bluuebunny/crossref_metadata_2025 huggingface dataset:
Adrenocortical Carcinoma: Surgery and Mitotane for Treatment and Steroid Profiles for Follow‐up
Authors: Khorram‐Manesh A. , Ahlman H. , Jansson S. , Wängberg B. , Nilsson O. , Jakobsson C.E. , Eliasson B. , Lindstedt S. , Tisell L.E.
Published: August 2002

Adrenocortical carcinoma (ACC) is a rare disease with a poor prognosis. It has been difficult to establish a strict treatment program for ACC, and better treatment alternatives and diagnostic tools must be sought. Even though surgery is the treatment of choice, the role of surgery in advanced disease has been questioned. Eighteen consecutive patients were treated at our unit over a 22‐year period (1975–1997). All patients underwent surgery and were followed by our protocol, which includes urinary steroid profiles, clinical examinations, analysis of steroid hormones, and radiologic investigations. Twelve patients received mitotane with drug concentration measurements to deliver an effective, nontoxic dose. The median duration of mitotane treatment was 12 months. Few side effects were observed. Four patients with low‐stage tumors underwent second‐look operations with no pathologic findings. Five patients were subjected to repeat operations, and the mean duration of the disease‐free interval before repeat surgery for these patients was 59 months. There was a significant positive correlation between the disease‐free interval and the observed survival after repeat surgery. Eleven patients with intentionally curative surgery had their urinary steroid profiles tested several times postoperatively. For five patients preoperative urine samples were also available. Steroid profiles indicated recurrent disease despite normal radiologic findings in two of these five patients. The follow‐up ranged from 6 weeks to 24 years. The predicted 5‐year survival was 58% according to the Kaplan‐Meier method. We conclude that monitoring serum concentrations of mitotane makes long‐term treatment possible with few side effects; steroid profile analysis can be used for early detection of tumor recurrence; and repeat surgery for recurrence is of value for patients with long disease‐free intervals.
Efficacy of Single‐voided Urine Metanephrine and Normetanephrine Assay for Diagnosing Pheochromocytoma
Authors: Ito Yukio , Obara Takao , Okamoto Takahiro , Kanbe Masako , Tanaka Reiko , Iihara Masatoshi , Okamoto Joji , Yamazaki Kiyomi , Jibiki Kazuko
Published: August 2002

Urinary catecholamines (CAs) and their metabolites are usually measured during the process of diagnosing pheochromocytoma (pheo), but a 24‐hour urine collection is not convenient for outpatients. Since 1987 we have utilized “spot” urine metanephrine (MN) and normetanephrine (NMN) assays for management of patients with pheo or adrenal incidentaloma. MN and NMN were measured by radioimmunoassay in 82 patients with surgically proved pheo and 15 patients with incidentaloma. In 10 patients with pheo, MN and NMN were measured with fractional every‐3‐hour urine samples, which were accumulated and then measured as a 24‐hour urinary specimen. Fractions of 3‐hour MN and NMN excretion were constant (MN 98.5 ± 9.6%, NMN 97.6 ± 10.8%; 24‐hour MN and NMN 100%). The average levels of MN and NMN in patients with pheo were 6801 ng/mg creatinine (Cr) (range 93–88,248, median 1426) and 5627 ng/mg Cr (range 219–31,528, mean 3190), whereas the MN and NMN levels in patients with incidentaloma were 123 ng/mg Cr (range 36–246, mean 133) and 251 ng/mg Cr (range 84–472, mean 220), respectively. When we selected a cutoff value for MN + NMN of 1000 ng/mg Cr, the sensitivity was 97.6% and the specificity 100% for diagnosing pheo. When the standard was set as > 500 ng/mg Cr for either MN or NMN, both the sensitivity and specificity were 100%. The assay for MN and NMN is simple and effective, not only for screening but for diagnosing pheo and managing incidentaloma.
Repeat Hepatectomy for Recurrent Colorectal Metastases
Authors: Kin Tatsuya , Nakajima Yoshiyuki , Kanehiro Hiromichi , Hisanaga Michiyoshi , Ohyama Takao , Nishio Kazushi , Sho Masayuki , Nagao Mitsuo , Nakano Hiroshige
Published: August 2002

Recurrence rates after hepatic resection in patients with colorectal metastases are reported to range from 47% to 80%. Hepatic recurrence is seen in 35% to 50% of patients. Aggressive surgical resection appears to be a worthwhile treatment in patients with recurrent hepatic metastases to promote longer patient survival because surgical resection remains the only curative therapy available. This is a retrospective review of our experience with 15 patients undergoing repeat hepatic resection culled from 67 patients undergoing initial hepatectomy for metastatic colorectal cancer. Of 67 patients who underwent hepatectomy for colorectal hepatic metastases, 33 developed hepatic recurrence at a median interval of 23 months (range 1–176 months) after the first hepatectomy. The second hepatectomy was performed in 15 patients 5 to 29 months after the first hepatectomy, with no mortality. The mean operating time and blood loss at the second hepatectomy were similar to those at the first hepatectomy. The mean hospital stay at the second hepatectomy was significantly shorter than that at the first hepatectomy. The cumulative survival rate for the 15 patients was 42.4% at 3 years and 21.2% at 5 years, respectively, which compared favorably with the survival rate of the 67 patients who underwent initial hepatectomy. Patients who underwent the second hepatectomy had significantly higher survival rates from the first hepatectomy than the 18 patients with unresectable hepatic recurrence. Repeat hepatectomy can be performed safely and provides long‐term survival rates similar to those of first hepatectomies. In appropriately selected patients, repeat hepatectomy for colorectal metastases is a worthwhile treatment.
Evidence‐based Surgery: A Passing Fad?
Authors: Black Nick
Published: August 2002

Recent years have witnessed the development of a new movement within health care: the promotion of “evidence‐based medicine” (EBM). EBM is about integrating individual clinical expertise and the best external evidence derived from scientific research. Advocates claim that much medical practice is based too much on opinion and experience and insufficiently on research evidence. Their approach would increase the quality of care and its efficiency. This paper describes the principal steps in the evidence‐based approach—systematic reviews of the literature and meta‐analyses—and its shortcomings in surgery. These include the reliance of EBM on randomized trials, the lack of generalizability of scientific evidence to individual patients, the lack of attention to third party interests, the threat to the “art” of medicine, and the dangers of an oversimplistic approach. Although EBM clearly has a place, it does not have all the answers.
Operative Management of Civilian Rectal Gunshot Wounds: Simpler Is Better
Authors: Velmahos George C. , Gomez Hugo , Falabella Andres , Demetriades Demetrios
Published: August 2002

Extraperitoneal rectal gunshot wounds have been managed with a variety of methods from simple diverting colostomy to combinations of rectal repair, proximal diversion, transperitoneal or presacral drainage, and distal bowel irrigation techniques. Treatment methodology is chosen based on anecdotal experience, and there is no clear evidence that any technique is superior to the others. The objective of this study was to compare 3 methods of managing civilian extraperitoneal gunshot wounds. Retrospective analysis of 30 consecutive patients with extraperitoneal rectal gunshot wounds was undertaken. Patients were treated with 1 of these 3 techniques: (1) simple diverting colostomy without rectal repair (group A, 12 patients); (2) diverting colostomy and rectal repair (group B, 12 patients); and (3) diverting colostomy and presacral drainage without repair (group C, 6 patients). Injury, hospital course, and outcome data were compared. The 3 groups were similar in age, injury severity, admission hemodynamics, preoperative and intraoperative time, blood loss, fecal contamination, and associated injuries. The overall incidence of complications was 27% (8/27): 25% (3/12) in group A, 33% (4/12) in group B, and 17% (1/6) in group C (p= NS). Complications directly associated with the rectal injury were found in 2 cases (7%): 1 group A patient developed a vesicorectal fistula and 1 group B patient developed a rectocutaneous fistula. For 10 patients with both rectal and bladder injuries, the complication rates for groups A, B, and C were 50%, 20%, and 0%, respectively (p= NS). No patient died. In conclusion, diverting colostomy without rectal repair or drainage appears to be safe for the management of most civilian retroperitoneal rectal gunshot wounds. Additional surgical maneuvers may be required for combined rectal and urinary trauma or other complex rectal injuries. Sound surgical principles, tailored to the individual case, should overrule any unproven dogmas.
Incisional Hernia after Laparotomy: Prospective Randomized Comparison between Early‐absorbable and Late‐absorbable Suture Materials
Authors: Hsiao Wei‐Chiang , Young Kung‐Chia , Wang Shan‐Tair , Lin Pin‐Wen
Published: August 2002

Incisional hernia is a serious postoperative complication of laparotomy. Selecting an appropriate suture material may lessen such morbidity. This study undertook a prospective, randomized comparison of early‐absorbable polyglactin 910 suture versus late‐absorbable polydioxanone loop suture for fascial closure after abdominal surgery. A series of 340 consecutive patients undergoing elective laparotomy were randomized to have fascial closure with either polyglactin 910 suture or polydioxanone loop suture between October 1993 and August 1996. A 2‐year follow‐up revealed that 23 patients had died, and the overall mortality rate was 6.8% (23/340). Ten (10/340, 2.9%) patients, including seven with polyglactin 910 suture and three with polydioxanone loop suture, developed incisional hernias. The early postoperative evaluation revealed an incidence of wound infection of 4.1% (14/340). The development of incisional hernia was not secondary to postoperative wound infection in this study. Among these 340 patients, 192 had malignant diseases and 148 had nonmalignant ones. Fascial closure with polyglactin 910 suture was associated with more incisional hernias than that with polydioxanone loop suture, with marginal significance for patients in the malignant group (4.7% versus 0%, p= 0.07) but not in the nonmalignant group (2.6% versus 4.2%, p= 0.67). In conclusion, abdominal closure with a late‐absorbable polydioxanone loop suture may be beneficial to patients with a malignant disease for preventing incisional hernia.
The “privileged” liver and hepatic tolerogenicity
Authors: Starzl Thomas E.
Published: August 2002

The mechanism underlying the immunological advantage of hepatic allografts relative to other organs is incompletely understood. We used molecular probes for the repetitive units on the Y chromosome, to identify an increasing number of male liver venous endothelial cells in needle biopsy samples of men who received female donor liver grafts. We have also shown repopulation of liver endothelium by bone marrow derived cells in a male to female mouse bone marrow transplant model. We conclude that the liver has unique venous endothelium characterized by turnover and replacement by bone marrow derived cells.
A randomized double-blind comparative study of mycophenolate mofetil and azathioprine in combination with cyclosporine and corticosteroids in primary liver transplant recipients
Authors: Wiesner Russell , Rabkin John , Klintmalm Goran , McDiarmid Sue , Langnas Alan , Punch Jeffrey , McMaster Paul , Kalayoglu Munci , Levy Gary , Freeman Richard , Bismuth Henri , Neuhaus Peter , Mamelok Richard , Wang Whedy
Published: August 2002

Acute hepatic allograft rejection occurs in approximately 50% to 60% of the patients undergoing liver transplantation. In this study, we compared the rate of acute rejection in liver transplant recipients randomized in a double-blind comparative study to treatment with mycophenolate mofetil (MMF) or azathioprine (AZA), both in combination with cyclosporine and corticosteroids. Five hundred sixty-five primary liver transplant recipients were randomly assigned to treatment with MMF, 1 g twice daily intravenously followed by 1.5 g twice daily orally (n = 278), or AZA, 1.0 to 2.0 mg/kg/d intravenously followed by oral administration (n = 287), in combination with cyclosporine and corticosteroids. Patients were followed up for at least 1 year, and efficacy analysis was based on intent-to-treat methods. Acute rejection was defined according to the Banff histological criteria. The two study groups were balanced for demographic and clinical baseline characteristics. The incidence of acute rejection or graft loss was 47.7% in the AZA patients and 38.5% in the MMF patients (P < .03). The incidence of biopsy-proven and treated rejection censoring for graft loss was 40.0% in the AZA group versus 31.0% in the MMF group (P < .06). Steroid-resistant rejection requiring treatment with either OKT3 or antithymocyte globulin occurred in 8.2% of AZA patients versus 3.8% in MMF patients (P < .02). Patient and graft survival rates at 1 year posttransplantation were 85.4% in the AZA group and 85.3% in the MMF group (P = not significant). MMF was superior to AZA in preventing acute rejection in the first 6 months posttransplantation. MMF and AZA were equivalent in preventing graft loss at 1 year, and the safety profiles between the two immunosuppressive agents were similar.
Very early tracheal extubation without predetermined criteria in a liver transplant recipient population
Authors: Biancofiore Gianni , Romanelli Anna Maria , Bindi Maria L. , Consani Giovanni , Boldrini Antonella , Battistini Michele , Filipponi Franco , Mosca Franco , Vagelli Antonio
Published: August 2002

This study of all patients undergoing orthotopic liver transplantation (OLT) at our center between January 1997 and December 1999 evaluated the feasibility and safety of very early tracheal extubation without previous selection. Anesthetic management was the same in all cases, and tracheal extubation was performed on the basis of standardized criteria routinely adopted in operating rooms throughout the world, i.e., no residual curarization or anesthetic action, ability to swallow efficiently, and stable hemodynamics. One hundred sixty-nine patients underwent 181 OLTs during the study period. Tracheal extubation was performed within 3 hours of surgery in 115 cases, 8 hours in 19 cases, and 8 to 24 hours in 10 cases. In 36 cases, artificial ventilation was required for more than 24 hours or weaning was not possible. One patient died of primary graft nonfunction within 24 hours and was excluded from the analysis. The feasibility of early extubation was influenced by the amount of intraoperative transfused blood; efficacy of kidney, cardiac, and pulmonary function; and presence of encephalopathy (P < .001). No correlation was found with age or pre-OLT severity of hepatic disease, and the postoperative period was not compromised by early weaning. Very early extubation was feasible and safe in a large number of unselected transplant recipients, thus suggesting that the definition of early tracheal extubation should be changed from 8 to 3 hours after surgery.
Concurrent de novo autoimmune hepatitis and recurrence of primary biliary cirrhosis post-liver transplantation
Authors: Tan Chee Kiat , Ho Jean May Sian
Published: August 2002

Primary biliary cirrhosis (PBC) is well known to recur after liver transplantation (LT). The recurrence is usually subclinical and evident only on histological examination. Recently, a new entity of de novo autoimmune hepatitis (AIH) has emerged that occurs after LT in patients who underwent transplantation for diseases other than AIH. This new condition occurs more often in children; however, there was a recent report of the first 2 cases in adults who originally underwent LT for PBC. We report the first case of concurrent de novo AIH and recurrence of PBC documented on the liver biopsy of an adult patient who underwent LT for end-stage PBC. Unlike the earlier report of 2 adults, our patient manifested an antinuclear antibody titer of more than 1/800 from a previously negative titer pre-LT, as well as fulfilled the International AIH Group criteria for a definite diagnosis of AIH. PBC recurrence was evidenced by typical florid duct lesion, antimitochondrial antibody titer increasing from 1/40 to greater than 1/800, and an elevated serum immunoglobulin M level. After the addition of azathioprine to baseline immunosuppression of tacrolimus and prednisolone, the patient responded rapidly, with complete normalization of liver test results.
Are posttransplantation protocol liver biopsies useful in the long term?
Authors: Berenguer Marina , Rayón José M. , Prieto Martín , Aguilera Victoria , Nicolás David , Ortiz Vicente , Carrasco Domingo , López-Andujar Rafael , Mir José , Berenguer Joaquín
Published: August 2002

Controversy exists about the usefulness of yearly protocol liver biopsies after liver transplantation, mainly among patients with normal transaminase levels. The aim of this study is to determine (1) the prevalence and cause of histological liver injury in transplant recipients with a minimum histological follow-up of 1 year (n = 254), and (2) the correlation between histological findings and transaminase values. The main indication for liver transplantation was viral-related cirrhosis (61%; 86% caused by hepatitis C virus [HCV]). Protocol liver biopsies were performed yearly for the first 5 years in HCV-infected transplant recipients and at 1 and 5 years in the remaining patients. Histological liver injury included several categories of liver damage (hepatitis, rejection, steatohepatitis, cholangitis, and Budd-Chiari-like lesions). Among biopsy specimens categorized as hepatitis, severe hepatitis was defined as the presence of stage 3 or greater fibrosis. The prevalence of liver injury increased significantly with time (42% v 56% at 1 and 5 years, respectively; P = .09) and was significantly greater in patients who underwent transplantation for HCV-related cirrhosis than in those who underwent transplantation for other reasons (P = .0001). The most frequent category of liver injury was hepatitis (97% and 96% at 1 and 5 years, respectively). Although a proportion of patients with liver injury (12% to 29%) had normal transaminase values, this percentage was almost null in patients with severe hepatitis. Normal histological characteristics were found in the vast majority of non-HCV-infected transplant recipients with normal transaminase values. Given the high prevalence of abnormal histological findings, particularly the increase over time of those defined as severe, protocol liver biopsies are clearly justified in HCV-infected transplant recipients. Conversely, given the rarity of abnormal histological findings, protocol liver biopsies should be questioned in non-HCV-infected transplant recipients with normal transaminase values.
Transmission of hepatitis B infection from hepatitis B core antibody-positive liver allografts is prevented by lamivudine therapy
Authors: Yu Andy S. , Vierling John M. , Colquhoun Steven D. , Arnaout Walid S. , Chan Chuek-Kee , Khanafshar Elham , Geller Stephen A. , Nichols Stephen W. , Fong Tse-Ling
Published: August 2002

Donor shortage has led to the use of hepatitis B core antibody (anti-HBc)-positive (anti-HBc+) liver allografts for patients in need of relatively urgent orthotopic liver transplantation (OLT). Because anti-HBc+ allografts transmit hepatitis B virus (HBV) infection at a high rate, effective prophylaxis is required. We assessed the effectiveness of lamivudine in preventing HBV transmission by anti-HBc+ allografts. Between March 1996 and March 2000 at Cedars-Sinai Medical Center (Los Angeles, CA), 15 of 169 patients (8.9%) received liver allografts from anti-HBc+ donors. Six patients were hepatitis B surface antigen (HBsAg)+ (group 1), and 9 patients were HBsAg negative (HBsAg−; group 2) before OLT. All patients were administered lamivudine, 100 or 150 mg/d, orally after OLT. Patients who were HBsAg+ before OLT also were administered hepatitis B immunoglobulin (HBIG) prophylaxis. Hepatitis B serological tests were performed on all patients, and HBV DNA was determined in liver tissues in 10 patients. All 15 patients remained HBsAg− at their last follow-up 2 to 40 months (mean, 17 months) post-OLT. All patients in group 1 had antibody to HBsAg (anti-HBs) titers greater than 250 mIU/mL post-OLT (mean follow-up, 20 months; range, 7 to 40 months). Of the 2 patients in group 1 who underwent liver biopsy after OLT, 1 patient had detectable hepatic HBV DNA despite being anti-HBs+ and HBsAg−. Among the patients in group 2, none acquired anti-HBc or HBsAg. Hepatic HBV DNA was undetectable in the 7 patients in group 2 who underwent liver biopsy after OLT. Anti-HBc+ allografts can be safely used in patients who undergo OLT for chronic hepatitis B and susceptible transplant recipients if prophylaxis with combination HBIG and lamivudine or lamividine alone is administered after OLT, respectively. However, more data are needed to determine the efficacy of lamivudine monotherapy in preventing transmission of HBV infection from anti-HBc+ liver allografts to susceptible recipients.
Role of hepatocytes and bile duct cells in preservation-reperfusion injury of liver grafts
Authors: Kukan Marián , Haddad Pierre S.
Published: August 2002

In liver transplantation, it is currently hypothesized that nonparenchymal cell damage and/or activation is the major cause of preservation-related graft injury. Because parenchymal cells (hepatocytes) appear morphologically well preserved even after extended cold preservation, their injury after warm reperfusion is ascribed to the consequences of nonparenchymal cell damage and/or activation. However, accumulating evidence over the past decade indicated that the current hypothesis cannot fully explain preservation-related liver graft injury. We review data obtained in animal and human liver transplantation and isolated perfused animal livers, as well as isolated cell models to highlight growing evidence of the importance of hepatocyte disturbances in the pathogenesis of normal and fatty graft injury. Particular attention is given to preservation time-dependent decreases in high-energy adenine nucleotide levels in liver cells, a circumstance that (1) sensitizes hepatocytes to various stimuli and insults, (2) correlates well with graft function after liver transplantation, and (3) may also underlie the preservation time-dependent increase in endothelial cell damage. We also review damage to bile duct cells, which is increasingly being recognized as important in the long-lasting phase of reperfusion injury. The role of hydrophobic bile salts in that context is particularly assessed. Finally, a number of avenues aimed at preserving hepatocyte and bile duct cell integrity are discussed in the context of liver transplantation therapy as a complement to reducing nonparenchymal cell damage and/or activation.
A multicenter study of lamivudine treatment in 33 patients with hepatitis B after liver transplantation
Authors: Fontana Robert J. , Hann Hie-Won L. , Wright Teresa , Everson Gregory , Baker Alfred , Schiff Eugene R. , Riely Carolyn , Anschuetz Gaya , Riker-Hopkins Melanie , Brown Nathaniel
Published: August 2002

Hepatitis B virus (HBV) infection after liver transplantation (LT) may lead to severe and rapidly progressive graft failure. Antiviral treatment may be of benefit in selected patients with recurrent hepatitis B post-LT. The aim of this prospective open-label study is to determine the safety and efficacy of lamivudine in 33 liver transplant recipients with active HBV infection. The median time from LT to study enrollment was 51 months, all patients were hepatitis B surface antigen positive, and 75% and 94% of subjects had detectable hepatitis B e antigen (HBeAg) and HBV DNA at entry, respectively. The median duration of lamivudine treatment on study was 85 weeks, during which time median HBV DNA levels became undetectable by 16 weeks and 9% of patients lost previously detectable HBeAg. Serum alanine aminotransferase (ALT) levels improved in most patients and normalized in 27% of patients with elevated values pretreatment. Serum bilirubin and albumin levels significantly improved in patients with abnormal values at entry (P < .05). Virological breakthrough was detected in 13 subjects after a median of 61 weeks of lamivudine treatment and was confirmed to be caused by YMDD mutants in all patients tested. None of the patients with virological breakthrough showed a complete loss of clinical response to lamivudine. Serum ALT and bilirubin levels in patients with and without virological breakthrough were not significantly different at last study follow-up. Study results show that lamivudine is safe and effective in liver transplant recipients with recurrent hepatitis B. However, the high rate of virological breakthrough with prolonged therapy indicates the need for further studies of combination antiviral therapy in this patient population. Our results and others further establish the improving long-term outcomes with LT for patients with hepatitis B through advances in prevention of reinfection, as well as the availability of safe and effective antiviral therapies to treat patients with HBV recurrence.
Effects of prostaglandin E1 on the efficacy of xenogeneic extracorporeal pig liver perfusion in a canine model of acute liver failure
Authors: Takeyama Osamu , Ikai Iwao , Yagi Toshikazu , Satoh Seiji , Kanazawa Akiyoshi , Uesugi Takehiko , Nishitai Ryuta , Okabe Hiroshi , Katsura Nagato , Terajima Hiroaki , Yamaoka Yoshio
Published: August 2002

Xenogeneic extracorporeal liver perfusion (ECLP) has the potential to become an important tool in the management of patients with severe liver failure. We previously showed that xenogeneic pig liver perfusion may be prolonged for up to 9 hours by the administration of prostaglandin E1 (PGE1). In this study, we used a canine model of acute liver failure to evaluate the effects of PGE1 on the efficacy of ECLP as a liver-assist device. Liver failure was surgically induced in 12 beagle dogs, with a control group (group 1, n = 4) not connected to the ECLP circuit. Direct cross-circulation between the dogs and the ECLP circuit using a pig liver was performed without (group 2, n = 4) or with (group 3, n = 4) continuous administration of PGE1 through the portal vein of the pig liver. The duration of cross-circulation in group 3 (9.4 ± 1.2 hours) was significantly longer than in group 2 (4.3 ± 1.0 hours). In addition, elevation of blood ammonia, total bile acid, and hyaluronic acid levels was less marked in group 3 compared with the other 2 groups. The ratio of branched-chain amino acids to aromatic amino acids was also improved in group 3. The mean survival time in group 3 (26.6 ± 0.4 hours) was significantly longer than in group 1 (15.5 ± 1.3 hours) or group 2 (17.1 ± 2.9 hours). Continuous administration of PGE1 to xenogeneic ECLP resulted in a significant improvement in both liver function and survival time of dogs with surgically induced liver failure. (Liver Transpl 2001;7:526-532.)
Recurrent portopulmonary hypertension after liver transplantation: Management with epoprostenol and resolution after retransplantation
Authors: Kett Daniel H. , Acosta Rita C. , Campos Michael A. , Rodriguez Miguel J. , Quartin Andrew A. , Schein Roland M.H.
Published: August 2002

We report a case of portopulmonary hypertension in which the pulmonary hypertension resolved after initial orthotopic liver transplantation. Portopulmonary hypertension recurred when the transplanted liver failed and again resolved after a second liver transplantation. Intravenous epoprostenol was administered perioperatively to control the pulmonary hypertension in both instances.
Stenosis of the suprahepatic inferior vena cava as a complication of transjugular intrahepatic portosystemic shunt in Budd-Chiari patients
Authors: Turnes Juan , García-Pagán Juan Carlos , González-Abraldes Juan , Real Maribel , Moitinho Eduardo , Gilabert Rosa , Escorsell Angels , Muntanya Xavier , Ginès Pere , Bosch Jaume , Rodés Joan
Published: August 2002

We report 2 patients with Budd-Chiari (BC) syndrome secondary to thrombogenic conditions who underwent transjugular intrahepatic portosystemic shunt (TIPS) placement because of refractory ascites and impending liver failure. After TIPS placement, there was marked symptomatic relief and improvement in liver function, but the courses of both patients were complicated by the development of an inferior vena cava (IVC) syndrome caused by segmental stenosis of the suprahepatic IVC just at the outflow jet of the TIPS at 11 and 9 months later. One patient underwent liver transplantation, and the other patient, caval angioplasty and stenting. Stenosis of the IVC represents an unrecognized complication of TIPS in patients with BC syndrome.
Allocation of transplantable organs: Do people want to punish patients for causing their illness?
Authors: Ubel Peter A. , Jepson Christopher , Baron Jonathan , Mohr Tara , McMorrow Stacey , Asch David A.
Published: August 2002

Some people believe patients with alcoholic cirrhosis should not receive equal priority for scarce transplantable organs. This may reflect a belief that these patients (1) are personally responsible for causing their own illnesses, (2) have poor transplant prognoses, or (3) are unworthy because they have engaged in socially undesirable behavior. We explore the roles that social desirability and personal responsibility have in people’s judgments about transplant allocation. We presented prospective jurors with 4 scenarios, asking them to distribute 100 transplantable organs among 2 groups of 100 patients each. In each scenario, 1 group of patients, but not the other, was described as having a history of unhealthy behavior (alcohol or cigarette use) associated with a poorer prognosis. In some scenarios, alcohol or cigarette use was said to cause the organ failure. In others, it only contributed to the patients’ transplant prognosis. We also obtained self-reports of subjects’ own smoking status. Subjects allocated significantly fewer than half the organs to those with unhealthy behaviors and worse prognoses (33%; P < .001), but the specific behavior (alcohol versus cigarette use) was not significantly associated with subjects’ allocation choices. Significantly fewer organs were allocated to patients with behavior responsible for causing their diseases than to other patients (P < .0001). Subjects who never smoked discriminated the most and current smokers discriminated the least against patients with a history of unhealthy behavior (P < .0001). The public’s transplantation allocation preferences are influenced by whether patients’ behaviors are said to have caused their organ failure.
T-cell clones derived by CD3 stimulation from hepatitis C virus explanted liver tissue are not representative of dominant clones present in vivo
Authors: Davey Michael P. , Rosen Hugo R. , Woody Carolyn N. , Haley Daniel P. , Kurkinen Julie , Lewinsohn David M.
Published: August 2002

Liver tissue from hepatitis C virus (HCV)-related end-stage disease contains T-cell infiltrates. The goal of this study is to determine whether CD4 T-cell clones established in vitro using an antigen-independent technique from explanted liver tissue (n = 3) are representative of dominant clones present in vivo. T-cell receptor (TCR) use by intrahepatic CD4 T cells was assessed by spectratype analysis. Clones were established from single CD4 T cells by culturing in vitro with anti-CD3 and interleukin-2 (n > 25 per patient). TCR genes expressed by each clone were identified by sequencing. When identical clones were isolated, the original spectratype was analyzed further to determine whether the clone was a dominant T-cell expansion in vivo. Evidence for clonal expansions was found in all patients by spectratyping. T cells expressing the same TCRBV genes used for spectratyping were cloned in vitro. Duplicate clones expressing the same TCR genes were observed in 2 patients. Confirmation that clones established in vitro matched those present in vivo was obtained for 2 clones. Many dominant clones identified by spectratyping did not proliferate in vitro. Although spectratyping suggested the widespread accumulation of clonal expansions in HCV-related end-stage liver disease, clones established in vitro using anti-CD3 were poorly representative of dominant clones present in vivo. Although cloning with anti-CD3 has the advantage of generating T-cell clones not biased a priori toward a specific antigen, modified cloning strategies will need to be developed to expand those clones that appear dominant in end-stage organs.
Cerebral blood flow velocity increases during a single treatment with the molecular adsorbents recirculating system in patients with acute on chronic liver failure
Authors: Schmidt Lars E. , Svendsen Lars Bo , Sørensen Vibeke Rømming , Hansen Bent Adel , Larsen Fin Stolze
Published: August 2002

The aim of this uncontrolled pilot study is to determine the effect of treatment with the molecular adsorbents recirculating system (MARS) on cerebral perfusion in patients with acute on chronic liver failure (AOCLF). In 8 patients (median age, 44 years; range, 35 to 52 years) admitted with AOCLF, a single 10-hour MARS treatment was performed. Hepatic encephalopathy (HE) was graded according to the Fogarty criteria. Changes in cerebral perfusion were determined by transcranial Doppler as mean flow velocity (Vmean) in the middle cerebral artery. Arterial ammonia and bilirubin levels were monitored as a measure of the capability of the MARS to remove water-soluble and protein-bound toxins. During MARS treatment, HE grade improved in 3 patients and remained unchanged in 5 patients (P = .11). Vmean increased from 42 cm/sec (range, 26 to 59 cm/sec) to 72 cm/sec (range, 52 to 106 cm/sec; P < .05), whereas arterial ammonia level decreased from 88 μmol/L (range, 45 to 117 μmol/L) to 71 μmol/L (range, 26 to 98 μmol/L; P < .05) and bilirubin level from 537 μmol/L (range, 324 to 877 μmol/L) to 351 μmol/L (range, 228 to 512 μmol/L; P < .05). In conclusion, cerebral perfusion is increased and levels of ammonia and bilirubin are reduced during MARS treatment in patients with AOCLF.
Temporal profile of total, bound, and free Gc-globulin after acetaminophen overdose
Authors: Schiødt Frank Vinholt , Ott Peter , Tygstrup Niels , Dahl Benny , Bondesen Stig
Published: August 2002

Low admission values of the actin scavenger Gc-globulin are associated with an adverse outcome in acetaminophen (paracetamol) overdose. This prospective longitudinal study including 84 patients with acetaminophen overdose characterizes the temporal profile of Gc-globulin during the entire length of hospitalization. Serum Gc-globulin (total, actin bound, and free) levels and actin-complex ratio were measured on admission and every 12 hours until discharge. In 32 patients without hepatotoxicity (non-HEPTOX group; peak transaminase levels < 1,000 U/L), total and free Gc-globulin levels and complex ratio remained within normal range during hospitalization. Among 52 patients with hepatotoxicity (HEPTOX group; peak transaminase levels > 1,000 U/L), 15 patients had hepatic encephalopathy (HE), and 37 patients did not. In these 2 groups, total and free Gc-globulin levels decreased to 97 and 50 mg/L and 148 and 86 mg/L, respectively (normal mean, 340 and 299 mg/L), the nadir occurring at 72 hours postoverdose. Complex ratio peaked at 60 hours at levels more than 3-fold greater than normal. Conversely, bound Gc-globulin remained within normal levels for all patients throughout the observation period. At day 2, a total Gc-globulin cutoff value of less than 120 mg/L correctly predicted HE in 75%, and a value greater than 120 mg/L correctly predicted the absence of HE in 91% of patients. In conclusion, Gc-globulin is severely stressed in patients with hepatotoxicity. Extreme values occurred at 60 to 72 hours postoverdose, a period in which Gc-globulin protection against actin toxicity may be inadequate. A total Gc-globulin level less than 120 mg/L on day 2 is a good predictor of later HE. Bound Gc-globulin is maintained at constant levels independent of total Gc-globulin levels, suggesting a balanced upregulation of the removal of bound Gc-globulin even under conditions with increased actin release.
Steroid-free liver transplantation using rabbit antithymocyte globulin induction: Results of a prospective randomized trial
Authors: Eason James D. , Loss George E. , Blazek Jamie , Nair Satheesh , Mason Andrew L.
Published: August 2002

Steroids have been 1 of the primary modes of immunosuppression since the inception of transplantation and have been credited with both the prevention and treatment of rejection. Steroids also have been held responsible for increased infections, posttransplantation diabetes, and recurrent hepatitis after orthotopic liver transplantation (OLT). The purpose of this ongoing prospective randomized trial is to eliminate steroid use in OLT through induction with rabbit antithymocyte globulin (RATG). This is the first report of a prospective randomized trial in OLT achieving complete absence of steroids. Seventy-one adult patients were prospectively randomized to administration of RATG or steroids. Thirty-six patients were randomized to the administration of RATG induction at a dose of 1.5 mg/kg intravenously (IV) beginning during the anhepatic phase. No steroids were administered. Patients were administered a second 1.5-mg/kg dose of RATG post-OLT day 1. Thirty-five patients were randomized to the administration of methylprednisolone, which had been our standard immunosuppressive protocol. These patients were administered methylprednisolone, 1,000 mg IV, initiated during the anhepatic phase and followed by steroid taper. Maintenance immunosuppression consisted of tacrolimus and mycophenolate, with or without prednisone. Three patients died in each group, for an overall survival rate of 91% in each group. One patient in each group required re-OLT, for a graft survival rate of 89% in each group. Seven patients administered RATG had biopsy-proven rejection (20.5%), all of whom were successfully treated by increasing tacrolimus doses. Eleven patients administered steroid had biopsy-proven rejection (32%), 7 (64%) of whom required additional steroids for treatment, whereas 4 patients (36%) were successfully treated by increasing tacrolimus doses. The incidence of rejection was not statistically significant; however, there was a significant difference in the incidence of steroid-requiring rejection (P = .01). The incidence of recurrent hepatitis C was 50% in RATG patients and 71% in steroid patients (P = not significant). The incidence and severity of infectious complications were slightly lower in RATG patients, accounted for by a greater incidence of cytomegalovirus (CMV) infection in the steroid patients. RATG induction enables complete avoidance of steroid use in OLT with a trend toward a lower rejection rate, decreased incidence of post-OLT diabetes and recurrent hepatitis C, and decreased CMV infection. This prospective randomized trial gives encouraging support that steroids can be safely eliminated in OLT.
Reconstruction of double hepatic arterial and portal venous branches for right-lobe living donor liver transplantation
Authors: Marcos Amadeo , Orloff Mark , Mieles Luis , Olzinski Ann , Sitzmann James
Published: August 2002

Double hepatic arterial and portal venous branches are common anatomic variations of the isolated right hepatic lobe. Reconstruction of these vessels during transplantation can be challenging because of their small caliber, close proximity to other hilar structures, and abnormal alignment with the native vasculature. Practical techniques for the creation of these anastomoses would simplify the recipient surgery and might minimize the incidence of vascular complications. Alternative methods for management of these structures are summarized. The recipient’s proper hepatic artery and its bifurcation are resected for use as an arterial Y-type graft. The donor arteries are individually anastomosed at the bifurcation of the recipient’s hepatic artery at the back table. The free end of the Y graft is then replaced at the origin of the gastroduodenal artery using standard branch-patch technique. Reconstruction of a second donor portal branch is similarly facilitated by ex situ placement of a Y-type vascular conduit derived from the recipient’s portal vein. Surgical management of these vessels and reconstruction of other hilar structures are noticeably less cumbersome. There have been no short-term vascular complications. The use of autologous vascular conduits with ex situ reconstruction facilitates management of double donor arterial and portal venous branches. The incidence of complications attributable to these methods is expected to be low.
Liver transplantation from situs inversus to situs inversus
Authors: Sugawara Yasuhiko , Makuuchi Masatoshi , Takayama Tadatoshi , Yoshino Hiroyuki , Mizuta Koichi , Kawarasaki Hideo
Published: August 2002

Congenital anatomic anomalies often present technical obstacles during liver transplantation. Biliary atresia (BA) is the most common indication for liver transplantation in children, and up to 28% of children with situs inversus are complicated by BA. A boy aged 2 years 11 months with BA, situs inversus, and dextrocardia received a liver transplant from his father. The donor also had situs inversus and dextrocardia without other anomalies. Graft function was excellent postoperatively, and no significant complications were encountered. This is only the second report of the successful use of a living related donor graft for a patient with BA and situs inversus. This case was particularly rare because the donor also had situs inversus, which made the present procedure more feasible.
Kaposi’s sarcoma in liver transplant recipients: Morphological and clinical description
Authors: Aseni Paolo , Vertemati Maurizio , Minola Ernesto , Arcieri Katia , Bonacina Edgardo , Camozzi Mario , Osio Chiara , Forti Domenico
Published: August 2002

The clinical course and outcome of 5 adult patients who underwent orthotopic liver transplantation (OLT) and developed Kaposi’s sarcoma (KS) is reported. From October 1986 to July 2000, a total of 459 patients underwent 499 OLTs at our hospital. The immunosuppressive regimen consisted of cyclosporine, azathioprine, prednisone, and antithymocyte globulin. Tacrolimus was administered only in selected patients. Five patients developed KS, and the pathological diagnosis was established months 9 to 23 after OLT. Four of 5 patients died of KS, surviving 0 to 6 months after pathological diagnosis. The fifth patient, with KS confined to the skin, is disease free 6 months after diagnosis. All patients were treated with reduction of immunosuppressive therapy and/or chemotherapy. Retrospective molecular investigation by polymerase chain reaction for human herpesvirus type 8 DNA detected specific viral sequences in histological specimens of tissues involved by KS. In our experience with adult liver transplant recipients, we registered a slightly lower prevalence of KS compared with other reported data, but observed a high rate of graft involvement and mortality.
Use of autologous radial artery for revascularization of hepatic artery thrombosis after orthotopic liver transplantation: Case report and review of indications and options for urgent hepatic artery reconstruction
Authors: Rogers Jeffrey , Chavin Kenneth D. , Kratz John M. , Mohamed Hussein K. , Lin Angello , Baillie Mark G. , Shafizadeh Stephen F. , Baliga Prabhakar K.
Published: August 2002

Hepatic artery thrombosis (HAT) is the most common vascular complication after orthotopic liver transplantation (OLT) and has traditionally been managed with re-OLT. However, several reports have shown that urgent revascularization is frequently an effective means of graft salvage. This most often involves hepatic artery (HA) thrombectomy and thrombolysis, with reestablishment of arterial inflow through a donor iliac artery conduit based on the supraceliac or infrarenal aorta. We report a 46-year-old man who developed HAT 13 days after OLT after angiographic splenic artery embolization to reduce splenic artery steal. A suitable donor iliac artery was not available for arterial reconstruction and could not be obtained from neighboring transplant centers. The patient underwent urgent HA thrombectomy, intrahepatic arterial thrombolysis, and revascularization using an autologous radial artery (RA) conduit based on the supraceliac aorta. The patient is alive more than 1 year after revascularization, with normal liver function and documented flow in the arterial conduit by Doppler ultrasound and arteriography. He has not developed late biliary complications or adverse sequelae of RA harvest. Autologous RA can be safely and successfully used as an aortic-based arterial conduit in urgent revascularization of HAT after OLT. RA should be considered for use in HA revascularization if an adequate donor iliac artery is not available and other potential conduits are not usable or desirable. The availability of autologous RA expands the armamentarium of vascular conduits that can be used in HA revascularization and may help minimize re-OLT for otherwise potentially salvageable liver allografts.
Intracardiac thrombus formation and pulmonary thromboembolism immediately after graft reperfusion in 7 patients undergoing liver transplantation
Authors: Gologorsky Edward , De Wolf Andre M. , Scott Victor , Aggarwal Shushma , Dishart Michael , Kang Yoogoo
Published: August 2002

Intravascular and/or intracardiac thrombus formation followed by pulmonary thromboembolism with right ventricular dysfunction immediately after graft reperfusion during orthotopic liver transplantation (OLT) is described in 7 patients. This complication may have been related to excessive activation of the coagulation system by graft reperfusion, which overwhelmed anticoagulation mechanisms and was disproportionate to fibrinolysis. Activation of the coagulation system may be more pronounced in patients who receive less than optimal grafts, require massive transfusion, or have septic complications at the time of OLT. It is unclear whether antifibrinolytic therapy during the anhepatic stage had a role. Transesophageal echocardiography was useful in diagnosing and managing intracardiac thrombus and pulmonary thromboembolism.
Aprotinin reduces red blood cell transfusion in orthotopic liver transplantation: A prospective, randomized, double-blind study
Authors: Findlay James Y. , Rettke Steven R. , Ereth Mark H. , Plevak David J. , Krom Ruud A.F. , Kufner Ronald P.
Published: August 2002

The effect of an aprotinin infusion on blood and blood product transfusion during adult primary orthotopic liver transplantation (OLT) was investigated in a prospective, randomized, double-blind study. Sixty-three patients were enrolled; 33 patients were administered an aprotinin regimen of a 1,000,000-KIU loading dose, followed by a 250,000-KIU/h infusion during surgery, and 30 patients were administered equivalent volumes of normal saline. Red blood cell (RBC) and blood product transfusion intraoperatively and for the first 24 hours postoperatively was by protocol. Intraoperative coagulation testing and thromboelastography (TEG; Hemoscope Corp, Skokie, IL) were performed. Intraoperative RBC transfusion was significantly less in the aprotinin group versus controls: median, 5 units (interquartile range [IQR], 3 to 9 units) versus 7 units (IQR, 5 to 16 units; P = .0016). No significant differences were found for intraoperative blood product transfusion or transfusion of RBCs or blood products in the 24-hour postoperative period. No significant differences were observed in intraoperative coagulation testing or TEG parameters. We conclude that aprotinin infusion reduces RBC transfusion requirements in OLT.