S-1 and CPT-11 Plus Ramucirumab (IRIS+Rmab) as Second-Line Chemotherapy for Patients with Oxaliplatin-Refractory Metastatic Colorectal Cancer (mCRC): A Multicenter Phase II Study in Japan (N-DOCC-F-C-1701).

This multicenter phase II N-DOCC-F-C-1701 trial is being planned in order to investigate the efficacy and safety of CPT-11+S-1 +Ramucirumab (IRIS+Rmab), which is anticipated to have a stronger anti-tumor effect than IRIS+Bmab in patients with metastatic colorectal cancer (mCRC) previously treated with oxaliplatin (L-OHP) containing regimen, in consideration of the result of RAISE, FIRIS and some phase II trials of IRIS+Bevacicizumab (Bmab). The number of patients is set at 38 for the statistical analysis, assuming an expected median PFS of 5.0 months (threshold: 3.0 months). The primary endpoint of the study is the progression free survival (PFS), and the secondary endpoints are the overall response rate (ORR), overall survival (OS), adverse events (AE), quality of life (QOL) and review of nausea and vomiting. This trial is registered in the UMIN Clinical Trials Registry as UMIN000028170. We intend to start conducting the trial in September 1, 2017. If this trial meets the endpoint, IRIS+Rmab might be supported as a new optional standard regimen for mCRC.

Impact of Anatomical Resection for Hepatocellular Carcinoma With Microportal Invasion (vp1): A Multi-institutional Study by the Kyushu Study Group of Liver Surgery.

OBJECTIVE: The aim of the present study was to evaluate the value of anatomical resection for hepatocellular carcinoma (HCC) with microportal vascular invasion (vp1) between 2000 and 2010. BACKGROUND: Vascular invasion has been reported as a prognostic factor of liver resection for HCC. Anatomical resection for HCC has resulted in optimum outcomes of eradicating intrahepatic micrometastases through the portal vein, but opposite results have also been reported. METHODS: A clinical chart review was performed for 546 patients with HCC with vp1. We retrospectively evaluated the recurrence-free survival (RFS) between anatomical (AR) and nonanatomical resection (NAR). The site of recurrence was also compared between these groups. The influence of AR on the overall survival (OS) and RFS rates was analyzed in patients selected by propensity score matching, and the prognostic factors were identified. RESULTS: A total of 546 patients were enrolled, including 422 in the AR group and 124 in the NAR group. There was no difference in the 5-year OS and RFS rates between the 2 groups. Local recurrence was significantly more frequent in the NAR group than in the AR group. In a multivariate analysis, hepatitis C virus, serum protein induced by vitamin K absence II of 380 mAU/mL or more, tumor diameter of 5 cm or more, and age of 70 years or older were significant predictors of a poor RFS after liver resection. There were no significant differences in the OS or RFS between the AR and NAR groups by a propensity score-matched analysis. CONCLUSIONS: Although local recurrence around the resection site was suppressed by AR, AR for HCC with vp1 did not influence the RFS or OS rates after hepatectomy in the modern era.

CXCL12 expression in intrahepatic cholangiocarcinoma is associated with metastasis and poor prognosis.

Intrahepatic cholangiocarcinoma is a rare malignant biliary neoplasm that causes a poor prognosis even after curative hepatectomy. Liver metastasis is the major recurrence pattern of intrahepatic cholangiocarcinoma; therefore, the prevention of liver metastasis is a desirable objective. The aim of this study is to identify gene(s) related to liver metastasis of intrahepatic cholangiocarcinoma and to examine the inhibitory effects on metastasis of intrahepatic cholangiocarcinoma by controlling such gene(s). We collected 3 pairs of intrahepatic cholangiocarcinoma frozen samples, and 36 pairs (primary and metastatic lesions) of intrahepatic cholangiocarcinoma formalin-fixed paraffin-embedded samples, from patients who underwent surgical resection at hospitals related to the Kyushu Study Group of Liver Surgery between 2002 and 2016. We carried out cDNA microarray analyses and immunohistochemistry to identify candidate genes, and evaluated one of them as a therapeutic target using human cholangiocarcinoma cell lines. We identified 4 genes related to liver metastasis using cDNA microarray, and found that CXCL12 was the only gene whose expression was significantly higher in liver metastasis than in primary intrahepatic cholangiocarcinoma by immunohistochemistry (P = .003). In prognosis, patients in the high CXCL12 group showed a significantly poor prognosis in disease-free (P < .0001) and overall survival (P = .0004). By knockdown of CXCL12, we could significantly suppress the invasive and migratory capabilities of 2 human cholangiocarcinoma cell lines. Therefore, CXCL12 might be associated with metastasis and poor prognosis in intrahepatic cholangiocarcinoma.

Training for laparoscopic pancreaticoduodenectomy.

In recent years, laparoscopic procedures have developed rapidly, and the reports of laparoscopic pancreatic resection including laparoscopic pancreaticoduodenectomy (LPD) have increased in number. Although LPD is a complex procedure with high mortality, the training system for LPD remains unestablished. Ensuring patient safety is extremely important, even in challenging surgeries such a LPD. At present, several tools have been developed for surgical education to ensure patient safety preoperatively, such as video learning, virtual reality simulators, and cadaver training. Although LPD is reported as a safe and feasible choice, LPD is still a challenging operation. An LPD training system should be established with a board-certified system.

The Feasibility and Efficacy of Laparoscopic Extended Total Mesorectal Excision for Locally Advanced Lower Rectal Cancer.

BACKGROUND/AIM: Extended total mesorectal excision (ETME) is defined as en bloc resection of the adjacent organs outside the mesorectal fascia, that is indicated in cases with locally advanced lower rectal cancer (T4 tumor). The aim of this study was to evaluate the clinical and oncological outcomes of laparoscopic ETME (L-ETME) for locally advanced lower rectal cancer. PATIENTS AND METHODS: The present study analyzed clinical outcomes and oncological outcomes of 11 consecutive patients who underwent L-ETME for cT4 lower rectal cancer in Nagasaki Medical Center between 2012 and 2015. RESULTS: Of the 11 patients, 7 underwent neoadjuvant therapy, and 7 underwent pelvic node dissection. One case (7.1%) underwent resection of anterior organs (prostate), 6 cases (54.5%) had resection of the lateral organs (neurovascular bundle, hypogastric nerve, pelvic plexus, ovary, and internal iliac blood vessels) and 4 cases (36.4%) had resection of both anterior and lateral organs. In all cases enrolled in this study, R0 resection was achieved. The median operation time and intraoperative blood loss were 416 min and 350 ml, respectively. The postoperative complication rate was 18.2% (2/11). The 3-year overall survival rate was 79.5%, and the 3-year local recurrence-free survival rate was 87.5%. There was no mortality and no re-operation in this series. CONCLUSION: The results of the present study suggest that L-ETME is feasible and has efficacy for locally advanced lower rectal cancer.

Predictors of portal and splenic vein thrombosis after laparoscopic splenectomy: a retrospective analysis of a single-center experience.

PURPOSE: Laparoscopic splenectomy (LS) has become the standard operative approach for splenectomy. Portal or splenic vein thrombosis (PSVT) is a serious and common complication after LS, and lethal complications of PSVT can occur when the portal vein is completely occluded by portal vein thrombosis (PVT). We aimed to clarify the predictors of PSVT after LS and to determine which of them were also predictors of PVT. METHODS: A total of 56 consecutive patients who underwent elective LS were enrolled in this study. The patients were divided into two groups based on the presence or absence of PSVT after LS. In addition, patients with PSVT were divided into two groups: a PVT group and a non-PVT group. The preoperative and intraoperative clinical data were compared among the groups. RESULTS: Thirty (53.6%) patients developed PSVT. The splenic vein diameter was the most useful predictor for the development of PSVT, and 10 mm was an accurate splenic vein diameter cut-off value for use as a predictive factor for PSVT. In addition, the splenic vein diameter was the most useful predictor of the development of PVT from splenic vein thrombosis (SVT), and 14 mm was found to be an accurate cut-off value. CONCLUSION: PSVT is a common postoperative complication that is identified on enhanced computed tomography. The splenic vein diameter is not only a predictor of PSVT but also of the development of PVT from SVT.

Adherence to Adjuvant Endocrine Therapy in Women With Breast Cancer: A Prospective Observational Study in Japanese Women.

INTRODUCTION: Nonadherence to adjuvant endocrine therapy has been poorly studied in Asian patients with breast cancer. We therefore assessed adherence to endocrine therapy among women with breast cancer in Japan. PATIENTS AND METHODS: We conducted a prospective observational study among Japanese women with hormone receptor-positive breast cancer. Patients brought their pill packets to visits for 1 year and answered a questionnaire. We also examined prescription records during the study period. Adherence to endocrine therapy was defined as patients who had taken > 80% of the pills according to the packets during the study. Clinicopathologic features and questionnaires were compared between adherent and nonadherent patients. RESULTS: A total of 234 patients completed the trial, of whom 85% demonstrated adherence based on pill packets, and 98% demonstrated adherence based on prescription records. Mastectomy, higher stage, nodal metastasis and adjuvant chemotherapy were correlated with adherence based on pill packets. Adjuvant chemotherapy was an independent factor associated with adherence. According to the questionnaire, adherent patients were more likely to consult a nurse when they had trouble with their medication. These patients also emphasized the efficacy rather than the side effects of the medication. Nonadherent patients were aware that they were being nonadherent. CONCLUSION: The results of this study revealed that 85% of patients were adherent to endocrine therapy, but physicians were unaware of the nonadherent patients. Raised awareness of nonadherence and information sharing between patients and medical teams might increase adherence to endocrine therapy.

The long-term survival in primary retroperitoneal mucinous cystadenocarcinoma: a case report.

BACKGROUND: Primary retroperitoneal mucinous cystadenocarcinoma (PRMC) is extremely rare, and its biological behavior, pathogenesis, optimum treatments, and prognosis remain to be elucidated. We herein report a case of PRMC with an 80-month follow-up. CASE PRESENTATION: A 29-year-old woman was diagnosed with unknown retroperitoneal tumor with benign right ovarian cyst and uterine fibroids, and she underwent laparotomy. The tumor was completely resected with a subsequent histopathological diagnosis of primary retroperitoneal mucinous cystadenocarcinoma (PRMC). Eighty months after surgery, she remains recurrence-free. CONCLUSION: PRMC is an extremely rare tumor. Only around 60 cases have so far been published in the literature. The preoperative diagnosis of PRMC is difficult, and a definitive diagnosis can usually only be made based on the findings of histopathological examinations after surgery. Presently, only radical resection is useful for both diagnostic and therapeutic purposes. The optimal long-term management after surgery is still not well established. Further studies on PRMC are therefore needed to elucidate the etiology and establish effective treatments.

Clinical and Oncological Outcomes of Laparoscopic Lateral Pelvic Lymph Node Dissection in Advanced Lower Rectal Cancer: Single-institution Experience.

AIM: The aim of this study was to compare the clinical outcomes of laparoscopic versus open surgery for total mesorectal excision (TME) with lateral pelvic lymph node dissection (LPLD) in advanced lower rectal cancer. PATIENTS AND METHODS: Forty-four patients who underwent TME with LPLD for lower rectal cancer (pStage II/III) between January 2008 and December 2014 were divided into two groups according to the type of surgical approach as follows: open LPLD group (OLD, n=17) and laparoscopic LPLD group (LLD, n=27). RESULTS: Operative time was comparable between the groups (p=0.15), whereas intraoperative blood loss and complication rates were significantly less in LLD than in OLD. Postoperative hospital stay was shorter in LLD than in OLD. Overall survival and local recurrence-free survival were similar in the two groups. Disease-free survival was better in LLD than in OLD, although the difference was not significant. CONCLUSION: Laparoscopic TME with LPLD is safe and feasible.

A case of single incision laparoscopic total colectomy for intestinal neuronal dysplasia type B.

INTRODUCTION: Intestinal neuronal dysplasia type B (IND-B) is an infrequent disease of the submucosal plexus of intestine manifesting chronic intestinal obstruction or severe chronic constipation. IND is rarely reported in adult patients. PRESENTATION OF A CASE: The present study reports on the case of a 36 year-old woman suffering from longstanding chronic constipation and who was diagnosed with severe constipation in more than 20 years. Although she began to take a large amount of stimulant laxatives, such as "senna" and "bisacodyl", constipation symptoms did not improve, she was admitted to our hospital. It was diagnosed with refractory constipation of the medication treatment-resistance, total colectomy with ileorectal anastomosis by single incision laparoscopic surgery (SILS) was performed. The final pathological diagnosis was IND-B. DISCUSSION: Refractory constipation after medical treatment is often seen in young generation. SILS has benefits of better cosmesis, reduced morbidity, reduced postoperative pain, and reduced length of hospital stay. CONCLUSION: For the patients with refractory constipation associated with neuropathy such as IND, total colectomy by SILS was very effective.

Anterior approach for right hepatectomy with hanging maneuver for hepatocellular carcinoma: a multi-institutional propensity score-matching study.

BACKGROUND: This multi-institutional study aimed to assess the benefits of anterior approach for right hepatectomy with hanging maneuver (ARH-HM) for hepatocellular carcinoma (HCC) compared with conventional right hepatectomy (CRH). METHODS: From January 2000 to December 2012, 306 patients with HCC ≥5 cm were divided into two groups: ARH-HM (n = 104) and CRH (n = 202). RESULTS: After one-to-one propensity score-matched analysis, 72 ARH-HM and 72 CRH patients presented comparable background factors. Patients in the ARH-HM group demonstrated significantly less intraoperative blood loss (480 vs. 1,242 g, P < 0.001) and a lower frequency of red cell concentrate transfusion (21.1% vs. 50.7%, P < 0.001) compared with patients in the CRH group. The 5-year overall survival rate was significantly better in the ARH-HM group compared with the CRH group (50.2% vs. 31.4%, P = 0.021). Limited to patients with HCC ≥10 cm, recurrence-free and overall survival of the ARH-HM group was significantly greater than those of the CRH group. CONCLUSION: In comparison with CRH, ARH-HM for large HCC can provide better overall survival rates with a decrease in intraoperative blood loss and transfusion rates. Survival impact was evident especially in patients with HCC ≥10 cm.

Surgical management of recurrent intrahepatic cholangiocarcinoma: predictors, adjuvant chemotherapy, and surgical therapy for recurrence: A multi-institutional study by the Kyushu Study Group of Liver Surgery.

Objectives of the present study were to identify predictors of the recurrence of intrahepatic cholangiocarcinoma (ICC), and to evaluate the survival benefit of adjuvant chemotherapy and surgical treatment for ICC recurrence. A multi-institutional retrospective study was carried out in 356 patients with ICC who underwent curative surgery at one of 14 institutions belonging to the Kyushu Study Group of Liver Surgery. A total of 214 patients (60%) had recurrence. Predictors of ICC recurrence were as follows: positive for pathological intrahepatic metastasis (im), positive for lymph node metastasis (n), positive for pathological lymphatic infiltration (ly), pathological bile duct invasion (b), and tumor size ≥4.4 cm. Adjuvant chemotherapy was given to 120 patients (34%) and, in the patients with im or tumor size ≥4.4 cm, adjuvant chemotherapy showed a survival benefit. Only 37 patients (17%) underwent surgical treatment for ICC recurrence. The surgical treatment resulted in a good 5-year survival rate (44%), which is similar to the rate obtained by the first operation for primary ICC. Prognosis of patients with primary im after the second operation was significantly worse (5-year survival 18%) compared to patients without primary im. Primary im+ should be considered a contraindication for surgical treatment for ICC recurrence.

Total thyroidectomy versus thyroid lobectomy for papillary thyroid cancer: Comparative analysis after propensity score matching: A multicenter study.

BACKGROUND: In patients with papillary thyroid carcinoma (PTC), the role of total thyroidectomy (TT) versus that of thyroid lobectomy (TL) has been controversial. METHODS: This retrospective study was approved by our institutional review board, and the requirement to obtain informed consent was waived. In total, 173 patients with 1- to 5-cm stage cN0 and cM0 PTC tumors treated by curative surgery from 1994 to 2008 were evaluated. Clinicopathologic features and adverse events were compared between patients who underwent TT and those who underwent TL. After adjustment for differences in baseline clinicopathologic factors using propensity score matching, we compared recurrence-free survival (RFS) and OS. RESULTS: TL was performed in 120 patients and TT in 53 patients. Patients who underwent TT were older; had larger tumors; more frequently had nodal metastasis, multifocal tumors, and extracapsular invasion; and more frequently underwent radioactive iodine ablation than patients who underwent TL. Hypocalcemia requiring medication and recurrent laryngeal nerve paralysis were more frequent in TT than TL. The 10-year RFS and OS of all patients were 93.3% and 96.7%, respectively. There was no significant difference in RFS (90.6% vs 93.0% in TT and TL groups, respectively) or OS (96.2% vs 96.9% in TT and TL groups, respectively) according to the extent of surgical resection after propensity score matching. CONCLUSION: Equivalent prognoses were observed for patients with 1- to 5-cm stage cN0 and cM0 PTC tumors treated by TL or TT after propensity score matching. Adverse events occurred less frequently in patients who underwent TL than TT.

Clinical and Oncological Outcomes of Laparoscopic Versus Open Surgery for Advanced Rectal Cancer.

AIM: To compare the clinical and oncological outcomes of laparoscopic and open approaches in patients with advanced rectal cancer. PATIENTS AND METHODS: In this study, 78 patients who underwent surgery for advanced middle and lower rectal cancer (pStage II - III) were divided into two groups according to type of surgical approach: laparoscopic surgery (LS group; n=40) and open surgery (OS group: n=38). The clinical outcomes and oncological outcomes were compared between the two groups. RESULTS: The operation time was comparable, whereas operative blood loss and complication rates were significantly less in the LS group compared to the OS group. Cancer-specific survival (CSS) and local recurrence-free survival (LRFS) were similar in the two groups. Disease-free survival (DFS) was better in the LS group than in the OS group. CONCLUSION: LS for advanced rectal cancer was safe and not inferior to OS in clinical and oncological outcomes.

Portal Vein Embolization Followed by Right-Side Hemihepatectomy for Hepatocellular Carcinoma Patients: A Japanese Multi-Institutional Study.

BACKGROUND: Portal vein embolization (PVE) is useful to expand the indications of major hepatectomy; however, its oncologic effects are not fully understood. This study aimed to confirm the efficacy of preoperative PVE for hepatocellular carcinoma patients. STUDY DESIGN: Between 2000 and 2012, five hundred and ten patients with hepatocellular carcinoma undergoing right-side hemihepatectomy were enrolled (PVE group, n = 162 and non-PVE group, n = 348). To equalize background factors, one-to-one propensity case-matched analysis and multivariate analysis were performed. Short- and long-term outcomes were evaluated. RESULTS: Propensity score-matched patients, 148 in each group, were selected. The percentage of resected liver volume on admission was significantly greater in the PVE group (60.5% vs 48.3%; p < 0.001), but decreased considerably after PVE, from 60.5% to 50.3% (p < 0.001). The 5-year cumulative recurrence-free survival (36.4% vs 35.3%) and overall survival (58.6% vs 52.8%) rates were comparable. Extrahepatic recurrences were less common in the PVE group (18.1% vs 38.8%; p = 0.004). Independent prognostic factors for recurrence-free survival were morbidity (hazard ratio [HR] = 1.56), multiple tumors (HR = 1.97), red cell concentrate administration (HR = 1.57), older age (HR = 2.09), and massive portal invasion (HR = 2.33); and those for overall survival were morbidity (HR = 2.37), multiple tumors (HR = 1.71), and massive hepatic venous invasion (HR = 3.49). CONCLUSIONS: Even though hepatocellular carcinoma patients who underwent preoperative PVE and right-side hemihepatectomy had a significantly larger resected liver volume on admission, they have a comparable long-term prognosis as patients with up front hepatectomy. In addition, PVE might decrease extrahepatic recurrences.

Multidisciplinary therapy for granulocyte-colony-stimulating factor producing carcinosarcoma of the esophagus: report of a case.

The granulocyte-colony-stimulating factor (G-CSF)-producing esophageal carcinosarcoma is extremely rare in esophageal cancer. In the present case, multidisciplinary therapy, which is surgical resection with preoperative chemotherapy, has been effectively treatment to granulocyte-colony-stimulating factor producing esophageal carcinosarcoma of the esophagus.

Hepatic inflammatory pseudotumor associated with xanthogranulomatous cholangitis mimicking cholangiocarcinoma.

Inflammatory pseudotumor (IPT) is a rare benign condition often misdiagnosed as malignancy. An 80-year-old man was referred to our clinic for an asymptomatic hepatic mass detected on plain abdominal CT. Abdominal ultrasonography identified the lesion as a poorly defined hypoechoic mass. Although a liver biopsy did not provide any evidence of malignancy, imaging modalities suggested a diagnosis of cholangiocarcinoma. The patient underwent left lobectomy, and the pathological findings were consistent with the features of xanthogranulomatous cholangitis. This case is the first report of hepatic IPT originating from xanthogranulomatous cholangitis without symptoms and illustrates the importance of obtaining a preoperative diagnosis in order to avoid a misdiagnosis of malignant tumor.

Prognostic Impact of Preoperative Lymph Node Enlargement in Intrahepatic Cholangiocarcinoma: A Multi-Institutional Study by the Kyushu Study Group of Liver Surgery.

BACKGROUND: Although lymph node metastasis (LNM) has been considered an important prognostic factor for intrahepatic cholangiocarcinoma (ICC), the impact of lymph node enlargement on the prognosis of ICC, and the accuracy of diagnosis of LNM, have not been fully clarified. METHODS: Using a chart review of 225 patients with ICC, we compared survival times between patients with and without lymph node enlargement, and we evaluated the accuracy of diagnosis of LNM. We also performed a multivariate analysis to determine the variables affecting overall survival in the study population. RESULTS: The survival time of patients without lymph node enlargement was significantly longer than that of patients with lymph node enlargement (median survival time [MST] 43.7 vs. 20.1 months; p = 0.007). However, in the group with enlarged lymph nodes, survival time was prolonged as a result of hepatectomy (MST 20.1 vs. 7.6 months; p < 0.01). The sensitivity of lymph node size and positron emission tomography-computed tomography findings for diagnosing LNM were 50.0 % (23/46) and 31.2 % (5/16), respectively, and were thus insufficient. Multivariate analysis identified the serum carcinoembryonic antigen (hazard ratio [HR] 1.830) and carbohydrate antigen 19-9 (HR 2.189) levels, blood transfusion (HR 1.792), intrahepatic metastasis (HR 1.988), and final stage (HR 8.684) as prognostic factors for overall survival, but lymph node enlargement was not identified as a prognostic factor. CONCLUSION: Preoperative evaluation of LNM proved to be difficult, and survival time in ICC patients with lymph node enlargement was prolonged as a result of hepatectomy. Thus, ICC patients with preoperative lymph node enlargement should not be prematurely deemed non-curative cases.

Intraductal papillary mucinous neoplasm in an annular pancreas: a case report.

Annular pancreas is a rare anomaly in which a ring of pancreatic tissue encircles the second portion of the duodenum. We herein report a case involving a 79-year-old Japanese man with an intraductal papillary mucinous neoplasm (IPMN) of the pancreas. Imaging studies showed that the pancreatic tissue encircled the descending part of the duodenum and that a 30-mm-diameter cystic tumor was present in the annular segment, leading to the diagnosis of pancreatic IPMN. Limited pancreatic resection was successfully performed by careful division of the annular segment from the second portion of the duodenum. The postoperative course was uneventful, and the patient's pancreatic function was retained without the need for supplementation. To the best of our knowledge, this is the first report of IPMN occurring in the annular segment of the pancreas. Limited resection of the pancreatic annular segment is a feasible surgical treatment for noninvasive IPMN of the annular pancreas.

A novel animal model for in vivo study of liver cancer metastasis.

AIM: To establish an animal model with human hepatocyte-repopulated liver for the study of liver cancer metastasis. METHODS: Cell transplantation into mouse livers was conducted using alpha-fetoprotein (AFP)-producing human gastric cancer cells (h-GCCs) and h-hepatocytes as donor cells in a transgenic mouse line expressing urokinase-type plasminogen activator (uPA) driven by the albumin enhancer/promoter crossed with a severe combined immunodeficient (SCID) mouse line (uPA/SCID mice). Host mice were divided into two groups (A and B). Group A mice were transplanted with h-GCCs alone, and group B mice were transplanted with h-GCCs and h-hepatocytes together. The replacement index (RI), which is the ratio of transplanted h-GCCs and h-hepatocytes that occupy the examined area of a histological section, was estimated by measuring h-AFP and h-albumin concentrations in sera, respectively, as well as by immunohistochemical analyses of h-AFP and human cytokeratin 18 in histological sections. RESULTS: The h-GCCs successfully engrafted, repopulated, and colonized the livers of mice in group A (RI = 22.0% ± 2.6%). These mice had moderately differentiated adenocarcinomatous lesions with disrupted glandular structures, which is a characteristics feature of gastric cancers. The serum h-AFP level reached 211.0 ± 142.2 g/mL (range, 7.1-324.2 g/mL). In group B mice, the h-GCCs and h-hepatocytes independently engrafted, repopulated the host liver, and developed colonies (RI = 12.0% ± 6.8% and 66.0% ± 12.3%, respectively). h-GCC colonies also showed typical adenocarcinomatous glandular structures around the h-hepatocyte-colonies. These mice survived for the full 56 day-study and did not exhibit any metastasis of h-GCCs in the extrahepatic regions during the observational period. The mice with an h-hepatocyte-repopulated liver possessed metastasized h-GCCs and therefore could be a useful humanized liver animal model for studying liver cancer metastasis in vivo. CONCLUSION: A novel animal model of human liver cancer metastasis was established using the uPA/SCID mouse line. This model could be useful for in vivo testing of anti-cancer drugs and for studying the mechanisms of human liver cancer metastasis.