Efficacy of Sorafenib for the Treatment of Post-Transplant Hepatocellular Carcinoma Recurrence.

BACKGROUND: The role of sorafenib in patients with hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) has been rarely studied. The aim of this study was to evaluate the efficacy of sorafenib in post-LT era. METHODS: Consecutive patients with post-transplant HCC recurrence not eligible to resection or locoregional therapy were included. Patients receiving best supportive care (BSC) until 2007 were compared with those treated by sorafenib thereafter. RESULTS: Of a total of 65 patients, 20 patients received BSC and 45 received sorafenib. Clinical characteristics were similar between two groups except that sorafenib group received tacrolimus and mammalian target-of-rapamycin inhibitors more frequently than BSC group. Treatment with sorafenib conferred a survival advantage as compared with BSC for survival after recurrence (median, 14.2 vs. 6.8 months; P = 0.01). In multivariate analyses, high serum α-fetoprotein level, synchronous intrahepatic recurrence and distant metastasis at the time of recurrence, and BSC were independently associated with poorer survival after recurrence. Sorafenib treatment was associated with better survival after recurrence as compared with BSC (hazard ratio, 0.25; 95% confidence interval, 0.10-0.62; P = 0.002). In addition, sorafenib group showed tolerable toxicity in the post-transplant setting. CONCLUSION: Sorafenib may be beneficial in patients with post-transplant HCC recurrence.

Comparison of treatment outcome between living donor liver transplantation and sorafenib for patients with hepatocellular carcinoma beyond the Milan criteria.

For patients with advanced hepatocellular carcinoma (HCC), sorafenib is the only systemic treatment recommended by international guidelines. We recently reported that HCC patients with a low MoRAL (model to predict tumor recurrence after LDLT) score (≤ 314.8) have excellent treatment outcomes after living-donor liver transplantation (LDLT), even though they are beyond the Milan criteria. In the present study, we investigated whether LDLT offers a better treatment outcome than sorafenib for patients with HCC beyond the Milan criteria according to the MoRAL score. A retrospective cohort study of 325 consecutive patients who were treated with either LDLT (n = 122) or sorafenib (n = 203) for HCC beyond the Milan criteria from 2005 to 2014 at a tertiary hospital was performed. The primary and secondary endpoints were overall survival (OS) and time-to-progression. When baseline characteristics were balanced using inverse probability weighting, OS was significantly longer in the LDLT group than in the sorafenib group (5-year OS rate, 71.9% vs. 4.9%; HR=0.1; P < 0.001). The LDLT group exhibited a significantly lower risk of tumor progression (5-year recurrence rate, 34.7% vs. 96%; HR=0.14; P < 0.001) than the sorafenib group. The increase in OS with LDLT was predominantly among patients with a low MoRAL score (5-year OS rate, 81.1% vs. 5.8%; HR=0.06; P < 0.001) compared with those with a high MoRAL score (5-year OS rate, 28.3% vs. 4.3%; HR = 0.42; P = 0.047). Patients with a low MoRAL score and without extrahepatic metastasis or hepatic vein invasion might be good candidates for LDLT instead of sorafenib treatment if there is a willing living related donor.

Metastatic follicular struma ovarii complicating pregnancy: a case report and review of the literature.

A 35-year-old woman was determined to have an ovarian cyst and underwent a right ovarian cystectomy at 10 weeks of gestation. A histopathological examination revealed follicular carcinoma arising in a teratoma. No evidence of metastasis was found after delivery. She underwent a total thyroidectomy, followed by radioactive iodine (RAI) therapy. However, her serum thyroglobulin level increased to 1,437 ng/ml (normal range: 0-52 ng/ml) after 10 months. Radioiodine scintigraphy and abdominal computed tomography revealed liver metastasis and peritoneal seeding. She underwent debulking surgery of the liver, right salpinx, and peritoneal seeding nodules. A pathological examination showed metastatic follicular carcinoma with focal poorly differentiated features. Adjuvant RAI therapy was restarted, and her serum thyroglobulin levels returned to normal. In conclusion, metastatic lesions were successfully treated with a combination of debulking surgery and RAI therapy. Close medical follow-up monitoring serum thyroglobulin levels is mandatory in such patients.

Adjuvant chemoradiation therapy in gallbladder cancer.

BACKGROUND AND OBJECTIVES: Gallbladder cancer is a relatively uncommon gastrointestinal malignancy. Indications for adjuvant chemoradiation therapy after surgical resection have not yet been determined. We aimed this study to elucidate the effectiveness of adjuvant chemoradiation therapy according to TNM stage for gallbladder cancer. METHODS: Between March 2001 and March 2009, 100 patients with gallbladder cancer underwent surgical resection. We divided the patients according to TNM stage, and subdivided further according to whether adjuvant chemoradiation therapy was added or not. The clinicopathologic factors, recurrence and survival were retrospectively analyzed. RESULTS: Patients with gallbladder cancer at T2N0M0, T2N1M0, T3N0M0, and T3N1M0 stages were enrolled in this study. Among the four stages, the two lymph node-negative stages (T2N0M0 and T3N0M0) did not show any gain in survival by adding adjuvant chemoradiation therapy. Conversely, the remaining lymph node-positive stages (T2N1M0 and T3N1M0) showed gain in disease-free survival, and the lymph node-positive T2 stage (T2N1M0) showed gain in disease-specific survival. In patients with lymph node-positive T2/T3 GB cancers, adjuvant chemoradiation therapy was an independent prognostic factor for survival. CONCLUSIONS: Adjuvant chemoradiation therapy is recommended for lymph node-positive T2/T3 gallbladder cancer following surgical resection.

Learning curve for living-donor liver transplantation in a fledgling cancer center.

Hepatocellular carcinoma (HCC) has become one of the main indications for liver transplantation. To keep abreast of the times, a comprehensive cancer center may have to perform liver transplantation as a treatment option for HCC. We introduce a learning curve for living-donor liver transplantation(LDLT) and present our initial experience in a new cancer center as an example to any center considering LDLT. A total of 51 consecutive adult right liver LDLTs performed from January 2005 to January 2008 were analyzed by comparing the first 17 transplants performed with the help of an outside experienced team (group 1) with the middle 17 (group 2) and the last 17 cases(group 3) performed in our center independently. There was no hospital mortality in donors and recipients. In a mean follow-up of 34 months (range: 12-48 months), there was only one case of late mortality in donor and recipient,respectively. A total of four donors and 12 recipients underwent re-operations.The warm ischemic time was significantly longer in group 2 than that in groups 1 and 3. Otherwise, there was no significant difference in the operative outcomes among the three groups. Thorough preparation and the assistance of an experienced liver transplantation team at the beginning can facilitate a more rapid learning curve and bring about a good outcome even in a small, newly established institution.

Hepatocyte transplantation for glycogen storage disease type Ib.

Glycogen storage disease type I (GSD-I) is a group of autosomal recessive disorders with an incidence of 1 in 100,000. The two major subtypes are GSD-Ia, caused by a deficiency of glucose-6-phosphatase (G6Pase), and GSD-Ib, caused by a deficiency of glucose-6-phosphate transporter (G6PT). We report that a substantial improvement was achieved following several infusions of hepatocytes in a patient with GSD-Ib. Hepatocytes were isolated from the unused cadaveric whole livers of two donors. At the first transplantation, approximately 2 x 10(9) cells (2% of the estimated recipient's total hepatocytes) were infused. Seven days later 1 x 10(9) (1% of liver mass) cryopreserved hepatocytes from the same donor were infused, and an additional 3 x 10(9) (3% of liver mass) cells from the second donor were infused 1 month after the second transplantation. After the hepatocyte transplantation, the patient showed no hypoglycemic symptoms despite the discontinuation of cornstarch meals. Liver biopsies on posttransplantation days 20 and 250 showed a normal level of glucose-6-phosphatase activity in presolubilization assay that was very low before transplantation. This was the first and successful clinical hepatocyte transplantation in Korea. In this study, hepatocyte transplantation allowed a normal diet in a patient with GSD-Ib, with substantial improvement in their quality of life. Hepatocyte transplantation might be an alternative to liver transplantation and dietary therapy in GSD-Ib.