Impact of surgical treatment after sorafenib therapy for advanced hepatocellular carcinoma.

BACKGROUND: For advanced hepatocellular carcinoma (HCC), surgical treatment after sorafenib induction has rarely been reported. We examined the survival benefit of additional surgical treatment in sorafenib-treated patients. METHODS: Thirty-two advanced HCC patients were given sorafenib from July 2009 to July 2012, and we statistically analyzed the relevant predictive factors of the long-term survival. The institutional review board of Kumamoto University Hospital approved this study (Approval number 1038). RESULTS: The median duration of sorafenib administration was 56.5 days (range 5-945). The cumulative overall survival rate was 44.6, 33.4, 26.0 and 17.8% at 1, 2, 3 and 5 years, respectively. The median survival time was 11.2 months. A survival of more than 3 years after the initiation of sorafenib induction was observed in seven patients, five of whom were subjected to additional surgical intervention. Additional surgery was the most significant factor predicting a survival exceeding 3 years (P < 0.0001) and represents an independent prognostic factor [hazard ratio (HR) 0.07; P = 0.01], followed by the total dose of sorafenib. The surgical interventions comprised two hepatic resections ± radiofrequency ablation, two radiofrequency ablations and one lung resection. CONCLUSIONS: A long-term survival might be obtained for select HCC patients given adequate additional surgical treatment, even after sorafenib induction.

Recurrence-free survival of a hepatocellular carcinoma patient with tumor thrombosis of the inferior vena cava after treatment with sorafenib and hepatic resection.

Sorafenib (Nexabar, Bayer, Berlin, Germany), one of multikinase inhibitors, can infrequently downstage advanced hepatocellular carcinoma (HCC). There are some reports that sorafenib in combination with other modalities, such as transcatheter arterial chemoembolization (TACE) or radiation therapy, could represent a bridge to surgery. We have observed a progressive HCC case with hepatic vein tumor thrombosis proceeding to the inferior vena cava (IVC-HVTT) convert to a state of feasible curative resection after a multidisciplinary treatment which included sorafenib. The patient underwent a successful resection in consequence of this therapy. A 45-year-old male with Hepatitis B Virus-associated chronic hepatitis was diagnosed as HCC with IVC-HVTT. To obtain oncological curative resection, we performed TACE, radiation therapy followed by administration of sorafenib (800 mg per day, total 72 g). The tumor including IVC-HVTT remarkably shrank, therefore, an extended posterior sectionectomy and total removal of the IVC-HVTT was successfully performed. The operation time was 736 minutes and the amount of intraoperative hemorrhage was 805 mL. No postoperative complication occurred. Adjuvant therapy with sorafenib was started four weeks after the operation and continued for 6 months (800 mg per day, total 144 g). The patient is alive without recurrence for about 4 years from the initial therapy. Multidisciplinary therapy including sorafenib, TACE, radiation, and hepatic resection may be an effective strategy to treat HCC patients with IVC-HVTT.

Effect of branched-chain amino acid supplementation on functional liver regeneration in patients undergoing portal vein embolization and sequential hepatectomy: a randomized controlled trial.

BACKGROUND: Portal vein embolization (PVE) can decrease the resection ratio for major hepatectomy. (99m)Tc-galactosyl human serum albumin (GSA) scintigraphy is useful for evaluating quantitative functional liver volume. Branched chain amino acids (BCAAs) modulate liver function and regeneration. We analyzed the effects of BCAAs, in terms of liver function and regeneration after PVE, in combination with major hepatectomy. METHODS: This randomized controlled trial was conducted for patients receiving PVE through to complete hepatectomy from September, 2011 to June, 2013. BCAA granules were added two times a day to a conventional diet in the BCAA administration group (BCAA group). The primary end point was functional liver regeneration of the future remnant liver after PVE followed by hepatic resection. Functional liver regeneration was assessed by the liver uptake value obtained from (99m)Tc-GSA scintigraphy single-photon-emission computed tomography/computed tomography fusion images. The secondary end points were volumetric liver regeneration and changes in liver function and laboratory data. RESULTS: A BCAA group (n = 13) and a non-BCAA group (control group; n = 15) were included. The primary end point was partially met: the liver uptake value significantly increased in the BCAA group compared with the control group 6 months after hepatic resection (266.7% vs 77.6%, P = 0.04) and marginally increased after PVE (43.8% vs 17.4%, P = 0.079). Following PVE, the increment of the uptake ratio of the liver to the liver plus heart at 15 min was significantly less in the BCAA group than in the control group (0.0 and 0.01, P = 0.023). CONCLUSIONS: BCAA supplementation improved functional liver regeneration and function in patients undergoing PVE followed by major hepatic resection.

[The possible role of sorafenib as a part of the multimodal treatment for hepatocellular carcinoma].

The role of sorafenib is unclear in multimodal treatment for hepatocellular carcinoma (HCC). We analyzed patients who underwent multimodal treatment including surgical operation for advanced HCC after administration of sorafenib. A 79- year-old man underwent extended right hepatectomy for Stage III huge HCC. Three years later, multiple recurrences observed in the liver, and an extrahepatic tumor was diagnosed. Peritoneal seeding was suspected, thus we decided to start a sorafenib administration. After 11 months, new intrahepatic lesions were detected, but extrahepatic tumor was unchanged. We considered the extrahepatic tumor was solitary and resectable, and new lesions in the liver were still treatable, then we attempted a surgical treatment with partial hepatectomy and ablation therapy. The tumor was successfully resected, and residual viable tumors were treated by radiofrequency ablation. The patient remains alive without recurrence at 7 months. We could perform a surgical treatment for another 2 patients with sorafenib treatment. These results suggested that there are cases of advance HCC in which multimodality treatment including surgical treatment can be achieved after sorafenib administration.

A new approach to percutaneous transhepatic portal embolization using ethanolamine oleate iopamidol.

PURPOSE: We aimed to examine the therapeutic efficacy of ethanolamine oleate iopamidol (EOI) as an embolic material for percutaneous transhepatic portal embolization (PTPE). METHODS: Eighty-two patients with liver tumors were treated with PTPE. Fifty-eight patients had hepatocellular carcinomas, 11 had liver metastases, and 13 had other liver tumors. A total of 55 patients (group E) were treated with 5% ethanolamine oleate after gelatin sponge administration. As a control, we evaluated 27 patients (group F) who were treated with fibrin glue and iodized oil. PTPE was mainly indicated before hepatic resection, for patients with high nontumorous volumetric resection ratios (the nontumorous volumetric resection ratio was estimated to be greater than 65% in patients with an indocyanine green retention ratio of 15 min (ICG R15) of 10% or less, and the nontumorous volumetric resection ratio was estimated to be greater than 40% in the patients with an ICG R15 of 10-20%). RESULTS: All patients were successfully treated percutaneously under local anesthesia. Balloon-occluded and ipsilateral approaches were used in 81 patients (99%) and 62 (75%) patients, respectively. The rate of insufficient embolization or recanalization was significantly lower in group E (7.3%) in comparison to group F (25.9%; p < 0.05). The volumetric resection ratios, before and after PTPE, decreased from 60 to 45% in group E and from 63 to 55% in group F. The post-PTPE resection ratio was significantly decreased in group E. Before and after PTPE, average ICG R15 values changed from 17 to 27% in group E and from 18 to 26% in group F. The complication rates in groups E and F were similar (7.3 vs. 7.4%). CONCLUSION: EOI is a safe embolic material that can be used to induce greater liver hypertrophy, in comparison to fibrin glue, in PTPE for liver tumors.

[A long-term survival case of liver and mediastinal LN metastases from colon cancer treated with intensive multimodal therapy].

A 50-year-old man with multiple liver and mediastinal LN metastases from sigmoid colon cancer was admitted to our hospital in May 2005. In October 2002, a radical resection of the original tumor and liver metastases were performed at a previous hospital. Histologically, the tumor was diagnosed as Stage IV. He was treated with an oral anticancer agent as an adjuvant therapy. In January 2005, the CEA level was increased to 3.2 ng/ml and CT scan revealed a solitary liver metastasis. Partial resection of the liver was performed. On admission to our hospital, a systemic chemotherapy by FOLFOX4 was begun. The liver metastases showed 61% reduction in size and were judged to be PR. However, the intrathoracic lymph node size was not changed. Therefore, VATS extirpation of the mediastinal lymph node was performed. After 10 courses of FOLFOX4, abdominal CT revealed liver metastases remained to be almost the same size. In January 2006, radio frequency ablation (RFA) and partial hepatectomy were enforced and then, the tumor marker returned to normal. There were no serious adverse events or postoperative complications. He has been alive without any sign of recurrence for 42 months from the initial treatment. In conclusion, intensive combination therapies for remote metastases of colon cancer might be promising to obtain a long-term survival without ruining QOL.

[A 42-month disease free survival case of combined hepatocellular-cholangiocarcinoma with lymph node metastases treated with multimodal therapy].

Combined hepatocellular and cholangiocarcinoma (HCC-CC) is a rare type of liver cancer. We herein report a case of HCC-CC with lymph node metastases treated by multimodality therapy. The patient has been alive for more than 42 months. A 52-year-old man with a 9 cm diameter mass lesion in the liver was admitted to our hospital. The tumor was diagnosed as peripheral type of cholangiocarcinoma. Preoperative transhepatic arterial chemoenbolization (TACE) was performed. An accumulation pattern of lipiodol after TACE and an increase of serum alpha-fetoprotein led us to diagnosis of combined HCC-CC. A three segmentectomies of the liver and dissection of the local lymph nodes were performed. A histological examination of the resected specimen showed combined HCC-CC with lymph node metastases. Alpha fetoprotein, cytokeratins 7 and 19 were partially positive with immunohistochemical staining. The final diagnosis was a mixed type of combined HCC-CC. To improve a poor prognosis of combined HCC-CC, adjuvant chemotherapy with CDDP, 5 FU and radiation therapy were achieved. Fortunately, the patient is alive without any recurrence for 42 months after the operation.