Isolated liver metastasis detected 11 years after the curative resection of rectal cancer: A case report.

BACKGROUND: The duration of surveillance after curative resection of colorectal cancer (CRC) is generally 5 years. The overall incidence of recurrence more than 5 years after surgery for CRC in Japan has been reported to be 0.6%. Moreover, it is rare for CRC to have metachronous liver metastasis more than 10 years after surgery. Here, we present a case of liver metastasis detected 11 years after the curative resection of rectal cancer. CASE SUMMARY: A 72-year-old man was referred to our hospital after a liver tumor was detected by abdominal ultrasonography at another hospital. He had undergone surgery for rectal cancer 11 years previously. Contrast-enhanced computed tomography (CT) showed a tumor with a diameter of approximately 8 cm in the posterior segment, which was weakly and gradually enhanced. 18F-fluorodeoxyglucose-positron emission tomography/CT showed an abnormally high uptake on the tumorous lesion, which showed that the tumor appeared to spread convexly along the intrahepatic bile ducts. Intrahepatic cholangiocarcinoma was therefore diagnosed, and he had an extended right posterior sectionectomy and regional lymph node dissection. Histopathological examination showed that the tumor was a moderately differentiated adenocarcinoma and showed the same pathological characteristics as the rectal cancer. Immunohistological examination showed that the cancer cells of both the liver tumor and rectal cancer were positive for cytokeratin (CK) 20 and weakly positive for CK 7. These findings were consistent with the liver metastasis from the rectal cancer. CONCLUSION: It is possible that a liver tumor is metastatic in a patient with a previous history of CRC, even if it was more than 10 years earlier.

Gallbladder cancer detected by elevated serum KL-6 levels during the follow-up of interstitial pneumonia: a case report.

Serum Krebs von den Lungen-6 (KL-6) is clinically used for the diagnosis of interstitial pneumonia (IP) as well as the evaluation of its disease activity. A female patient was diagnosed with idiopathic IP when she was 62 years old. Four years later, serum levels of KL-6 had been elevated gradually from 2400-3821 U/ml, and she was found to have gallbladder cancer detected by contrast-enhanced computed tomography (CT) and 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT. She thus underwent a radical extended cholecystectomy. After the operation, serum levels of KL-6 showed a steep decline to 590 U/ml. Immunohistological examination revealed that KL-6 presented in gallbladder cancer cells. Taken together, serum KL-6 was shown to be produced by gallbladder cancer cells. Here, we present the first patient in whom increased serum KL-6 levels led to the diagnosis of gallbladder cancer during follow-up of IP. When serum levels of KL-6 are elevated during the follow-up care of IP despite no worsening of IP, an examination of the whole body should be performed to find possibly existing malignant tumors.

[Multiple Intussusceptions Caused by Small Intestinal Metastases of the Nasal Cavity from Malignant Melanoma-A Case Report].

A 77-year-old woman, who underwent surgery for malignant melanoma of the nasal cavity 15 months prior and radiation and interferon-ß therapy for local recurrence, presented with epigastric discomfort. PET-CT examination showed multiple intussusceptions due to small intestinal tumors. Four intussusceptions were detected during laparotomy, and she underwent partial resection of the small intestine. Pathological findings revealed small intestinal metastases that originated from malignant melanoma. Following administration of nivolumab, local recurrence disappeared, and she was well. Because the prognosis of malignant melanoma with systemic metastases has improved due to the administration of new drugs, such as nivolumab, the incidence of indications for surgery for metastatic melanomas of the gastrointestinal tract is expected to increase.

[A Case of Alcoholic Liver Disease Presenting as Prominent Accumulation of Ascites Associated with Liver Damage Due to CapeOX].

A 75-year-old man with rectal cancer had consumed an average of6 6 g of alcohol per day for 47 years. However, his liver function was within normal limits and his Child-Pugh classification was A before initiation of therapy. He underwent neoadjuvant chemoradiation and a low anterior resection. The patient then received CapeOX as an adjuvant therapy. During the fourth cycle of CapeOX, computed tomography(CT)showed massive ascites. The chemotherapy was discontinued and treatment including a diuretic agent was initiated. The ascites gradually decreased and 8 months after the discontinuation of CapeOX, CT showed neither the presence ofascites nor recurrence ofthe cancer or metastasis. When a patient has a history ofexcessive alcohol intake, even iftest results for liver function are within normal limits, we should be aware ofthe hepatic toxicity ofCapeOX.

Short- and long-term outcomes after pancreaticoduodenectomy following total gastorectomy: Report of case series and literature review.

PURPOSE: Pancreaticoduodenectomy (PD) following gastrectomy (TG) should be considered challenging even currently although its procedure and clinical value have been being standardized. Short- and long-term outcomes as well as standard reconstruction method following these procedures remain unclear. In order to clarify these issues, we reviewed worldwide English literature and 4 of our own cases of PD for patients with previous TG. METHODS: Clinicopathological variables of 11 cases of PD for patients with previous TG were evaluated. Seven of these 11 were abstracted from a review of worldwide English literature and 4 of 11 were our own cases. RESULTS: 3 cases was reconstructed using Y-limb made in previous TG and afferent loop syndrome (ALS) was observed in 2 of 3, in these cases whereas no cases of ALS were found in cases reconstructed using newly-made Y-limb. In cases where PD was indicated for cancer, early cancer death, defined as death related to cancer recurrence observed within 2 years after PD, was observed in 6 of 9 cases. Notably in cases of pancreatic cancer recurrent cancer was diagnosed within 1year after PD in 5 of 7 cases and 4 of these patients died of pancreatic cancer soon after recurrence. CONCLUSION: In cases of PD following TG, previously-made Y-limb should not be used for reconstruction following PD because of probable cause of previously-made Y-limb for ALS. Long-term outcomes of PD after TG seemed unsatisfactory notably in cases of pancreatic cancer and thus application of PD for patients with previous TG should be carefully decided until reasonable explanation for this dismal outcome is obtained.

Localized 18F-fluorodeoxyglucose uptake at the pancreatic head during remission phase of autoimmune pancreatitis: A case report.

Autoimmune pancreatitis (AIP) is a unique form of pancreatitis, histopathologically characterized by dense lymphoplasmacytic infiltration and fibrosis of the pancreas with obliterative phlebitis. AIP is associated with a good response to steroid therapy. Differentiation between AIP and pancreatic cancer to determine a preoperative diagnosis is often challenging, despite the use of various diagnostic modalities, including computed tomography (CT), magnetic resonance imaging and endoscopic retrograde cholangiopancreatography. It has been reported that 18F-fluorodeoxyglucose (18F-FDG)-positron emission tomography (PET)/CT may be a useful tool for distinguishing between the two diseases. In the present case report, a 71-year-old male patient presented with a well-circumscribed, solitary, nodular and homogenous 18F-FDG uptake at the pancreatic head, while receiving maintenance steroid therapy in the remission phase of AIP; preoperatively, the patient had been strongly suspected of having pancreatic cancer. Pathological examination revealed post-treatment relapse of AIP. The present case highlights the diagnostic and management difficulties with AIP in the remission phase. In certain cases, it remains challenging to differentiate the two diseases, even using the latest modalities.

Pancreatic-type Acinar Cell Carcinoma of the Stomach Included in Multiple Primary Carcinomas.

BACKGROUND/AIM: Pancreatic-type acinar cell carcinoma (ACC) in the stomach is extraordinarily rare. We pathologically examined two cases with multiple primary carcinomas, including gastric tumors. PATIENTS AND METHODS: Gastric cancer specimens were examined by immunostaining and electron microscopy. RESULTS: Both cases had cancer cells with acinar patterns, resembling pancreatic ACC. The cancer cells in the first case were positive for exocrine markers, including chymotrypsin, lipase and alpha-1 antichymotrypsin (ACT), as well as neuroendocrine markers, including chromogranin A and synaptophysin. The cancer cells in the second case were positive for chymotrypsin and alpha-1 ACT, while being slightly positive for chromogranin A and synaptophysin. Ultrastructurally, cancer cells contained zymogen granules in both cases. The final diagnosis was pancreatic mixed acinar-neuroendocrine carcinoma and pure pancreatic ACC, respectively. CONCLUSION: We confirmed two cases with gastric pancreatic-type ACC included in multiple primary carcinomas. This type of double cancer has not been reported previously.

[A Case of Squamous Cell Carcinoma of the Esophagus with Achalasia -- Conversion from Chemoradiotherapy to Surgery].

The patient was a 67-year-old woman with achalasia and squamous cell carcinoma(SCC)of the esophagus. She presented with a difficulty in swallowing. The cancer was on the surface of the esophagus. The patient initially received systemic chemotherapy with 5-FU and cisplatin, and radiation therapy. The difficulty in swallowing persisted due to insufficiency of radiation treatment caused by achalasia. Therefore, we shifted the treatment plan from chemoradiotherapy to surgery. Endoscopic examination performed before surgery showed that there was no obvious cancer in the esophagus. We resected the esophagus routinely. On the specimen, no cancer cells were detected upon macroscopic and microscopic examinations; metastasis was not detected in the lymph node. Achalasia is a recognized risk factor for esophageal SCC. In the treatment of superficial SCC, no difference of therapeutic effect was observed between surgery and chemoradiation. However, for the treatment of certain cases of SCC with achalasia, including the treatment of achalasia itself, surgery can be the preferred option of treatment.

Sarcoidosis manifesting as hepatic and splenic nodules mimicking ovarian cancer metastases: A case report.

The current study presents a case of sarcoidosis manifesting as hepatic and splenic nodules, which was difficult to differentiate from ovarian cancer metastases. A 24-year-old female, who was previously diagnosed with right ovarian cancer and underwent surgery at the age of 21, was found to have two nodules in the spleen revealed by contrast-enhanced computed tomography (CT). 18F-fluorodeoxyglucose positron emission tomography/CT revealed two abnormal high uptake lesions in the spleen and one abnormal high uptake lesion in the liver. Under a diagnosis of hepatic and splenic metastases from right ovarian cancer, a laparoscopic splenectomy and partial hepatectomy were performed. Histopathological examination showed that a large number of non-caseating epithelioid cell granulomas formed these nodules, which was compatible with sarcoidosis. This case indicates that it is difficult to distinguish sarcoidosis from metastatic disease even using the latest modalities, and that laparoscopic surgery is a minimally invasive and useful tool for forming a differential diagnosis.

[Clinical Response of Metastatic Colon Cancer to Chemotherapy with S-1 and Oxaliplatin - A Case Report].

Chemotherapy with S-1 and oxaliplatin is a new treatment for metastatic colorectal cancer. We present the first case of S-1, oxaliplatin, and bevacizumab therapy in our hospital. The patient was a 69-year-old woman with ascending colon cancer and multiple lung and liver metastases. She tended to suffer from constipation; stenoses at the cecum and colon cancer were detected by colon fiberscopy. Following surgical resection of the primary tumor, the patient received systemic chemotherapy with S-1, oxaliplatin, and bevacizumab. Following chemotherapy, CT showed no cancer in the lung and cancer reduction in the liver or dissemination. The patient had diarrhea and no appetite at first, so we reduced the oxaliplatin dose by 80%. After reduction of the oxaliplatin dose, we could treat the patient with S-1 and oxaliplatin continuously with no toxicity. S-1 and oxaliplatin chemotherapy is cost-effective, and has less toxicity than other chemotherapies, if proper measures are taken. It seemed to have a non-inferior response rate and disease control compared to other chemotherapies, such as FOLFOX. Thus, this chemotherapy is a valid choice for metastatic colorectal cancer.

Xanthogranulomatous cholecystitis complicated with primary sclerosing cholangitis: report of a case.

Patients with primary sclerosing cholangitis (PSC) are at an increased risk for biliary tract carcinoma. The preoperative diagnosis of a biliary tract tumor as a malignancy is difficult, even using new modalities such as multidetector computed tomography (MD-CT), magnetic resonance cholangiopancreatography (MRCP), endoscopic retrograde cholangiography (ERC), and (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET). Surgery is considered to be first line of treatment when these examinations suggest the presence of malignancy in the biliary tract, depending on both the curability of the cancer and the impaired liver function due to PSC. The management of gallbladder masses in patients with PSC remains problematic due to difficulties with the precise diagnosis and adequate surgery. Xanthogranulomatous cholecystitis (XGC) is a type of chronic cholecystitis, and sometimes coexists with gallbladder cancer. It is very difficult to make a preoperative diagnosis differentiating these two diseases. This report presents the case of a patient with XGC, who had been suspected of having gallbladder cancer before surgery, because the tumorous lesion emerged within a year and showed a focally increased uptake by FDG-PET during the follow up for PSC for years. This is the first case of XGC discovered during treatment for PSC.

Successful left hemihepatectomy and perioperative management of a patient with biliary cystadenocarcinoma, complicated with MELAS syndrome: report of a case.

Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like syndrome (MELAS) is a rare, fetal disease caused by a mutation in mitochondrial DNA that leads to impaired oxidative metabolism in skeletal muscle, the central nervous system, and liver function. This report presents the case of a 50-year-old woman with biliary cystadenocarcinoma complicated by MELAS who underwent a successful left hemihepatectomy. In this case, the diagnostic key for the malignant tumor was an (18)F-fluorodeoxyglucose positron emission tomography study, which was useful even in a patient with MELAS, which causes abnormal glucose metabolism. The perioperative management of such patients includes special precautions to prevent lactic acidosis and deterioration of the reserved liver function after a hepatectomy, since the mitochondrial function in MELAS patients is abnormal. The patient in this report has remained free of liver dysfunctions and cancer recurrence for 2 years following the hepatectomy. This is the first report of a successful major hepatectomy for a patient with MELAS.

All-trans-retinoic acid attenuates radiation-induced intestinal fibrosis in mice.

BACKGROUND: Intestinal fibrosis leading to severe bowel dysmobility or obstruction is a troublesome adverse effect of abdominal or pelvic radiation therapy. We have recently reported that all-trans-retinoic acid (ATRA) prevents radiation- or bleomycin-induced lung fibrosis. Here, we examined the impact of ATRA on the mouse model of radiation-induced intestinal fibrosis. MATERIALS AND METHODS: We evaluated the histology of late radiation fibrosis in surgical samples. We then performed histological examinations and quantitative measurements of mRNA of interleukin-6 and transforming growth factor-beta(1) in intestinal tissues of irradiated mice with or without intraperitoneal administration of ATRA and investigated the effect of ATRA on the transdifferentiation and the production of collagen of irradiated human intestinal fibroblasts. RESULTS: Human samples of late radiation enteritis showed thickened submucosa and serosa, consistent with mouse model. Administration of ATRA attenuated irradiation-induced intestinal fibrosis and reduced mRNA of interleukin-6 and transforming growth factor-beta(1). In vitro studies disclosed that ATRA suppressed the transdifferentiation of irradiated intestinal fibroblasts and diminished the production of collagen from the cells. CONCLUSIONS: Our findings indicate that ATRA ameliorates irradiation-induced intestinal fibrosis. ATRA could be a novel approach in the treatment of fibrosis associated with chronic radiation enteritis.

The administration of naked plasmid DNA into the liver induces antitumor innate immunity in a murine liver metastasis model.

BACKGROUND: Gene therapy is a promising strategy against advanced cancer; however, the safety of viral vectors and the effectiveness of non-viral vectors have not yet been established. Recently, a hydrodynamics-based procedure was reported to be an effective and safe method to deliver and transduce DNA into the liver. Herein, we propose a strategy for liver metastasis by a hydrodynamics-based procedure to deliver naked non-coding plasmid DNA (pDNA) into the liver as an immunocompetent organ. METHODS AND RESULTS: Mice received a rapid intravenous (i.v.) injection of naked pDNA in a large volume of saline (0.1 ml/g body weight). The single administration of a naked non-coding pDNA by the hydrodynamics-based procedure before tumor cell inoculation strongly suppressed liver metastasis formation. However, the usual i.v. injection (200 microl/body) of the same dose of naked pDNA could not suppress liver metastasis formation. Following the methylation of CpG sequences within the pDNA using CpG methylase, injection of the methylated pDNA by the hydrodynamics-based procedure could not suppress liver metastasis formation. Gadolinium chloride pretreatment did not interfere with this antitumor effect, but anti-asialo GM1 antiserum treatment did. These findings indicated that natural killer (NK) cells, not Kupffer cells, were involved in this antitumor effect. The NK cytotoxic activities of liver mononuclear cells were strongly enhanced after receiving a naked pDNA by the hydrodynamics-based procedure. CONCLUSIONS: These observations suggest that unmethylated CpG motifs in pDNA stimulated immune cells, resulting in the activation of NK cells in the liver to suppress liver metastases in a murine model.

Tumour plasticity and extravascular circulation in ECV304 human bladder carcinoma cells.

BACKGROUND: The concepts of vasculogenic mimicry and mosaic vessels have been proposed as novel modes of tumour neovascularisation. However, the presence and significance of these types of neovascularisation remain unclear. MATERIALS AND METHODS: ECV304 human bladder carcinoma cells were used to determine how tumour cells take part in tumour neovascularisation. RESULTS: Subcutaneous ECV304 xenografts in mice showed various vessel types, including angiogenic vessels, tumour cell-related vessels and extracellular matrix networks. A tracer experiment demonstrated perfusion of beads in these structures. ECV304 cells, cultured on collagen I gels, formed tube networks with expressions of several endothelial-related markers. In coculture models of ECV304 cells and human umbilical vein endothelial cells, the two cells collaborated to form sprouts or networks. CONCLUSION: ECV304 cells possess an endothelial character which confers the ability to mimic and collaborate with vascular endothelial cells and facilitates the acquisition of tumour microcirculation.

Absence of smooth muscle actin-positive pericyte coverage of tumor vessels correlates with hematogenous metastasis and prognosis of colorectal cancer patients.

OBJECTIVES: Immature microvessels, which are not covered by pericytes, are irregular and leaky. We hypothesized that tumor cells can penetrate immature microvessels more easily than mature microvessels. In this study, we investigated the maturation of angiogenesis by the immunohistochemical staining of colorectal cancer specimens and determined the correlation between the microvessel count or the maturity of microvessels and clinicopathological variables. METHODS: Ninety-two surgical specimens from our department were used. Double immunostaining of endothelial cells with anti-CD34 antibody and pericytes with anti-alpha-smooth muscle actin antibody was performed. The microvessel density (MVD) and microvessel pericyte coverage index (MPI) as an index of microvessel maturation were evaluated. RESULTS: The MVD showed a significant positive correlation with tumor size, depth of invasion and Dukes' stage. The MPI showed a significant positive correlation with the histological differentiation of the tumor tissues and distant metastasis at the time of operation. The high MVD group (> or =26.0, n = 50) tended to have a poorer prognosis than the low MVD group (<26.0, n = 42) (p = 0.097). Next, the 50 patients in the high MVD group were classified into two subgroups of high MPI (> or =78.1%, n = 25) and low MPI (<78.1%, n = 25). MPI showed a significant negative correlation with hematogenous metastasis, and the low MPI group demonstrated a significantly poorer survival than the high MPI group (p = 0.040). CONCLUSIONS: These findings demonstrate that immature neovascularization was observed in poorly differentiated tumors and was correlated with metastasis, resulting in a poorer prognosis. Taken together, not only microvessel density but also vascular maturation were crucial factors for colorectal cancer patients.

Fas/CD95 signaling rather than angiogenesis or proliferative activity is a useful prognostic factor in patients with resected liver metastases from colorectal cancer.

BACKGROUND: The selection of resective therapy for colorectal hepatic metastases remains controversial. The aim of this study is to investigate the prognostic factors for patients with resected liver metastases from colorectal cancer by analyzing not only clinicopathological factors but also recent immunohistological markers. METHODS: Eighty-five patients underwent hepatic resection for metastatic colorectal cancer over the past 20 years. Fas/CD95 expression, microvessel density, and proliferating cell nuclear antigen (PCNA) proliferative activity were assessed with immunohistochemical methods in addition to the clinicopathological factors. Survival analysis was performed using the Kaplan-Meier method and Cox proportional hazards model, both univariately and multivariately. RESULTS: Univariate and multivariate analyses revealed that the number of metastases, Fas/CD95 expression, and postoperative carcinoembryonic antigen doubling time (CEADT) were significant prognostic indicators, whereas the mode of hepatic resection, chemotherapy, and other clinicopathological factors had no influence on survival. Fas/CD95 index correlated with postoperative CEADT (p=0.039), number of metastases (p=0.018), and survival (p=0.023). CONCLUSIONS: Our study confirmed the number of metastases and CEADT as prominent prognostic factors after hepatic resection for metastatic colorectal cancer. These two factors reflect the degree of Fas/CD95 signaling rather than angiogenesis or cancer growth rate.

Reappraisal of surgical treatment for radiation enteritis.

Although radiation enteritis is a well-recognized sequel of therapeutic irradiation, the standard surgical method is not universally agreed upon. Not only the short-term effect but also the long-term effect after a surgical intervention has been fairly well reported. To reassess the surgical therapy for radiation enteritis, we retrospectively analyzed 48 patients (5 males and 43 females, mean age 58.6 years) who had been operated on in our department. These patients were divided into two types according to the time of surgery or the clinical manifestation, and operative methods were analyzed. Patient's status such as bowel movement, body weight, and serum albumin value after surgery were analyzed, together with the patients survival. Our surgical methods were small intestinal resection for the intestinal obstruction, and pull-through reconstruction for proctitis. Two patients died of multiple organ failure caused by perforated peritonitis irrespective of emergent operation. Although the overall morbidity was 21.7%, there was no leakage when bowels were anastomosed. Overall survival after radiation-related complication in patients without previous neoplastic disease recurrence was 89%, 79%, and 69%, at 1, 3, and 5 years after surgery, respectively. Bowel motility, serum albumin level, and body weight recovered gradually soon after the operation and reached satisfactory levels within 6 months. Our analysis showed that small bowel injury should be treated by generous resection of the affected bowel followed by careful anastomosis of the disease-free ends, while rectal resection is best dealt with by restorative proctectomy. This may provide a good quality of life and minimize major postoperative complications such as leakage.

Vascular endothelial growth factor reduces mural cell coverage of endothelial cells and induces sprouting rather than luminal division in an HT1080 tumour angiogenesis model.

Vascular endothelial growth factor (VEGF) plays a central role in tumour angiogenesis. In a mouse intramuscular tumour model using VEGF-transfected HT1080 human fibrosarcoma, we investigated the morphological features and patterns of remodelling in size-matched tumours. Compared with the control tumours (C group), the VEGF-transfected tumours (V group) showed vigorous neovascularization with larger vessels. Fenestrations and disruptions of endothelia were specific to the V group. Three types of vascular remodelling, i.e. sprouting, luminal division and intussusceptive microvascular growth, were present in both groups. Morphometric analyses revealed that mural cell coverage of the endothelial cells was significantly smaller in the V group compared with that in the C group (V group, 28.2 +/- 18.6%; C group, 41.6 +/- 21.1%; P < 0.0001). To determine the prevalence of remodelling patterns, the occurrences of abluminal and luminal processes on endothelial cell surfaces were quantified. Abluminal processes are defined as cytoplasmic protrusions of the abluminal membrane of endothelial cells, which can vary from tiny spurs to solid sprouts of the cell. On the other hand, luminal processes are defined as intraluminal protrusions of the endothelial cell membrane, including various membranous changes from filiform processes to rather thick cytoplasmic bulges. An abluminal process is thought to represent an initial morphological change in sprouting type angiogenesis, and a luminal process to be a sign of implementation of luminal division. The frequency of abluminal processes was significantly higher in the V group than in the C group (V group, 0.243 +/- 0.138/microm; C group, 0.114 +/- 0.101/microm; P < 0.0001). In contrast, the number of luminal processes on the endothelial cells per micrometre was statistically comparable between the groups (V group, 0.285 +/- 0.252/microm; C group, 0.309 +/- 0.236/microm, P = 0.381). These results indicate that sprouting is the main mode of VEGF-induced tumour angiogenesis.

Hexokinase II and VEGF expression in liver tumors: correlation with hypoxia-inducible factor 1 alpha and its significance.

BACKGROUND/AIMS: We analyzed the expressions of hexokinase II (HK II), a key enzyme in glycolysis, and VEGF in hepatocellular carcinoma (HCC) and metastatic liver cancer in relation to tumor vascularity, and the participation of hypoxia-inducible factor-1 (HIF-1) was studied. METHODS: A real-time quantitative reverse transcription-polymerase chain reaction was performed to examine the HK II and VEGF mRNA expression. Expression of HIF-1 alpha and HK II protein, and microvessel density (MVD) were examined immunohistochemically. RESULTS: MVD was significantly higher in HCCs than in metastatic liver cancers, and VEGF mRNA expression was positively correlated only with MVD of HCCs. HK II mRNA expression was significantly higher in metastatic liver cancers, however, some cases of HCC pretreated with transcatheter arterial embolization (TAE) showed marked HK II mRNA expression. Both HIF-1 alpha and HK II protein expressions were co-localized in the cancer cells near necrosis, and the intensity of HIF-1 alpha protein expression was significantly correlated with HK II mRNA expression in both tumors. CONCLUSIONS: These results suggest that, in metastatic liver cancers, glycolysis induced by HIF-1 is the predominant energy source under the hypoxic environment and, at least in some TAE-pretreated HCC cases, cancer cells obtain energy for growth by switching the metabolic profile to glycolysis through HIF-1.