Successful Liver Transplantation in Two Cases of Metastatic Gastrointestinal Stromal Tumors

Abstract

Orthotopic liver transplantation (OLT) for malignant liver tumors can be performed if long-term results are expected to be similar to those of OLT for benign liver diseases. OLT is thus a recognized treatment for hepatoblastoma and epithelioid hemangioendothelioma (EHE) (1). Until now, liver metastases of neuroendocrine tumors are the only metastatic tumors which have been accepted for OLT (2). We re-evaluated two cases of OLT for unresectable liver metastases of primary mesenchymal tumors. Both cases showed c-kit positivity for the initial gastric tumors and the liver metastases, allowing their classification as gastrointestinal stromal tumors (GISTs) with liver metastases. The GIST of the second patient was part of a Carney triad, a rare tumor syndrome that includes pulmonary hamartochondromatosis, extra-adrenal paraganglioma, and adrenocortical tumors (3). Case 1 In 1996, a 39-year-old male patient underwent partial resection of the stomach for a leiomyosarcoma (LMS) of 4.5 cm. Four years later, multilobar liver metastasis was diagnosed (Fig. 1A). Neither chemotherapy nor chemoembolization were effective. In the same year, OLT of the right liver lobe from a living donor was performed. Follow-up examinations have not shown any tumor recurrence over a period of 48 months.FIGURE 1.: (A) Computer tomography of the abdomen before liver transplantation, without (left) and with (right) contrast medium in the portal venous phase. The multifocal liver metastasis of the in part cystic, in part solid GIST is clearly visible. Nearby there is demonstrated the fill-in-sign and rim-sign in contrast-enhanced scan. The metastasis in segment II/III has a maximal diameter of 10 × 7 cm. (B) T1-weighted magnetic resonance tomography of the abdomen native (left) and contrast-enhanced (right) after atypical liver resection of segment III, V, and VIII, and cholecystectomy. The uptake of contrast medium by the metastases is demonstrated.Case 2 In 1989, a then 29-year-old female patient underwent a Billroth II operation for a mesenchymal tumor of the stomach. In 1991, a paraganglioma of 3.5 cm was resected at the left carotid bifurcation. In 1997, a computed tomography scan of the abdomen revealed several liver nodules of up to 1.6 cm in diameter and a tumor in the left adrenal gland of 1.5 cm. The following year, atypical liver resection of the segments III, V, and VIII and cholecystectomy were performed (Fig. 1B). The tumors were histologically classified as EHE. A spread into other liver segments could not be excluded. In preparation of OLT, two nodules of high CT density in the right lung were resected. Examination revealed central ossificating hamartochondromas of 4.0 and 2.5 cm. In 1999, OLT from a cadaveric donor was performed. Follow-up examinations during the past 69 months have not shown any tumor recurrence. Resection of liver metastases is a treatment option for metastatic mesenchymal tumors, including GISTs (4). Common chemo- and radiotherapies are ineffective. OLT has not yet been reported for metastasis of sporadic GIST or within the Carney triad. When the liver metastases became apparent, neither the diagnosis of GIST was made, nor was the therapy with the selective tyrosine kinase inhibitor Imatinib (Gleevec) for GIST available. OLT was the successful treatment in both cases with a long-term, recurrence-free survival. In advanced GIST, a sustained response with Imatinib can be achieved in more than half of the patients but without complete disease-free state (5). On the other hand, tumor progress under Imatinib therapy occurs in 11% of the cases (6), and resistance against Imatinib can be observed after long-term use of the drug. Therefore, because GISTs almost exclusively metastasize to the liver, tk;4OLT should be considered for advanced metastatic GIST if local resection is not feasible and Imatinib therapy is ineffective. Silke Cameron Giuliano Ramadori Department of Gastroenterology and Endocrinology University Clinic of the Georg August University Göttingen, Germany Laszlo Füzesi Burkhart Sattler Bastian Gunawan Department of Gastroenteropathology University Clinic of the Georg August University Göttingen, Germany Dieter Müller Department of Diagnostic Radiology University Clinic of the Georg August University Göttingen, Germany Burkhardt Ringe Thomas Lorf Department of Transplant Surgery University Clinic of the Georg August University Göttingen, Germany