מנחם בן-חיים

הפער בין מספר הילדים הנזקקים להשתלת כבד לבין היצע שתלי כבד בגודל מתאים גדל והולך, וגורם להארכת זמן ההמתנה, ובעקבות זאת לעלייה בשיעורי התחלואה והתמותה בזמן ההמתנה. בעשור האחרון פותחו שיטות להשתלת שתלים חלקיים (segmental), שמקורם בהקטנת כבד מלא (reduced size), בפיצול כבד מלא בין שני מקבלים, בדרך-כלל מבוגר וילד (split liver transplantation) או בחלקי כבד שמקורם בתורם חי (living donor liver transplantation). אולם יישום שיטות אלו עדיין מוגבל ומתבצע במספר מרכזים רפואיים מובילים בעולם. מובאות במאמר זה תוצאות המרכז הרפואי "הר-סיני" בהשתלות מסוג זה.

מתוך 195 השתלות כבד בילדים (גיל<18), 48 (25%) היו מתורם חי, וב-47 (24%) מהם הושתל חלק שמקורו בהקטנה (27=n) או בפיצול (20=n) של כבד מתורם מת (מוות מוחי). בוצעה השוואה רטרוספקטיבית בין שתי קבוצות אלו מבחינת מאפייני המושתלים, שיעורי הסיבוכים מהניתוח, והישרדות השתל והחולה. להשתלות מפיצול נבחרו כבדים מתורמים מיטביים, והפיצול או ההקטנה בוצעו בדרך-כלל לאחר ניתוח תקציר (ex-vivo), תוך שימור הווריד החלול התחתון עם אונת הכבד הימנית והגבעול הוואסקולרי (vascular pedicle) עם החלק הימני. ההשתלה בוצעה תוך השקת וריד הכבד לגדם וריד הכבד התואם (piggy-back). במרבית ההשתלות מתורם חי בוצעה השקת עורק הכבד השמאלי בסיוע מיקרוסקופ. במרבית ההשתלות בוצע חיבור צינור (או צינורות) המרה ללולאת מעי (hepatico-jejunostomy).

הגיל והמשקל הממוצעים בקרב המושתלים מתורם חי היו 1.8+-3 שנים ו- 8.1+-9 ק"ג לעומת 3.5+-4 שנים ו- 15.2+-14.5 ק"ג בקבוצה המקבילה. התפלגות האטיולוגיות לאי-ספיקת כבד בחולים במצב סופני היתה דומה, וכך גם חומרת מחלת הכבד לפני ההשתלה. יותר כבדים (6 לעומת 1) שמקורם מתורם מת נוצלו להשתלה נשנית דחופה. זמן האיסכמיה החמה היה דומה (43 דקות לעומת 45 דקות), וזמן האיסכמיה הקרה היה ארוך משמעותית בהשתלות מתורם מת (340 דקות לעומת 60 דקות). שיעור הסיבוכים הוואסקולריים ובמרה היה דומה בשתי הקבוצות. שיעור תיפקוד מוקדם ירוד של השתל (poor early graft function ) היה גבוה משמעותית לאחר השתלות מתורם מת (18% לעומת 2%, בהתאמה, p<0.005). הישרדות השתלים והמושתלים היתה טובה יותר בין מקבלי שתל מתורם חי: הישרדות שתל בשיור של 89% לאחר שנה ו-77% לאחר 5 שנים לעומת 59% ו-52%, בהתאמה. שיעור הישרדות החולים היה 91% כעבור שנה ו-89% שנה לאחר 5 שנים לעומת 70% ו-62%, בהתאמה, p<0.001.

לסיכום, למרות הדמיון במורכבות הניתוח, השתלות כבד מתורם חי המבוצעות בילדים מניבות תוצאות טובות יותר על-פני אלה המושגות בהשתלת חלקי כבד דומים שמקורם בתורם מת.

מנחם בן חיים

המצוקה הקשה במצאי שתלי כבד מתורמים לאחר מוות מוחי, העלייה בשיעור התמותה בזמן ההמתנה להשתלה והניסיון המצטבר בהשתלות כבד מתורם חי בילדים – כל אלה מצביעים על השתלות מתורם חי (living donor) בין בוגרים כחלופה המתבקשת. במאמר זה מובאות התוצאות של עשרים ההשתלות הראשונות מסוג זה במרכז הרפואי "הר סיני", תוך השוואה בין שתלי אונה ימנית לשתלי אונה שמאלית.

עשרים בוגרים (גיל ממוצע 15+-46 שנה; משקל ממוצע 12+-68 ק"ג) עברו השתלת כבד; בעשרה חולים הושתל שתל מאונה שמאלית (מיקטעים II, III, IV, במשקל ממוצע של 115+-805 ג').

התורמים (גיל ממוצע 10+-38 שנה, משקל ממוצע 9+-85 ק"ג) היו קרובי משפחה מדרגה ראשונה (8), שניה (3) בני זוג (4) או מקורבים רגשית (5). כריתת הכבד החלקית בתורמים בוצעה ללא חסימה של אספקת הדם (inflow occlusion), תוך הסתייעות במספרי על שמע (ultrasonic scissors) ומיחזור דם (cell saver). כריתת הכבד השלמה במושתלים בוצעה בחדר ניתוח צמוד ובתיאום זמנים. ההשתלה בוצעה תוך השקה ורידית לגדמים של ורידי הכבד (piggy-back). בשמונה מושתלים (אונה שמאלית) נדרשה הסתייעות במיקרוסקופ לביצוע ההשקה העורקית. בשתלי אונה שמאלית נדרש חיבור בין צינוריות המרה למעי (hepatico-enterostomy) עם מיקטע IV יחיד, זאת לעומת הצורך בהשקה לשתיים (בשמונה חולים) או לשלוש (בשני חולים) צינוריות מרה בשתלי אונה ימנית.

כל התורמים החלימו, ללא סיבוכים משמעותיים, ללא צורך בעירוי-דם זר וללא סימנים של אי-ספיקת כבד. שיעור התמותה הסב-ניתוחי בקרב המושתלים היה 15%, ושיעור הישרדות השתל (graft survival) – (70%-80% בשתלי אונה ימנית לעומת 60% בשתלי אונה שמאלית; זמן מעקב ממוצע – 8 חודשים). תיסמונת ייחודית (small for size syndrome) ניצפתה בארבעה מושתלים בשתלי אונה שמאלית קטנים יחסית [יחס בין משקל: שתל=מושתל (GRWR) < 0.8%].

שיעור הסיבוכים בקרב מושתלי אונה שמאלית היה גבוה יותר: דלף מרה (billary leak) היה 50% לעומת 20%, ופקקת עורק הכבד (hepatic artery thrombosis) היתה 20% לעומת 10%.

בהשתלת כבד מתורם חי בין בוגרים, מאפשרים שתלי אונה ימנית התאמת גודל מיטבית וכרוכים בפחות סיבוכים, כל זאת מבלי לפגוע בבריאותו של התורם.

אורן שבולת, רפעת ספדי, יפה אשור, אחמד עיד וירון אילן

סיבוכים עצביים בעקבות השתלת כבד מתרחשים בשכיחות גבוהה – ב-30%-90% מהמושתלים. סיבוכים אלה מייצגים מיגוון רחב של אטיולוגיות ומציבים לעתים בעיה איבחונית. סיבוכים עצביים יכולים להוות ביטוי למחלת כבד ראשונית שבעטיה עבר החולה השתלת כבד, או לנבוע ממיגוון רחב של הפרעות בחילוף- החומרים או בכלי-הדם. הטיפול מדכא החיסיון הניתן למושתלי כבד יכול אף הוא לגרום להפרעות עצביות, אם באופן ישיר כהשפעת-לוואי תרופתית ואם באופן עקיף בעקבות דיכוי חיסוני וזיהומים מזדמנים של מערכת העצבים המרכזית. במאמר זה יובאו שתי פרשות חולים לא שיגרתיות של סיבוכים נירולוגיים לאחר השתלת כבד.

Secondary Bone Grafting in Cleft Lip and Palate

M. Peled, D. Aisenbud, D. Goldstein, A. Rachmiel, D. Laufer

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

Results of reconstruction of residual alveolar bone defects in 52 patients operated between 1990-1998 were evaluated clinically and radiographically in a retrospective study.

Ages ranged between 9-37; 30 were males. The donor site of bone grafts in all was particulate cancellous marrow from the anterior iliac crest. 32 had unilateral clefts and 20 bilateral. Total cleft sites treated was 72.

Best results were achieved when bone grafting was carried out prior to the eruption of the canine tooth. The cleft space was closed and oro-nasal fistulas were eliminated in 42 (80%). Success rates in unilateral and bilateral cases were significantly different.

Penile Prosthesis for Erectile Dysfunction: Long-Term Follow-Up 

Ofer N. Gofrit, Ofer Z. Shenfeld, Ran Katz, Amos Shapiro, Ezekiel H. Landau, Dov Pode

Urology Dept., Hadassah University Hospital, Jerusalem

Our armamentarium for the treatment of erectile dysfunction has recently been expanded by addition of Viagra and the MUSE. However, their long-term results are still unknown. The insertion of a penile prosthesis is invasive, expensive, and irreversible, but under optimal condition provides an acceptable, definitive solution for erectile dysfunction. We evaluated our long-term results with penile prosthesis insertion (PPI).

From 1987-1998, 57 patients underwent PPI in our department. Mean age was 55 years and the common causes of erectile dysfunction were atherosclerotic disease (23), radical pelvic surgery (15), and diabetes mellitus (14). Semirigid prostheses were inserted in 12 and inflatable prostheses in 45, including 42 single-component and 3 multi-component prostheses.

Recently we interviewed these patients by telephone, using a standard questionnaire. Those not satisfied with the surgical results (83% of the living patients) were examined in our clinic. Mean follow-up was 53 months. In 37 (84%) the prosthesis was mechanically functional (rates after 1, 5 and 10 years were 87.8%, 80%, and 75%, respectively). In only 2 (2.5%) had serious complications led to prosthesis removal.

All mechanical failures had occurred in those with inflatable prostheses after a mean of 48.5 months (range 4-113). At the time of the survey 68% were sexually active and 64% were satisfied with the surgical result. We conclude that PPI is safe treatment for erectile dysfunction. Although the rate of mechanically functioning prostheses decreases with time, modern multi-component prostheses may lead to better mechanical results.

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.

Experience with 100 Liver Transplant Recipients 

Ezra Shaharabani, Ziv Ben-Ari, Nathan Bar-Nathan, Alex Yusim, Rivka Shapira, Ran Tur-Kaspa, Zaki Shapira, Eytan Mor

Transplantation Dept., Liver Institute, Rabin Medical Center; and Pediatric Gastroenterology Institute, Schneider Children's Medical Center, Petah Tikva

Liver transplantation is the treatment of choice for end- stage liver disease. During the past 8 years we performed 102 liver transplants in 84 adults and 16 children. In the adults, 9 were combined transplants: 1 a liver-pancreas transplant for type I diabetes, and 8 liver-kidney transplants. In the children, transplants included 5 whole-livers, 5 left-lateral liver segments from living-related donors, 4 reduced-grafts of right or left lobes, and 2 split left-lateral segments.

At a mean follow-up of 31 months (range 1-96) 70 were alive, 3 had died during surgery and 15 during the first postoperative months. Mortality was due to primary graft non-function (7), sepsis (10), intracranial hemorrhage (1), tumors (4), recurrent hepatitis B (2), biliary strictures (2) and chronic rejection (1). The 1- and 4-year survival rates were 79.5% and 69.6%, respectively.

After transplantation, 10 developed biliary stricture (5 corrected by balloon dilatation) and 8 anastomotic stricture (7 corrected by surgery), and there were 2 multiple intra-hepatic strictures. There was hepatic artery thrombosis in 5, including 4 children. In 3, grafts were salvaged by thrombectomy and 2 others underwent re-transplantation. In those who survived transplantation by more than 1-month, recurrent hepatitis B was seen in 6 of 17 (35%) and recurrent hepatitis C in 12 of 19 (63%).

Thus, results of our first 100 liver transplants are similar to those reported by larger centers, showing that in an appropriate setting good results can be achieved by small transplant programs.

Non-Penetrating Deep Sclerectomy without Collagen Implantfor Glaucoma

Ben Zion Silverstone, Isaac Aizenman, Carmit Landau, Yaacov Rozenman

Ophthalmology Dept., Shaare Zedek Medical Center, Jerusalem

Deep sclerectomy (DS) can be used in glaucoma with increased intraocular pressure when medical treatment fails. It involves removing part of the ocular drainage apparatus. Resistance to intraocular fluid drainage is decreased, improving drainage and decreasing intraocular pressure. By avoiding anterior chamber penetration, DS diminishes frequency of the complications of filtering surgery.

24 eyes of 23 patients underwent DS for primary or secondary open angle glaucoma with elevated intraocular pressure not controlled medically. It included preparation of a 4.0 x 4.0 mm limbal-based external scleral flap, dissecting and removing most of an internal scleral flap (leaving it 1 mm smaller than the external flap), unroofing Schlemm's canal and removing fine endothelial tissue lining its inner walls. The external scleral flap was then repositioned and sutured. Collagen implants were not used. In some cases DS was combined with extracapsular cataract extraction and intra-ocular lens implantation.

Mean intraocular pressure decreased from 24.8‏3.9 mmHg initially to 12.8‏4.4 mmHg 6 months after operation (p<0.0001). There was no difference in postoperative intra-ocular pressure between DS as a single procedure or as part of a combined operation. Comations were mild and of short duration.

If long-term follow-up shows that lowered intraocular pressures are maintained, DS should be a surgical option in earlier stages of glaucoma.

EBV-Related Post-Transplantation Lymphoproliferative Disorder

D. Doron, O. Papo, O. Portnoy, E. Granot

Depts. of Pediatrics, Pathology, and Radiology, Hadassah University Hospital, Jerusalem

We describe a 4.5-year-old girl in whom post transplantation lymphoproliferative disorder was diagnosed 1 year after liver transplantation. She ran a complicated course with multiple organ involvement: respiratory failure which required mechanical ventilation, renal failure, bone marrow depression and severe protein-losing enteropathy.

Laparoscopic Donor Nephrectomy: Initial Experience

Amir Szold, Joseph M. Klausner, Richard Nakache

Advanced Endoscopic Surgery Unit, Transplantation Unit and Depts. of Surgery B-C, Tel Aviv-Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University

We present our initial experience in laparoscopic nephrectomy. 6 patients were operated for a kidney donation and 2 for treatment of a benign disease. All procedures were completed successfully, with no conversion to laparotomy or intra-operative complications. Mean operating time was 210 minutes, and in the donor kidneys the mean warm-ischemic time was 165 seconds. There were 3 postoperative complications, and mean hospitalization was 3.5 days. The transplanted kidneys are all functioning.

From our initial experience, laparoscopic nephrectomy appears to be both feasible and safe. Its implementation requires a combined team with experience in donor surgery and advanced laparoscopic skills. The procedure may increase the availability of living donor kidneys, due to the smaller impact on the donor compared to conventional donor nephrectomy.

Preliminary Report of Experience with Laparoscopic Splenectomy

Joseph Kuriansky, Ron Bilik, Moshe Shabtai, Itamar Avigad, Amram Ayalon

Depts. of General Surgery and Transplantation and Pediatric Surgery, Sheba Medical Center, Tel Hashomer; and Sackler School of Medicine, Tel Aviv University

Laparoscopic splenectomy is effective and technically feasible for treating various hematological diseases such as idiopathic thrombocytopenic purpura (ITP), congenital sphero„cytosis, hemolytic anemia, and Hodgkin's lymphoma. An anterior approach to the vascular pedicle is usually described. However, in this approach to the splenic hilum, the dissection of the splenic artery is frequently difficult. The laparoscopic posterolateral approach involves dissection of the posterolateral attachments to the diaphragm, followed by the disection and ligation of all splenic branches near the splenic parenchyma. We used it in 9 adults and 4 children: 11 patients had ITP, 1 spherocytosis and 1 Hodgkin's lymphoma.

This procedure was completed in 13 patients, but in 2 it had to be converted to open surgery. Mean operating time was 3 hours and mean postoperative stay 3 days. Blood transfusion was not required and there were no postoperative complications.

Laparoscopic splenectomy is safe in both adults and children, and the posterolateral approach provides excellent visualization and allows control of the branches of the splenic vein and artery in the splenic hilum.

Intestinal Transplantation: World Experience and Future Perspective

Eytan Mor, Moshe Rubin, Yaron Niv

Depts. of Transplantation, Surgery B and Gastroenterology Institute, Rabin Medical Center, Beilinson Campus, Petah Tikva

Intestinal transplantation, which until recently has been considered an experimental procedure, is now undergoing considerable change and becoming a standard treatment for patient with intestinal failure. The major improvement in results is due to the introduction of new immunosuppressive agents that have led to significant reduction in acute rejection. Nevertheless, reduction in severe infectious complications, which are the main cause of mortality after transplant, as well as improved techniques for early diagnosis of rejection are needed before intestinal transplantation can be widely used.

We describe our experience in post-transplant follow-up of a woman, aged 32-years, who had undergone intestinal transplantation for short bowel syndrome after extensive bowel resection.

Willingness to Donate Organs: Attitude Survey among Israeli Jews

Peri Kedem-Friedrich, Rina Rachmani

Psychology Dept., Bar-Ilan University, Ramat Gan and Information and Education Unit, Israel Transplant Center

A public opinion survey of Israeli Jewish adults (September) showed a large potential willingness to donate organs after death, while only a third of the sample was opposed. Nevertheless, only a very minor proportion held donor's cards, and over half expressed opposition to holding a donor card. As to next-of-kin's organs, when the wishes of the relative were not known, a quarter of the sample opposed, a quarter agreed, and the remaining half hesitated to make a decision.

Willingness to donate was not correlated with gender, age or income, but was related to religiosity: the more religious, the less willing to donate. And the religious reason was the salient one given for hesitation about donating, although there were many who could give no reason for their hesitation. Family members, doctors and rabbis (in ascending order) influenced willingness to consent to next-of-kin donations.

Emergency Stenting for Acute Left Main Coronary Artery Closure during Cardiac Catheterization

Alberto Hendler, Oren Agranat

Catheterization Laboratory, Rama Marpeh Hospital, Petah Tikva

We report a case of acute closure of the left main coronary artery, a rare complication of diagnostic cardiac catheterization, treated by emergency stenting prior to aorto-coronary by-pass surgery. We suggest encroachment of the Judkins catheter into a calcified left main ostium, with dissection and acute thrombosis of this segment, as the possible mechanism.

Clinically, the patient's condition deteriorated to cardiogenic shock and loss of consciousness. Remarkably, there was no angiographic evidence of significant left main coronary artery disease, besides the presence of calcification in the proximal part of the left coronary system and ventricularization of coronary pressure at the time of engagement. We chose to slide quickly the angioplasty guidewire through the left main coronary artery, which allowed prompt mechanical recanalization and rapid restoration of coronary flow, with dramatic clinical and hemodynamic improvement. This relatively simple procedure allowed stenting the left main artery after brief predilation, and the patient came to by-pass surgery in excellent condition. The rationale for surgery in this case was the need for complete coronary revascularization because of significant 3-vessel coronary artery disease.

Living-Related Liver Transplantation

N. Bar-Nathan, Z. Shapira, E. Shaharabani, A. Yussim, Y. Ben-Ari, T. Sheinfeld, I. Zehavi, R. Shapira, G. Dinari, Z. Ben-Ari, R. Tur-Kaspa, E. Mor

Dept. of Transplantation and Liver Institute, Rabin Medical Center (Beilinson Campus), and Pediatric Intensive Care and Pediatric Gastroenterology Units, Schneider Children's Medical Center, Petah Tikva

Our experience with living-related liver transplantation is described. In 2 boys and 1 girl, aged 4-4.5 years with acute, fulminating hepatitis A, the presence of very severe jaundice (bilirubin levels > 18 mg%) associated with severe coagulopathy (INR>10) and encephalopathy indicated the need for urgent liver transplantation. In all 3 cases the left lateral hepatic segment of a matched blood type parent was transplanted. None of the donors suffered a serious complication postoperatively and all returned to full activity in 6-16 weeks. The post-transplantation course was uneventful in 1 child, but in the other 2 there was hepatic arterial thrombosis in 1 at 1 day and in the other at 8 days post-transplantation. Early detection of arterial thrombosis by Doppler sonography permitted salvage of the 2 hepatic grafts after thrombectomy and re-anastomosis. In 1 of these 2 children an anastomotic biliary stricture was found 2 months after transplantation. It was corrected at surgery and a percutaneous stent was inserted. All 3 children are alive with normal graft function at 2, 7 and 8 months post-transplantation, respectively. This initial experience indicates that living-related liver transplantation is feasible in Israel. The technique might help to solve our severe organ shortage for children awaiting liver transplantation.