Aggressive Surgical Treatment for Cholangiocarcinoma

M. Shimonov, P. Schecter, Y. Avni¹, E. Rabin², A. Rosen, A. Czerniak,

¹Department of Surgery A, Gastroenterology and ²Invasive-Radiology, Wolfson Medical

Center, Sackler Faculty of Medicine, Tel-Aviv University, Israel

Surgery remains the only curative approach to cholangiocarcinoma. Despite operative difficulties concerning tumor location, vascular involvement or hepatic invasion curative resection (i.e. achievement of tumor free margins) carries good survival rates and is associated with low morbidity and mortality. Our experience with 31 patients with cholangiocarcinoma operated during the years 1993-1999 is presented.

Twenty-five patients were found to have hilar cholangiocarcinoma, 3 carcinoma of mid-choledochus and 3 distal cholangiocarcinoma. All patients were evaluated by a diagnostic protocol including laparoscopy and laparoscopic ultrasound. Surgery consisted of local resection of the tumor with Roux en Y hepaticojejunostomy reconstruction. Three patients had concomitant hepatic resection for hilar cholangiocarcinoma while 3 patients had pancreaticoduodenectomy for distal cholangiocarcinoma. Adenocarcinoma was diagnosed in all patients. Curative resection was achieved in 19 patients and palliative resection (microscopically involved resected margins) in 12. One patient died at 60 days postop (3.5% mortality). Postoperative complications included cholangitis occuring in 10 patients who were referred with biliary drains, intraabdominal abscess (2 patients) and biliary leakage (1 patient) all treated conservatively.

Overall survival rate was 82% at one year, 73% at two years and 45% at 5 years. When comparing curative resection with palliative resection, survival rates were 92% versus 71% for 1 year, 72% versus 50% for 2 year and 57% versus 14% for 5 years.

Selection of patients using Laparoscopic Ultrasound combined with aggressive surgical approach enable curative or palliative resection 15 the only treatment modality which is significantly improved survival.

א' אבירם וא' וינברום

היח' להתעוררות והשהייה והמח' להרדמה וטיפול נמרץ, מרכז רפואי סוראסקי והפקולטה לרפואה סאקלר, אוניברסיטת תל-אביב

היתרון ההישרדותי של מערכת העצבים, הרגישה לנוכחות פגיעה ברקמות ומאפשרת החלמה על ידי הימנעות ממגע מכל גירוי חיצוני, הוא חזק וקיים במרביתם המכריע של זני בעלי-החיים. למרות שהאבולוציה שימרה מנגנון זה גם בבני-אדם, לא אובחנה הבעיה טמונה במנגנון זה במצבים של "פגיעה מבוקרת", כמו בניתוח. רגישות-היתר לכאב הקיימת לאחר ניתוח גורמת למערכת העצבים לאבד את יתרונה ההישרדותי לנוכח הרפואה המודרנית: כתוצאה מכך, על האחרונה לדכא מנגנון הגנה זה, הגורם לאי-נוחות, למצוקה ולכאב למיליוני חולים מדי שנה.

כאב בתר-ניתוחי מהווה חוויה רבת-גורמים, המערבת אותות תחושתיים מתמשכים המופקים מריקמה פגועה וממערכת העצבים המרכזית, שגמישותה ותפקידה המווסת עברו שינוי. באורח מיטבי, על החולים לחוות אי-נוחות מיקטית בתקופה התבר-ניתוחית המיידית, דבר שהוא אפשרי בכוח ורצוי בפועל. התהליך אמור לכלול טיפול מקדים (טרום-ניתוחי) בכאב וגם טיפול תוך-ניתוחי, ומניעת הכאב הבתר-ניתוחי באופן קבוע, כל זמן שקיים שידור עצבי לא-תקין מהפצע והריקמה הסובבת אותו. על השיטות לשיכוך כאב להיות מכוונות לשלושה אזורים: נקודת הנזק בהיקף, שטף המידע העצבי הזורם לכיוון מערכת העצבים המרכזית והתאים במערכת העצבים המרכזית עצמה.

Pleomorphic Carcinoma of the Lung Heralded as Bilateral Leg Pain

George Habib, Hanna Rawashdi, Jonathan Peleg, Walid Saliba

Depts. of Medicine B, Neurology and Radiology, Lady Davis Medical Center, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel

This is a case of a 70 year old male patient suffering from bilateral leg pain for 2 months. Physical examination disclosed clubbing. X-rays of the legs showed bilateral periosteal elevation with subperiosteal bone formation. ⁹⁹T^M-diphosphonate bone scan was negative. A search for malignancy revealed pleomorphic carcinoma of the right lung. Pain symptom disappeared 2 days after resection of the tumor. Repeated X-rays of the legs, three and a half months later showed no change and the clubbing persisted.

Hence, unexplained bilateral leg pain should raise suspicion of hypertrophic osteoarthropathy, and elicit a search for secondary disease especially lung tumor. It is interesting to point out the negative bone scan and the rapid resolution of patient symptoms after resection of the tumor.

מחמוד אבו-שקרה

היח' למחלות אוטואימוניות שיגרוניות, מרכז רפואי סורוקה ואוניברסיטת בן-גוריון, באר-שבע

בשנים האחרונות, בעבודות מרובות הודגם קשר בין ממאירות ותופעות אוטואימוניות ושיגרוניות. קשר זה הוא דו-כיווני. מחד גיסא, קיימת שכיחות יותר גבוהה של סך הממאירות בחולים עם דרמאטומיוזיטיס, פולימיוזיטיס וסקלרודרמה בהשוואה לכלל האוכלוסייה. כמו כן, בחולים עם דלקת מיפרקים שיגרונתית וחולי זאבת אדמנתית מערכתית, קיים סיכון מוגבר ללקות בממאירות המאטולוגית או לימפו-פרוליפרטיבית.

מאידך גיסא, מיגוון רחב של תופעות אימונולוגיות וביטויים שיגרוניים שונים יכולים להתרחש בחולים עם מחלקה ממארת. תופעות אלו יכולות להוות תוצאה של ייצור נוגדנים עצמיים, חדירה של ריקמה שאתית למיפרקים, תיסמונות פארא-ניאופלסטיות שונות, או ביטויים שיגרוניים מישניים לכימותרפיה.

בגיליון זה של "הרפואה" מדווחים חביב וחב' על חולה עם סרטן הריאה אשר הביטוי הראשוני למחלתו היה כאב בברכיים ותיסמונת אוסטואתרופתיה היפרטרופית.

בבמה זו, אסקור את המנגנונים והתופעות האוטואימוניות השונות בקרב חולים עם מחלה ממארת ואתייחס לתיסמונת אוסאוארתרופתיה היפרטרופית.

Aggressive Surgical Approach in Pancreatic Cancer - Is it Justified?

V. Catz-Snir, P. Schachter, M. Shimonov, Y. Avni, G. Gvirtz, A. Czerniak

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

Resection presents the only possible cure for pancreatic cancer. An aggressive surgical approach may extend the limits of resection and offer cure for more patients. 37 women and 28 men, mean age 67 years (range 33-84) with focal lesions underwent pancreatic resection (1993-1999). Cancer of the pancreatic head was found in 45, in the ampulla in 4 and in the body or tail in 16. There was a tumor larger than 5 cm in 9, vascular involvement in 8, and a combination of both in 6.

All were evaluated prior to exploration by standard imaging techniques and 44 by laparoscopic ultrasound. 42 underwent pancreatico-duodenectomy, 16 distal subtotal pancreatectomy and 3 local excision of an ampullary tumor. Benign lesions were found in 8 (focal pancreatitis in 4 and a serous cystic lesion in 4).

Curative resection (microscopically negative margins, negative lymph nodes) was achieved in 44. 2 died 1-2 months after operation of septic complications (2% operative mortality). The most frequent complication (in 8) was pancreatic fistula. Additional complications included anastomotic-line bleeding (3), intra-abdominal abscess (2), and 1 developed portal vein thrombosis (treated surgically).

1- and 2-year survival in those after curative pancreatic resection was 81% and 55% respectively. 2-year survival in those after palliative resection (positive resection margins or positive lymph nodes) was 50% and 11%, respectively.

After proper selection of those in whom it is possible to perform curative resection, regardless of size or vascular involvement, an aggressive surgical approach is justified.
 

אבי בן-הרוש(1), טלי זילברשטיין(2), מרדכי חלק(2), בוריס קפלן(1)

המח' לנשים ויולדות, מרכז רפואי רבין, קמפוס בילינסון, פתח תקווה(1), החטיבה למיילדות וגינקולוגיה, מרכז רפואי סורוקה, באר שבע(2)

בסוף שנות ה-60, הציגו Driscoll’O וחב', מדבלין, "חבילת" טיפול וניהול פעיל ללידה ראשונה. לבד מתמיכה פסיכולוגית ומעקב צמוד לאורך הלידה, הוכנסו מספר חידושים מהפכניים; פקיעה מלאכותית של קרומי השפיר (amniotomy) ומתן אוקסיטוצין במינונים גבוהים מוקדם בתהליך הלידה, שהוגבלה ל-12 שעות בלבד. מסקנתם היתה אז, ששיטה זאת יעילה למניעת לידה ממושכת. בניגוד לסברה שרווחה שהגבלת זמן הלידה תוביל לשיעור גבוה יותר של חיתוכי דופן (cesarean section), במהלך שנות ה-70 נמצא, שבעוד שברחבי העולם שיעור חיתוכי הדופן עולה והולך, הרי ששיעור זה נותר נמוך יחסית בדבלין. מאוחר יותר, דיווחה אותה הקבוצה מדבלין, כי למעשה ניהול פעיל הוא זה המוריד את שיעור חיתוכי הדופן. מאז, חלוקות הדעות בדבר יעילות שיטת ניהול לידה זאת והישגיה, לעומת ניהול לידה שמרני וברירני יותר. בסקירה זאת, נעמוד על הקשר שבין ניהול לידה פעיל לשיעור חיתוכי הדופן.

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. 
 

Prevention and Treatment of Procedural Pain in Pediatric Wards

R. Gorodischer, L. Herzog, E. Herzog

Depts. of Pediatrics A and Anesthesiology, Soroka University Medical Center; and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheba

Present knowledge and available pharmacological agents allow for adequate prevention and treatment of pain in children. We present guidelines we prepared for the prevention and treatment of procedural pain in children in our general pediatric ward. This followed extensive review of the literature, participation in scientific meetings, discussions with experts and consultation with interested clinicians. Successful implementation of the guidelines requires increased appreciation of the importance of pain prevention, participation of the nursing, as well as medical staff, and ability to evaluate pain in children of various ages.
 

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.

Nutritional Status and Vitamin B⁶ Supplementation in the Institutionalized Elderly

Felicia Stern, Yitshal N. Berner, Zeev Polyak, Sophya Bernadiner, Margarita Komarnitsky, Ben Ami Sela, Ram Doolman, Yoseph Dror

Institute of Biochemistry, Food Science, and Nutrition, Hebrew University of Jerusalem; Subacute Dept. and Clinical Nutrition, Hartzfeld Geriatric Hospital, Kaplan Medical Center, Gedera; and Institute of Chemical Pathology, Sheba Medical Center, Tel Hashomer

Nutritional status and vitamin B⁶ status were assessed in 18 men and 32 women, average age 84, living in a home for the aged. Average proportion of energy derived from protein was higher than the recommended; fiber intake was very low. Also low were intakes of calcium, magnesium, zinc, copper, vitamins D and E, thiamin, folic acid and vitamin B⁶.

Supplementation with vitamin B⁶ (10mg/d) for 28 days in those with the lowest B⁶ status assessed by B⁶ intake, activation coefficient of aspartate transaminase and plasma pyridoxamine concentrations led to improved B⁶ status (marked decrease in activation coefficient) and increased synthesis and decreased degradation of many short-lived neutrophil proteins. Though our elderly enjoy a variety of foods, some have marginal deficiencies that can be improved. Therefore, in the institutionalized elderly, micronutrient supplementation should be administered at a level low enough to be safe (below recommended upper level of intake) but high enough to be effective.

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.

Multiresistant Escherichia Coli from Elderly Patients

Ilana Slucky-Shraga, Moshe Wolk, Sofia Volis, Israel Vulikh, David Sompolinsky

Dept. of Medicine and Microbiology Laboratory, Mayanei Hayeshua Hospital, Bnei Brak; Central Laboratories, Ministry of Health, Jerusalem; and Faculty of Life Sciences, Bar Ilan University, Ramat Gan

We examined all ceftriaxone-resistant Escherichia coli isolates obtained from clinical samples during 16 months (1 Dec. '97 - 31 Mar. '99). A total of 97 resistant isolates from 36 patients were obtained, mostly from urine specimens. Of these patients, 35/36 were over 75 years old, most lived in nursing homes, were dependent on nursing in their daily lives, and were incontinent and/or had indwelling catheters.

All 97 isolates had similar susceptibility profiles: resistant to ciprofloxacin, gentamicin, ampicillin, amoxycillin/clavulanate, tricarcillin/clavulanate, aztreonam, and cefuroxime; decreased susceptibility to ceftazidime and cefepime; and susceptible to imipenem and meropenem. Double-disc tests indicated that all strains produced extended spectrum beta-lactamase(s). All the isolates belonged to 1 of 3 E. coli serotypes: 79 were 0153:H31, 13 were 0142:H10, and 5 were 0102:H6.

Diabetes and Premature Delivery: Etiology and Risk Factors 

Avi Beigelman, Arnon Wiznitzer, Ilana Shoham-Vardi, Hilel Vardi, Gershon Holtcberg, Moshe Mazor

Depts. of Obstetrics and Gynecology and of Epidemiology and Health Services Evaluation, Soroka Medical Center and Faculty of Health Science, Ben-Gurion University of the Negev, Beer Sheba

Preterm birth is the leading cause of perinatal morbidity and mortality, while preterm labor and delivery in diabetes mellitus (DM) carries an increased risk of perinatal complications. We investigated the hypothesis that DM (gestational and pregestational) is an independent risk factor for preterm birth and evaluated the hypothesis that the risk factors for preterm birth in diabetics are different from those in non-diabetics.

The study population consisted of all singleton deliveries at this hospital between 1990-1997. Excluded were those of mothers who had not had prenatal care, or who had only partial care or multiple gestations. There were 3 subgroups: 834 women with pregestational DM, 3,841 with gestational DM, and 66,253 non-diabetics.

The combined spontaneous and induced preterm delivery rate was determined in each subgroup. Potential risk factors for spontaneous preterm deliveries were assessed by a univariate model. A logistic regression model was used to assess the unique contribution of DM (gestational and pregestational) to preterm delivery in the presence of the other risk factors, and to compare risk factors for preterm delivery between subgroups.

The prevalence of spontaneous preterm delivery was: 7.1% in non-diabetics, 10.0% in those with gestational DM and 25.5% in those with pregestational DM. When adjusted by a multivariate model for other risk factors for preterm delivery, DM still remained an independent risk factor for spontaneous preterm delivery (gestational DM: odds ratio 1.28, 95% CI: 1.1-1.48; pregestational diabetes: odds ratio 3.4, 95% CI: 2.65-4.36).

The main difference in risk factors for preterm birth between the 3 subgroups was the amount of amniotic fluid. Polyhydramnios was an independent risk factor for preterm delivery in non-diabetics and in pregestational DM, but not in gestational DM. On the other hand, oligohydramnios was associated with a higher risk for preterm delivery only in gestational DM compared to non-diabetics.

DM (gestational and pregestational) is an independent risk factor for spontaneous preterm delivery. Polyhydramnios is an independent risk factor for preterm delivery in pregestational but not in gestational DM. Oligohydramnios is a greater risk factor for preterm delivery in gestational DM compared to non-diabetics.

New Psychopharmacological Approaches in Mental Health as Applied by the Israel Defense Forces

Moshe Zvi Abramowitz, M. Shmushkevich, Avraham Weizman, Mordechai Mark

Mental Health Department, Medical Corps, Israel Defense Forces; Sackler Faculty of Medicine, Tel Aviv University; Jerusalem Mental Health Center; and Geha Psychiatric Hospital

In the past decade there have been far-reaching developments in psychopharmacology. Previously, only a few classes of medication were at the disposal of psychiatrists, as many had serious side effects that limited their use. Now our psychopharmacological armamentarium has grown considerably, allowing for greater choice of treatment in the military.

We review these developments, and discuss the special considerations to be taken into account when treating soldiers with psychiatric medication. We discuss suitable medication for ongoing outpatient treatment, as well as the standard list of medication currently used by units deployed in the field.

Advances in psychopharmacologic treatment should enable more soldiers to serve safely in the military with fewer restrictions on their duties.

Israel Naval Medical Institute: 20 Years of Applied Research, and Future Goals 

Ran Arieli, Avi Shupak

Israel Naval Medical Institute, Medical Corps, Israel Defense Forces

The Israel Naval Medical Institute (INMI) is unique as a research center located in a naval base and having close inter-relations with naval underwater units. It is ideal for applied research, and for mutual exchange of needs and of ideas and instructions.

Factors making this institute so suitable for applied research include: direct personal communication with combat divers, professional naval divers, submariners, civilian recreational divers and professional civilian divers, as well as naval vessel crews prone to seasickness; hyperbaric oxygen therapy is administered in cooperation with a large neighboring hospital.

Close spatial and personal relations with an academic institution (the Technion, with its Faculties of Medicine, Biology and Biophysics) provide a basis for cooperative research which expands research capabilities, and allows access to extensive expertise, instrumentation and equipment. Close ties with physicians who served at the INMI in the past also bring them into this research community.

During their specialization, physicians may spend up to 6 months working with us on a research project. Undergraduate, graduate and post-graduate students may complete their research at our institute with the agreement of their parent academic institutions.

Much of the research can be released to the international community. However, some is classified, serves only internal needs or is not of public interest. The number of published papers has stabilized since 1991 at about 16 a year.

Studies of gas exchange and oxygen toxicity originate mainly in the Hyperbaric Research Unit, research on motion sickness in the Motion Sickness and Human Performance Laboratory, and work on hyperbaric and diving medicine in the Clinical Section of the INMI.