Guide Disease Recurrence After Liver Transplantation: Natural History, Treatment and Survival

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Recurrence of primary biliary cirrhosis following liver transplantation — Mayo Clinic

They followed 82 patients over a year period. One would have to postulate, therefore, that the additional CSA doses given to the recurrence-group patients during the second half of the first year immediately translated into rapid tumor growth. More recently, there has been some interest in the possible efficacy of adding rapamycin immunosuppression to the antirejection regimen following transplantation for HCC.

Because of its antiproliferative effects, it is postulated that this drug could potentially inhibit growth of any residual tumor cells. A pilot clinical trial assessing this hypothesis is now beginning. The efficacy of adjuvant chemotherapy as prophylaxis for tumor recurrence has not been systematically evaluated. This drug is generally well tolerated, except for bone marrow and cardiac toxicities.

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The explanted liver tumor burden in all liver allograft recipients enrolled in the study met the Milan criteria. Sixteen were enrolled into the study. Seven patients were excluded because they received multidrug regimens two patients , had early complications precluding adjuvant chemotherapy four patients , or had left the region one patient. All patients completed the treatment course with only occasional interruptions for reversible myelosuppression. Of the patients enrolled, one died from unrelated causes and two developed recurrent HCC within 4 years. Thirteen were alive with excellent liver function and no evidence of recurrent disease with a median follow-up of These observations were compared with those from a cohort of patients receiving liver allografts for HCC at other centers in our UNOS region during the same time period.

In contrast, the survival rates for our cohort receiving post-OLT chemotherapy were Similarly encouraging observations have been reported by other groups [ 46 ], but no controlled studies of adjuvant chemotherapy have been completed. Fibrolamellar carcinoma is a rare, less-aggressive form of HCC. This tumor does not appear to be related to underlying viral disease or cirrhosis. The malignant hepatocytes are large and polygonal in shape, and calcifications are not uncommon. In an excellent review, El-Serag and Davila [ 47 ] investigated the outcomes of fibrolamellar carcinoma patients compared with those of HCC patients in a population-based study.

They identified 68 patients with fibrolamellar carcinoma and 7, patients with HCC during the years — The mean patient age at diagnosis of fibrolamellar carcinoma was 39 years; that of HCC was 65 years. The survival rate was significantly better for patients with fibrolamellar carcinoma, most notably at 1 year, at Ringe et al.

Fourteen patients underwent radical and complete resections and six patients underwent hepatectomies and liver transplantations. The 5-year survival rates were The resection-alone group, as expected, had an overall lower tumor stage, which undoubtedly accounted for their superior outcome over those treated by transplantation [ 48 ]. The largest single-center series was reported by investigators at the University of Pittsburgh.

One-third of the patients undergoing transplantation required concomitant resection of adjacent organs, the vast majority having stage IVa and IVb tumors [ 49 ]. Appropriate staging studies are the same as for HCC; extrahepatic disease is a contraindication for liver transplantation. In the early days of liver transplantation, CCC was considered an appropriate indication for transplantation, since survival after resection for CCC was so poor and these patients were generally in good overall condition without the complications of cirrhosis and portal hypertension.

However, the initially treated allograft recipients quickly established that CCC was not an acceptable indication for liver transplantation due to early disease recurrence and poor long-term survival.


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This observation was confirmed by the Cincinnati Transplant Tumor Registry. From —, patients were registered after undergoing a liver transplantation for CCC. Of those who died, the median survival time was only 8. This view is also supported by the publication by Goss et al.

Liver Transplantation for Patients with Cholestatic Liver Diseases

These data have led to a general consensus that, in light of limited donor organ availability, liver transplantation is not a suitable therapeutic approach for patients with CCC. Recently, the Mayo Clinic group suggested that this practice should be re-evaluated. They have designed a protocol that includes pretransplant external-beam irradiation followed by transcatheter irradiation and 5-fluorouracil 5-FU infusion.

An exploratory laparotomy is then performed to exclude extrahilar lymph node disease, following which the patient is activated on the waiting list. In their initial report, 19 patients had been treated under this protocol, 11 of whom proved to be eligible for liver transplantation. All 11 patients were alive 17—83 months after the OLT.

Only one patient, who had unrecognized stage IV disease at the time of transplantation, manifested disease recurrence in mediastinal lymph nodes but was alive 40 months after the transplantation [ 53 , 54 ]. Those investigators concluded that liver transplantation after pretransplant conditioning with radiation and chemotherapy provides effective therapy for patients with CCC with disease limited to stage I or stage II. Under these stringent criteria, liver transplantation could be an option in very selected cases. Epitheloid hemangioendothelioma is a disease that was first described in , affecting mainly younger females and resulting from a malignant transformation of vascular endothelium.

An association with oral contraceptives has been suggested but not completely established. Clinical presentation may be with abdominal pain, but more frequently the lesion is an incidental finding.


  • Post-Liver Transplantation Management.
  • Recurrence of hepatocellular carcinoma after liver transplant: patterns and prognosis..
  • Is disease recurrence still relevant to graft survival?.
  • Since the tumor is often widespread within the parenchyma, complete resection may not be possible, even in the noncirrhotic liver. The results after liver transplantation are quite acceptable, being comparable with those after OLT for viral-induced cirrhosis. The largest single-center report comes from the Pittsburgh Transplant Center. In 16 patients with a median follow-up of 4. The disease-free survival rates were In contrast, angiosarcoma also originates from the endothelium; but unlike epitheloid hemangioendothelioma, this tumor is very aggressive, typically filling the hepatic sinusoids and causing hepatocyte atrophy.

    Surgical resection is complicated by a high early recurrence rate, and there is clearly no role for liver transplantation for this endothelial cell tumor. Diagnosis and staging of both vascular tumors are done by biopsy and imaging.

    Post-Liver Transplantation Management

    Diagnosis is usually at a late stage. Liver transplantation plays a role only in those patients whose tumors cannot be completely resected after appropriate chemotherapy. The most complete report of liver transplantation was published by Otte et al. A multivariate analysis showed that the only variable adversely impacting outcome was the presence of macroscopic venous invasion. Additional encouraging results were published by the London group at Kings College Hospital: 13 children 11 boys, two girls were alive after liver transplantation at a mean follow-up of 33 months.

    One child was alive with tumor recurrence. Most remarkably, some of these long-term remissions were achieved in children who had received pretransplant chemotherapy for pulmonary metastases and extrahepatic intra-abdominal tumor growth [ 58 ]. A similar experience was reported by the Birmingham group. Thirty-four children with hepatoblastomas were treated over a period of 10 years. Three of the five patients whose tumors were not chemosensitive were alive with no evidence of recurrent disease. Two patients died, one of recurrence 23 months after transplantation and the second of unrelated causes [ 59 ].

    As already noted, metastatic disease is a contraindication for liver transplantation except when the primary disease is a neuroendocrine tumor. Neuroendocrine tumors are also referred to as apudomas amine precursor uptake and decarboxylation. These tumors are usually hormone producing serotonin, insulin, gastrin, glucagon, etc. The clinical presentation is diverse, depending upon the hormone secreted.

    These tumors typically metastasize to the liver, and some patients note pain, resulting from capsule distention, as a first symptom. Even after metastasizing, these tumors often remain slow growing so that approximately one-third of the patients survives for 5 years after the development of liver metastases. Because of the somewhat indolent nature of their liver metastases, these patients are considered appropriate candidates for liver transplantation.

    In the French experience [ 60 ], 31 patients diagnosed with neuroendocrine tumors underwent liver transplantations. In 14 patients, the primary tumors were also removed at the time of transplantation. Other authors support this view. The Milan group compared resection with liver transplantation for patients with neuroendocrine tumors of comparable sizes and histology.

    The conclusion of that study was that OLT can be proposed for young patients with carcinoid tumors confirmed by histology, with primary tumors originating in the gastrointestinal tract, previously removed surgically, controlled for at least 6 months after the resection, and without signs of extrahepatic metastases.

    The importance of removing the primary tumor before the liver transplantation was confirmed by Lang et al. Three of four patients who were free of recurrence 2, 57, 58, and months after transplantation did not have extrahepatic tumor manifestations at the time of transplantation. In contrast, 5 of 12 patients with recurrences had extrahepatic disease, including four patients with unknown primaries.

    Adjunctive procedures like RFA, chemoembolization, or cryotherapy might be indicated to limit tumor progression for patients on waiting lists. And finally, while gallbladder cancers are never an indication for liver transplantation, rare cases of CCC might qualify if aggressive combination therapies, including chemotherapy and radiotherapy followed by OLT, are carried through. User Name Password Sign In. Accepted January 14, L earning O bjectives After completing this course, the reader will be able to: List the indications for liver transplantation in patients with hepatobiliary malignancies.

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