can we see the tumor?

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Vol. 9, No. 4 2005 Abstracts 565 150 IMPACT OF REPEATED STEROID PULSE THERAPIES ON OUTCOME IN HCV-POSITIVE PATIENTS AFTER OLT Jan M. Langrehr, MD, PhD, Marcus Bahra, MD, Ulf P. Neumann, MD, PhD, Peter J. Neuhaus, MD, PhD, Charite Virchow Clinic, Berlin, Germany The optimal immunosuppressive regimen for HCV-positive liver transplant recipients has not been established. Treatment for acute rejection with steroids is associated with increased viral replication and graft hepatitis. We retrospectively analyzed 232 patients after orthotopic liver transplantation (OLT) for HCV cirrhosis to de- termine the influence of methylprednisolon pulse therapy on long-term outcome after OLT. Two hundred thirty-two liver transplants in HCV recipients between 1989 and 2001 were analyzed. Median follow-up was 4.4 years, and median age of patients was 53 years (15–72 years). Immunsuppression consisted of tacrolimus (Tac) or cyclosporine A (CyA) in different protocols. All rejection episodes were histologically proven. Of 232 graft losses, 28 occurred due to severe hepatitis C reinfection (12.06%); 105 of 232 patients showed a minimum of one episode of acute rejection (45.25%); 71 of 86 patients received methylprednisolon pulse therapy for one time (82.55%); 15 of 86 required treatment with OKT3 for steroid-resistant rejection (17.44%); and 19 of 232 patients required repeated steroid pulse therapy due to more than one episode of acute rejection (8.1%). In patients with more than one episode of acute rejection, the risk of HCV-related graft loss was significantly enhanced (6/19, P 0.017). The primary immunosuppresion had no influence of the outcome in our data. Our data show that outcome of HCV-positive patients with repeated steroid pulse therapy for acute rejection is significantly worse compared to patients with single pulse therapy. Therefore, repeated steroid pulse therapies should be avoided in HCV-positive transplant recipients. New strategies in managing acute rejection in these patients are required. 151 A PROSPECTIVE RANDOMIZED TRIAL COMPARING TACROLIMUS AND MMF VERSUS TACROLIMUS AND STEROIDS AS PRIMARY IMMUNOSUPPRESSION FOR HCV-RELATED LIVER TRANSPLANTATION Jan M. Langrehr, MD, PhD, Martina Mogl, MD, Ulf P. Neumann, MD, PhD, Jochen Klupp, MD, PhD, Peter J. Neuhaus, MD, PhD, Charite Virchow Clinic, Berlin, Germany End-stage hepatitis C virus (HCV) infection is a frequent indication for orthotopic liver transplantation (OLT). Recurrence of HCV is almost universal, and up to 30% of the patients will develop severe graft hepatitis and cirrhosis again after OLT. HCV genotype and steroid administration after OLT are known to play a major role in the severity of reinfection. The aim of the study was to examine whether a steroid-free immunosuppressive induction regimen is safe and possibly beneficial for the course of recurrent hepatitis and outcome. In a prospective analysis 59 consecutive patients with end-stage HCV hepatitis were randomly assigned to receive either tacrolimus (Tac)/mycophenolate mofetil (MMF) or tacrolimus/pre- dnisolone (Pred). The groups consisted of 29 and 30 patients, respec- tively. Follow-up ranged from 14 to 60 months. The 1-year patient survival was 89.7% in the Tac/MMF-group compared to 83.3% with 5 of 30 in the Tac/Pred-group. The 1-year graft survival was 79.3% in the Tac/MMF-group and 83.3% in the Tac/Pred-group. The inci- dence of rejection was 31% in the Tac/MMF-group suffered from an episode of acute rejection (31%), whereas 6 of 30 patients in the Tac/Pred-group and 20% in the Tac/Pred-group (not statistically different). However, two of the patients in the Tac/Pred-group had a steroid-resistent rejection with the need for OKT3-therapy. Viral load after two months was significantly lower for patients in the Tac/ MMF-group (P 0.004). Biopsy-proofen necroinflammatory activity and graft fibrosis after 1 year were similar in both groups as well as the incidence for re-transplantation or death because of severe recurrence of hepatitis (2 patients in the Tac/MMF-group and 3 patients in the Tac/Pred-group). Our data demonstrate that a steroid- free immunosuppressive induction protocol with Tac/MMF after OLT for HCV is safe and effective, reaching a similar risk for rejection compared to treatment with Tac/Pred. Biopsy-proven reinfection as well as HCV-related graft loss were equally low in both groups. The lower viral load after 2 months in the Tac/MMF-group indicates a milder course of reinfection and favours immunosuppression with MMF. However, longer follow-up is needed to show a beneficial effect of a steroid free immunosuppressive protocol on the course of recurrent HCV after OLT. 152 LIVING RELATED LIVER TRANSPLANTATION IN PEDIATRIC AGE GROUP: EARLY TWO CENTERS’ EXPERIENCE Ibrahim K. Marwan, MD, H. Gad, E. Hamad, T. Ibrahim, A. Shawky, H. Saafan, Ml Osman, B. Hegab, Hl Konsowa, Ml Khalil, Alaa Hamza, Ml Elmeteny, National Liver Institue, Cairo, Egypt Living related liver transplantation (LRLT) is known to be an estab- lished acceptable therapeutic modality for end stage liver diseases, especially for children when cadaveric liver transplantation is not available. We present the early experience of pediatric LRLT in two centers in Egypatient Twenty-three cases of pediatric LRLT were done from October 2001 through March 2004. There were 12 girls and 11 boys with an age range from 9 months to 15 years with a mean of 7.3 years. The body weight of the recipients ranged from 7.8 to 45 kg with a mean of 22.5 kg. All recipients received left-lateral segment, extended left-lateral segment, or left lobe grafts. The donors were 21 parents (15 mother and 6 fathers), one sister, and one unrelated with mean body weight of 72.5 kg. The pretransplant primary dis- eases were biliary atresia in 6 patients, Budd-Chiari in 4 cases, meta- bolic liver disease in 3 cases, Byler’s disease in 2 cases, congenital hepatic fibrosis in 2 cases, and cryptogenic cirrhosis in 2 patients. The remaining four patients were hepatblastoma in one case, a case of fulminant hepatitis, one case of primary sclerosing cholangitis, and a case of autoimmune hepatitis. There was no donor mortality. Chest infection and wound seroma were observed in 2 donors, pleural effu- sion in two, and bile leak in one, which was treated successfully by endoscopic stinting. Recipients’ postoperative morbidity was observed in the form of biliary leakage in two, burst abdomen in one, hematem- esis in one, and chest infection in four cases. There was no operative mortality in recipients. Four recipients died postoperatively on days 20, 23, 92, and 127, with survival of 82.6%. Pediatric LRLT is a potentially safe procedure, especially in centers where there is no cadaveric liver transplantation. The initial results are encouraging and that progress in this field is remarkable, especially for children. 153 CAN WE SEE THE TUMOR? Dmitriy A. Nikitin, MD, Burckhardt H. Ringe, MD, Drexel University College of Medicine, Philadelphia, PA It is a well-known fact that many of the patients on the waiting list for liver transplantation also have liver tumors. In fact, patients with Stage II HCC may receive extra priority on the waiting list. For this

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Page 1: Can we see the tumor?

Vol. 9, No. 42005 Abstracts 565

150

IMPACT OF REPEATED STEROID PULSE THERAPIESON OUTCOME IN HCV-POSITIVE PATIENTS AFTEROLTJan M. Langrehr, MD, PhD, Marcus Bahra, MD, Ulf P. Neumann,MD, PhD, Peter J. Neuhaus, MD, PhD, Charite Virchow Clinic,Berlin, Germany

The optimal immunosuppressive regimen for HCV-positive livertransplant recipients has not been established. Treatment for acuterejection with steroids is associated with increased viral replicationand graft hepatitis. We retrospectively analyzed 232 patients afterorthotopic liver transplantation (OLT) for HCV cirrhosis to de-termine the influenceofmethylprednisolonpulse therapyon long-termoutcome after OLT. Two hundred thirty-two liver transplants inHCV recipients between 1989 and 2001 were analyzed. Medianfollow-up was 4.4 years, and median age of patients was 53 years(15–72 years). Immunsuppression consisted of tacrolimus (Tac) orcyclosporine A (CyA) in different protocols. All rejection episodeswere histologically proven. Of 232 graft losses, 28 occurred due tosevere hepatitis C reinfection (12.06%); 105 of 232 patients showeda minimum of one episode of acute rejection (45.25%); 71 of 86patients received methylprednisolon pulse therapy for one time(82.55%); 15 of 86 required treatment withOKT3 for steroid-resistantrejection (17.44%); and 19 of 232 patients required repeated steroidpulse therapy due to more than one episode of acute rejection (8.1%).In patients with more than one episode of acute rejection, the risk ofHCV-related graft loss was significantly enhanced (6/19, P � 0.017).The primary immunosuppresion had no influence of the outcome inour data. Our data show that outcome of HCV-positive patients withrepeated steroid pulse therapy for acute rejection is significantly worsecompared to patients with single pulse therapy. Therefore, repeatedsteroid pulse therapies should be avoided in HCV-positive transplantrecipients. New strategies in managing acute rejection in these patientsare required.

151

A PROSPECTIVE RANDOMIZED TRIAL COMPARINGTACROLIMUS AND MMF VERSUS TACROLIMUS ANDSTEROIDS AS PRIMARY IMMUNOSUPPRESSION FORHCV-RELATED LIVER TRANSPLANTATIONJan M. Langrehr, MD, PhD, Martina Mogl, MD, Ulf P. Neumann,MD, PhD, Jochen Klupp, MD, PhD, Peter J. Neuhaus, MD, PhD,Charite Virchow Clinic, Berlin, Germany

End-stage hepatitis C virus (HCV) infection is a frequent indicationfor orthotopic liver transplantation (OLT). Recurrence of HCV isalmost universal, and up to 30% of the patients will develop severegraft hepatitis and cirrhosis again after OLT. HCV genotype andsteroid administration after OLT are known to play a major role inthe severity of reinfection. The aim of the study was to examinewhether a steroid-free immunosuppressive induction regimen issafe and possibly beneficial for the course of recurrent hepatitis andoutcome. In a prospective analysis 59 consecutive patients withend-stage HCV hepatitis were randomly assigned to receive eithertacrolimus (Tac)/mycophenolate mofetil (MMF) or tacrolimus/pre-dnisolone (Pred). The groups consisted of 29 and 30 patients, respec-tively. Follow-up ranged from 14 to 60 months. The 1-year patientsurvival was 89.7% in the Tac/MMF-group compared to 83.3% with5 of 30 in the Tac/Pred-group. The 1-year graft survival was 79.3%in the Tac/MMF-group and 83.3% in the Tac/Pred-group. The inci-dence of rejection was 31% in the Tac/MMF-group suffered froman episode of acute rejection (31%), whereas 6 of 30 patients in theTac/Pred-group and 20% in the Tac/Pred-group (not statisticallydifferent). However, two of the patients in the Tac/Pred-group had

a steroid-resistent rejection with the need for OKT3-therapy. Viralload after two months was significantly lower for patients in the Tac/MMF-group (P� 0.004). Biopsy-proofen necroinflammatory activityand graft fibrosis after 1 year were similar in both groups as wellas the incidence for re-transplantation or death because of severerecurrence of hepatitis (2 patients in the Tac/MMF-group and 3patients in the Tac/Pred-group). Our data demonstrate that a steroid-free immunosuppressive induction protocol with Tac/MMF afterOLT for HCV is safe and effective, reaching a similar risk for rejectioncompared to treatment with Tac/Pred. Biopsy-proven reinfection aswell as HCV-related graft loss were equally low in both groups. Thelower viral load after 2 months in the Tac/MMF-group indicates amilder course of reinfection and favours immunosuppression withMMF. However, longer follow-up is needed to show a beneficialeffect of a steroid free immunosuppressive protocol on the course ofrecurrent HCV after OLT.

152

LIVING RELATED LIVER TRANSPLANTATION INPEDIATRIC AGE GROUP: EARLY TWO CENTERS’EXPERIENCEIbrahim K.Marwan, MD, H. Gad, E. Hamad, T. Ibrahim, A. Shawky,H. Saafan,MlOsman, B. Hegab,HlKonsowa,Ml Khalil, AlaaHamza,Ml Elmeteny, National Liver Institue, Cairo, Egypt

Living related liver transplantation (LRLT) is known to be an estab-lished acceptable therapeutic modality for end stage liver diseases,especially for children when cadaveric liver transplantation is notavailable. We present the early experience of pediatric LRLT in twocenters in Egypatient Twenty-three cases of pediatric LRLT weredone from October 2001 through March 2004. There were 12 girlsand 11 boys with an age range from 9 months to 15 years with amean of 7.3 years. The body weight of the recipients ranged from7.8 to 45 kg with a mean of 22.5 kg. All recipients received left-lateralsegment, extended left-lateral segment, or left lobe grafts. The donorswere 21 parents (15mother and 6 fathers), one sister, and one unrelatedwith mean body weight of 72.5 kg. The pretransplant primary dis-eases were biliary atresia in 6 patients, Budd-Chiari in 4 cases, meta-bolic liver disease in 3 cases, Byler’s disease in 2 cases, congenitalhepatic fibrosis in 2 cases, and cryptogenic cirrhosis in 2 patients. Theremaining four patients were hepatblastoma in one case, a case offulminant hepatitis, one case of primary sclerosing cholangitis, and acase of autoimmune hepatitis. There was no donor mortality. Chestinfection and wound seroma were observed in 2 donors, pleural effu-sion in two, and bile leak in one, which was treated successfully byendoscopic stinting. Recipients’ postoperative morbidity was observedin the form of biliary leakage in two, burst abdomen in one, hematem-esis in one, and chest infection in four cases. There was no operativemortality in recipients. Four recipients died postoperatively on days20, 23, 92, and 127, with survival of 82.6%. Pediatric LRLT is apotentially safe procedure, especially in centers where there is nocadaveric liver transplantation. The initial results are encouraging andthat progress in this field is remarkable, especially for children.

153

CAN WE SEE THE TUMOR?Dmitriy A. Nikitin, MD, Burckhardt H. Ringe, MD, DrexelUniversity College of Medicine, Philadelphia, PA

It is a well-known fact that many of the patients on the waiting listfor liver transplantation also have liver tumors. In fact, patients withStage II HCC may receive extra priority on the waiting list. For this

Page 2: Can we see the tumor?

Journal ofGastrointestinal Surgery566 Abstracts

year later the patient is doing well, without evidence of recurrentfungal disease and with excellent graft function. SA infection afterliver transplantation has been shown to progress to invasive diseasewhen opportune and appropriate therapy is not instituted. Thiscase illustrates that aggressive treatment of SA infection after livertransplant can lead to successful eradication of this potentially fatalpathogen.

155

EXPERIENCE WITH 151 SUPRACELIAC AORTICANASTOMOSIS FOR ARTERIAL REVASCULARIZATIONIN LIVER TRANSPLANTATIONKarl J. Oldhafer, Alexandra Denz, Hans J. Schlitt, Celle GeneralHospital, Celle, Germany; Klinikum Lippe-Detmold, Detmold,Germany; University of Regensburg, Regensburg, Germany

Between 1991 and , the aortic anastomosis for arterial reconstructionwas encouraged at our institution to achieve high perfusion pressuresfor the liver allograft and to avoid technical problems in case ofanatomical variations or small sizes of the hepatic artery. The aimof this study was to analyze the experience with the supraceliac aorticanastomosis for arterial revascularization during liver transplantationin this time period. Between January 1991 and January 1996, 367liver transplantations were performed. Pediatric patients and patientsreceiving split-livers or auxiliary transplants were excluded fromthis study; 151 adult patients receiving a new liver with aortic anasto-moses were analyzed. The 1-year survival rate was 59% (79/133).After 3 years 69 (52%) patients were alive. The causes of death weresepsis (n� 38), recurrent diseases (n� 11), pneumonia and respiratoryfailure (n � 6), and brain death (n � 3). The overall rate of hepaticartery�related complications was 28 complications in 17 transplants(17/151; 11%). The most frequent artery related complications were12 arterial occlusions in 11 transplants in 11 patients (12/28; 43%).Stenosis was observed in 6 of 28 complications (6/28; 21%) Bleedingfrom the side of the anastomosis occurred at the same rate (6/28;21%). Kinking of the hepatic artery was observed in 3 cases (3/28; 11%). The rate of re-transplantation after hepatic artery complica-

group of patients it becomes vitally important to correctly identifythe presence and size of the tumor. The assessment of such patientsaccording to UNOS recommendations should include ultrasound ofthe patient’s liver, a CT or MRI of the abdomen that documentsthe tumors, a CT of the chest that rules out metastatic disease, and thealpha-fetoprotein level.We used the database of our Liver TransplantCenter to analyze the relationship between the preoperative diagnosisand results of the pathological examination of explanted liver.We alsoused our data to assess the impact of the tumor on the transplantoutcome.Werealize the limitationsof this study due to small numberofpatients and short follow-up time (average 421 days, SD 297 days).Our Liver Transplant Program is young, having started in 2002. Of36 liver transplants performed at our center by 10/12/2004, 19 patientshad liver tumor diagnosis before or after transplant. One had angiosar-coma, one had leiomyosarcoma, three had CCC, and 14 had HCC;11 patients were diagnosed with HCC preoperatively and 10 of themreceived UNOS priority status; and 7 of 14 patients had elevated AFP.MRI was most sensitive tool in our hands (11 of 14), far better thenconventional CT (3 of 14) or ultrasound (4 of 14). Three of 14 patientshad HCC detected only after transplant (incidentals). In 9 of 14patients HCC diagnosis was documented by pathology of explantedliver or by preoperative biopsy. Average MELD score for this groupof patients was 22.5 (mean 24, ST 7.4). Average time on waitinglist was 151 day (median 130, ST 98). Six of 14 patients receivedpreoperative treatment for HCC. One patient died after transplantfrom sepsis. No recurrences were detected so far. Preoperative detec-tion of the liver tumors in liver transplant candidate has importantimplications on the priority status of the patient and on the postopera-tive prognosis. Preoperative MRI in our hands appears to be thebest test to detect theHCC in liver transplant candidates. The correla-tion of preoperative and postoperative staging is poor (5 of 11 preoper-ative HCC diagnoses were not conformed by pathology or biopsy, 3of 7 explanted liver HCC diagnoses were not detected preoperatively).Further follow-up studies will be necessary to determine the clinicalsignificance of these findings. Perhaps newer more sensitive and morespecific diagnostic modalities will help to improve the detection andstaging of the liver tumors in liver transplant candidates in the future.

154

CUTANEOUS SCEDOSPORIASIS AFTER LIVERTRANSPLANTATION: REPORT OF A SUCCESSFULLYTREATED CASEKristian Noto, MD, David J. Reich, MD, Abdaal Khan, MD, PaolaSolari, MD, Jose Briceno, MD, Oscar Martinez, MD, VergillioMathews, MD, Cosme Manzarbeitia, MD, Albert Einstein MedicalCenter, Philadelphia, PA

Long-term immunosuppression places transplant recipients at an in-creased risk of acquiring opportunistic infections. Scedosporium api-ospermum (SA), the asexual form of the fungus Pseudallescheria boydii,has been sporadically reported as the cause of both cutaneous anddisseminated infections in transplant recipients, often with fatal conse-quences. A 68-year-old white male presented with an asymptomatic17-mm red plaque on the dorsum of his right foot 5 months afterliver transplantation for Stage 2 hepatocellular carcinoma in the settingof hepatitis C. The borders of the lesion were well demarcated andslightly elevated. There was no pain to palpation or increased tempera-ture. The patient was a farmer in central Pennsylvania and deniedany trauma or barefoot walking. His immunossupression consisted oftacrolimus andprednisone. Punchbiopsyreported the presenceofhifaeand spores, and the culture grew SA.Management consisted on tempo-rary reduction of tacrolimus as well as oral itraconazole. The lesionwasthen excised surgically with 1-mm margins and the patient continuedantifungal treatment for 21 days. The specimen contained dark sporesand hifae. The culture confirmed SA, susceptible to itraconazole. One

tion was 40% (6/15) and the 1-year survival after arterial complicationwas 47% (7/15). Arterial occlusion of the hepatic artery occurredin the early postoperative phase as well as in the later course. Thepresence of variations of arterial anatomy of the transplanted liverand the need for arterial reconstruction have no statistically significantimpact on the rate of arterial occlusion. The only significant risk factorfor arterial occlusion was the re-use of vascular graft from the firsttransplantation if re-transplantation was performed. If there is anydoubt about a sufficient arterial blood supply or the possibility of aperfect arterial anastomosis, an aortic anastomosis should be used forre-vascularisation. As demonstrated in this study, this is an equivalentway of arterial reconstruction, it is a well-known treatment for arterialcomplications, and it is advantageous in cases of anatomical variationsof the graft’s arterial supply as complex arterial reconstruction can beavoided in most cases.

156

THE INCLUSION OF THE MIDDLE HEPATIC VEIN INPARTIAL LIVER GRAFTSJorge M. Padilha, MD, M.A.F. Ribeiro, Jr., L.C. D′Albuquerque,J.L.M. Copstein, G. Peron, F. Serpa, M. Casagrande, A.O. Silva,Beneficiencia Portuguesa Hospital, Sao Paulo, Brazil

In Brazil, the living related liver transplantation (LRLT) has increasedin the last few years due to the insufficiency number of organ donorsas well as to the exponential increase in the number of patients in thewaiting list. Nearly 25% of the liver transplant cases performed