Hiroya Iida

Comparison of percutaneous transhepatic portal vein embolization and unilateral portal vein ligation

AIM To compare the effect of percutaneous transhepatic portal vein embolization (PTPE) and unilateral portal vein ligation (PVL) on hepatic hemodynamics and right hepatic lobe (RHL) atrophy. METHODS Between March 2005 and March 2009, 13 cases were selected for PTPE (n = 9) and PVL (n = 4) in the RHL. The PTPE group included hilar bile duct carcinoma (n = 2), intrahepatic cholangiocarcinoma (n = 2), hepatocellular carcinoma (n = 2) and liver metastasis (n = 3). The PVL group included hepatocellular carcinoma (n = 2) and liver metastasis (n = 2). In addition, observation of postoperative hepatic hemodynamics obtained from computed tomography and Doppler ultrasonography was compared between the two groups. RESULTS Mean ages in the two groups were 58.9 ± 2.9 years (PVL group) vs 69.7 ± 3.2 years (PTPE group), which was a significant difference (P = 0.0002). Among the indicators of liver function, including serum albumin, serum bilirubin, aspartate aminotransferase, alanine aminotransferase, platelets and indocyanine green retention rate at 15 min, no significant differences were observed between the two groups. Preoperative RHL volumes in the PTPE and PVL groups were estimated to be 804.9 ± 181.1 mL and 813.3 ± 129.7 mL, respectively, with volume rates of 68.9% ± 2.8% and 69.2% ± 4.2%, respectively. There were no significant differences in RHL volumes (P = 0.83) and RHL volume rates (P = 0.94), respectively. At 1 mo after PTPE or PVL, postoperative RHL volumes in the PTPE and PVL groups were estimated to be 638.4 ± 153.6 mL and 749.8 ± 121.9 mL, respectively, with no significant difference (P = 0.14). Postoperative RHL volume rates in the PTPE and PVL groups were estimated to be 54.6% ± 4.2% and 63.7% ± 3.9%, respectively, which was a significant difference (P = 0.0056). At 1 mo after the operation, the liver volume atrophy rate was 14.3% ± 2.3% in the PTPE group and 5.4% ± 1.6% in the PVL group, which was a significant difference (P = 0.0061). CONCLUSION PTPE is a more effective procedure than PVL because PTPE is able to occlude completely the portal branch throughout the right peripheral vein.

Influence of Rictor and Raptor Expression of mTOR Signaling on Long-Term Outcomes of Patients with Hepatocellular Carcinoma

BackgroundAberrant signaling mediated by the mammalian target of rapamycin (mTOR) occurs at high frequency in hepatocellular carcinoma (HCC), indicating that mTOR is a candidate for targeted therapy. mTOR forms two complexes called mTORC1 (mTOR complexed with raptor) and mTORC2 (mTOR complexed with rictor). There are minor studies of the expression kinetics of mTORC1 and mTORC2 in HCC.MethodsWe studied 62 patients with HCC who underwent curative resection. We used univariate and multivariate analyses to identify factors that potentially influence disease and overall survival after hepatectomy. The mRNA and protein levels of mTOR, rictor and raptor in cancer and non-cancer tissues were analyzed using quantitative RT-PCR, immunohistochemistry and Western blotting.Results/ConclusionHigh ratio of the levels of rictor and raptor mRNAs in tumors was identified as independent prognostic indicators for disease-free survival. Low and high levels of preoperative serum albumin and mTOR mRNA in the tumor, respectively, were identified as independent indicators of overall survival. HCC is likely to recur early after hepatic resection in patients with high levels of mTOR and rictor mRNAs and high rictor/raptor ratios in cancer tissues. We conclude that analysis of mTOR expression in cancer tissues represents an essential strategy to predict HCC recurrence after curative treatment.

Effects of implementing an “enhanced recovery after surgery” program on patients undergoing resection of hepatocellular carcinoma

PurposeTo evaluate the effects of implementing an “enhanced recovery after surgery” (ERAS) program on the feasibility, safety, and effectiveness of extensive and potentially curative liver resection for hepatocellular carcinoma (HCC).MethodsWe compared clinicopathologic factors, surgical factors, and outcomes of patients who underwent extended hepatectomy (defined as resection of more than two sections) for HCC, before and after the introduction of an ERAS program.ResultsOperating times and postoperative hospital stay were significantly shorter, and total volume infused during surgery was significantly lower, for the ERAS group than for the control group. Although the ERAS group had a significantly lower percentage of patients with retention of abdominal drainage, this group had a higher frequency of abdominal paracentesis in patients without intraoperative abdominal drainage. Oral dietary intake and the ability to walk steadily resumed significantly earlier in the ERAS group. Postoperative serum concentrations of albumin and cholinesterase were significantly higher in the ERAS group than in the control group.ConclusionsThe ERAS program was feasible and effective for patients with chronic liver disease undergoing extended liver resection for HCC, because it allowed earlier oral dietary intake and promoted faster postoperative recovery.

Increased FGF19 copy number is frequently detected in hepatocellular carcinoma with a complete response after sorafenib treatment

The multi-kinase inhibitor sorafenib is clinically approved for the treatment of patients with advanced hepatocellular carcinoma (HCC). We previously reported that fibroblast growth factor 3 and 4 (FGF3/FGF4) amplification is a predictor of a response to sorafenib. This study aims to analyze the relationship between FGF-FGF receptor (FGFR) genetic alterations and the response to sorafenib. Formalin-fixed, paraffin-embedded tissue specimens from HCC patients who had achieved a complete response (CR, N=6) or non-CR (N=39) to sorafenib were collected and were examined for FGF-FGFR gene alterations using next generation sequencing and copy number assay. FGFR mutations were detected in 5 of 45 (11.1%) cases. There was no significant association between FGFR mutation status and the response to sorafenib. We detected no increase in the FGF3/FGF4 copy number in CR cases. An FGF19 copy number gain was detected more frequently among CR cases (2/6, 33.3%) than among non-CR cases (2/39, 5.1%) (P = 0.024, Chi-squared test). In conclusion, a copy number gain for FGF19 may be a predictor of a response to sorafenib, in addition to FGF3/FGF4 amplification.

A comparative study of therapeutic effect between laparoscopic microwave coagulation and laparoscopic radiofrequency ablation.

BACKGROUND/AIMS We retrospectively compared the therapeutic effect of microwave coagulation needle (Lap-MCT) and radiofrequency ablation needle (Lap-RFA). METHODOLOGY Between January 2001 and May 2012, 71 patients underwent laparoscopic ablation therapy for HCC with no extra hepatic metastasis. These patients were divided into 3 groups, according to the surgical strategies: Lap-MCT (n=40), Lap-MCT+RFA (n=13) and Lap-RFA (n=18). The patient background, tumor characteristics, cumulative survival rate, recurrence-free survival rate, time of operation and duration of hospitalization were compared between the groups. RESULTS The maximal tumor size, the number of tumors and the hepatic reserve from each group had no significant difference. Likewise, the time of operation and the duration of hospitalization had no significant difference. However, the number of needle punctures in the Lap-MCT group was significantly larger than that in the Lap-RFA group (p<0.05). Postoperative liver function had no significant difference between the groups. The 5-year cumulative survival rate was 71.5% (Lap-MCT), 66.7% (Lap-MCT+RFA) and 80.0% (Lap-RFA) showing no significant difference. Also, the recurrence-free survival rate and the local recurrence rate had no significant difference. CONCLUSIONS In the laparoscopic setting, MCT and RFA are equally effective in terms of short- and long-term results.

Oncocytic non-functioning endocrine tumor of the pancreas

Herein is presented the case of a malignant non‐functioning endocrine tumor of the pancreas with oncocytic features, and a discussion on the high incidence of malignancy in oncocytic endocrine pancreatic tumors. The patient was a 65‐year‐old woman who showed no paraneoplastic symptoms produced by functioning pancreatic endocrine tumors. The primary tumor was located in the body and tail of the pancreas, and had metastasized to the liver. Tumor cells were arranged in a ribbon‐like or trabecular pattern and had an abundant eosinophilic cytoplasm containing numerous mitochondria and neurosecretory granules. The cytoplasm of the tumor cells was intensely stained with an antimitochondrial antigen antibody. Most tumor cells stained positively with Grimelius stain and for chromogranin A. Some tumor cells also stained for synaptophysin. However, the tumor cells negatively stained for hormones such as insulin, glucagon, somatostatin, gastrin, vasoactive intestinal peptide and pancreatic polypeptide, for serotonin, and for pancreatic enzymes such as amylase and trypsin. Analysis of 18 oncocytic pancreatic endocrine tumors, consisting of those reported previously and that in the present case, suggests that the high incidence of malignancy in oncocytic endocrine tumors is associated with the high incidence of non‐functioning endocrine tumors among them, most of which are malignant.

Optimal combination of radiofrequency ablation with chemoradiotherapy for locally advanced pancreatic cancer.

Problems have been reported in the treatment of pancreatic cancer with radiofrequency ablation (RFA), such as the friability of the organ itself. This report presents possible solutions to such problems. Although our patient suffered from locally advanced unresectable pancreatic cancer, she remained well at 18 mo after RFA with no evidence of recurrence. To ameliorate the side effects of RFA, after a palliative bypass procedure, the subject was treated with combined radiotherapy and chemotherapy. After this regimen had been administered, a contrast-enhanced computed tomography scan confirmed that RFA is a viable approach to the treatment of pancreatic cancer as the chemoradiotherapy had resulted in marked tumor shrinkage and pancreatic fibrosis; i.e., sufficient tumor ablation was achieved without serious RFA-related complications, such as pancreatitis or pancreatic fistulae. The present case suggests that RFA combined with preceding chemoradiotherapy is safe and effective for the palliative treatment of locally advanced pancreatic cancer.

Effectiveness of impedance monitoring during radiofrequency ablation for predicting popping.

AIM To retrospectively evaluate the effectiveness of impedance monitoring for predicting popping during radiofrequency ablation (RFA) using internally cooled electrodes. METHODS We reviewed 140 patients (94 males, 46 females; age range 73.0 ± 11.1 year) who underwent RFA between February 2006 and November 2008 with a modified protocol using a limited power delivery rather than a conventional one to avoid popping. All the patients provided their written informed consent, and the study was approved by the institutional review board. Intraprocedural impedances were measured for the study subjects, and the tumors were classified into three types according to the characteristics of their impedance curves: increasing, flat, or decreasing. The tumors were further sorted into seven subtypes (A-G) depending on the curvature of the impedance curves increase or decrease. Relative popping rates were determined for the three types and seven subtypes. A chi-square test was performed to estimate statistical significance. RESULTS A total of 148 nodules treated by RFA were analyzed. The study samples included 132 nodules of hepatocellular carcinoma, 14 nodules of metastatic liver cancer, and two nodules of intrahepatic cholangiocarcinoma. The numbers of nodules with each impedance curve type were as follows: 37 increasing-type nodules, 43 flat-type nodules, and 68 decreasing-type nodules. Popping occurrence rates were 24.3%, 46.5% and 64.7%, respectively. Flat-type nodules exhibited a significantly higher rate of popping compared to increasing-type nodules (P = 0.039). Decreasing-type nodules exhibited a significantly higher rate of popping compared to increasing-type nodules (P < 0.0001). Notably, nodules that showed a sharp decrease in impedance in the latter ablation period (subtype E) exhibited a significantly higher rate of popping compared to other subtypes. CONCLUSION Intraprocedural impedance monitoring can be a useful tool to predict the occurrence of popping during liver tumor RFA performed with internally cooled electrodes.

Comparative study of percutaneous radiofrequency ablation and hepatic resection for small, poorly differentiated hepatocellular carcinomas.

Histologically, poorly differentiated hepatocellular carcinomas (HCC) are considered highly malignant. Here, we aimed to evaluate the relative efficacy and safety of hepatic resection or radiofrequency ablation (RFA) for treating this malignancy.

Simultaneous bile duct and portal venous branch ligation in two-stage hepatectomy

Hepatectomy is an effective surgical treatment for multiple bilobar liver metastases from colon cancer; however, one of the primary obstacles to completing surgical resection for these cases is an insufficient volume of the future remnant liver, which may cause postoperative liver failure. To induce atrophy of the unilateral lobe and hypertrophy of the future remnant liver, procedures to occlude the portal vein have been conventionally used prior to major hepatectomy. We report a case of a 50-year-old woman in whom two-stage hepatectomy was performed in combination with intraoperative ligation of the portal vein and the bile duct of the right hepatic lobe. This procedure was designed to promote the atrophic effect on the right hepatic lobe more effectively than the conventional technique, and to the best of our knowledge, it was used for the first time in the present case. Despite successful induction of liver volume shift as well as the following procedure, the patient died of subsequent liver failure after developing recurrent tumors. We discuss the first case in which simultaneous ligation of the portal vein and the biliary system was successfully applied as part of the first step of two-stage hepatectomy.