Preservation of the Larynx in Advanced Cancer

Edward Rosenblatt, Nava Siegelmann-Danieli, Jemal Zidan, Nisim Haim, Abraham Kuten

Oncology Dept., Rambam Medical Center and Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa

The effectiveness of sequential chemo-radiotherapy in preserving the larynx in advanced laryngeal carcinoma was assessed. 4 Unselected patients (19 men and 2 women, mean age 60 years) with advanced squamous cell carcinoma of the larynx (T3-4/N0-3) received induction chemotherapy consisting of 2-3 cycles of cisplatin (100 mg/m²) and 5-flourouracil (1000 mg/m²/day) as a continuous infusion on days 1-5 followed by definitive radiotherapy: 50 Gy to the whole neck, 70 Gy to the larynx and clinically involved nodes, using a combination of 6 MV photons and 9-12 MeV electrons.

19 of The 21 patients responded to combined therapy but there was no response to induction therapy in 2 (10%) and 2 did not complete therapy due to severe toxicity. At a mean follow-up of 40 months, 7 had undergone total laryngectomy (33%), for an overall 5-year laryngeal preservation rate of 66%. Reasons for total laryngectomy in 2 patients were no response and in 5 tumor recurrence.

Mean survival was 39 months (range 11-46 months); at last follow-up 17 of 21 were alive and disease-free, 11 of whom had a functional larynx (65% of survivors). 2 died due to disease progression and 1 due to a cardiovascular event. Sequential chemo-radiation allows laryngeal preservation in about 2/3 of surviving patients without compromising survival.

Marked Creatine-Phosphokinase Elevation in Myopathy after Treatment with Bezafibrate

G. Slobodin, D. Yeshurun

Medicine A Dept. and Hyperlipidemia Clinic, Bnai Zion Medical Center,Bruce Rappaport Faculty of Medicine and Technion-Institute of Technology, Haifa

Bezafibrate is a fibric acid derivative which has been widely used in the past 15 years. Recent studies have elucidated much of its mechanism of action, which mainly results in reduction of VLDL and triglyceride levels and in elevation of HDL. The drug is relatively safe and its side-effects well known, mild, and reversible.

The most severe side-effect is myositis, varying from mild flu-like symptoms to rhabdomyolysis, which is extremely rare. The underlying situations most frequently associated with bezafibrate-induced myositis are renal insufficiency and concomitant treatment with certain other drugs.

We describe 2 women who developed severe myositis with bezafibrate treatment. 1, aged 43, who had moderate diabetes but no renal insufficiency, was treated with metformin and warfarin, which can interact with bezafibrate and affect its metabolism. The other, aged 54, had renal insufficiency and was on home peritoneal dialysis. Her bezafibrate dose had been increased because of very high triglyceride levels.

The aim of the study is to call attention to this significant side-effect of benzafibrate and to ways of preventing it.

Cells-Preliminary Report Immunohistochemical Identification of Testicular Germ

Batia Bar-Shira Maymon, Gedalia Paz, Leah Yogev, Ron Hauser, Letizia Schreiber, Amnon Botchan, Haim Yavetz

Institute for Fertility Study, Lis Maternity Hospital; Pathology Institute, Tel Aviv-Sourasky Medical Center; and Sackler Faculty of Medicine, Tel Aviv University

The use of testicular spermatozoa for intracytoplasmic sperm injection introduced a new treatment modality for management of male infertility.

Since testicular biopsies of non-obstructive azoospermic men are not homogenous in their histological patterns, identification with certainty of focal spermatogenesis might be difficult, particularly in those with small foci of spermatogenesis. We used an immunohistochemical marker of the male germ line, an antibody generated against RBM (RNA-binding-motif), to recognize with high precision the presence of germ cells in the biopsy. Biopsies of 30 men with azoospermia, most with non-obstructive azoospermia and a few with obstruction of the vas deferens, were evaluated.

Immunohistochemical staining for RBM protein contributed to the detection and accuracy of the identification of germ cells. Furthermore, this immunohistochemical technique aided the histopathologist to focus on even small foci of spermatogenesis. Absence of the protein expression confirmed the diagnosis of Sertoli-cell-only syndrome. The results indicate that expression of RBM can be a diagnostic marker for identifying the germ cells of small concentrations of spermatogenesis. This method can enhance the accuracy of histopathological evaluation of testicular biopsies that had formerly relied mainly on hematoxylin-and-eosin staining.

Testicular Cancer: Self-Awareness and Testicular Self-Examination in Soldiers and Military Physicians

Thomas Tichler, Rony Weitzen, Aharon Feinstone, Raoul Orvieto, Marian Moskovitz, Adam Singer

Depts. of Oncology and Medicine B, Sheba Medical Center, Tel Hashomer; Medical Corps, Israel Defence Forces; Gynecology Dept., Hasharon Medical Center, Petah Tikvah; and Medical Dept. B, Fleaman Hospital, Haifa

Testicular cancer is the most common malignancy in young men. To evaluate knowledge and awareness of that cancer, and of the practice of testicular self-examination (TSE), we developed a questionnaire which was distributed to 717 male soldiers and 200 of their military physicians.

21% of the soldiers had received some explanation of the importance of TSE, but only 16% were actually instructed how to perform TSE, and only 2% practiced it regularly. 24% had never examined their testicles before, 185 only rarely, and 6% often. With increased age, TSE frequency increased, but previous education, type of military unit, and ethnic origin had no affect. 99% of military physicians had been taught how to examine breasts, but only 70% had been taught routine testicular examination. 22% performed it, but 27% never did. 84% had never taught their soldiers the importance of TSE, although 51% taught female soldiers breast self-examination.

There was a significant lack of awareness of the importance of regular practice of TSE among both soldiers and their army physicians.

Hospitalization for Renal Colic: Epidemiological Features and Clinical Manifestations

Yahav Oron, Amir Shahar, Eran Dolev

Sheba Medical Center, Tel Hashomer; Israel Defense Forces Medical Center; Meir General Hospital, Sapir Medical Center, Kfar Saba; and Dept. of Medicine H, Sourasky-Tel Aviv Medical Center

The medical records of all patients referred to the emergency department (ED) of Sheba Medical Center for renal colic during 1996 were analyzed. Patients discharged from the ED and those hospitalized were compared.

There was no significant difference between the 2 groups with regard to average age or sex distribution. Statistically significant differences were found with regard to frequency of chills and fever, history of renal colic, referral for renal colic during that year or hospitalization for renal colic or nephrolithiasis, previous positive imaging, stone removal by surgery or extracorporeal shock wave lithotripsy, fever exceeding 37.5^o and administration of fluids, pethidine or pramin in the ED, prolonged stay in the ED and previous appendectomy.

A conditional regression model tested the predictive value of each of those factors. Inclusion of independent variables into the model led to an overall correct classification rate of 84.43%, with 44.83% sensitivity and 93.16% specificity. There were correlations between referrals for renal colic, overall renal colic rate and average monthly temperature, so there was no pure correlation between average monthly temperature and referrals to the ED for renal colic.

The major indications for hospitalization were actually the clinical ones, indicating either an active metabolic disease or suspected obstruction of the urinary tract. Treatment in the ED and duration of the visit indicated disease severity.

רונית חיימוב-קוכמן¹, ראובן ברומיקר², אריאל מילויצקי¹

¹מחלקת נשים ויולדות ²והמחלקה לטיפול נמרץ בילוד, בי"ח הדסה הר הצופים, הפקולטה לרפואה, האוניברסיטה העברית, ירושלים

Familial Parinaud Oculo-Glandular Syndrome in Cat-Scratch Disease 

Nir Shoham, Dan Miron, Raul Raz, Hanna J. Garzozi

Depts. of Ophthalmology and Pediatrics A, and Infectious Diseases Unit, HaEmek Medical Center, Afula

Cat-scratch disease is manifested by subacute, regional lymphadenitis and occurs mainly in children. The causative agent is a pleomorphic, gram-negative bacillus, Bartonella henselae carried by asymptomatic cats. Parinaud oculoglandular syndrome is the most common ocular manifestation of this disease. It is characterized by unilateral conjunctivitis with polypoid granuloma, usually of the palpebral conjunctiva, and preauricular lymphadenopathy. The diagnosis is supported by a history of exposure to cats and is confirmed by positive serologic tests or positive PCR assay.

The occurrence of more than 1 case of Parinaud syndrome in a family is rare. We describe 2 sisters with Parinaud oculoglandular syndrome, proven by serologic tests. They reported that they used to cuddle with their cats, among them a kitten. Because of the refractory conjunctivitis and signs of imminent periorbital cellulitis, they were treated with oral tetracycline with apparently good responses.

We recommend asking about contacts with cats in any atypical conjunctivitis accompanied by regional lymphaden-opathy, especially in young patients. Systemic antibiotics should be given when there is any suspicion of significant ocular involvement, if the patient is immunosuppressed, or if there are systemic manifestations of cat-scratch disease.

Giant Lesions in Multiple Sclerosis: A Diagnostic Challenge 

Bruria Shalmon, Dvora Nass, Zvi Ram, Anat Achiron

Institute of Pathology, Neurosurgery Dept. and Neuroimmunology Unit, Sheba Medical Center, Tel Hashomer

Multiple sclerosis is the most common demyelinating disease of the central nervous system affecting young adults, in which destruction of the axon myelin sheath disturbs signal transduction. The disease course is usually remitting and relapsing, but sometimes there is steady neurological deterioration.

The diagnosis depends mainly on an adequate clinical history and neurological examination. Evoked potentials, elevated cerebrospinal fluid gamma globulin with oligoclonal bands, and imaging studies, mainly magnetic resonance imaging (MRI), also contribute to the diagnosis.

Multiple sclerosis may occasionally present as a mass lesion that clinically and radiologically is indistinguishable from a brain tumor. We present 2 cases of giant tumefactive lesions, proven by brain biopsy to be of demyelinating nature.

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.

Tacrolimus does not Accentuate Hepatic Damage due to Hypoperfusion 

Ron Ben Abraham, Ivgeni Isartal, Richard Nakache, Vallery Rudick, Daniel Ogorek, Gideon Paret, Avi Weinbroum

Dept. of Anesthesiology and Critical Care Medicine, Organ Transplantation and Postoperative Care Units, Tel Aviv-Sourasky Medical Center; and Pediatric Intensive Care Units, Sheba Medical Center, Tel Hashomer; and Sackler Faculty of Medicine, Tel Aviv University

Deterioration of hepatic function following liver transplantation is a known complication, sometimes attributed to the use of cyclosporin A. Reaction to tacrolimus (Prograf), a relatively new and effective immunosuppressant drug, is thought to result in a much lower grade of organ dysfunction, especially in the transplanted liver.

Using the ex-vivo rat model of isolated perfused liver, we evaluated hepatocellular damage and oxygen extraction when tacrolimus was administered following liver hypoperfusion. Tacrolimus did not worsen hepatic dysfunction caused by the hypoperfusion. Therefore using tacrolimus in the perioperative period might be safer than cyclosporin A, which tends to worsen hepatic damage in the presence of hypoperfusion.

Use of Civilian Emergency Departments by Israel Defense Force Soldiers 

A.D. Cohen, A. Porath, R. Bessorai, A. Shulman, Y. Snir

Medical Corps, Israel Defense Forces; Depts. of Medicine F and Orthopedics and Emergency Dept., Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheba

Many physicians, civilian as well as in military, feel that some referrals of soldiers to civilian emergency departments are inappropriate and that soldiers should receive medical attention within their military units. We therefore evaluated referrals of soldiers to our emergency department.

707 referral letters from military physicians and the corresponding emergency room discharge letters were evaluated. Most soldiers were referred for mild trauma (45.0%) or miscellaneous diseases (52.9%); 22 (3.1%) were hospitalized.

It appears that some military physicians use the civilian hospital emergency department as a surrogate for an out-patient specialty clinic and for x-ray and laboratory services. This is in contrast to the designated functions of the emergency department which are to provide emergency and trauma services and to evaluate the need for hospitalization of referred patients.

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.

Acipimox as a Secondary Hypolipidemia in Combined Hypertriglyceridemia and Hyperlipidemia

D. Yeshurun, H. Hamood, N. Morad, J. Naschitz

Hyperlipidemia Clinic, Dept. of Medicine A, Bnai-Zion Medical Center, and Rappaport Faculty of Medicine, Technion, Haifa

32 patients with hypertriglyceridemia, excessive hypertri- glyceridemia, and combined hyperlipidemia, were treated with the nicotinic acid derivative acipimox (Olbetam). First line treatment with bezafibrate, or statins in some with combined hyperlipidemia, had failed. In 10 acipimox was discontinued due to side effects or absence of clinical response. The other 22 completed 6 months of treatment with no side effects.

Acipimox caused a significant 54% decrease in triglyceride levels, a 23% decrease in total cholesterol, and a 12% increase in HDL-cholesterol. LDL-cholesterol was difficult to calculate because of the high triglyceride levels, so no results are presented.

Although acipimox was much better tolerated than nicotinic acid, it also had side effects, but fewer. Acipimox can therefor be used as a second-line drug, mainly in those with combined hyperlipidemia and hypertriglyceridemia.

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.

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.