Sentinel Lymph Node Biopsy in Breast Cancer: A Validation Study and Preliminary Results

Aviram Nissan, Ram M. Spira, Roland Chisin, Oded Zamir, Diana Prus, Martin Klein, Mahmoud Badriyyah, Herbert R. Freund

Departments of Surgery. Biophysics and Nuclear Medicine, and Pathology. Hadassah University Hospital Mount Scopus and Hebrew University - Hadassah Medical School, Jerusalem

Introduction: Sentinel lymph node biopsy (SLNB) has been recently proven to be an accurate staging method for breast cancer, replacing axillary lymph node dissection (ALND) in selected cases. We present our initial experience and the process of introduction and implementation of SLNB in a University Hospital setting.

Material and methods: 46 SLNB were performed in 42 consecutive female patients with invasive breast cancer. Treatment included 0.4mCi-2mCi of Tc-99m rhenium colloid injected either 2 hours before surgery (0.4 mCi) or the night before surgery (2 mCi). Four milliliters of Patent Blue V were injected peritumoral 10 minutes prior to skin incision in all patients. Following SLNB all women underwent subsequent ALND. Sentinel nodes were processed both with multiple (10-15) H&E sections and immunohistochemistry with cytokeratin antibodies stain.

Results: Blue dye, isotope or the combination of both identified 43/46 (93%) of the sentinel lymph nodes. ALND was performed only unilaterally in 4 patients with bilateral breast cancer bringing the total evaluable SLNB to 39. In the 39 patients in whom the sentinel node was successfully identified and underwent ALND, the SLNB was true positive (TP) in 17/39 (44%) true negative (TN) in 20/39 (51%) and false negative in 2/39 [(5%), both T2 lesions] with overall accuracy of 95%. In the last 10 cases all sentinel nodes were successfully identified with 70% TP and 30% TN.

Conclusions: Experience with at least 30-40 consecutive cases for safe implementation of SLNB in clinical practice. Specific training and dedication is required for the entire team involved, including surgeons, nuclear medicine physicians and technicians and pathologists.  

Traumatic Brain Injury: The National Trauma Registry*

Einat Peles, Vita Barell, Valentina Boyko, Arnona Ziv, Giora Kaplan

Health Services Research Unit, Ministry of Health, Sheba Medical Center Tel-Hashomer

Background: Traumatic Brain Injury (TBI) has been established as a category in reporting systems. Uniform data systems case definition has been suggested for hospital discharge data surveillance systems cases based on ICD-9-CM diagnostic codes. These include fractures and specific mention of intracranial injuries such as contusion, laceration, hemorrhage, and concussion. Inspection of data from the Israel National Trauma Registry suggested that two diagnostic groups of very different severity and outcome were being unjustifiably combined.

Aim: To evaluate the validity of categorizing TBI into two discrete groups, using the presence of specific mention of intracranial injury and/or loss of consciousness for more than one hour as the definition of definite TBI. Possible TBI includes skull fractures with no mention of intracranial injury and/or concussion with no loss of consciousness.

Methods: The study population includes all traumatic injuries admitted to hospital, dying in the ER or transferred to other hospitals and recorded in the 1998 Trauma Registry in all 6 level I trauma centers in Israel and two level II centers.

Results: The significant difference in severity between groups supports the validity of sub-dividing the TBI classification into definite and possible subcategories. As a result, we obtain two different severity groups without measuring specific severity scores which are limited in the reporting system.

Conclusion: The groups were significantly different in severity, hospital resource use, immediate outcome, demographic and injury circumstances.

*           Level I: Rambam, Beilinson-Schneider, Sheba, Ichilov (Tel Aviv Sourasky Medical Center), Hadassah Ein Karem and Soroka.

            Level II: Hillel Yaffe and Kaplan

Primary Gastrointestinal Stromal Tumors

Y. Wiener¹, R. Gold¹, S. Zehavy², J. Sandbank², A. Halevy¹

¹Dept. of General Surgery and Dept. of Pathology, ²Assaf Harofeh Medical Center, Israel

Stromal tumors of the GI tract are rare. In the retrospective and prospective study we investigated the relationship between tumor symptomatology, tumor grade and prognostic factors. During the period May 1993 - September 1999, 11 female and 13 male patients with a mean age of 62 (range-29-81) years were operated for primary gastrointestinal stomal tumors (GIST) in our department. Observed signs and symptoms were: GI bleeding (65%), abdominal pain (45%), abdominal mass (15%) and weakness (5%). In 4 patients tumor was an incidental finding during investigation or operation for another tumor. Tumor location (in decreasing order) was: stomach (15), small bowel (SB, 6), esophagus (1), duodenum (1) and colon (1). Preoperative biopsy or FNA were diagnostic in less than 50% of the cases. Operative procedures included wedge resection (8 patients), resection of segment of bowel (10) and extended resection (6), of diaphragm, SB, colon, bladder, kidney and liver. The mean tumor size was 7.8 (range-0.9-22) cm. Four tumors were graded as benign, 8 of indeterminate malignant potential and 12 malignant.

Conclusion: The main presentation of GIST is acute GI bleeding. Endoscopy is most effective for studying proximal tumors, and CT should be used to identify distal GI tract tumors. Tumor size or malignancy were not necessarily predictive of GI bleeding. When invasive to adjacent organs is present, wide excision should be contemplated as long-term survival can be achieved.

אורי שולמן, רם סילפן, אברהם אמיר, דניאל האובן

המח' לכירורגיה פלסטית והיח' לכוויות, קמפוס בילינסון, מרכז רפואי רבין, פתח-תקווה

מלאנומה ממארת של העור (ממ"ע) היא שאת ששיעור היארעותה עולה בקצב מהיר בעולם כולו והיא מהווה אתגר טיפולי נרחב. כיום, הניתוח הוא הטיפול העיקרי בממ"ע, ואם השאת מאובחנת ומטופלת בשלב מוקדם, לפני חדירה עמוקה לשיכב הדרמיס, היפגעות קישיות לימפה והתהוות גרורות מרוחקות, הרי שסיכויי ההישרדות גבוהים.

ממ"ע באזור ראש-צוואר המתהווה בשכיחות של כ-20% מתוך כלל החולים במלאנומה ממארת, שונה במספר מובנים מאשר באזורים אחרים בגוף: כריתה נרחבת של השאת מוגבלת בגודלה עקב המיקום האנטומי באזור ראש-צוואר, הניקוז הלימפטי עשיר ביותר, ההשלכות האסתטיות עלולות להיות מרחיקות לכת וההשפעות התיפקודיות יכולות להיות בלתי הפיכות.

ממ"ע באזור ראש-צוואר מתרחשת בשכיחות שווה בנשים ובגברים. השאת ממוקדת בעיקר בפנים, ובשכיחות יורדת באזור הצוואר, הקרקפת והאוזניים.

קיימים מספר גורמי סיכון להתהוות מלאנומה ממארת בכל אזורי הגוף, ביניהם אנשים עם שומות מלאנוציטיות מרובות, שומה מלידה גדולה בקוטר מעל 20 ס"מ (giant congenital nevi), שומה דיספלסטית (dysplastic nevi) בעלי עור, עיניים ושיער בהירים עם נטייה להיכוות לאחר חשיפה קצרה לקרני השמש, בעלי עור עם נמשים, אנשים שנחשפו רבות לקרני השמש במהלך חייהם, אנשים בעשור החמישי לחייהם ואילך, אנמנזה משפחתית של מלאנומה ממארת המגבירה את הסיכון ללקות במחלה בשיעור של פי 2-8, אנמנזה של סרטני עור בעבר ואנשים עם דיכוי המערכת החיסונית. הסיכון במהלך החיים להתהוות מלאנומה ממארת בפעם השנה הוא 1%-8%.

Newer Diagnostic and Therapeutic Methods in Lung Cancer

R. Rubinstein, R. Breuer, R. Chisin

Dept. of Medical Biophysics and Nuclear Medicine, and Institute of Pulmonology, Hadassah University Hospital, Ein Karem, Jerusalem

Positron emission tomography (PET), when used with F-18 fluoro-deoxyglucose (FDG), contributes to the evaluation of patients with lung cancer. This technique of imaging detects active tumor tissue by showing increased radiopharmaceutical uptake by metabolically active cells.

Thus, PET assists in the early diagnosis of pulmonary malignancies that appear only as non-specific findings on CT-scan or chest X-ray. In addition, it is helpful in staging lung cancer before and after resection, chemotherapy or radiotherapy, or their combined use.

We performed 135 FDG-PET studies between July '97-April '99. and present our preliminary results with examples of the main indications for PET in lung cancer.
 

Screening for Early Detection of Prostatic Cancer

A. Neheman, Y. Shotland, Y. Metz, A. Stein

Dept. of Urology, Carmel Hospital, Lady Davis Medical Center, Haifa

Prostatic cancer (PC) is second only to lung cancer as a cause of cancer mortality in men word-wide. In Israel it is the most common cause of cancer mortality in men, after lung cancer and colo-rectal cancer.

We screened, for the first time in Israel, for prostatic cancer using serum levels of PSA and a digital rectal examination (DRE). The purpose was not only to diagnose PC but also to increase public awareness of the condition.

300 men in the Haifa area who met statistical criteria for early diagnosis of PC participated. They filled a questionnaire regarding risk factors for PC (age, family history (FH) of prostatic and breast cancer, cigarette smoking, alcohol consumption, previous PSA sampling) and were examined. Those who had out-of-ragne, age-related PSA values, or a pathologic DRE underwent trans-rectal ultrasound (TRUS) examination and guided biopsy of the prostate. Those with a positive biopsy for PC underwent radical prostatectomy or radiation therapy.

41 (14.3%) had out-of-range, age-related PSA levels and 10 (3.5%) had a pathologic DRE. 39 (13.3%) underwent TRUS and biopsy and 6 (2.04%) had clinically significant PC, all early stages (Gleason 4-6).

Correlation between age and PSA has been proven statistically significant (p<0.05). Symptoms of urinary tract obstruction and nocturia were related to a high PSA (p=0.035 and 0.002, respectively). Those with PC had at least 1 symptom of urinary tract obstruction; 6 (15.3%) who underwent TRUS and biopsy and a FH of prostate cancer. However, no subject with a FH of PC had biopsy-proven cancer. Those with PC had PSA values from 4.9 to 31.8 ng/ml (9.6 median). Age-related PSA had a positive predictive value of 17.1%.

Results of our annual screening for early detection of PC using age-related PSA, and DRE are encouraging: cases detected were clinically significant and treatable. It would appear that screening for PC will result in decreasing the incidence of metastatic cancer and therefore mortality. 
 

Atrophic Gastritis Presenting with Pulmonary Embolism

Muhammad A. Abdul-Ghani, Rima Feldman, Moshe Shai, Jacob Varkel

Dept. of Medicine C, Western Galilee Hospital, Naharia

Atrophic gastritis is an autoimmune gastropathy in which there is destruction of gastric parietal cells. This results in intrinsic factor deficiency and disturbance in vitamin B12 absorption. Its clinical manifestationa are therefore the consequences of B12 deficiency and include anemia and neurological defect. In addition, lack of B12 results in metabolic changes, including disturbances of methionine metabolism and accumulation of homocysteine.

In recent years, there has been increasing evidence suggesting that hyperhomocysteinemia is a risk factor for thrombo-embolic disease. We describe a 51-year-old man with atrophic gastritis, severe B12 deficiency and hyperhomocystein-emia. The initial clinical manifestation was pulmonary embolism, without either anemia or neurological signs. B12 deficiency should therefore be considered in patients being investigated for hypercoagulability.

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.

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.

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.

Laparoscopic Ultrasound in Predicting Resectability of Choriocarcinoma

M. Shimonov, P. Schachter, G. Gvirtz, Y. Avni, A. Rosen, A. Czerniak

Depts. of Surgery, Ultrasound, and of Gastroenterology, Wolfson Medical Center, Holon and Sackler Faculty of Medicine, Tel Aviv University

Cholangiocarcinoma accounts for about 1% of all malignant tumors. They are difficult to diagnose because of their small size and their location. Although surgical resection is the best therapeutic approach, most patients undergo unnecessary exploratory laparotomy due to incorrect preoperative diagnosis.

We present our experience with laparoscopic ultrasound (LU) in the evaluation of cholangiocarcinoma and determination of tumor spread and vascular involvement. Of 25 patients referred for surgery, 6 were excluded following LU and were referred instead for palliative treatment. Diagnosis of the tumor was successful in 92%, and vascular involvement was diagnosed in 46%. LU should be an integral diagnostic test in the evaluation of choriocarcinoma.

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.

Thrombolytic Therapy or Primary Coronary Angioplasty in Acute Myocardial Infarction?

David Pereg, Shlomo Behar, Alexander Battler, Valentina Boyko, Shmuel Gottlieb, Jonathan Leor: Israel Thrombolytic Survey Group

Cardiology Division, Soroka Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheba; Neufeld Cardiac Research Institute, Tel Hashomer and Tel Aviv University; and Cardiology Dept., Rabin Medical Center, Petah Tikva

There has been continuous debate over the superiority of primary percutaneous, transluminal, coronary angioplasty (PTCA) over thrombolysis for acute myocardial infarction (AMI). It was questioned whether this advantage of primary PTCA reported in selected populations by experienced centers can be replicated in our clinical practice.

We compared demographic and clinical variables, therapies and outcome in AMI treated with primary PTCA vs thrombolytic therapy. Clinical and demographic variables of 1,678 unselected AMI patients (admitted January/February and May/July 1996) were analyzed in 16 cardiac care units with on-site catheterization facilities and ability to perform PTCA. Of these 803 (48%) were treated by thrombolysis and 99 (6%) by primary PTCA.

The prevalence of adverse prognostic variables, such as anterior wall MI, heart failure on admission or during hospital stay, pulmonary edema, and ventricular tachycardia or fibrillation, was higher in the PTCA group. The 7-day, 30-day and 1-year mortality rates were similar in the 2 groups: 4%, 7.2% and 12.8%, respectively, in the PTCA group and 5%, 7.2% and 11.1% in the thrombolysis group. There was a trend toward lower mortality in subgroups of high-risk patients: those with heart failure on admission (Killip class >1), the elderly (>65 years), and those with previous MI treated with PTCA. After adjusting for confounders, treatment with primary PTCA was not found to be associated with lower mortality.

Only a small proportion of AMI patients in Israel were treated with primary PTCA in 1996. The frequency of adverse prognostic factors among them was higher but their short and long term outcomes were similar to those of high risk patients treated with thrombolysis.

Breast Tumors Demonstrated by Tc-99m Sestamibi Scintimammography 

Itzhak Pappo, Tifha Horne, Herbert Merdad, Ruben Orda

Dept. of Surgery A, Institute of Nuclear Medicine and Dept. of Pathology, Assaf Harofeh Medical Center, Zrifin; and Sackler Faculty of Medicine, Tel Aviv University

Breast cancer can be detected by scintimammography using Tc-99m sestamibi (MIBI). The method is highly accurate, sensitive and specific. Histologically, most of the tumors have been adenocarcinomas.

We present 2 women with rare breast tumors, primary squamous cell carcinoma and malignant phyllodes tumor. In both, mammography and cytological biopsy were not diagnostic, but MIBI scintimammography demonstrated focal uptake in the diseased breast.

Man in a Hot Climate - Early Studies of the Institute of Military Physiology 

Ezra Sohar, Yair Shapiro, Yoram Epstein

Institute of Military Medicine, Medical Corps, Israel Defense Forces and Heller Institute of Medical Research, Sheba Medical Center, Tel Hashomer

In the 1950's many IDF soldiers were hospitalized for heat stroke - about 25% of whom died. Analyzing these cases revealed that commanders misinterpreted human ability to perform in the heat and ignored basic concepts of fluid and electrolyte balance and heat load.

In the early 1960's a series of studies was conducted with regard to soldiers' performance in the heat. The first study (1959), which later became a classic, was conducted during a 21-day march from Eilat to Metula, crossing all climatic zones of Israel. The study was followed by other investigations which approached the issues of voluntary dehydration, fluid consumption vs sweat loss, salt additives, and the effect of heat load on performance.

Based on these early studies, proper regulations were issued to field officers. Over the years, the lessons learned from these studies saved many lives. The number of cases of heat stroke and of other climate-related injuries was dramatically reduced, and performance was enhanced.