An early regional experience with expansion of Milan Criteria for liver transplant recipients.

The Milan Criteria (MC) showed that orthotopic liver transplantation (OLT) was an effective treatment for patients with nonresectable, nonmetastatic HCC. There is growing evidence that expanding the MC does not adversely affect patient or allograft survival following OLT. The adult OLT programs in UNOS Region 4 reached an agreement allowing lesions outside MC (one lesion <6 cm, ≤3 lesions, none >5 cm and total diameter <9 cm-[R4 T3]) to receive the same exception points as MC lesions. Kaplan-Meier curves and log-rank tests were used to compare survival data. Chi-squared and Mann-Whitney U tests were used to compare patient data. A p-value of <0.05 was considered significant. All statistical analyses were performed on SPSS 15 (SPSS, Chicago, IL). Four hundred and forty-five patients were transplanted for HCC (363-MC and 82-R4 T3). Patient demographics were found to be similar between the two groups. Three year patient, allograft and recurrence free survival between MC and R4 T3 were found to be 72.9% and 77.1%, 71% and 70.2% and 90.5% and 86.9%, respectively (all p > 0.05). We report the first regionalized multicenter, prospective study showing benefit of OLT in patients exceeding MC based on preoperative imaging.

Liver and intestine transplantation in the United States 1998-2007.

Liver transplantation numbers in the United States remained constant from 2004 to 2007, while the number of waiting list candidates has trended down. In 2007, the waiting list was at its smallest since 1999, with adults > or =50 years representing the majority of candidates. Noncholestatic cirrhosis was most commonly diagnosed. Most age groups had decreased waiting list death rates; however, children <1 year had the highest death rate. Use of liver allografts from donation after cardiac death (DCD) donors increased in 2007. Model for end-stage liver disease (MELD)/pediatric model for end-stage liver disease (PELD) scores have changed very little since 2002, with MELD/PELD <15 accounting for 75% of the waiting list. Over the same period, the number of transplants for MELD/PELD <15 decreased from 16.4% to 9.8%. Hepatocellular carcinoma exceptions increased slightly. The intestine transplantation waiting list decreased from 2006, with the majority of candidates being children <5 years old. Death rates improved, but remain unacceptably high. Policy changes have been implemented to improve allocation and recovery of intestine grafts to positively impact mortality. In addition to evaluating trends in liver and intestine transplantation, we review in depth, issues related to organ acceptance rates, DCD, living donor transplantation and MELD/PELD exceptions.

Graft function and outcome of older (> or = 60 years) donor livers.

Livers from donors > or = 60 years of age are often considered inadequate for transplantation by many centers. With waiting times exceeding 1 year in our region, we have aggressively used livers from this donor age group. Between 1990 and 1994, 209 patients received 223 liver grafts at our institution. Of these, 29 (13%) were from donors > or = 60 years of age (group A) and 194 (87%) were from donors < 60 years of age (group B). The two groups were matched for recipient diagnosis and severity of disease. Group A and B donors had similar liver, renal, and hematologic studies prior to donation. Weight, sex, race and vasopressor requirement were also similar. Postoperative alanine aminotransferase, aspartate aminotransferase,and prothrombin time were not significantly different over the first 10 postoperative days. Group A grafts were significantly more cholestatic than group B grafts on postoperative days 6-10. The retransplantation rate for primary graft nonfunction was not significantly different from group A (6.7%) and group B (3.4%; P=0.04). Patient and graft survival rates at 1 year were 58.6 % and 44.8% for group A and 79.2% and 74.5% for group B (P<0.001 for both). Four of 12 deaths in the first year in group A were completely unrelated to graft function. If these are excluded, patient and graft survival rates were 68% and 52%, which are better but still significantly less than in group B. Initial graft function of older donor livers are similar to that of the matched younger group. However, patient and graft survival rates were significantly worse for the older donors, even when corrected for unrelated deaths. Livers should not be discarded based on age alone without inspection and/or biopsy to rule out significant steatosis. Prompt retransplantation for primary graft nonfunction of older donors are generally more cholestatic than those from the younger donor age group; however, many of them function quite well. At the present time, given the inability to identify donor variables associated with decreased recipient survival, we recommend cautious use of older liver grafts in healthier recipients.

A regional experience with emergency liver transplantation.

Liver transplantation for patients requiring life-support results in the lowest survival and highest costs. A ten year (1983-1993) regional experience with liver transplantation for critically ill patients was undertaken to ascertain the fate of several subgroups of patients. Of the 828 liver transplants performed at six transplant centers within the region over this period, 168 (20%) were done in patients who met today's criteria for a United Network of Organ Sharing (UNOS) status 1 (emergency) liver transplant candidate. Recipients were classified according to chronicity of disease and transplant number (primary-acute, primary-chronic, reTx-acute, reTx-chronic). Overall one-year survival was 50% for all status 1 recipients. The primary-acute subgroup (n = 63) experienced a 57% one-year survival compared with 50% for the primary-chronic (n = 51) subgroup (P = 0.07). Of the reTx-acute recipients (n = 43), 44% were alive at one year in comparison with 20% for the reTx-chronic (n = 11) group (P = 0.18). There was no significant difference in survival for the following: transplant center, blood group compatibility with donors, age, preservation solution, or graft size. For patients retransplanted for acute reasons (primary graft nonfunction (PGNF) or hepatic artery thrombosis [HAT]), survival was significantly better if a second donor was found within 3 days of relisting (52% vs. 20%; P = 0.012). Over the study period progressively fewer donor organs came from outside the region. No strong survival-based argument can be made for separating, in allocation priority, acute and chronic disease patients facing the first transplant as a status 1 recipient. Clearly patients suffering from PGNF or HAT do far better if retransplanted within 3 days. Establishing an even higher status for recipients with PGNF, perhaps drawing from a supraregional donor pool, would allow surgeons to accept more marginal donors, thus potentially expanding the pool, without significantly compromising patient survival. Retransplantation of the recipient with a chronically failing graft who deteriorates to the point of needing life-support is nearly futile, and in today's health care climate, not an optimal use of scarce donor livers.

Aggressive surgical resection for cholangiocarcinoma.

OBJECTIVES: To review the spectrum of cholangiocarcinoma in patients treated by a single team of hepatobiliary surgeons over an 8-year period, to evaluate the predictors of survival, and to assess the results of an aggressive approach to surgical resection. DESIGN: Retrospective review of all clinical records of patients referred for treatment of cholangiocarcinoma, with univariate analysis of clinical and pathologic factors in relation to patient survival. SETTING: New England Deaconess Hospital, Boston, Mass. PATIENTS: Eighty-eight consecutive patients referred with the established diagnosis of cholangiocarcinoma, from December 31, 1985, to April 15, 1994. INTERVENTIONS: Seventy-five of 88 patients were treated surgically, with 59 undergoing major resection for cure. Of the 29 patients treated palliatively, 16 had operations and 13 had wire mesh stents placed nonoperatively. MAIN OUTCOME MEASURES: Morbidity, mortality, and patient survival. RESULTS: Survival correlates directly with the pathologic stage (TNM). Tumor location had no impact on survival. Patients undergoing resection survived significantly longer (median, 23.2 months) than palliated patients (median, 7.7 months; P = .0015). Nonoperative palliation resulted in better survival than surgical palliation (P = .045). Major hepatic resection was used alone in eight patients with predominating intrahepatic lesions, while 18 patients with hilar lesions underwent en bloc skeletonization in conjunction with major hepatic resection. Resection with microscopically free margins significantly improved survival. Only patients undergoing major resection enjoyed survival greater than 2 years. CONCLUSIONS: Patient survival can be significantly improved by aggressive surgical resection. Hepatic resection should be used aggressively to achieve disease-free margins to optimize survival. Hepatic resection can be performed with low morbidity and mortality. Liver transplantation should be avoided as a treatment for cholangiocarcinoma. The best palliation for unresectable disease remains debatable. We advocate nonoperative treatment with endobiliary expandable wire mesh stents for patients with unresectable disease.

A single-center experience with six-antigen-matched kidney transplants.

OBJECTIVES: To review our center's experience with the United Network of Organ Sharing six-antigen-matched (6-AgM) kidney program. Specifically, to determine whether recipients of 6-AgM cadaver kidney transplants have less perioperative and short-term (< 1 year) morbidity in comparison with living-related donor (LRD) recipients and a control group of immunologically less well-matched cadaver recipients. DESIGN: A retrospective review of all solitary kidney transplantations performed over a 24-month period, from 1992 to 1993. SETTING: A large urban tertiary care referral center with a long history of renal and extrarenal transplantation. PATIENTS: Adult patients receiving a solitary kidney transplant from either a cadaver or a living donor. MAIN OUTCOME MEASURES: Mortality, morbidity, and patient and graft survival. Other variables measured included rejection episodes, length of stay, readmissions, postoperative complications, waiting time, and delayed postoperative graft function. RESULTS: Recipients of 6-AgM kidney transplants were at higher risk than the control groups of cadaver and LRD recipients, with more retransplantations, higher sensitization, and more with diabetes. There were fewer rejection episodes in the 6-AgM group, and these were more steroid responsive. They had fewer hospital days (22.6 days) in the first year following transplantation, compared with the remaining cadaver group (28 days). The delayed postoperative graft function rate was also significantly lower than that of the cadaver control group. Graft and patient survival were excellent for all groups. Analysis of these factors showed similar results when comparing the LRD and 6-AgM groups and a marked improvement over the cadaver control group. CONCLUSIONS: Identical HLA matching for cadaver recipients provides superior results for graft and patient survival. There is much less perioperative morbidity in comparison with the less well-matched cadaver recipients. The effect of HLA matching is reflected in the perioperative courses of these patients, in addition to the long-term benefits of graft survival. Allograft survival is superior for this select group of cadaver recipients. The 6-AgM recipients behave similarly to LRD recipients in this cohort of patients. Our results would support the continued sharing of 6-AgM kidneys to optimize outcome and best use the limited resources available to the patients undergoing transplantation.

Hepatitis C viral infection in liver transplantation.

OBJECTIVE: To study the outcomes of patients who underwent liver transplantation for the primary diagnosis of chronic active hepatitis secondary to hepatitis C virus (HCV). DESIGN AND SETTING: Retrospective review within a university medical center. PATIENTS: Seventy-four adult recipients who received 78 orthotopic liver allografts for the primary diagnosis of chronic active hepatitis secondary to HCV between January 1990 and December 1994. Sixty-seven patients (91%) survived more than 2 months and were analyzed further for recurrent HCV infection. MAIN OUTCOME MEASURE: Recurrence of HCV infection, hepatitis, or cirrhosis and survival rates for patients who were undergoing orthotopic liver transplantation for chronic active hepatitis secondary to HCV. RESULTS: Actuarial survival rates for the entire group were 79.3%, 70.9%, and 64.5% at 1,2, and 3 years, respectively. Four patients (5% underwent retransplantation with an actuarial survival rate of 14.3% at 1 year (P<.05). Thirty-eight patients (57%) had evidence of posttransplant HCV infection, 31 patients (46%) showed histologic evidence of viral hepatitis, and 11 patients (16%) experienced portal fibrosis or cirrhosis. Seven (33%) of the deaths and all retransplantations were secondary to recurrent HCV infection. There were no significant differences in age, sex, United Network of Organ Sharing status, associated diagnoses, intraoperative packed red blood cell requirements, OKT3 use, or 1-, 2-, and 3-year survival rates in the recurrent vs nonrecurrent HCV infection groups. A higher incidence of posttransplant cirrhosis was observed in patients who were treated with tacrolimus (FK 506) (31.8% vs 8.9%, P<.05). Twenty-one patients (70%) received interferon alfa antiviral therapy with a significant benefit in the liver function test results during therapy (P<.01). CONCLUSIONS: Despite recurrence of HCV infection in most patients after transplantation, survival following primary orthotopic liver transplantation for chronic active hepatitis secondary to HCV infection remains favorable, and these patients should continue to be candidates for liver transplantation. In contrast, survival following retransplantation for HCV infection is poor and should be reconsidered. There is an apparent association between the intensity of immunosuppression and recurrent HCV infection and cirrhosis that warrants continued evaluation. Interferon therapy appears to afford benefit to patients in whom recurrent HCV hepatitis develops after transplantation.

Multimodality treatment of hepatocellular carcinoma in a hepatobiliary specialty center.

OBJECTIVES: To review the experience of the treatment of hepatocellular carcinoma by a single multimodality team during a 6-year period, including all patients who were referred for possible surgical intervention, to evaluate prognostic factors at presentation, and to determine the results of the different modalities of treatment that were used. DESIGN: Retrospective study of 154 patients who were referred to our Hepatobiliary Surgical Unit with the diagnosis of hepatocellular carcinoma from January 1988 through August 1995. SETTING: Tertiary care center. RESULTS: Methods of treatment included surgical resection (n=49), transplantation (n=22), hepatic artery chemoembolization (n=30), systemic chemotherapy (n=25), and no treatment (n=22). Predictive prognostic factors included coexisting cirrhosis, symptoms at presentation, and abnormal liver function test results. Unfavorable tumor characteristics were size (diameter, >5 cm) and multicentricity. For patients who underwent surgical exploration, advanced staging according to the manual of the American Joint Committee on Cancer, vascular invasion, and a margin of less than 1 cm in the group for patients who underwent resection impacted negatively on the prognosis. The median survival (42.4 months) for the group of patients who underwent resection was significantly higher than that for the groups of patients who did not undergo resection. Chemoembolization was associated with significantly better survival results than was systemic chemotherapy. CONCLUSIONS: Hepatic resection offers the best chance at cure for patients with hepatocellular carcinoma. The high association between hepatocellular carcinoma and cirrhotic liver disease makes surgical resection, even in favorable tumor types, a difficult task based on low hepatic reserve whose tumors are considered unresectable can be considered for chemoembolization. Liver transplantation should be reserved for selected patients with cirrhotic liver disease who have tumors (diameter, <5 cm) in the contest of neoadjuvant protocols.

Impact of recipient MELD score on resource utilization.

The model for end stage liver disease (MELD) system prioritizes deceased donor organs to the sickest patients who historically require higher healthcare expenditures. Limited information exists regarding the association of recipient MELD score with resource use. Adult recipients of a primary liver allograft (n = 222) performed at a single center in the first 27 months of the MELD system were analyzed. Costs were obtained for each recipient for the 12 defined categories of resource utilization from the time of transplant until discharge. True (calculated) MELD scores were used. Inpatient transplant costs were significantly associated with recipient MELD score (r = 0.20; p = 0.002). Overall 1-year patient survival was 85.0% and was not associated with MELD score (p = 0.57, log rank test). Recipient MELD score was significantly associated with costs for pharmacy, laboratories, radiology, dialysis and physical therapy. Multivariate linear regression revealed that MELD score was most strongly associated with cost compared to other demographic and clinical factors. Recipient MELD score is correlated with transplant costs without significantly impacting survival.

Percutaneous venovenous bypass in orthotopic liver transplantation.

Since January 1994, we have used percutaneous placement of both the subclavian and femoral cannulae to establish access for venovenous bypass during orthotopic liver transplantation. Percutaneous subclavian and femoral cannulae were used in 36 patients of which 5 had portal decompression by placement of a cannula in inferior mesenteric vein percutaneously through the abdominal wall. Intraoperative placement of the subclavian cannula is facilitated by placing a subclavian central venous line before the abdominal incision. One patient underwent exploration for femoral vein bleeding early in our experience. Another patient sustained hypotension as a result of a kinked subclavian cannula. In 4 patients, early in this experience, we had difficulty placing the subclavian cannula and resorted to axillary vein cut-down. There were no episodes of deep venous thrombosis detected by routine postoperative duplex ultrasonography. Minimum and maximum flow rates were significantly better (P < .01), with percutaneously placed cannulae in comparison to a control group of patients who underwent transplantation in whom we used the standard venous cut-down approach with a #7 Gott shunt (2.14 and 3.17 L/min v 1.65 and 2.41 L/min, respectively). Percutaneous placement of cannulae for venovenous bypass during liver transplantation is quick, safe, and effective. We would advocate this technique as an alternative approach for patients in whom bypass is deemed necessary.

Liver transplantation with incidental gallbladder carcinoma in the recipient hepatectomy.

Gallbladder carcinoma (GBCA) is the most common malignancy of the biliary tract and is often found seredipitiously after cholecystectomy. We report the first two cases of incidental GBCA in the native gallbladder of two liver transplant recipients. Both patients are 2.5 years following uneventful orthotopiic liver transplantation (OLTx) with no evidence of recurrent disease. Pathology of both recipients was early and favorable. Neither patient received any further therapy. Given the incidence of GBCA and the evolution of OLTx we would anticipate this finding to be more prevalent.

Primary malignant melanoma of the biliary tract.

Primary malignant melanoma of the biliary tract is an obscure entity, with only four previously reported cases. We report two cases involving the common bile duct. A 43-year-old male who underwent a right hepatectomy and excision of the extrahepatic biliary tree for a lesion at the bifurcation of the common bile duct. He remains alive and well 11 months after resection. The second patient is a 45 year old male with obstructive jaundice due to an ampullary lesion. Pancreaticoduodenectomy was performed with no signs of metastatic disease. He is 6 years following resection without evidence of disease. This is an unusual cause of obstructive jaundice and a definitive search for a possible extra-biliary primary should be pursued. In appropriately selected patients without evidence of metastatic disease, resection can potentially afford long-term survival if these lesions are true primary lesions and not metastatic from an undefined primary. However, given the high metastatic potential of melanoma it is unclear whether resection of these lesions results in cure or just effective long-term palliation.

Late stroke after carotid endarterectomy: the role of recurrent stenosis.

Perioperative stroke after carotid endarterectomy has been well studied, although little information is available regarding later strokes. We determined the etiology of late stroke after carotid endarterectomy by examining the records of those patients in our carotid registry who had a stroke more than 30 days after surgery. Thirty-five (5.1%) of the 688 patients in our registry had a stroke more than 30 days after surgery (mean follow-up, 59.3 months; standard error, 1.8 months; range, 1 to 292 months). The cause of late stroke was established by input from consulting neurologists, CT scanning of the head, magnetic resonance imaging results, angiograms, noninvasive studies, and postmortem examinations. Eight of the 11 strokes of unknown origin were massive fatal events for which no further evaluation was undertaken. Restenosis or occlusion accounted for fewer strokes (3 of 20, 15%) in the 1- to 36-month postoperative interval than in the greater than 36-month interval (8 of 15, 53.7%) (p less than 0.02 by Fisher's Exact Test). These data support the hypothesis that the early pseudointimal hyperplastic lesion is less likely to result in stroke than is later recurrent stenosis, which is usually related to atherosclerosis.

PGG-glucan, a leukocyte-specific immunostimulant, does not potentiate GVHD or allograft rejection.

PGG-glucan is an immunomodulator which can enhance the host response to infection. Phase I/II clinical trials have documented the safety and potential efficacy of this compound to reduce postoperative infectious complications in high risk surgical patients. Organ transplant recipients may benefit from this drug due to their high rates of postoperative infectious complications. A rat cardiac rejection model (ACI --> Lew) and a mouse skin graft model (C3H/HeJ --> B6AF1/J) were used with four treatment arms (control, Cyclosporine A (CsA), antilymphocyte serum (ALS), and CsA + ALS with and without PGG-glucan). Small intestinal allografts (Lew --> LBNF1) were performed in rats to evaluate GVHD. In the mouse GVHD model, donor splenocytes were given to irradiated recipients (C57BL/6 --> B6AF1), with and without PGG-glucan treatment. There was no difference in survival between PGG-glucan treatment and placebo for the control, CsA, and CsA + ALS groups in rat cardiac recipients. Recipients receiving ALS and treated with PGG-glucan survived a median of 42.5 days versus 63.5 days for those ALS-treated animals not receiving PGG-glucan (P = 0.045). In the remaining groups there was no difference in survival between PGG-glucan-treated groups and the control groups. PGG-glucan did not shorten survival in three of four treatment groups in the rat cardiac rejection model. High dose ALS with PGG-glucan did result in a marginal decrease in survival in cardiac allograft recipients. If the one outlying animal with indefinite survival is excluded, the difference is not statistically significant (P = 0.098). These results show that even though PGG-glucan has immunostimulatory properties, it does not significantly potentiate rejection or GVHD in these animal models. This preliminary work may be important in determining whether PGG-glucan can be safely given to immunosuppressed organ transplant recipients to reduce postoperative infectious complications.

Liver transplantation for adult polycystic liver disease.

Patients with adult polycystic liver disease and massive cystic replacement of the liver may present with severe debilitation and impairment of functional performance or, rarely, with signs of portal hypertension or hepatic dysfunction. In those patients incapacitated by severe hepatomegaly secondary to massive cystic replacement with predominantly small cysts (2 cm) without areas of parenchymal sparing, liver transplantation is a therapeutic option. Five patients with incapacitating symptoms from polycystic liver disease underwent liver transplantation as a final therapeutic procedure. Two patients had previous fenestration procedures without significant relief. All patients had radiographic evidence of concomitant polycystic kidney disease; two of these patients were dialysis-dependent at the time of liver transplantation. One patient underwent combined liver-kidney transplantation, whereas another received a six-antigen matched kidney transplant 64 months after liver transplantation. Four of five patients are alive 84, 39, 20, and 8 months after successful liver transplantation. All four have returned to normal functional status with complete resolution of symptoms. Liver transplantation is a suitable option for the patient with bilobar small cystic liver disease without areas of parenchymal sparing. However, only patients with severely compromised functional status should be offered this therapy. Concomitant renal evaluation is mandatory, and a knowledge of the natural history of this disease will aid in the decision of whether a combined liver-kidney transplantation is indicated.

MR angiography of the portal venous system: techniques, interpretation, and clinical applications.

Magnetic resonance (MR) angiography is a noninvasive means of assessing the portal venous system that has potential advantages over currently used modalities. Time-of-flight and phase-contrast MR angiography are useful techniques that differ fundamentally in their means of data acquisition but are comparable in their ability to demonstrate normal anatomy as well as abnormalities of the portal venous system. Occasionally, artifacts caused by respiratory motion, implanted metallic devices or surgical clips, in-plane saturation, or areas of complex flow are seen at MR angiography of the portal venous system. However, most artifacts can easily be identified as such and either remedied or ignored. In addition, the suppression of signal from surrounding soft tissues may result in poor detection of parenchymal lesions. The utility of standard projection angiograms and source images can be increased through the use of intravenously administered contrast material and postprocessing techniques such as partial-volume maximum intensity projection reconstructions and shaded surface renderings. In addition to providing information on portal venous anatomy and portosystemic collateral vessels, MR angiography of the portal vein has clinical application in portal venous thrombosis and stenosis, liver transplantation, and the evaluation and planning of surgical and transjugular intrahepatic portosystemic shunts.