disorder Unit, Tel Aviv Medical Center; and Sackler Faculty of Medicine, Tel Aviv University

Therapeutic injection of botulin toxin is well-recognized for reducing tonus in local dystonia. However, its efficacy in reducing spasticity in spinal cord injuries is still unproven. 4 men and 1 woman (mean age 39 years, range 20-56) with spinal cord injury and debilitating spasticity, and no response to standard treatment for spasticity received injections of botulin, 200-300 U, into 4-8 points in their legs to block muscle-nerve synapses.

In all 5 tonus was reduced in the area of the block, while in some it was also reduced in more distal muscles. In 1 there was reduced tonus in both the injected and contralateral leg. The therapeutic effect on tonus persisted for 3 months. In spite of objective improvement in tonus in all 5, only 3 felt subjective improvement, but in none was there improvement on standard functional scaling.

We found injection of botulin toxin effective in reducing tonus in the spinal cord-injured, and to some extent in improving subjective feeling of well-being in some of them. Obective measurement might show functional improvement after larger doses of toxin injected into more muscles. This might be necessary because the muscle mass of the legs is large and the intensity of involuntary contraction is especially high in these patients.

Brief Preoperative Radiotherapy reduces Local Recurrences and Improves Survival in Rectal Cancer

T. Peretz, Z. Weshler,* Y. Goldberg, A.L. Durst, H.R. Freund

Depts. of Surgery and Oncology, Hadassah University Hospitals, and Hebrew University-Hadassah Medical School, Ein Kerem and Mt. Scopus, Jerusalem

Locoregional recurrence of rectal cancer ranges between 20%-50% following apparently radical surgery. Radiation has the potential of reducing this high rate of recurrence and residual disease. A retrospective analysis of 78 patients with locally advanced, biopsy proven, adenocarcinoma of the rectum treated between 1980-1987 was conducted. 28 (36%) were treated by surgery alone (surgery); 29 (37%) by surgery and postoperative radiotherapy (post-op); and 21 (27%) by surgery and preoperative radiotherapy (pre-op). 41 were females and 37 males. The median age was 62 years (range 25-90).

All tumors were resectable. 42 patients (54%) underwent abdomino-perineal resection and 36 (46%) anterior resection patients [8 Dukes B₁ (10%); 37 B₂ (47%); 2 C₁ (3%); 31 C₂ (40%]. Local recurrences were verified by transanal or ultrasound guided needle biopsy.

The 5-year actuarial survival rates by the Kaplan-Meier method for 75 evaluated patients was 55%. Overall 5-year actuarial survival was significantly higher (p=0.001) in pre-op radiotherapy (95%) compared to surgery alone (45%), or surgery with postoperative radiotherapy (32%). The data were significant (p=0.006) for patients with stage B tumors, but not stage C. This trend of improved survival held also at 8-year follow-up (80% pre-op; 32% post-op; 27% surgery). The 5-year actuarial local control was significantly better (p=0.03) for the pre-op irradiated patients (22%), compared with surgery only (56%) and post-op radiotherapy (38%). Local control was better (p=0.02) for Dukes B tumors in the preoperative group, but not Dukes C tumors.

Actuarial 5-year survival of those without distant metastases was 87% for pre-op patients, 62% for surgery alone and 48% for post-op radiotherapy. As all patients were clinically classified as advanced rectal tumors, tumor downstaging by preoperative radiotherapy seems to be paramount for local control. Improved local control translates into a siginificant advantage in overall actuarial survival.

*DECEASED.