The Chemotherapeutic Treatment of Advanced Hodgkin's Disease

R. Epelbaum¹, N. Haim¹, M. Ben-Shahar¹, I. Valtuch¹, D. Faraggi³, A. Sharabi-Nov³, Y. Ben-Arie², Y. Cohen⁴

Departments of Oncology¹ and ²Pathology, Rambam Medical Center, and Faculty of Medicine, Technion-Israel Institute of Technology; ³Department of Statistics, Haifa University, Haifa; and ⁴Department of Oncology, Soroka University Medical Center, Beer Sheba

Between 1972 and 1994, 121 adult patients with advanced Hodgkin's disease received MOPP (M) combination chemotherapy, MOPP alternating with ABVD (M-A) or MOPP and ABV hybrid (M/A). Radiation therapy was given to 1/3 of them. The median age was 35 years, 58% had stage III and 42% had stage IV disease. Failure-free survival at 10 years was 43.9%. It was 66.7%, 48.4% and 29.9% for patients treated by M/A, M-A and M, respectively. Overall survival at 10 years was 40.8%, and 78.2%, 48% and 27.7% for patients treated by M/A, M-A and M, respectively. Multivariate analysis found age (above or below 65 years) and combination chemotherapy (with or without adriamycin) to be significant prognostic factors. M/A combination was more myelotoxic, while M combination caused more second primaries. Today, 80% of patients with advanced Hodgkin's disease may be cured, with low rate of long-term toxicity.

Metallic Stents for Acute Colonic Obstruction

M. Itkin, E. Atar, H. Neuman, D. Kravarosic, Z. Fuko, M. Kaz

Radiology and General Surgery B Depts., Golda Campus; and General Surgery Dept., Beilinson Campus; Rabin Medical Center, Petah Tikva

The traditional treatment of acute colonic obstruction, usually caused by malignant tumor, is a 2-stage surgical procedure. The first operation is emergent and includes primary tumor resection and end colostomy followed by scheduled colostomy closure. These operations are associated with high mortality and morbidity. Recently, insertion of self-expanding metallic stents for temporary colonic decompression has been was introduced. With this new technique colostomy can be avoided in the acute phase.

In advanced colonic cancer stent-insertion is the only palliative treatment. It is done in the radiology department under fluoroscopic guidance. We present 2 cases of malignant colonic obstruction treated successfully by stent insertion.

Diagnosis and Therapy in Acute Stroke: A Rehabilitation Center Viewpoint

M. Motin, J. Streifler, A. Tsur, H. Ring

Neurological Rehabilitation Dept., Loewenstein Rehabilitation Center, Ra'anana; Neurological Unit, Rabin Medical Center, Golda Campus, Petah Tikva and Sackler School of Medicine, Tel Aviv University, Ramat Aviv

The extent of the diagnostic work-up of patients with acute stroke was evaluated in 101 patients admitted for rehabilitation during a 4-month period in 1997. This included specific blood tests and neuro- and cardiac imaging, and compared the extent of work-up in a community hospital versus a rehabilitation center. Comparisons were also made with similar investigations 10 and 20 years earlier.

Results demonstrated that the trend to admit younger stroke patients (<50 years) to neurological (as opposed to medical) departments observed between 1977-1987 persisted in 1997.

The use of CT scan increased dramatically from 1977 to 1987 (19% vs 78%), and in 1997 was actually 100% The use of carotid duplex and echocardiography increased steadily during the 3 decades reaching 26% and 28% respectively. Tests for thrombophilia were seldom done. However, in neurological departments it was done in about 50% of the younger stroke patients. In neurology departments carotid duplex was done 2 to 3 times more often than in medical departments.

During rehabilitation imaging tests were done once or more in almost half the patients. The results and those of additional blood tests, have led to modification of antithrombotic treatment in 14% of the younger group and 4% of the older group.

We have clearly shown that while stroke work-up has become more comprehensive in recent years, there is still much to do in this field. Stroke units or teams in our general hospitals will increase stroke awareness, improve work-up and hasten definitive treatment.
 

A Molecular Method of Diagnosis of Congenital Adrenal Hyperplasia

Shoshana Israel, Chaim Brautbar

Tissue Typing Unit, Hadassah Medical Center, Jerusalem

Congenital adrenal hyperplasia (CAH) is caused mainly by deficiency of the 21-hydroxylase enzyme. The disease may appear in the classical salt-losing, simple virilizing forms or as a mild, nonclassical form. 21-hydroxylase is encoded by the CYP21B gene on the short arm of chromosome 6, in the midst of the human leukocyte antigen (HLA) complex, between HLA Class I and Class II regions.

We describe a method for identifying mutations in the CYP21B gene. It is based on amplification of the gene using the polymerase chain reaction and identification of mutations with sequence-specific oligo-probes. The mutations identified were: V281 and P30L responsible for nonclassical CAH, and I2 splice, Q318X, I172N, cluster E6, and a deletion including 8bP in the third exon (8bP del) responsible for the classical form of CAH.

We also analyzed 2 families affected with the classical form of CAH which demonstrate possible complications in genotyping. Typing for HLA haplotypes can be helpful in certain cases, as demonstrated in 1 of the families presented. In this case it was necessary to distinguish between 2 possible genotypes: 1 with the mutations in tandem on 1 chromosome and the other with the mutated genes on both chromosomes. HLA haplotyping enabled the assignment of the mutations to the relevant chromosomes and thus allowed correct genetic counseling.

The other family demonstrated the importance of CYP21B genotyping in individuals with the nonclassical form of CAH. This form may consist of 1 mild and 1 severe mutation, representing a serious potential for transmitting the classical form of CAH.

Laparoscopic Cholecystectomy - 1,000 Procedures in a Surgical Department

Uri Freund, Ami Mayo, Ivan Schwartz, David Neufeld, Haim Paran

Dept. of Surgery A, Meir Hospital, Kfar Saba; and Sackler School of Medicine, Tel Aviv University

The first 1,000 laparoscopic cholecystectomies performed in our department were reviewed. There was no operative mortality; conversion to open cholecystectomy was necessary in 2%. In the last 600 cases the rate of conversion had decreased to 0.5%. There was common bile duct injury in 0.3%, with the injuries identified during primary surgery. This clinical experience is consistent with previous studies, which proved that laparoscopic cholecystectomy is safe and should replace open operation as the procedure of choice. 

Life-Threatening Echovirus 11 Infection During First Month of Life

U. Rubinstein, M. Weisbrod, B. Garty

Neonatal Dept., Laniado Hospital, Kiriat Zans, Natanya; and Pediatrics B, Dept., Schneider Children's Medical Center, Petah Tikva

Infection with Echovirus 11 is mostly asymptomatic, but it may cause a wide variety of clinical diseases, from gastroenteritis to serious diseases such as meningitis and myocarditis. In small infants, especially during the first days of life, echovirus infection may appear as a sepsis-like illness, and cause disseminated intravascular coagulopathy and shock.

We present 2 infants with severe echovirus 11 infections. A 3.5-month old died within 24 hours of shock and probably myocarditis. The other, 6-days old, presented with meningitis, hepatitis and disseminated intravascular coagulopathy. It recovered after treatment with intravenous immunoglobulin.

Echovirus 11 may cause life-threatening infections in small infants. Pediatricians should be alert to the special characteristics of this disease.

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.

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.

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.

Drug Abuse among Patients Requiring Psychiatric Hospitalization 

Gregory Katz, Emi Shufman, Haim Y. Knobler, Mark Joffe, Rachel Bar-Hamburger, Rimona Durst

Kfar Shaul Mental Health Center, (Affiliated with the Hebrew University-Hadassah Medical School, Jerusalem); and Jerusalem Institute for Treatment of Substance Abuse, Israel Antidrug Authority

We assessed the incidence of drug abuse among patients requiring psychiatric hospitalization, and characterized the population at risk. The data on drug abuse were obtained from self-reports and urine tests in 103 patients, aged 18-65, hospitalized in the Kfar Shaul Psychiatric Hospital (autumn 1998).

There was close correspondence between the self-reports and the results obtained from urine tests. 1/3 admitted to having used illegal drugs and signs of drug abuse were found in about 1/4 of the urine tests. The most prevalent drugs were cannabis products (hashish and/or marijuana) and in 15 patients opiates.

Drug users were younger than non-users. With regard to psychiatric symptomatology, fewer negative symptoms were recorded among cannabis abusers with schizophrenia, compared to schizophrenic patients with no history, past or present, of cannabis abuse.

The present findings confirm the clinical impression that there has been an increase in drug abuse among mental patients, parallel to that found in society at large. Confirmatory surveys are necessary. Our findings clearly suggest that a change in attitude has occurred in Israel to what has been considered a marginal problem. Hospitalized mentally-ill patients, the younger in particular, should be considered at risk for drug abuse.

Decompression Sickness in Divers Treated at the Israel Naval Medical Institute 

A. Gil, A. Shupak, H. Lavon, Y. Adir

Israel Naval Medical Institute, Israel Defense Forces, Haifa

Clinical characteristics of 125 divers treated for decompression sickness (DCS) in the hyperbaric multiplace chambers of this Institute during 1992-1997 were analyzed retrospectively. In 62 (51%) the diagnosis was DCS Type I (joint pain or skin involvement) and in 60 (49%) DCS Type II (neurological, inner ear or pulmonary disease). Risk factors for the evolution of DCS were depth and duration of the dives involving accidents, violation of recommendations of the decompression tables, and repeated dives.

Results were available for 112 of the 125 patients. 54 of them (48%) recovered completely, and another 54 recovered partially; 4 did not respond to treatment. Inner ear DCS was less responsive to hyperbaric oxygen treatment (p=0.0001). There was significant improvement of neurological function in those with severe neurological injury (p=0.0001). Rapid diagnosis and transportation of divers with DCS to a hyperbaric chamber is of crucial importance.

Jet Lag Causing or Exacerbating Psychiatric Disorders

Gregory Katz, Rimona Durst, Josef Zislin, Hilla Knobler, Haim Y. Knobler

Kfar Shaul Mental Health Center, Jerusalem (Affiliated with the Hebrew University-Hadassah Medical School, Jerusalem)

Desynchronization of circadian rhythmicity resulting from rapid travel through at least 4 time zones leads to symptoms of jet lag syndrome. The most commonly experienced symptoms in normal individuals are sleep disorders, difficulties with concentrating, irritability, mild depression, fatigue, and gastrointestinal disturbances.

There is strong evidence relating affective disorders to circadian rhythm abnormalities, such as occur in jet lag. Less convincing suggestions relate jet lag to psychosis. We presume, relying on the literature and our accumulated experience, that in predisposed individuals jet lag may play a role in triggering exacerbation of, or de novo affective disorders, as well as, though less convincing, schizophreniform psychosis or even schizophrenia. An illustrative case vignette exemplifies the possible relationship between jet lag following eastbound flight and psychotic manifestations.

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.

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.