Reconstruction of the middle hepatic vein in a modified right liver graft of living-donor liver transplantation while preserving the recipient's middle hepatic vein.
Explore the source record for details and available documents.
Hepatic Veins↗
Biomedical subjects
Masato Sakon
Publications and source records attributed to Masato Sakon.
Expression of Id proteins in human hepatocellular carcinoma: relevance to tumor dedifferentiation.
Several studies reported that Id (Inhibitor of DNA binding or Differentiation) proteins, helix-loop-helix transcription factors, have important roles in differentiation, cell cycle and angiogenesis in various cells. However, the role of Id proteins in hepatocellular carcinoma (HCC) remains unclear. We examined the immunohistochemical expression of Id1, Id2 and Id3 proteins in 54 surgically resected HCCs with surrounding HCV or HBV-related chronic hepatitis (n=30) and liver cirrhosis (n=24). All non-cancerous livers exhibited immunoreactivity for Id proteins and the expression increased from chronic hepatitis to cirrhosis. In HCCs (n=45), well-differentiated tumors mostly exhibited strong or moderate immunostaining for all Id proteins, while proportion of the samples with weak or no expression increased with tumor dedifferentiation and frequently observed in poorly (66.7, 93.3 and 93.3% respectively for Id1, 2, 3) or undifferentiated (100% for all Ids) HCCs. Clinicopathological survey demonstrated a significant correlation between Id1, 2 and 3 expression and differentiation of carcinoma (p=0.0044, 0.0014 and 0.0014, respectively) although univariate analysis indicated that high expression of Id1 was significant predictive factor for longer disease-free survival of the patients (p=0.047). A similar tendency was also observed with Id2 and Id3. The present study demonstrate high expression of Id1, 2 and 3 in well-differentiated HCC and low expression in advanced dedifferentiated HCC, in contrast to its continuous expression during breast, prostate and colon carcinogenesis. These findings suggested that Id1, 2 and 3 might play a role in the early stages of hepatocarcinogenesis, but not in the development of advanced carcinoma, and might consequently be related to HCC dedifferentiation.
Blotting, Western↗
[Postoperative pulmonary thromboembolism and its prevention from the perspective of the establishment of Japanese guidelines].
The incidence of venous thromboembolism (VTE) is rapidly increasing in Japan. Ideally, the guidelines for its prevention should be based on solid evidence, but there are few clinical data on the prevalence and prophylaxis of VTE in Japan. Comprehensive, standard guidelines for the prevention of VTE were recently established by applying the risk-prophylaxis relationship of the sixth American College of Chest Physicians (ACCP) consensus recommendations. Since patients undergoing cancer surgery make up a relatively homogenous, "highest-risk" group, we could precisely evaluate the difference in VTE risk between Japan and the West. The risk of clinical PE in Japanese cancer surgery was found to be one or two risk levels lower than that in the West. Therefore the Japanese risk stratification was set to be one level lower than that in the sixth ACCP guidelines. For prophylaxis, the recommendations of the Japanese guidelines are basically identical to those of the sixth ACCP guidelines. Since the present guidelines are not sufficiently based on Japanese evidence, they should be reviewed in a prospective, nationwide epidemiologic study. In this review article, the theoretical background of and future perspectives on the Japanese guidelines are discussed.
Humans↗
[Palliation of malignant bile duct obstruction with metallic stent-clinical effectiveness in aged patients].
To evaluate the clinical effectiveness of metallic stent in the palliation of malignant bile duct obstruction in aged patients, 30 patients over 65 years of age with malignant biliary obstruction were investigated retrospectively. Overall survival duration after the stent placement was 13-1,275 (mean: 278, median: 169) days. The period of tube-free on the outpatient basis after stent insertion was 0-1,162 (mean: 192, median: 121) days. The estimated cost savings by eliminating hospitalization was greater than the stent cost. Four patients survived over 18 months despite their advanced clinical stages. It seems difficult to develop guidelines for the indication of stent placement in the treatment of malignant bile duct obstruction for aged patients.
Aged↗
[Chemotherapy for liver metastasis of colorectal cancer].
In colorectal cancer, liver metastasis is the most common and most important prognostic factor. Although surgical resection is the first choice of treatment for liver metastasis of colorectal cancer, there are many cases we cannot choose the surgical treatment. The chemotherapy is very important in such cases. We examined 18 cases of unresectable liver metastases from colorectal cancer which were adapted a hepatic arterial infusion of 5-FU (HAI) with a weekly high-dose infusion method (WHF) as the first-line treatment, and then systemic chemotherapy of CPT-11 in combination with 5-FU as the second-line treatment. The response rate of this treatment is 72% (13/18) and the 1-, 2-, 3-year survival rates were 100% (16/16), 83% (10/12), and 50% (5/10), respectively. The combination chemotherapy of HAI with systemic chemotherapy using CPT-11 seemed to be an effective treatment method.
Aged↗
[A case of gastric cancer with liver metastasis resected after the combination chemotherapy with CDDP and TS-1].
A 44 year-old woman presented with epigastralgia in March 2004 was diagnosed as having type II gastric cancer by gastrofiberscope, and histological diagnosis of biopsy specimens was group V (tub2, por1). Since multiple liver metastases were observed in subsegments 2, 3, and 5 by abdominal ultrasonography, systemic chemotherapy was first conducted for tumor down sizing. The patient was treated by three cycles of the one month regimen (CDDP 70 mg/m2, day 8, for 24hrs, and TS-1 80 mg/m2, day 1-14; 2 week cessation of the drugs). CT scan taken on May 16, 2005 revealed that the tumor diameters in subsegments 2, 3, and 5 were 1 cm, 3 cm, and 1.5 cm, respectively. On September 14, liver tumors were markedly shrunk. Tumor in subsegment 2 became undetectable, and the diameters in those in subsegments 3 and 5 were 1.5 cm, and 0.5 cm, respectively. On September 28, a distal gastrectomy associated with S3 partial hepatectomy and microwave coagulation therapy for S5 tumor was performed without any macroscopic residual lesions. The prognosis of liver metastasis of gastric cancer is generally poor, and there is no comprehensive therapy. The marked clinical response in this patient suggests that this combination therapy with CDDP and TS-1 might be a promising preoperative chemothepapy for unresectable gastric cancer.
Adult↗
[Rectal stenosis due to Schnitzler metastasis following surgery for gastric cancer--a case successfully treated with TS-1 and CDDP combination chemotherapy].
The patient, a 40-year-old woman, underwent total gastrectomy and excision of the pancreatic tail, spleen and gallbladder for gastric cancer in September 2000. The lesion was judged to be P1, SE, H0, N2 and Stage IV and the patient was managed on a regular schedule as an outpatient. In September 2004, she passed blood-stained feces and rectal palpation detected a hard nodule at the anterior rectal wall. A fiber optic examination of the sigmoid colon detected an ulcerous lesion with a hemorrhage at the anterior rectal wall. A biopsy revealed the lesion to be Group V poorly differentiated adenocarcinoma. Starting in October 2004, 100 mg/day of TS-1 was administered for 3 weeks; intravenous drip infusion of 100 mg/body of CDDP was conducted in the second week for a period of 24 hours. After 3 courses of this regimen, a fiber optic examination of the colon conducted in February 2005 no longer detected the rectal tumor, leaving only a cicatrix. Upon a CT examination, the para-aortic lymph nodes that had been enlarged were notably reduced in size and an improvement was eminent in the hypertrophic rectal wall. The patient no longer experienced constipation or melena. Her clinical course is being observed while an oral administration of 100 mg/day of TS-1 continues.
Adenocarcinoma↗
[A case of HCC with inferior caval vein tumor thrombus and multiple pulmonary metastases that remarkably responded to combination therapy of TS-1 and interferon-alpha].
A 56-year-old male was admitted to our hospital for hepatoma with portal vein thrombus and multiple intrahepatic metastases. He underwent an extended left lobectomy and a partial resection of the liver in May 2002. After two weeks from the surgery, he received intra arterial 5-FU infusion chemotherapy combined with subcutaneous interferon-alpha injection to treat the lesions in the residual liver. Four months after the surgery, hepatic vein tumor thrombus appeared in the remnant liver and it extended to the inferior caval vein. And another 4 months later, multiple pulmonary metastases were detected with computed tomography and they grew rapidly in the view of their sizes and numbers. Because the combined therapy of 5-FU/interferon-alpha was not effective to distant metastases, we started a new regimen of oral administration of TS-1 and a subcutaneous interferon-alpha injection. After 1 treatment cool, hepatic vein thrombus was markedly reduced the size and vascularity in the CT. Multiple pulmonary metastases also decreased in their sizes and numbers. No adverse effect was seen during this treatment. It was suggested that a combination therapy of TS-1 and interferon-alpha may be one of the most effective treatment modalities against advanced HCC with distant metastasis.
Administration, Oral↗
[A case of advanced pancreatic cancer treated with chemoradiation].
A 56-year-old man is presented with diarrhea, which he had experienced since February 2004. He was diagnosed as having advanced pancreatic cancer by enhanced abdominal CT scan in May 2004. He was diagnosed with unresectable pancreatic cancer, and treated with a combination of radiation (3 Gy/day) and injections of gemcitabine (GEM) 1,200 mg/week (800 mg/m2, BSA 1.6). Abdominal CT scan revealed a minor response (tumor diameter 5.7 x 4.8 --> 5.2 x 4.4). Accordingly, the improvement of performance status and reduction in serum levels of arcinoembryonic/carbohydrate antigen 19-9 (CA19-9) were observed. In July 2004, chemotherapy and radiotherapy were switched to GEM+UFT (UFT 360 mg/day, a total of 4,320 mg, GEM 1,200 mg according to the body mass, a total of 2,400 mg). The patient's performance state was stable for 6 months but serum levels of CA19-9 increased from March 2005, and he complained of diarrhea and back-pain. Therefore, the combination chemotherapy with GEM and cisplatin (CDDP) was started in April 2005, but there was no clinical effect. GEM and TS-1 are currently being administered. Pancreatic cancer is one of the worst prognoses of any malignant disease. Although the prognosis of unresectable pancreatic cancer is very poor, we presented a case where performance status and survival benefits were obtained by undergoing chemoradiation with GEM and combination chemotherapy with UFT and GEM.
Antimetabolites, Antineoplastic↗
Partial contribution of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/TRAIL receptor pathway to antitumor effects of interferon-alpha/5-fluorouracil against Hepatocellular Carcinoma.
PURPOSE: Our purpose was to explore the contribution of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/TRAIL receptor pathway to antitumor effects of IFNalpha and 5-fluorouracil (5-FU) combination therapy for hepatocellular carcinoma (HCC). EXPERIMENTAL DESIGN: Susceptibility of HCC cell lines to TRAIL and/or 5-FU was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The effects of 5-FU, IFNalpha, or both on the expression of TRAIL receptors (R1, R2, R3, and R4) on HCC cells or TRAIL in peripheral blood mononuclear cells (PBMC) were examined by flow cytometry. IFNalpha-induced cytotoxic effects of PBMC on HCC cell lines were examined by (51)Cr release assay. TRAIL expression in peripheral blood mononuclear cells and liver tissue from patients was examined by real-time reverse transcription-PCR or immunohistochemistry. RESULTS: HLE and HepG2 were sensitive to TRAIL, but HuH7, PLC/PRF/5, and HLF were resistant. 5-FU had synergistic effect on TRAIL in HLF and additive effect in four other HCC cell lines. TRAIL receptors on HCC cells were up-regulated by 5-FU, and IFNalpha induced TRAIL on CD4(+) T cells, CD14(+) monocytes, and CD56(+) NK cells. Treatment of effector cells by IFNalpha and target HCC cells by 5-FU enhanced the cytotoxicity of CD14(+) monocytes and CD56(+) NK cells against HCC cells via a TRAIL-mediated pathway. TRAIL mRNA overexpression was noted in PBMC of HCC patients who clinically responded to IFNalpha/5-FU combination therapy, and TRAIL(+) mononuclear cells were found in cancer tissue of a responder. CONCLUSION: Our results suggest that modulation of TRAIL/TRAIL receptor-mediated cytotoxic pathway might partially contribute to the anti-HCC effect of IFNalpha and 5-FU combination therapy.
Adult↗
Molecular prediction of response to 5-fluorouracil and interferon-alpha combination chemotherapy in advanced hepatocellular carcinoma.
PURPOSE: The prognosis of hepatocellular carcinoma (HCC) is very poor, particularly in patients with tumors that have invaded the major branches of the portal vein. Combination chemotherapy with intra-arterial 5-fluorouracil and subcutaneous interferon-alpha has shown promising results for such advanced HCC, but it is important to develop the ability to accurately predict chemotherapeutic responses. EXPERIMENTAL DESIGN: We analyzed the expression of 3,080 genes using a polymerase chain reaction-based array in 20 HCC patients who were treated with combination chemotherapy after reduction surgery. After unsupervised analyses, a supervised classification method for predicting chemotherapeutic responses was constructed. To minimize the number of predictive genes, we used a random permutation test to select only significant (P < 0.01) genes. A leave-one-out cross-validation confirmed the gene selection. We also prepared an additional 11 cases for validation of predictive performance. RESULTS: Hierarchical clustering analysis and principal component analysis with all 3,080 genes revealed distinct gene expression patterns in responders (those with complete response or partial response) and nonresponders (those with stable disease or progressive disease) to the combination chemotherapy. Using a weighted-voting classification method with either all genes or only significant genes as assessed by permutation testing, the objective responses to treatment were correctly predicted in 17 of 20 cases (accuracy, 85%; positive predictive value, 100%; negative predictive value, 80%). Moreover, patients in the validation dataset could be classified into two distinct prognostic groups using 63 predictive genes. CONCLUSIONS: Molecular analysis of 63 genes can predict the response of patients with advanced HCC and major portal vein tumor thrombi to combination chemotherapy with 5-fluorouracil and interferon-alpha.
Adult↗
Expression level of valosin-containing protein (p97) is associated with prognosis of esophageal carcinoma.
PURPOSE: Esophageal squamous cell carcinoma (ESCC) frequently shows a poor prognosis because of the occurrence of systemic metastasis, mainly via lymphatic vessels. Valosin-containing protein (VCP) has been shown to be associated with antiapoptotic function and metastasis via activation of the nuclear factor-kappaB signaling pathway. In the present study, we examined the association of VCP with the recurrence and prognosis of ESCC. EXPERIMENTAL DESIGN: VCP expression in 156 ESCC patients [139 males and 17 females; age range, 38-82 (median, 60) years] was analyzed by immunohistochemistry. Staining intensity in tumor cells was categorized as weaker (level 1) or equal to or stronger (level 2) than that in endothelial cells. The correlation of VCP expression between the mRNA and protein levels was examined in 12 patients. RESULTS: Fifty-seven (37.3%) cases showed level 1 and 96 (62.7%) level 2 VCP expression. Quantitative reverse transcription-PCR analysis revealed greater VCP mRNA expression in level 2 (n = 6) than level 1 cases (n = 6; P < 0.05). ESCC with level 2 expression showed higher rates of lymph node metastasis (P < 0.01) and deep tumor invasion (P < 0.01), and poorer disease-free and overall survival rates (P < 0.001 for both analyses) than ESCC with level 1 expression. Multivariate analysis revealed that VCP expression level is an independent prognosticator for disease-free and overall survival. Furthermore, VCP level was an indicator for disease-free survival in the early (pT1) and the advanced (pT2-pT4) stage groups. CONCLUSION: This study demonstrated the prognostic significance of VCP expression in ESCC.
Adenosine Triphosphatases↗
[Recent progress in chemotherapy for hepatocellular carcinoma].
Explore the source record for details and available documents.
Antineoplastic Combined Chemotherapy Protocols↗
Prognostic significance of activated Akt expression in pancreatic ductal adenocarcinoma.
PURPOSE: Akt is a serine/threonine kinase that plays a central role in tumorigenesis. Among the members of Akt family, Akt2 is associated with the development of human cancers. The present study was designed to clarify the prognostic significance of Akt2 and activated Akt expression in pancreatic ductal adenocarcinoma (PDAC). In addition, activated extracellular signal-regulated kinase 1 and 2 (ERK1/2) and the proliferation activity of tumor cells detected by Ki-67 immunohistochemistry were examined. EXPERIMENTAL DESIGN: Immunohistochemical analysis was performed on paraffin-embedded specimens from 65 patients with PDAC; 36 males and 29 females with ages ranging from 48 to 79 years (median, 66 years) of age. Expression levels of Akt2, phosphorylated Akt (p-Akt), and phosphorylated ERK 1/2 (p-ERK 1/2) were categorized as either weaker (low intensity) or equal to stronger (high intensity) compared with those in the endothelial cells of the same specimens. For Ki-67 immunohistochemistry, cases were divided into two groups: level 1, Ki-67 labeling index (LI), <20%; level 2, Ki-67 LI, > or = 20%. RESULTS: Twenty-six (42.6%), 28 (45.9%), 39 (63.9%), and 46 (75.4%) of the tumors showed high intensity of Akt2, p-Akt, and p-ERK 1/2 expression, and Ki-67 LI level 2, respectively. A significant positive correlation was observed between Akt2 and p-Akt expression (P < 0.01). Multivariate analysis revealed that p-Akt expression, Ki-67 LI, and histological differentiation are independent prognosticators for PDAC. CONCLUSIONS: p-Akt expression is a significant prognostic indicator for PDAC. Inhibition of Akt is a possible molecular approach for treatment of PDAC.
Adenocarcinoma↗
Expression of valosin-containing protein in colorectal carcinomas as a predictor for disease recurrence and prognosis.
PURPOSE: Valosin-containing protein (VCP or p97) is associated with antiapoptotic function and metastasis via activation of the nuclear factor-kappaB signaling pathway. The present study was designed to investigate the prognostic significance of VCP expression in colorectal adenocarcinoma. EXPERIMENTAL DESIGN: We analyzed VCP expression immunohistochemically in 129 patients with colorectal carcinoma ages 35-84 years. The staining intensity of tumor cells was categorized as either weaker-to-equal (low VCP expression) or stronger (high expression) than that in noncancerous colonic mucosa. We also analyzed 8 colorectal adenomas and 10 metastatic foci. RESULTS: Low VCP expression was noted in 41 (31.8%) cases and high expression in 88 (68.2%) cases. A low level of VCP expression was noted in all adenomas, whereas a high level was seen in all metastatic tumors. A significant difference was observed in depth of invasion (T(1-2) versus T(3-4), P < 0.05), presence or absence of venous invasion (P < 0.05), and tumor stage (I and II versus III and IV; P < 0.05) between adenocarcinomas with low and high VCP expression. Patients with high VCP-expressing tumors had a higher recurrence rate (P < 0.001) and poorer disease-free and overall survival (P < 0.01 and P < 0.05, respectively) compared with the low expression group. Multivariate analysis revealed VCP expression level to be an independent prognosticator for both disease-free and overall survival. VCP level was an indicator of disease-free survival in both stage II and III (pathological Tumor-Node-Metastasis classification, P < 0.05 and <0.01, respectively). CONCLUSIONS: A high expression level of VCP in tumors is a poor prognostic marker in patients with colorectal carcinomas.
Adenoma↗
Hepatic expression of ANG2 RNA in metastatic colorectal cancer.
We examined the RNA content of the gene encoding angiopoietin (Ang)-2, a modifier of angiogenesis, in hepatic metastases of colorectal cancer (CRC) to explore the role of this protein in neovascularization of metastatic foci. Metastatic CRC exhibited notable blood flow and tumor vessel formation at tumor frontiers. Reverse-transcription polymerase chain reaction assays indicated that the ANG2 RNA content was greater in metastatic CRC than in primary CRC. Investigation of metastatic foci using laser capture microdissection revealed that the RNA content of ANG2, but not ANG1, increased from the bordering liver region to the periphery of the metastatic disease, and also from the periphery to the intermediate portion of the metastatic lesion; immunohistochemical analysis confirmed that there was a corresponding gradual increase in Ang-2 protein expression. Tie-2, a receptor for angiopoietins, was preferentially expressed in the bordering liver region rather than in metastatic CRC. Vascular endothelial growth factor (VEGF) also exhibited an expression pattern similar to that of Ang-2, and there was a significant correlation between the RNA content of ANG2 and that of VEGF in dissected samples (P =.002). Western blot analysis suggested that expression of Ang-1, Ang-2, Tie-2, and VEGF may be regulated at a transcriptional level. The increase in ANG2 RNA content from the peripheral portion of the tumor to the intermediate portion, coinciding with the decrease in recruitment of periendothelial supporting cells around the vascular endothelial cells, suggests that Ang-2 may play a role in the immaturity of tumor vessels. In conclusion, the current study suggests that Ang-2 and VEGF may cooperate to enhance the formation of new blood vessels in metastases of CRC to the liver.
Angiopoietin-1↗
Interstitial pneumonia induced by combined intraarterial 5-fluorouracil and subcutaneous interferon-alpha therapy for advanced hepatocellular carcinoma.
Previously we reported combined chemo-immunotherapy, using interferon (IFN)-alpha and 5-fluorouracil (5-FU) for patients with advanced hepatocellular carcinoma (HCC), and this regimen improved the prognosis. Recently, we experienced an HCC patient who died of severe interstitial pneumonia during the combined IFN-alpha and 5-FU therapy. This is the first report of the occurrence of interstitial pneumonia during combined IFN-alpha and 5-FU treatment. A 60-year-old-man was admitted to Osaka University Hospital to receive systemic chemo-immunotherapy for recurrent HCC. In the second week of the chemo-immunotherapy, he showed a decreased level of consciousness, and respiratory insufficiency. Emergency roentgenogram revealed diffuse infiltration in both lungs. Respiratory dysfunction due to interstitial pneumonia was suspected, and steroid pulse therapy was started. However, the patient showed respiratory failure, and he died 32 days after the start of the therapy. Autopsy findings showed atelectasis in the bilateral lungs, which showed elastic hard solidity and a dark red color; esophageal varices were also shown, and there was cirrhosis with a large tumor in the liver. Microscopically, the alveolar wall showed marked fibrous thickness and moderate inflammatory change, which is consistent with acute interstitial pneumonia, and the acute pulmonary change was suspected to have been the cause of death. The association of IFN with the development of interstitial pneumonia has been reported. However, the prognosis of IFN-induced interstitial pneumonia has mostly been favorable when the medication was discontinued. It has been postulated that interstitial pneumonia induced by the combination of IFN and 5-FU may be therapy-resistant. The combination of IFN-alpha and 5-FU is a useful therapy for patients with advanced HCC, such as that with portal vein invasion or multiple metastatic foci. Thus, interstitial pneumonia in these patients should be carefully managed.
Antineoplastic Combined Chemotherapy Protocols↗
Current status of pulmonary embolism in general surgery in Japan.
The true incidence of pulmonary embolism (PE) after general surgery in Japan is unknown. We searched the PubMed and Japana Centra Revuo Medicina 1985-2002 databases, entering "surgery" and "pulmonary embolism" or "thromboembolism", and reviewed the reported incidence of clinical PE associated with general surgery in Japan. The overall incidence of PE after general surgery was 0.33%. Fatal PE was reported in 0.08% of the surgical population and the mortality rate of patients with PE was 31%. The incidence of PE after cancer surgery ranged from 0.57% after colon malignancy to 3.85% after pancreatic cancer surgery, and was significantly higher than that after surgery for noncancerous conditions (0.20%). The incidence of PE after various cancer operations corresponded to a moderate or high risk, as defined by the 6th American College of Chest Physicians consensus recommendations. There was no significant difference in the incidence of PE after laparoscopic and open abdominal surgery. The incidence of PE was four to six times lower in patients who had received mechanical prophylaxis, although the difference was not significant. In conclusion, the incidence of PE in Japanese surgical patients is not as low as previously thought. Perioperative prophylaxis against venous thromboembolism is important, but its benefits need to be confirmed by prospective clinical studies.
Humans↗