Late recurrence of hepatocellular carcinoma after liver transplantation: is an active surveillance for recurrence needed?

INTRODUCTION: Liver transplantation (OLT) is considered the most efficient therapeutic option for patients with liver cirrhosis and early stage hepatocellular carcinoma (HCC) in terms of overall survival and recurrence rates, when restrictive selection criteria are applied. Nevertheless, tumor recurrence may occur in 3.5% to 21% of recipients. It usually occurs within 2 years following OLT, having a major negative impact on prognosis. The efficacy of active posttransplantation surveillance for recurrence has not been demonstrated, due to the poor prognosis of recipients with recurrences. AIM: To analyze the clinical, pathological, and prognostic consequences of late recurrence (>5 years after OLT). METHOD: We analyzed the clinical records of 165 HCC patients including 142 males of overall mean age of 58 ± 6.9 years who underwent OLT between July 1994 and August 2011. RESULTS: Overall survival was 84%, 76%, 66.8%, and 57% at 1, 3, 5, and 10 years, respectively. Tumor recurrence, which was observed in 18 (10.9%) recipients, was a major predictive factor for survival: its rates were 72.2%, 53.3%, 26.7%, and 10% at 1, 3, 5, and 10 years, respectively. HCC recurrence was detected in 77.8% of patients within the first 3 years after OLT. Three recipients (100% males, aged 54-60 years) showed late recurrences after 7, 9, and 10 years. In only one case were Milan criteria surpassed after the examination of explanted liver; no vascular invasion was detected in any case. Recurrence sites were peritoneal, intrahepatic, and subcutaneous abdominal wall tissue. In all cases, immunosuppression was switched from a calcineurin-inhibitor to a mammalian target of rapamycin inhibitor. We surgically resected the extrahepatic recurrences. The remaining recipient was treated with transarterial chemoembolization with doxorubicin-eluting beads and sorafenib. Prognosis after diagnosis of recurrence was poor with median a survival of 278 days (range, 114-704). CONCLUSIONS: Global survival, recurrence rate, and pattern of recurrence were similar to previously reported data. Nevertheless, in three patients recurrence was diagnosed >5 years after OLT. Although recurrence was limited and surgically removed in two cases, disease-free survival was poor. Thus, prolonged active surveillance for HCC recurrence beyond 5 years after OLT may be not useful to provide a survival benefit for these patients.

Strategies of immunosuppression for liver transplant recipients with hepatocellular carcinoma.

Liver transplantation is considered to be the most efficient therapeutic option for patients with liver cirrhosis and early stage hepatocellular carcinoma (HCC) in terms of overall survival and recurrence rate. The application of restrictive selection criteria based on tumor size and number of nodules is advised to obtain optimal results. Nevertheless, tumor recurrence occurs in 3.5% to 21% of recipients, despite careful pretransplant staging and patient selection. Post transplant recurrence of hepatocarcinoma clearly has a major negative impact on prognosis. Intuitively, an immunosupressed state is undesirable in cancer patients. Inversely, modulation or minimization of immunosuppressive therapy could influence tumor progression and reduce the negative impact of recurrence on posttransplant survival. Experimental evidence shows that mammalian target of rapamycin (mTOR) inhibitors have antiangiogenic and antiproliferative effects. Thus, their application has been proposed as antineoplastic agents for immunosuppressive protocols in liver transplant recipients with HCC and may reduce the rate or the impact of tumor recurrence. Clinical data about efficacy and safety of mTOR-based immunosuppressant protocols in liver transplant recipients with HCC show promising results, namely low recurrence and higher survival rates compared with standard calcineurin inhibitor-based immunosuppressive protocols, even among patients with extended morphological criteria. The safety profile is regarded generally as adequate.

The future of liver transplantation.

Liver transplantation has been a positive impact on both the survival and the quality of life of patients with advanced liver diseases. Progressive, spectacular improvements in the results of liver transplantation have been observed since the preliminary studies by Thomas Starzl in the United States and Roy Calne in Europe. This improvement is related to better knowledge of the natural history of liver diseases, allowing more adequate recipient selection, improvement of surgical techniques, progress in postoperative management, availability of potent antibacterial, antiviral, and antifungal drugs, as well as introduction of new immunosuppressive agents and protocols. These advances have occurred in the short interval of 45 years, suggesting future improvements in the liver transplantation field. The main investigative efforts in liver transplantation have been directed as follows: First attenuation of disproprortion between the numbers of available liver grafts versus waiting list recipients, by increasing the donor pool applying bioartificial support systems, or rendering grafts compatible by the use of stem cells. Second, improved knowledge about the biology of primary liver tumors establishes indications for and optimal moments of transplantation. Third, application of individualized immunosuppressive protocols, adapted to clinical status of the recipient, as well as the development of more selective, less toxic new immunosuppressive agents.

[Epidermoid cyst: a rare cause of cystic liver disease]. / Quiste epidermoide: una causa infrecuente de patología quística hepática.

We present the case of a 42-year-old male patient with a large hepatic cyst, simulating a hydatid cyst. Subtotal cystectomy was performed. Thirteen months after this procedure the patient relapsed and a second laparotomy and total cystectomy were performed. A histopathological diagnosis of epidermoid cyst of the liver was made. The differential diagnosis of epidermoid cysts of the liver is broad and definitive diagnosis is usually only obtained after pathological examination of the surgical specimen. For this reason, and because of the potential for neoplasia, complete resection of the hepatic lesion should be attempted.

[Technical solution in kidney retransplantation in a patient with femoro-femoral bypass]. / Solución técnica en el retrasplante renal de un paciente portador de un by-pass femoro-femoral.

Over the last decade kidney transplantation has become a common therapeutic procedure for patients with end-stage renal diseases. Between 1988 and 1998 donors rate per million population has dramatically increased in our environment, thus providing us with more chances to offer kidney transplantation to a larger number of patients. The technico-surgical difficulties that have to be faced however, are increasingly frequent and require a search for new approaches and innovative changes to the usual surgical techniques for our patient's benefit.

[Cancer of the gallbladder: survival and life quality depending on the type of surgical treatment]. / Cáncer de vesícula: supervivencia y calidad de vida según el tipo de tratamiento quirúrgico.

An analysis is made of the survival and life quality of 47 patients diagnosed by histopathology as gallbladder cancer, in relation to surgical treatment. The 47 patients, with a mean age of 70 years and a male female ratio of 1:3.7, were classified according to the Nevin stages: there were no stage I patients, 1 stage II, 8 III-IV and 38 V. The operations performed were 20 simple cholecystectomies with excision of a portion of adjacent hepatic tissue; 11 radical cholecystectomies; 10 surgical intubations; 3 percutaneous endoprosthesis; 2 gastroenteroanastomoses and 1 exploratory laparotomy. The results showed: 1) Radical cholecystectomy was the best therapeutic method, providing the longest survival (433 days) with the smallest proportion of days of poor life quality (10%). 2) In patients in stages II, III, IV, simple cholecystectomy with excision of the adjacent liver tissue yielded a survival of more than a year, even in patients of advanced age (greater than 80 years). 3) Although percutaneous and surgical intubation achieved a similar survival, the first technique produced a better quality of life. 4) In view of the diversity of the surgical techniques practiced in patients in stage V, a revaluation of this stage is necessary to individualize treatment.