Glucosamine Sulfate and Chondroitin Sulfates for Degenerative Joint Disease 

R. Debi, D. Robinson, G. Agar, N. Halperin

Orthopedic Dept., Assaf Harofeh Medical Center, Zrifin

Osteoarthritis results from progressive catabolic loss of cartilage proteoglycans due to imbalance between synthesis and degradation. The availability of glucosamine, an intermediate in mucopolysaccharide synthesis, can be rate-limiting for proteoglycan production in cartilage tissue culture.

57 patients suffering from osteoarthritis of the knee were randomized into a group treated for 4 weeks with daily IV glucosamine sulfate (GS) together with 800 mg chondroitin sulfate, and a placebo group. Knee pain at rest, on movement and on palpation, as well as range of knee motion were then recorded.

In the GS group, there was significant reduction of clinical symptoms (p<0.01), but no significant reduction in the placebo group. Physicians' assessment of tenderness and range of motion were significantly in favor of the GS group (p<0.01). In those treated with glycosamine there were no adverse reactions and no changes in laboratory blood tests.

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.

Microlaparoscopy in Diagnostic and Operative Gynecologic Procedures 

Dov Dicker, Shmuel Nitke, Itai Bar-Hava, Raul Orvieto, Zion Ben-Rafael, Arie Dekel

Depts. of Obstetrics and Gynecology, Rabin Medical Center, Beilinson and Golda Campuses, Petah Tikva; and Sackler School of Medicine, Tel Aviv University

A recent further development in laparoscopic surgery is microlaparoscoopy. The technique is identical to standard 10 mm laparoscopy except for the use of small, 2 mm scopes and trocars. We used this technique in 19 patients treated from June 1998 to February 1999.

The advantages of microlaparoscopy are: smaller incisions, less risk of damage to pelvic organs and less postoperative pain. However, the use of microlaparoscopy for operative procedures is limited to simple operations due to the limited field of vision. We urge our colleagues to consider microlaparoscopy whenever diagnostic laparoscopy is needed.

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.

Transarterial Oil Chemoembolization for Hepatocellular Carcinoma 

Izhar Levy, Anthony Verstandig, Talia Sasson, Dana Wolf, Ilia Krichon, Eugin Libson, Pinchas Levensart, Orit Papo, Oded Yurim, Ahmed Id, Daniel Shouval

Division of Medicine, Liver Unit and Invasive Radiology, Radiology, Pathology and Surgery Depts., Hadassah University Hospital, Ein Kerem, Jerusalem

Hepatocellular carcinoma (HCC) is a common malignancy with a grave prognosis. Most patients have both the malignant tumor as well as hepatic cirrhosis. Liver transplantation or hepatectomy are considered the only curative procedures, but can be applied in fewer than 10% of patients. In recent decades the most common treatments of HCC are transarterial chemoembolization with oil (TOCE) and percutaneous ethanol injection (PEI). We summarize our retrospective study of 100 patients (mean age 64) 3‏ treated by TE.

In 271 procedures between 1989-1998, in 16 patients hepatectomy was combined with TOCE and in 8 PEI was combined with TOCE, while the rest were treated by TOCE alone. Tumor mass was reduced in 36% of those treated by TOCE (tumor volume reduced 24-75%). Alpha-feto protein (AFP) was reduced 25-90% in 20/32 of those with elevated AFP levels. Median survival for the 100 in the entire group was 19 months (10.9 months in those with conservative treatment). Median survival in the 57 in Okuda stage 1 and the 43 in stages 2 or 3 was 30.1 months and 10.9 months, respectively (p<0.0001). Of the 57 in stage 1, 16 underwent hepatectomy in addition to TOCE and 41 were treated only by TOCE (median survival 15 and 26 months, respectively, p not significant).

Comparing Okuda 1 patients treated by TOCE only with the natural history of the disease and historical controls (Okuda 1 patients treated conservatively in 1984) median survival was 26 and 10 months respectively (p<0.001). The side effects of TOCE were relatively mild. There was 1 fatality (3 days after treatment), and quality of life was maintained. Despite progress in the treatment of HCC by TOCE, PEI, and liver transplantation, long-term survival has remained unsatisfactory.

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.

Thoracoscopic Splanchnicectomy for Intractable Pancreatic Pain

Joseph Kuriansky, Alejandro Saenz, Laureano Fernandez-Cruz

Dept. of Surgery, Sheba Medical Center, Tel Hashomer, and Sackler School of Medicine, Tel Aviv University; and Dept. of Surgery, Clinic Hospital, Barcelona

Intractable pain is the most distressing symptom in nonresectable pancreatic carcinoma and in chronic pancreatitis. Recently, thoracoscopic splanchnicectomy has been advocated as a minimally invasive method of pain control in these patients. Between May 1995 and April 1998, 24 patients with nonresectable pancreatic cancer and 4 with chronic pancreatitis, underwent 43 thoracoscopic splanchnicectomies. All suffered from intractable pain, were opiate-dependent and unable to perform normal daily activities. Unilateral left splanchnicectomy was done in 13 and bilateral in 15.

All procedures were completed thoracoscopically. Operative time ranged from 25 to 60 min and mean hospital stay was 3 days. Median pain intensity was reduced by 50% in 24 and no further narcotics or analgesics were required. We found thoracoscopic splanchnicectomy a safe and effective procedure for intractable pancreatic pain.

Laser Treatment of Airway Obstruction in Infants and Children

Y. Efrati, S.M. Sarfaty, S. Kromholz, G. Eshel, M. Weinberg, I. Vinograd

Depts. of Pediatric Surgery, Otolaryngology, Anesthesia and Pediatric Intensive Care, Assaf Harofeh Medical Center, Zerifin (Affiliated with Sackler Faculty of Medicine, Tel Aviv University)

Airway obstruction during infancy and childhood requiring surgical ablation is rare, and surgical intervention poses a significant challenge. During recent decades, appropriate endoscopic instrumentation, together with advanced laser beam technology have provided new operative modalities for such patients.

From 1993 to 1995 we treated 40 infants and children, 26 males and 14 females, 13 days to 11 years old (mean 3.3 years) with Nd-YAG or CO² laser. Obstructing lesions included granulation tissue or polyps (16 cases), septa or webs (27), or benign tumors (4). 7 had more than a single lesion.

All were treated endoscopically under general anesthesia without any operative or postoperative deaths. Surgical intervention removed the obstruction and related symptoms in 34. In 6, laser treatment failed, necessitating additional surgical procedures. 3 had circumferential subglottic web. Operative complications included bleeding during removal of a hemangioma in 1 and recrudescence in another. Postoperative complications were transient respiratory failure and pneumonia in 6, all of which resolved with appropriate treatment.

This series proves that laser technology is feasible in the treatment of airway obstruction during infancy and childhood, and is safe and effective.

Use of Unlicensed and Off-Label Drugs in Hospitalized Children

M. Lifshitz, V. Gavrilov, R. Gorodischer

Toxicology Unit, Pediatrics Dept. A, Soroka Medical Center, and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheba

Many drugs used in children are based on pharmacological data obtained in adults. Therefore, many drugs are either unlicensed for use in children or are prescribed outside the terms of the product license (off-label). This pilot study assessed use of unlicensed or off-label drugs in hospitalized children.

Drug orders of patients admitted to a general pediatric ward were reviewed retrospectively in a random sample. Assessment was based on the data of the Physicians' Desk Reference and the Israel Drug Compendium. 80 different drugs and 278 drug orders were written for 92 patients (0.5 months - 11 years old, mean 26.9 months) in 97 admissions. Of these 52.9% were either off-label or unlicensed. Patients received 1 or more unlicensed or off-label drugs in 64.9% of admissions. They were more often off-label than unlicensed. The main reasons for use of off-label drugs were unusual doses and inappropriate age. The main reason for unlicensed drugs was modification of a particular formulation of a licensed drug.

This pilot study indicates that use of drugs in an off-label or unlicensed manner in children is probably quite frequent in Israel. Our data emphasize the need for licensing a large number of drugs for use in children, based on the same scientific principles as in adults. Further collaborative studies in different pediatric centers in Israel, involving different types of pediatric settings (ambulatory and in-hospital), is required to evaluate comprehensively the magnitude of this preliminary finding.

Evaluation of Laparoscopy and Laparoscopic Ultrasound in Pancreatic Lesions

P. Schachter, Y. Avni, A. Rosen, A. Czerniak

Depts. of Surgery A and of Gastroenterology, Wolfson Medical Center, Holon

Pancreatic lesions present a diagnostic challenge. Even modern imaging techniques are not sensitive enough in determining resectability of pancreatic tumors. A substantial proportion of patients therefore undergo unnecessary surgical exploration. We determined the impact of laparoscopy and laparoscopic ultrasound (LAPUS) examinations on surgical decision-making in 60 patients with pancreatic lesions.

Of 48 with solid pancreatic lesions, 22 were defined by LAPUS as having nonresectable tumors, while conventional imaging studies defined only 9 of them as such. 3 of these 9 underwent successful resections of the pancreatic mass. Surgical intervention was ruled out by LAPUS in 16 patients (33.3%) but 26 had resectable lesions of whom 25 underwent surgery. 3 of this group were found to have nonresectable tumors at surgery, a false-positive rate of 6.2%. Overall sensitivity of LAPUS in our series was 88%.

In 12 patients with cystic pancreatic lesions LAPUS contributed significantly to the preoperative decision due to clear imaging of the cystic lesion. Additional information was obtained from ultrasound guided-biopsy of the cyst wall, as well as determination of tumor-marker levels in the cystic fluid aspirate. LAPUS contributed significantly to operative management in 58%.

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.

Left Ventricular Outflow Tract Obstruction without Left Ventric-Ular Hypertrophy Treated with Ace Inhibitors

Jacob Feldman, Irit Laxer, Abraham Yaretzky

Geriatric Dept., Meir Hospital, Sapir Medical Center, Kfar Saba, and Sackler Faculty of Medicine, Tel Aviv University

We describe a very unusual case of sudden, severe worsening of congestive heart failure which was caused by ACE inhibitors. Diagnosis was made by echocardiogram showing a typical picture of dynamic, left ventricular outflow tract obstruction without left ventricular hypertrophy, which disappeared on discontinuing ACE inhibitors. This phenomenon has already been described as a complication of other drugs such as nitrates, commonly used as provocative tests for latent obstructive cardiomyopathy. To our knowledge ACE inhibihave not been described as a causative factor.

Tension-Free Vaginal Tape Procedure for Female Stress Incontinence

David Gordon, Asnat Groutz, Joseph Lessing

Lis Maternity Hospital, Sourasky-Tel Aviv Medical Center

We evaluated the safety and efficacy of the tension-free vaginal tape procedure (TVT) in 20 consecutive women with urodynamically proven genuine stress incontinence. Mean operating time under spinal analgesia was 37.2‏13 minutes and 80% were discharged within 24 hours. There were 5 uncomplicated, intraoperative bladder perforations, but no defects in healing nor tape rejection. The objective cure rate was 95%, while the subjective rate was 100%. Although follow-up was short (9-16 months), the TVT method seems to be safe and effective for stress urinary incontinence.

Photodynamic Therapy for Dysphagia due to Esophageal Carcinoma

H. Kashtan, F. Konikoff, R. Haddad, M. Umansky, Y. Skornick, Z. Halpern

Dept. of Surgery A and Institute of Gastroenterology, Tel Aviv Medical Center and Sackler Faculty of Medicine, Tel Aviv University

Surgery is the mainstay in the treatment of esophageal carcinoma and is effective for palliation of dysphagia. Patients unfit for surgery are difficult therapeutic problems. We evaluated photodynamic therapy for palliation of dysphagia in this condition.

Patients were given 5-aminolevulinic acid, 60 mg/kg, orally and 24 hour later gastroscopy was performed during which red light illumination (100 j/cmŽ2 for 600 seconds) was administered. This was repeated 48 hours later. The degree of dysphagia was recorded before and 14 days after treatment.

8 patients with an advanced non-resectable tumor, or who were unfit for surgery, were thus treated. 4 had squamous cell carcinoma of the mid-esophagus and 4 had adenocarcinoma of the lower esophagus. There was mild, self- limited photosensitivity in all. Liver and renal function tests and blood count were not affected by the treatment. Dysphagia was improved in all except 1 patient. A patient with early stage disease continued to eat a normal diet.

We believe that photodynamic therapy with systemic aminolevulinic acid as a photosensitizer and a non-laser light source is feasible and safe in advanced esophageal cancer. It is an effective modality for relief of dysphagia in that condition.