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.

ינינה גלבויז (1), שרה שפירו (2), ניצה להט (2), אריאל מילר (1,3)

(1) היחידה לנירואימונולוגיה, המח' לנירולוגיה, (2) היחידה לחקר אימונולוגיה, המרכז הרפואי כרמל, הטכניון – הפקולטה לרפואה, (3) מכון רפפורט למחקר במדעי הרפואה, חיפה

אנזימי המטריקס-מטלופרוטאינאזות (matrix metal-loproteinases - MMP's) (אממ"פ)* הם משפחת אנזימים פרוטאוליטיים אשר, יחד עם מעכביהם הריקמתיים – TIMs, מעורבים בעיצוב המירקם החוץ-תאי (ECM) (מח"ת – מירקם חוץ-תאי) במיגוון מצבים פיזיולוגיים, כגון התפתחות עוברית וריפוי פצע. לאחרונה, מצטברות עדויות למעורבות אממ"פ גם במיגוון רחב של מחלות, כגון התפשטות גרורות, טרשת העורקים, מצבי דלקת ומחלות אוטואימוניות.

בתהליכים דלקתיים של מערכת העצבים המרכזית, האממ"פ הם הגורם העיקרי בהרס מחסום הדם-מוח, בהתהוות בצקת מוחית, בהסננת תאי דלקת, בתהליכי הרס מיאלין ובהתהוות צלקת הגליה במוח. פעילות מוגברת של MMPs אובחנה בבעלי-חיים חולים בדגם ניסיוני של מחלות דה-מיאליניות וטרשת נפוצה. רמות גבוהות של אממ"פ, בעיקר MMP-2 ו-MMP-9, התגלו שינויים בפרופיל האממ"פ דווחו גם בהקשר של דלקות עוצבה חיידקיות ונגיפיות. כמו כן, למרות סתירות מסוימות במימצאים, נראה כי אממ"פ מעורבים גם בתהליכי הצטברות חלבון הביתא-amyloid במחלת אלצהיימר. מעורבות אממ"פ במחלות מערכת העצבים המרכזית מעוררת עניין מיוחד בזכות יכולתם לשמש בסימנים לפעילות המחלה ובזכות הפוטנציאל הטיפולי הטמון בשימוש במעכבי אממ"פ.

Antioxidant Profile of Human Saliva and its Biological Significance

R. M. Nagler, A. Z. Reznick

Dept. of Oral and Maxillofacial Surgery, Salivary Clinic and Oral Biochemistry Laboratory; Rambam Medical Center and Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa

Saliva is the first biological medium to come in contact with materials entering the body through the oral cavity. These materials are contained in food and drink (or inhaled as volatile ingredients). Accordingly, saliva contains various defense mechanisms which have been thoroughly investigated. They include immunological and enzymatic systems aimed at pathological microorganisms. Saliva also can protect the mucosa against mechanical insults and when required, promote its healing via agents such as the epidermal growth factor.

Another defense mechanism in saliva which has been gaining increased attention and seems to be of paramount importance is its antioxidant system. We discuss both the molecular and enzymatic components of the salivary antioxidant system in respect to mixed, parotid, submandibular and sublingual saliva and under various physiological conditions of secretion.

שי שרוט¹, יואב צפמן¹, יהודה שינפלד²

¹המח' למחלות עצבים, המרכז הרפואית תל-אביב, ²מח' לרפואה פנימית ב' והמרכז למחלות אוטואימוניות, בי"ח שיבא, תל-השומר

תיסמונת האנטיפוספוליפידיים, antiphospholipid syndrome (APS) היא מחלה רב-מערכתית שבה מעורבים נוגדנים ואנטיגנים שונים. הפרעה האוטואימונית מתבטאת קלינית באירועים פקקתיים-תסחיפיים נשנים (עורקיים וורידיים), בהפלות עצמוניות נשנות, בתרומבוציטופניה ובכייל גבוה של נוגדנים כנגד פוספוליפידים ((antiphospholipid-antibodies - aPL וכן של נוגד קרישה זאבתי (lupus anticoagulant - LA). התיסמונת יכולה להתרחש משנית למחלות אוטואימוניות אחרות (כמו זאבת אדמנתית מערכתית systemic-lupus-erythematosus (SLE), לממאירויות או לזיהומים וכן כתגובה לתרופות. כשלא נמצאת סיבה ראשונית מעין אלו להתהוות התיסמונת, היא מוגדרת כראשונית (primary APS).

הנוגדנים הנמנים עם משפחת ה- aPL מאותרים בבדיקה שבה נמדדת תגובתיות (reactivity) חיסונית כלפי קרדיוליפין (aCL) ופוספוליפידים למיניהם הטעונים שלילית, בנוכחות או ללא נוכחות  ביתא 2 – גליקופרוטאין או קופקטורים חלבוניים אחרים, או ע"י תגובתיות חיסונית כלפי ביתא 2 – גליקופרוטאין (הידוע כקופקטור חיוני לקישור ה- aPL) או קופקטורים חלבוניים אחרים לבד, או על ידי יכולתם לעכב את מנגנון הקרישה בתבחיני קרישה התלויים בפוספוליפידים (LA=).

לא כל בני-האדם עם aPL יהיו תסמיניים. בסקר פרוספקטיבי של בנק הדם התגלה, שב- 6.5% מהאוכלוסייה הכללית אובחנו בתבחין ELISA נוגדנים מסוג IgP-aPL. לעתים קרובות, יורד כיל-ה- aPLלטווח התקין עם הזמן, ללא אירועים פקקתיים.

בחולים הלוקים ב- APS, דווח על ביטויים קליניים שונים, הכוללים סיבוכים המאטולוגיים, סיבוכים בעור, מחלת מסתמי הלב והיפגעות הכליות. בנוסף, דווח על ביטויים נירולוגיים שונים המערבים בעיקר את מערכת העצבים המרכזית. בסקירה זו, נדונים ההיבטים הנירולוגיים של תיסמונת הנוגדנים האנטיפוספוליפידיים.
 

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.

Folic Acid for Preventing Neural Tube Defects

Ziv Gil, Adi Aran, Orna Friedman, Liana Beni-Adani, Shlomo Constantini

Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheba; Division of Pediatric Neurosurgery, Dana Children's Hospital, Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv

Spina bifida and anencephaly are the most common, serious malformations in neural tube defects (NTD). Randomized trials in the last 2 decades have demonstrated that folic acid, 0.4 mg/d, reduces the incidence of NTD by more than 50%. We investigated the use of folic acid and multivitamins containing folic acid in childbearing women.

Of 221 women interviewed, 67 (30%) regularly took pills containing 0.4 mg folic acid. Women with higher educational levels were more likely to take multivitamins with folic acid than were the less educated (p=0.05). Of the women who took folic acid, only 5 (7.5%) used separate folic acid tablets, before and during their pregnancy. The rest used multivitamins containing folic acid. The 5 women who took folic acid separately were college-educated and nonreligious, and they took multivitamins in addition (p>0.05).

Of the women interviewed, 58 (26.2%) were Bedouin of the Negev. 24 (41.4%) of them took pills containing folic acid on a regular basis. This percentage is higher than that in the Jewish women in the study who took folic acid for prevention of NTD (17%; p=0.038).

Most of the women took folic acid after the first trimester. Only a minority took daily periconceptional folic acid. Multivitamins containing 0.4 mg of folic acid were more popular than folic acid tablets alone. This study emphasizes the need for continuing efforts to increase consumption of folic acid and awareness of its benefits among women of childbearing age.

Systemic Mastocytosis

K. Sade, I. Dotan, Y. Levo

Depts. of Pulmonary and Allergy Diseases and of Medicine T, Tel Aviv-Sourasky Medical Center

Mastocytosis has a highly variable clinical expression, and systemic mastocytosis is occasionally associated with a myeloproliferative or a myelodysplastic disorder. These patients often present without skin involvement and have a very poor prognosis. We report a 72-year-old man with this condition who had spells of flushing and dyspnea, myelo-fibrosis, and high serum and urine histamine levels.

Gastrointestinal Hemorrhage of Obscure Origin

Yoel Siegel, David Ergaz, Oscar Liphshitz, Felix Gottesfeld, Zev Sthoeger

Depts. of Medicine B and Surgery, and Gastroenterology Unit, Kaplan Medical Center, Rehovot (Associated with Hebrew University-Hadassah Medical School, Jerusalem)

Gastrointestinal bleeding of obscure origin consists of recurrent bouts of acute or chronic bleeding for which no definite source is discovered in routine endoscopic and barium contrast studies of the upper and lower gastrointestinal tracts. Usually its cause is angiodysplasia of the intestine, but many cases are due to tumors, mostly of the small bowel, which may be malignant.

In patients under the age of 50, the proportion with malignancy is relatively high (up to 14%) as compared to older patients. We describe a 45-year-old woman who suffered from gastrointestinal bleeding for 3 years. The cause of bleeding was not found despite extensive work-up.

In her last admission for acute gastrointestinal hemorrhage she was given a total of 30 units of blood. A tumor of the small intestine found by angiography was excised and found to be a stromal tumor of uncertain malignant potential. 1 year after operation she is asymptomatic without bleeding and her hemoglobin is stable without treatment.

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.

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.

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.

Physicians' Assessment of Computerized Prescribing

Daniela Zalman, Majed Odeh, Arie Oliven

Dept. of Internal Medicine B, Bnai Zion Medical Center, Technion Faculty of Medicine, Haifa

Prescription errors are a major source of preventable adverse drug events. Computerized prescribing (CP) which screens physicians' order for mistakes, drug-allergy, drug-disease, drug-laboratory and drug-drug interactions can prevent many of these errors and improve quality of care. However, computerized systems are often time-consuming, difficult to handle, and may create their own mistakes.

Following the introduction of CP on an internal medicine ward, we administered a questionnaire to evaluate physicians' opinions about the new system. The survey assessed computer literacy, ease of using CP, effects on time management, opinion of users regarding error prevention, and usefulness of the information provided. Opinions were generally favorable; most users felt that CP makes their work more accurate, reduces errors, is easy to learn and to use, and provides important and useful information. Physicians were most critical of equipment failure and drugs and dosages not included in the CP program, a result of rapid development of the system.

Errors resulting from the use of CP were considered minimal. Comparison of physicians, with and without previous experience with computer work, as well as local and foreign graduates, revealed minor differences. But once physicians learn to work with a well-organized CP system and computerized work stations, they appreciate the order, safety and knowledge they provide.

Presurgical Neuropsychological assessment in Epilepsy: The Wada Test

Fani Andelman, Miri Neufeld, Irith Reider-Groswasser, Uri Kremer, Yoram Segev, Itzhak Fried

Functional Neurosurgery and EEG and Epilepsy Units, Section of Neuroradiology; and Pediatric Neurology Unit; Tel Aviv-Sourasky Medical Center, Tel Aviv

37 candidates for epilepsy surgery underwent the intra-carotid amytal procedure (IAP; also known as the Wada test) to determine hemispheric speech dominance and memory capacity. 31 demonstrated left hemisphere speech dominance, 2 showed evidence for bilateral language and 4 demonstrated right hemispheric language dominance.

Our study supports a correlational relationship between handedness, lesion laterality and age of onset of seizures, as reported in earlier studies. Left-handed patients with a left hemisphere lesion whose seizures began to an early age had a strong tendency for reversed language dominance.

Asymmetry of at least 20% in performing the memory test was taken as the cutoff score for demonstrating laterality of lesions. The asymmetry score correctly predicted laterality of lesions in all 28 patients; 6 did not have asymmetry scores and 3 were examined for language only. None of the patients who successfully passed the Wada memory test had any significant postsurgical memory deficits; 1 had transient reduction in verbal memory and 4 who did not pass the test were not operated on for this reason.

Our results demonstrate the importance of the Wada test in determining cerebral speech dominance, in predicting post-surgical amnesia, and support its usefulness in predicting laterality of seizure focus in candidates for temporal lobectomy.

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%.

Patient Satisfaction and Hospital Services Evaluation by Regular and Private Patients

Sara Carmel, Jonathan Halevy

Dept. of the Sociology of Health, Faculty of Health Sciences, Ben-Gurion University of

the Negev, Beer Sheba; Sha'are Zedek Medical Center and Hebrew University-Hadassah Medical School, Jerusalem

"Sharap" is a private medical service integrated within our public clinic and hospital services. Clients may choose their physician by paying a fee in addition to what their health insurance agency (Kupat Holim) pays for. All other hospital services are supplied to all patients alike. The main purpose of this study was to evaluate the extent to which this declared policy is maintained in practice.

During 5 months in 1997, 198 Sharap patients and 198 regular patients were interviewed in the the general surgery, cardiac surgery, ENT, cardiology, newborn and gynecology wards of this hospital. Both groups were similar in regard to cause of hospitalization, gender, age group (10-year age ranges), and length of hospitalization (at least 24 hours).

Similar levels of satisfaction with hospitalization in general and with the nursing service and with supportive services were found in both groups. However, Sharap patients were more satisfied with their physicians than regular patients (87% vs 74%, respectively). Similar results were also found using indirect measures of satisfaction. About 86% in both groups reported having achieved the goal of improvement in health. A high proportion of respondents from both groups (82% and 88%, respectively) could not distinguish between Sharap and regular patients in the ward. However, a greater proportion of regular patients (35% vs 21%) wanted more extensive explanations from their physicians regarding their treatment.

Sharap patients belonged to higher socio-economic classes than regular patients. Our evaluation indicates that although the Sharap service enables the affluent to choose their preferred physician, resulting in a different doctor-patient relationship, the service does not create a significant feeling of discrimination among hospitalized patients, and does not interfere with the high level of health services available to the public at large.