Prospective validation of ab initio liver transplantation in hepatocellular carcinoma upon detection of risk factors for recurrence after resection

Abstract

A decade ago we proposed to enlist for transplantation those patients with resected hepatocellular carcinoma in whom pathology registered pejorative histological markers (microvascular invasion and/or satellites; ab initio indication) and not wait for the appearance of recurrence. This study evaluates the outcome of this approach. From 1995 to 2012, 164 patients with hepatocellular carcinoma underwent resection. Eighty-five patients were potential candidates for liver transplantation and were considered for it upon detection of pejorative histological markers. Patients without these markers were followed, and salvage liver transplantation was considered upon development of tumor recurrence/liver function impairment. Thirtyseven patients were at high risk and 48 at low risk of recurrence at pathology. Twenty-three out of 37 high-risk patients recurred during follow-up, but in nine of them the tumor burden extent contraindicated liver transplantation. Seventeen were finally transplanted: 10 of them presented recurrence at imaging/explant. After a median posttransplant follow-up of 50.9 months, hepatocellular carcinoma had recurred in two patients and five patients had died, the 5-year survival being 82.4%. Twenty-six of the 48 low-risk patients developed recurrence, and 11 of them were transplanted. After a median posttransplant follow-up of 59 months, two patients developed recurrence and five died, their 5-year survival being 81.8%. Conclusion: Enlistment of patients at high risk of HCC recurrence after resection but before recurrence development seems a valid strategy and is associated with excellent long-term outcome; as early (<6 months) recurrence reflects an aggressive tumor behavior leading to tumor extent exceeding transplant criteria, we propose to wait at least 6 months before enlistment; however, once included on the waiting list, priority strategies should be implemented in order to reach effective transplantation prior to the appearance of recurrence. (HEPATOLOGY 2016;63:839-849) H epatocellular carcinoma (HCC) is the most common primary tumor of the liver. The incidence of HCC is increasing in the United States and Europe, and it is currently the third leading cause of cancer-related death globally.(1,2) Liver transplantation (LT) is theoretically the treatment of choice because it allows removal not only of the tumor but also of the underlying cirrhosis. It offers a high survival rate and a low recurrence rate in well-selected cases. (3,4) Although Spain has the highest rate of

Liver Resection and Transplantation for Patients With Hepatocellular Carcinoma Beyond Milan Criteria

“…Although this approach has been previously employed and recently prospectively evaluated in patients with early stage HCC harboring worrisome histologic features such as microvascular invasion and/or satellitosis, 32 similar findings maybe applicable after resection of patients with HCC beyond Milan criteria and an interval of observation to exclude early progression.…”

Limitations of predicting microvascular invasion in patients with hepatocellular cancer prior to liver transplantation

“…Conversely, the concept of ab initio transplantation after liver resection in patients with a diagnosis of microvascular invasion in surgical specimen was suggested as an alternate strategy in order to maximize the benefit of liver transplantation over resection in the era of organ shortage47. Its feasibility was recently reported, yet the use of an additional criterion of a minimum 6-month recurrence-free interval was suggested to avoid early recurrences48. Accordingly, the results of this study indicate that such additional criterion may be replaced with preoperative stratification of patients into those with low and high risk microvascular invasion.…”

Prognostic factors in patients with recurrent hepatocellular carcinoma treated with salvage liver transplantation: a single-center study

“…Several previous studies have recommended the use of salvage LT prior to HCC recurrence in patients with unfavorable risk factors [9, 19, 27]. For example, Fuks et al recommended performing salvage LT before HCC recurrence in patients with ≥ 3 of the five pejorative factors (MVI, satellite nodules, tumor > 3 cm, poorly differentiated tumor, and liver cirrhosis) [9].…”

“…Another recent study conducted by Ferrer-Fabrega et al proposed a waiting time of > 6 months between resection and enlistment for transplant, even in patients at high risk or recurrence (MVI and/or additional nodules or satellites), such that they could identify patients with less aggressive tumors and avoid performing LTs on patients with aggressive tumors (associated with a high risk of post-LT HCC recurrence and decreased survival) [27]. They recommend the use of salvage LT before recurrence in high-risk patients but not in patients with biologically aggressive tumors, in order to avoid disease recurrence with a dismal prognosis post-LT.…”