Applicability of the histidine-tryptophan-ketoglutarate solution as a machine perfusion solution for marginal liver grafts.

BACKGROUND AND AIM: There are very few reports comparing the use of the University of Wisconsin solution and histidine-tryptophan-ketoglutarate solution as machine perfusion solutions for marginal liver grafts. We aimed to clarify whether the use of the histidine-tryptophan-ketoglutarate solution in hypothermic machine perfusion improves the split-liver graft function in a large animal model. METHODS: Porcine split-liver grafts were created by 75% liver resection. Hypothermic machine perfusion experimental groups were divided as follows: Group 1, perfusate, University of Wisconsin gluconate solution (UW group; n = 5), and Group 2, perfusate, histidine-tryptophan-ketoglutarate solution (HTK group; n = 4). After 4 h of preservation, the liver function was evaluated using an isolated liver reperfusion model for 2 h. RESULTS: In the HTK group, the portal vein and hepatic artery resistance during hypothermic machine perfusion and the portal vein resistance during isolated liver reperfusion were lower than those in the UW group. In addition, the total Suzuki score for hepatic ischemia-reperfusion injury in the HTK group was significantly better than that in the UW group. The number of anti-ETS-related genes staining-positive sinusoid epithelial cell nuclei in the HTK group was higher than that in the UW group (not significant). CONCLUSIONS: The histidine-tryptophan-ketoglutarate solution can be perfused with lower vascular resistance than the University of Wisconsin solution, reducing shear stress and preventing sinusoid epithelial cell injury in marginal grafts used as split-liver grafts.

The experience of 100 cases of 8K/two-dimensional laparoscopic colorectal surgery - The evaluation of 8K/two-dimensional laparoscopy and how to use it.

Background: The resolution of 8K ultra-high-definition imaging technology (7680 × 4320 pixels) is 16-fold higher than the current high-definition technology (1920 × 1080 pixels). 8K/two-dimensional (2D) laparoscopy was clinically available in 2014, but few reports concerning its application have been published. The aim of this study was to evaluate the appropriate methods of usage and problems learned from clinical use of 8K/2D laparoscopy. Subjects and Methods: The patients were 100 colorectal surgery patients who underwent 8K/2D laparoscopy at Asahikawa Medical University Hospital between November 2018 and March 2021. We evaluated the effectiveness, operating conditions, methods and issues of 8K/2D laparoscopy. Results: The median age was 68.5 years. The primary disease was malignancy of the left side of the colon and rectum in 92 patients. The right-sided colectomy was performed in five cases, total proctocolectomy of ulcerative colitis was performed in 3 cases. The proper application of 8K/2D laparoscopy can be achieved by adhering to certain tips, such as darkening the operation room and keeping an appropriate distance from the monitor. Regarding intraoperative complications caused by the 8K/2D laparoscope, skin burns due to heat from the tip of the laparoscope were observed in one patient. There were no cases of complications due to the 8K/2D laparoscopy. Conclusion: 8K/2D laparoscopy can be used safely in colorectal surgery. There are still some tips for proper use, such as keeping an appropriate distance to the monitor and darkening the room. However, 8K/2D laparoscopy can provide delicate images and can be used without any operational problems.

Serum fatty acid-binding protein 5 is a significant factor in hepatocellular carcinoma progression independent of tissue expression level.

Fatty acid-binding protein 5 (FABP5) is highly expressed in hepatocellular carcinoma (HCC) tissues and is related to HCC progression. In this study, we analyzed the potential of serum FABP5 (sFABP5) as a tumor marker in HCC and its clinical significance in HCC progression. We compared the sFABP5 concentration in patients with HCC (HCC group) with that of patients with hepatitis without HCC (hepatitis group). Moreover, we measured the FABP5 expression levels in resected HCC tissues (tFABP5) and analyzed their relationship with sFABP5. We also performed cell-based assays using FABP5 knockout and overexpressing HCC cell lines to analyze the effect of extrinsic FABP5 (exFABP5) on HCC cells. We showed that sFABP5 was not a useful tumor marker for HCC, as HCC and sFABP5 were not correlated. However, sFABP5 and tFABP5 significantly correlated with survival after surgery for HCC, while sFABP5 and tFABP5 were independent of each other. In cell-based assays, exFABP5 was taken up by HCC cell lines and positively affected cell survival under glucose-depleted conditions by complementing the endogenous FABP5 function. In conclusion, sFABP5 had a significant impact on HCC progression irrespective of tFABP5 by augmenting cell viability under glucose-depleted conditions. As tFABP5 and sFABP5 are important factors that are independent of each other in HCC progression, both of them should be considered independently in improving the prognosis of patients with HCC.

CD133 and epithelial cell adhesion molecule expressions in the cholangiocarcinoma component are prognostic factors for combined hepatocellular cholangiocarcinoma.

AIM: A new classification of combined hepatocellular cholangiocarcinoma (CHC) was recently reported. Cancer stem cells have been associated with CHC carcinogenesis. This study examined the association of cancer stem cell marker expression and prognosis in CHC classified using the new classification. METHODS: We enrolled 26 CHC patients and classified them according to the new classification. We evaluated the expression of cancer stem cell markers (CD56, CD133, and epithelial cell adhesion molecule [EpCAM]) by immunohistochemical staining in each component. We analyzed the association between expressions and prognosis. RESULTS: Seven cases were hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) (cHCC-CCA), 12 were HCC and intermediate cell carcinoma (HCC-INT), and seven were intermediate cell carcinoma (INT). The CD133-positive rate tended to be higher in the CCA (42.9%) and INT component (50.0%) than the HCC component (14.3%) in cHCC-CCA. In HCC-INT, the CD133-positive rate in the INT component (83.3%) was significantly higher than the HCC component (8.3%; P = 0.001). For EpCAM, the positive rate in the CCA component (71.4%) and INT component (50.0%) tended to be higher than the HCC component (14.3%) in cHCC-CCA. Overall survival and disease-free survival were significantly worse in cases with CD133-positive (P = 0.048 and P = 0.048, respectively) or EpCAM-positive (P = 0.041 and P = 0.041, respectively) CCA component in cHCC-CCA. CONCLUSIONS: INT and CCA components showed higher expression rates of cancer stem cell markers than the HCC component. CD133 or EpCAM expression in the CCA component was associated with poor prognosis in cHCC-CCA.

Circulating microRNA-1246 as a possible biomarker for early tumor recurrence of hepatocellular carcinoma.

AIMS: Early tumor recurrence (ETR) after hepatic resection is a crucial predictor of poor prognosis in patients with hepatocellular carcinoma (HCC). The aim of this study was to identify clinically significant serum microRNAs (miRNAs) involved in the ETR of HCC. METHODS: We compared expression profiles of circulating miRNAs from serum samples between five HCC patients with ETR (recurrence within 12 months after hepatectomy) and five HCC patients without recurrence using microarray analysis of miRNA. The identified miRNA associated with ETR was further verified in 121 HCC patients, 73 liver disease patients, and 15 health controls by real-time quantitative reverse transcription-polymerase chain reaction (PCR). RESULTS: Of the approximately 2000 miRNAs analyzed, we identified 15 miRNAs for which expression levels correlated significantly with ETR. Of these miRNAs, we further investigated expression of miRNA-1246 (miR-1246). Quantitative PCR confirmed that miR-1246 was upregulated in HCC with ETR, compared to the level in HCC without ETR (P < 0.001). Serum miR-1246 showed a receiver operating characteristic curve area of 0.762, with 77.4% specificity and 54.1% sensitivity in discriminating HCC patients with ETR from HCC patients without ETR. Altered expression of miR-1246 was associated with aggressive tumor characteristics, including tumor-node-metastasis classification (P = 0.0413), tumor differentiation (P = 0.0419), and portal vein invasion (P = 0.0394). Moreover, multivariate Cox regression analysis identified serum miR-1246 level as an independent risk factor for overall survival (hazard ratio, 2.784; 95% confidence interval, 1.528-5.071; P = 0.0008). CONCLUSION: Circulating miR-1246 in serum has strong potential as a novel ETR and prognostic biomarker for HCC.

Clinical and pathological features of combined hepatocellular-cholangiocarcinoma compared with other liver cancers.

BACKGROUND AND AIM: Combined hepatocellular-cholangiocarcinoma (CHC) is a primary liver cancer containing both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) elements. Its reported clinicopathological features and prognoses have varied because of its low prevalence. This study aimed to clarify these aspects of CHC. METHODS: We enrolled 28 patients with CHC, 1050 with HCC, and 100 with ICC and compared the clinicopathological characteristics and prognosis of CHC with HCC and ICC. We also analyzed prognostic factors, recurrence patterns, and management in CHC patients. RESULTS: The incidences of hepatitis B virus and high α-fetoprotein and protein induced by vitamin K absence or antagonists-II levels were significantly higher among CHC compared with ICC patients. Multiple tumors were more frequent in CHC compared with the other groups, while vascular invasion and lymph node metastasis were more frequent in the CHC than the HCC group. The 5-year overall survival and disease-free survival rates for CHC were 25.1% and 22.6%, respectively. Overall survival was significantly lower than for HCC (P < 0.001) but not ICC (P = 0.152), while disease-free survival was significantly lower than for HCC and ICC (P = 0.008 and P = 0.005, respectively). Multivariate analysis identified carcinoembryonic antigen levels and tumor size as independent predictors in patients with CHC. CONCLUSIONS: The clinical features of CHC, including sex, hepatitis B virus infection, α-fetoprotein, and protein induced by vitamin K absence or antagonists-II levels, were similar to HCC, while its prognosis and pathological features, including vascular invasion and lymph node metastasis, were similar to ICC. Carcinoembryonic antigen levels and tumor size were independent prognostic factors in patients with CHC.

Prognoses and Clinicopathological Characteristics for Hepatocellular Carcinoma Originating from the Caudate Lobe After Surgery.

BACKGROUND: The aim was to evaluate the prognoses and clinicopathological characteristics of solitary hepatocellular carcinoma (HCC) originating from the caudate lobe (HCC-CL). METHODS: We analyzed 584 patients with a solitary tumor <10 cm from January 1990 to November 2014. Patients were classified into a caudate lobe group (CL; n = 39) and a non-caudate lobe group (NCL; n = 545). We investigated the prognoses and clinicopathological characteristics of solitary HCC-CL. We compared the surgical procedures performed in these cases. RESULTS: HCC-CL had a similar rate of portal venous invasion (PVI) as HCC-NCL (21% vs. 19%); however, the frequency of tumor thrombus at the first branch of the portal vein (PV) or extension to the trunk or the opposite side of the PV was significantly higher in HCC-CL (8% vs. 2%). HCC-CL had similar OS rates compared to HCC-NCL; however, HCC-CL showed significantly poorer RFS. Although there were no significant differences among the three surgical procedures, blood loss and complication rates tended to be higher in cases who underwent an isolated caudate lobectomy. Tumor size ≥5 cm, PVI, and liver fibrosis or cirrhosis (LF or LC) were independent unfavorable factors for both OS and RFS. PIVKA-II ≥120 mAU/ml was an independent unfavorable factor for RFS. CONCLUSION: HCC-CL presented a poorer RFS rate. Patients with a tumor size ≥5 cm, PIVKA-II ≥120 mAU/ml, portal venous invasion, and LF or LC should be diligently followed up as these cases have a high risk of recurrence.

Hepatic hypertrophy and hemodynamics of portal venous flow after percutaneous transhepatic portal embolization.

BACKGROUND: Percutaneous transhepatic portal embolization (PTPE) is useful for safe major hepatectomy. This study investigated the correlation between hepatic hypertrophy and hemodynamics of portal venous flow by ultrasound sonography after PTPE. METHODS: We analyzed 58 patients with PTPE, excluding those who underwent recanalization (n = 10). Using CT volumetry results 2 weeks after PTPE, the patients were stratified into a considerable hypertrophy group (CH; n = 15) with an increase rate of remnant liver volume (IR-RLV) ≥ 40% and a minimal hypertrophy group (MH; n = 33) with an IR-RLV < 40%. We investigated the hemodynamics of portal venous flow after PTPE and the favorable factors for hepatic hypertrophy. RESULTS: Univariate and multivariate analysis identified the indocyanine green retention rate at 15 min (ICGR15) and increase rate of portal venous flow volume (IR-pFV) at the non-embolized lobe on day 3 after PTPE as independent favorable factors of IR-RLV. Patients with IR-pFV on day 3 after PTPE ≥100% and ICGR15 ≤ 15% (n = 13) exhibited significantly increased IR-RLV compared with others (n = 35). CONCLUSIONS: Cases with high IR-pFV on day 3 after PTPE exhibited better hepatic hypertrophy. Preserved liver function and increased portal venous flow on day 3 were important.

Salvage Hepatectomy for Recurrent Hepatocellular Carcinoma after Radiofrequency Ablation and/or Transcatheter Arterial Chemoembolization: A Propensity Score-Matched Analysis.

AIM: We aimed to evaluate the short- and long-term surgical outcomes of salvage hepatectomy for recurrent hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA) and/or transcatheter arterial chemoembolization (TACE). METHODS: We reviewed the surgical outcomes of 90 recurrent HCC patients after RFA and/or TACE (salvage group) and 490 HCC patients without preoperative treatment (primary group). We performed 1:1 propensity score matching (PSM) between the 2 groups and matched 87 patients in each group. RESULTS: Before PSM, the salvage group was pathologically more advanced than the primary group. After PSM, there were no significant differences in the clinicopathological features between the groups. The outcomes of propensity score-matched groups were compared and there was no statistically significant difference between the 2 groups regarding perioperative outcomes and survival. Univariate and multivariate analyses of propensity score-matched HCC patients revealed that stage, tumor size, differentiation, and portal vein invasion were independent prognostic factors for survival. Preoperative RFA and/or TACE was not a prognostic factor in a propensity score-matched cohort. CONCLUSIONS: The short- and long-term surgical outcomes of the primary and salvage groups were similar under the matched clinicopathological background. Salvage hepatectomy might be an acceptable treatment for recurrent HCC patients after RFA and/or TACE.

Transparenchymal glissonean approach: a novel surgical technique for advanced perihilar bile duct cancer.

PURPOSE: To increase the surgical opportunities for locally advanced perihilar bile duct cancers that require left-sided hepatectomies, we developed the transparenchymal glissonean approach (TGA); it comprises intra-hepatic exposure and dissection of the Glisson's sheath to gain access to the hepatic artery and portal vein for reconstruction. METHODS: Following skeletonization of the hepatoduodenal ligament, the proximal portions of invaded vessels are exposed. If extra-hepatic attempts to access the distal portions of the invaded vessels fail, TGA can be used. The distal portion of the invaded right or right posterior Glisson's sheath is exposed following liver transection. The anterior portion of the wall of bile duct is cut and transected circumferentially including the fibrous plate tissue. The non-invaded portal vein and hepatic artery are isolated and dissected towards the hepatic hilum until the invaded distal portion of the vessels, and vascular reconstructions are performed. RESULTS: TGA was performed in 9 patients; 5 patients underwent left hemihepatectomy and 4 underwent left tri-sectionectomy. Eight patients needed vascular reconstruction. Clavien-Dindo classification (CDC) grades IIIa and IIIb were recorded in 6 and 1 patients, respectively. No patients had CDC grades IV and V disease. Pathologically, all cases were pT4; 3 cases were R0, 5 were R1 with microscopic positive margin, and 2 were R1 with microscopic metastasis. The overall median survival time was 25.0 months. CONCLUSIONS: TGA is feasible with acceptable prognosis and expands the surgical opportunities.

[A Case of Locally Advanced Intrahepatic Cholangiocarcinoma Successfully Treated by Conversion Surgery after Hepatic Arterial Infusion Chemotherapy and Radiation Therapy].

The patient was a 63-year-old man. Computed tomography(CT)showed a 99mm in diameter low-density mass in hepatic segments 4 and 8 as the main locus. This tumor was diagnosed as intrahepatic cholangiocarcinoma and was suspected to invade to left and right Gleason's sheath, and radical cure was judged impossible. After hepatic arterial chemotherapy and radiotherapy were performed, tumor shrinkage was confirmed, and tumor markers also became negative. So he was referred to our hospital for surgical indication. CT revealed that the tumor did not invade to the left Gleason's sheath. After percutaneous transhepatic portal embolization, hepatic right trisectionectomy was performed. He was administered gemcitabine as an adjuvant chemotherapy for 1 year. One year 5 months after surgery, the patient is alive without relapse. Preoperative hepatic arterial chemotherapy and radiotherapy could be an effective treatment for unresectable locally advanced intrahepatic cholangiocarcinoma.

Huge hepatocellular carcinoma greater than 10 cm in diameter worsens prognosis by causing distant recurrence after curative resection.

BACKGROUND AND OBJECTIVES: This study aimed to evaluate the impact of huge (≥10 cm) hepatocellular carcinoma (HCC) to the recurrence pattern and the prognosis after hepatectomy. METHODS: 574 patients who underwent hepatectomy by 17 surgeons (Open 536 and Laparoscopic 38) for HCC without major vascular invasion from 1990 to 2013 at single institute were retrospectively analyzed. RESULTS: Huge tumor, age, HCV, multiple tumors and microscopic portal invasion are independent risk factors for overall survival (OS), and huge tumor, ICGR15 ≥16%, multiple tumors, moderate/poor histology, microscopic portal invasion and a positive pathological margin are risk factors for relapse-free survival (RFS). The 5-year OS and RFS of patients with huge HCC (n = 53) (42.9 and 14.2%) were significantly worse than those of patients with HCC <10 cm (n = 521) (71.3 and 33.1%). Huge tumor is an independent risk factor for initial extra-hepatic recurrence (Hazard ratio 7.86, P < 0.0001). The 5-year OS of patients with initial extra-hepatic recurrence (n = 55) was significantly worse than patients with intra-hepatic recurrence (n = 338) (16.8 vs. 50.5%). CONCLUSIONS: Huge HCC (≥10 cm) is an independent risk factor due to a high risk for initial extra-hepatic recurrence. Future systemic adjuvant therapy is needed for these patients. J. Surg. Oncol. 2017;115:324-329. © 2016 Wiley Periodicals, Inc.

Clinicopathological Characteristics of Hepatocellular Carcinoma with Microscopic Portal Venous Invasion and the Role of Anatomical Liver Resection in These Cases.

BACKGROUND: The aims of this study were to investigate predictive factors for microscopic portal venous invasion (mPVI) in hepatocellular carcinoma (HCC) and whether anatomical liver resection (ALR) was useful in such cases. METHODS: We analyzed 852 patients with HCC without macroscopic portal venous invasion who were treated at our hospital between January 1990 and May 2014. These patients were stratified into a microscopic portal venous invasion group (mPVI group; n = 153) and non-microscopic portal venous invasion group (NmPVI group; n = 699). RESULTS: PIVKA-II ≥100 mAU/ml, a tumor size ≥5 cm, a confluent lesion, and poor differentiation were found to be independent risk factors for mPVI. Among the mPVI group who had single HCC under 5 cm, serum albumin level <4.0 g/dl, PIVKA-II ≥100 mAU/ml, a positive surgical margin, and non-ALR (NALR) were independent unfavorable prognostic factors for overall survival (OS). PIVKA-II ≥100 mAU/ml, a positive surgical margin and NALR were independent unfavorable prognostic factors for relapse-free survival (RFS). ALR was significantly favorable factor for both OS and RFS of the mPVI group who had single HCC under 5 cm. CONCLUSIONS: Even if no portal venous invasion is detectable in HCC patients preoperatively, a PIVKA-II ≥100 mAU/ml, tumor size ≥5 cm, and a confluent lesion indicate a high risk of mPVI. ALR should be considered for the patients with these characteristics because it is a favorable prognostic factor in these cases with mPVI.

Survival outcomes of hepatectomy for stage B Hepatocellular carcinoma in the BCLC classification.

BACKGROUND: Because hepatectomy is not recommended in patients with stage B hepatocellular carcinoma (HCC) of the Barcelona Clinic Liver Cancer (BCLC) staging, we evaluated the survival outcomes of hepatectomy for stage B in the BCLC system. METHODS: Data were collected from 297 consecutive adult stage B patients who underwent curative hepatectomy for HCC between 1996 and 2014 in Hokkaido University Hospital. Overall survival (OS), disease-free survival (DFS), and risk factors were analyzed using the Kaplan-Meier method. Independent prognostic factors were evaluated using a Cox proportional hazards regression model. AP-factor (alpha-fetoprotein [AFP] × protein induced by vitamin K absence or antagonism factor II [PIVKA-II]) was categorized according to the serum concentrations of AFP and PIVKA-II: AP1 (AFP < 200 ng/ml and PIVKA-II < 100 mAU/ml), AP2 (AFP × PIVKA-II < 105), and AP3 (AFP × PIVKA-II ≥ 105). RESULTS: There were 130 deaths among our 297 stage B patients (43.8%). The causes of death in these cases were HCC recurrence (n = 106; 81.5%), liver failure (n = 7; 5.4%), and other causes (n = 17; 16.1%). The operative mortality rate was 0.34% (1/297). The 5-year OS and DFS rates for the stage B cases were 54.3 and 21.9%, respectively. By multivariate analysis, tumor number and AP-factor were risk factors for both survival and recurrence that were tumor related and could be evaluated preoperatively. The study patients with stage B HCC were classified into three groups by tumor number (B1, 1; B23, 2 or 3; B4over: ≥4) and into three groups stratified by AP-factor (AP1, AP2, and AP3). The 5-year OS rates of B1, B23, and B4over were 63.6, 52.3, and 29.0%. The 5-year OS rates of AP1, AP2, and AP3 were 67.6, 65.2, and 39.1%. Stratified by the 5-year OS rate, stage B HCC patients were classified into three subgroups (A-C).The 5-year OS rates of groups A (B1 or B23 and AP-1 or AP-2), B (B1 or B23 and AP-3, or B4over and AP-1 or AP-2), and C (B4over and AP-3) were 69.5, 43.7, and 21.3%. CONCLUSION: Stage B HCC patients with a tumor number ≤ 3 and/or AP-factor < 1 × 105 show acceptable 5-year OS rates and could be treated by hepatectomy.

Hepatectomy for Hepatocellular Carcinoma with Bile Duct Tumor Thrombus, Including Cases with Obstructive Jaundice.

BACKGROUND: This study aimed to evaluate the short- and long-term outcomes of hepatectomy for hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT), including cases with obstructive jaundice. METHODS: The study reviewed 42 HCC patients with BDTT, including six patients who needed preoperative biliary drainage due to obstructive jaundice, and 732 HCC patients without BDTT. The authors analyzed the impact of BDTT on the surgical outcomes and assessed the outcomes of hepatectomy for patients presenting with obstructive jaundice. RESULTS: The HCC patients with BDTT, almost all with stage 3 or 4 disease, had increased alpha-fetoprotein expression, larger tumors, and more portal vein invasion status. The survival of the HCC patients with BDTT was significantly inferior to that of the patients without BDTT (p = 0.0003). Survival did not differ significantly between the HCC patients with BDTT and those without BDTT when the two groups were matched by stage (p = 0.3366). The HCC patients with BDTT who presented with obstructive jaundice demonstrated outcomes similar to those for the HCC patients with BDTT who did not present with obstructive jaundice in terms of the overall survival rate (p = 0.5469). The perioperative outcomes for the HCC patients with BDTT did not depend on the presence or absence of preoperative jaundice. No patients in either BDTT group demonstrated 90-day mortality in this study. CONCLUSIONS: Hepatectomy should be considered for HCC patients with BDTT, even for patients with obstructive jaundice, because the surgical outcomes equivalent to those for HCC without BDTT can be achieved.

Our technique of preceding diaphragm resection and partial mobilization of the hepatic right lobe using a vessel sealing device (LigaSure™) for huge hepatic tumors with diaphragm invasion.

We describe and assess our technique of preceding diaphragm resection and partial mobilization of the hepatic right lobe to treat a huge hepatic tumor with diaphragm invasion. The right hepatic artery and portal vein were divided at the hepatic hilum, and the mesenteries were then dissected with a vessel sealing device (LigaSure Impact™). The invaded diaphragm was dissected roundly using a vessel sealing device and the right lobe was partially mobilized. A soft catheter was then passed along the anterior aspect of the retrohepatic inferior vena cava and the liver parenchyma was dissected via a liver hanging maneuver. We performed eight hepatectomies using this technique. The median blood loss was 532.5 ml and the mean excised liver weight was 1859 g. Our results demonstrate the safety and efficiency of the preceding diaphragm resection and partial mobilization technique using a vessel sealing device for right hepatectomy to resect a very large tumor with diaphragm invasion.

Strong cytoplasmic expression of NF-κB/p65 correlates with a good prognosis in patients with triple-negative breast cancer.

PURPOSE: Recent studies have indicated that constitutive NF-κB activity could be involved in the proliferation of triple-negative breast cancer. METHODS: The NF-κB/p65 expression and the effects of a NF-κB inhibitor, (-)-DHMEQ, were examined in triple-negative MDA-MB-231 breast cancer cells. Women with triple-negative breast cancer treated with neoadjuvant chemotherapy between 2002 and 2012 were retrospectively analyzed for their expression of NF-κB/p65, Bcl2 and Ki67 by immunohistochemistry in pre- and post-treatment specimens. The factors predicting the response to neoadjuvant chemotherapy and the prognosis were analyzed. RESULTS: NF-κB/p65 was predominantly expressed in the cytoplasm of MDA-MB-231 cells. Of 34 triple-negative breast cancer patients, positive staining for NF-κB/p65 expression was detected in the nuclei of a few cells in seven tumors before neoadjuvant chemotherapy, while the expression of NF-κB/p65 in the cytoplasm was detected in almost all tumor cells of 33 tumors. The expression levels of NF-κB/p65 were not associated with the response to neoadjuvant chemotherapy, although the cytoplasmic NF-κB/p65 staining intensity was significantly decreased in the post-treatment tumor samples compared with the pretreatment samples. All patients whose tumors showed strong cytoplasmic NF-κB/p65 expression before neoadjuvant chemotherapy are currently disease free. CONCLUSION: Our results suggest that strong cytoplasmic NF-κB/p65 expression could be a prognostic marker for patients with triple-negative breast cancer.

Multiplication of alpha-fetoprotein and protein induced by vitamin K absence-II is a powerful predictor of prognosis and recurrence in hepatocellular carcinoma patients after a hepatectomy.

AIM: To evaluate the oncological implications of multiplication of α-fetoprotein (AFP) and protein induced by vitamin K absence or antagonists-II (PIVKA-II) in patients with hepatocellular carcinoma (HCC). METHODS: Data were prospectively collected from 516 consecutive patients who underwent a curative primary hepatectomy for HCC between 1998 and 2010. The AP-factor (AFP × PIVKA-II) was evaluated in relation to 2-year survival outcomes by receiver-operator curve analysis to determine the cut-off values. Patient survival, recurrence-free survival and risk factors were analyzed in accordance with the preoperative AP-factor. RESULTS: The AP-factor was categorized into three groups depending on the serum concentrations of AFP and PIVKA-II as follows: AP1 (n = 206; AFP < 200 ng/mL and PIVKA-II < 100 mAU/mL), AP2 (n = 152; AFP × PIVKA-II < 10(5) ) and AP3 (n = 158; AFP × PIVKA-II ≥ 10(5) ). The AP-factor was found to be significantly related to pathological factors such as differentiation, portal vein invasion, hepatic vein invasion and intrahepatic metastasis. Multivariate analysis was performed to identify the risk factors for survival and recurrence. Albumin, AP-factor and pathological factors including portal vein invasion, hepatic vein invasion and intrahepatic metastasis are independent risk factors for survival. Tumor number, AP-factor, and a non-cancerous liver were determinants of recurrence. CONCLUSION: The AP-factor is closely related to differentiation and microscopic vascular invasion, and was selected by multivariate analysis as an independent factor for survival and recurrence, in HCC. Patients hopeful of obtaining good outcomes after a hepatectomy could be selected by the AP-factor evaluation.

Intratumoral artery on contrast-enhanced computed tomography imaging: differentiating intrahepatic cholangiocarcinoma from poorly differentiated hepatocellular carcinoma.

AIM: Differentiating intrahepatic cholangiocarcinoma (ICC) from poorly differentiated hepatocellular carcinoma (p-HCC) is often difficult, but it is important for providing appropriate treatments. The purpose of this study was to examine the features differentiating ICC from p-HCC on contrast-enhanced dynamic-computed tomography (CT). METHODS: This study examined 42 patients with pathologically confirmed ICC (n = 19) or p-HCC (n = 23) for which contrast-enhanced dynamic CT data were available. CT images were analyzed for enhancement patterns during the arterial phase, washout pattern, delayed enhancement, satellite nodules, capsular retraction, lesion shape, and presence of an intratumoral hepatic artery, intratumoral hepatic vein, intratumoral portal vein, and bile duct dilation around the tumor, portal vein tumor thrombus, lobar atrophy, or lymphadenopathy. RESULTS: Univariate analysis revealed the presence of rim enhancement (p = 0.037), lobulated shape (p = 0.004), intratumoral artery (p < 0.001), and bile duct dilation (p = 0.006) as parameters significantly favoring ICC, while a washout pattern significantly favored p-HCC (p < 0.001). Multivariate analysis revealed intratumoral artery as a significant, independent variable predictive of ICC (p = 0.037), and 15 ICCs (78.9%) showed this feature. Washout pattern was a significant, independent variable favoring p-HCC (p = 0.049), with 15 p-HCCs (65.2%) showing this feature. CONCLUSION: The presence of an intratumoral artery in the arterial phase on contrast-enhanced dynamic CT was a predictable finding for ICC, and the presence of a washout pattern was a predictable finding for p-HCC, differentiating between ICC and p-HCC.

[Efficacy of Sorafenib for Extrahepatic Recurrence of Hepatocellular Carcinoma after Liver Resection].

Sorafenib is the first molecularly targeted drug recommended as a treatment for advanced hepatocellular carcinoma (HCC). Herein, we report the efficacy of sorafenib for extrahepatic recurrence of HCC. From September 2004 to March 2015, 47 patients who were diagnosed with recurrent HCC after liver resection were treated with sorafenib. The overall response rate was 17.5% (complete response: CR 1, partial response: PR 6, stable disease: SD 17, progressive disease: PD 13, SD beyond PD 3), and the disease control rate was 67.5%. The median time to disease progression, including extrahepatic recurrence, was significantly better than in the group with only intrahepatic metastasis (p=0.034). Therefore, sorafenib might be an effective treatment for extrahepatic recurrence of HCC.