Biomedical subjects

H Yamaue

Publications and source records attributed to H Yamaue.

At least 19 recordsLinked to original sources

PubMed2006

Preoperative evaluation of the extrahepatic bile duct structure for laparoscopic cholecystectomy.

BACKGROUND: The incidence of aberrant bile duct injury associated with laparoscopic cholecystectomy (LC) has not yet been adequately examined. This study aimed to clarify the types of normal cystic ducts and the incidence of aberrant extrahepatic bile ducts, and to search for a method of avoiding injuries during LC. METHODS: Aberrant hepatic ducts were retrospectively categorized into five types according to the pattern of the cystic ducts and the accessory hepatic ducts by preoperative endoscopic retrograde cholangiography or multidetector three-dimensional computed tomography using drip infusion cholangiography. The aberrant bile ducts were classified as type A (merging at the right side of the common bile duct), type B (merging at the anterior side), or type C (merging at the posterior left side). RESULTS: The intrahepatic bile ducts and cystic duct were clearly shown for 1,044 of the 1,278 patients who underwent LC. Secondary branches of aberrant cystic ducts were observed in 37 cases (3.5%), and accessory hepatic ducts were observed in 30 cases (2.9%). A comparison of the difficulties encountered with LC for each type based on the merging patterns of cystic ducts showed that type C needed a much longer operation time for LC than the other types. CONCLUSIONS: A preoperative evaluation of the bile duct tract and the accessory hepatic duct before LC is important. Patients with a cystic duct merging normally into the posterior left side of the common hepatic duct (type C) experienced difficulty when undergoing LC. The authors have safely performed LC with the use of an endoscopic nasobiliary drainage tube in type D cases (cystic duct merging with the right hepatic duct), in type IV cases (cystic duct merging with an accessory hepatic duct).

Bile Ducts, Extrahepatic↗

PubMed2006

Gender differences in postoperative pain after laparoscopic cholecystectomy.

BACKGROUND: Some evidence suggests that females have a lower pain threshold and a lower tolerance to painful stimuli. This study investigated gender differences in postoperative pain after laparoscopic cholecystectomy (LC) on the basis of visual analog pain scale (VAS) scores and the clinical course. METHODS: The 100 patients in this study (46 males and 54 females) underwent LC for cholecystolithiasis or gallbladder polyps without intraoperative complications. An 8-mm Penrose drain was retained for 42 h below the liver bed. All the patients were hospitalized for 4 days after LC, and the pain reported by patients, the time course of changes in the highest body temperature, the leukocyte count, and the C-reactive protein level were studied comparatively for the male and female patients. RESULTS: The VAS scores were significantly higher for the female patients than for the male patients at 24 h (62.7 +/- 24.6 vs 47.0 +/- 23.3; p = 0.0015) and at 48 h (39.2 +/- 24.3 vs 28.3 +/- 19.1; p = 0.0137) after LC. The female patients used analgesics more frequently and had significantly higher body temperatures than the male patients on day 1 (37.2 +/- 0.6 vs 36.9 +/- 0.4; p = 0.0037) and day 2 (36.9 +/- 0.6 vs 36.6 +/- 0.4; p = 0.0037) after surgery. CONCLUSIONS: Early postoperative pain after LC was more severe in female patients, and patients with high VAS scores tended to use analgesics more frequently.

Adult↗

PubMed2006

Brachytherapy technique for abdominal wall metastases of colorectal cancer: ultrasound-guided insertion of applicator needle and a skin preservation method.

PURPOSE: To report a technique of interstitial brachytherapy for the treatment of subcutaneous metastatic abdominal wall tumors. MATERIAL AND METHODS: We developed a brachytherapy technique consisting of ultrasound-guided insertion of applicator needles to avoid the organs at risk, such as intestines, and saline injection into the subcutaneous tissue between the tumor and the skin to decrease the skin dose. We encountered three patients with painful metastases from rectal carcinoma in the abdominal wall refractory to external radiotherapy. They were subjected to this brachytherapy with a single dose of 20 Gy. RESULTS: The procedure was safely achieved in all three patients. Long-lasting pain reduction and tumor shrinkage was obtained without early or late complications. CONCLUSION: This interstitial brachytherapy technique seems to be feasible in the treatment of metastatic abdominal wall tumors.

Abdominal Neoplasms↗

PubMed2003

Specific T-cell immunity against Ki-ras peptides in patients with pancreatic and colorectal cancers.

Mutations of codon 12 in the Ki-ras gene are frequently found in pancreatic and colorectal cancers. It has been demonstrated that human T-cells have the potential to recognise tumours expressing mutated ras-derived peptides. However, it remains unclear whether T-cells from a given individual can recognise the mutant peptides, which are expressed in that individual's tumour tissues. Mutations of the Ki-ras oncogene were analysed by the mutant-allele-specific amplification (MASA) method in pancreatic and colorectal tumour tissues, and T-cell responses against mutated Ki-ras-derived peptides were measured by [(3)H]thymidine incorporation and IFN-gamma production assays. Specific T-cell responses against Ki-ras-products were found in cancer patients, whereas no immune response was observed in normal individuals (P<0.01). Six of the eight pancreatic cancer patients (75%) and nine of 26 colorectal cancer patients (35%) had T-cell responses to mutated Ki-ras-derived-peptides. T-cell response in a given individual cannot recognise the same mutated ras peptide, which is expressed in that individual's tumour tissues. However, pancreatic and colorectal cancer patients have T-cell immunity against Ki-ras-peptides, and this provides potential target for cancer immunotherapy.

Cell Division↗

PubMed2002

Effectiveness of the clinical pathway to decrease length of stay and cost for laparoscopic surgery.

BACKGROUND: Although clinical pathways have become popular strategies to improve the quality of medication in the field of laparoscopic surgeries, their economical effectiveness is not well defined. The aim of this study was to investigate the effect of clinical pathways for laparoscopic surgeries on cost and length of hospital stay. METHODS: From January 2000 to June 2001, clinical pathways were introduced for laparoscopic surgeries, such as laparoscopic cholecystectomy (Lap. C, n = 210), laparoscopically assisted distal gastrectomy with Billroth-I reconstruction (Lap. B-I, n=33), and laparoscopically assisted colectomy (Lap. colon, n=34). We compared total lengths of hospital stay and the economical efficiency before and after pathway implementation at Wakayama Medical University Hospital. RESULTS: The length of hospital stay in Lap. C was shortened from 7.8+/-2.6 (mean+/-SD) days to 6.9+/-2.0 days (p = 0.03) and the total costs during hospitalization decreased from yen 509,320+/-58,800 to yen 489,130+/-43,860 (p=0.009), resulting in less burden for patients. At the same time, the daily costs were increased from yen 66,230+/-8920 to yen 70,840+/-6820 (p=0.0001), indicating that more efficient medical care was being given to patients. Similar results were obtained in Lap. B-I and Lap. colon groups. CONCLUSIONS: In our study, the implementation of clinical pathways in the field of laparoscopic surgeries produced significant decreases in length of total hospital stay and cost while maintaining the quality of patient outcomes.

Cholecystectomy, Laparoscopic↗

PubMed2002

Overexpression of pyrimidine nucleoside phosphorylase enhances the sensitivity to 5'-deoxy-5-fluorouridine in tumour cells in vitro and in vivo.

5-Fluorouracil (5-FU) and 5'-deoxy-5-fluorouridine (5'-DFUR), a prodrug of 5-FU, are representative of the chemotherapeutic agents for colorectal adenocarcinomas. Pyrimidine nucleoside phosphorylase (PyNPase) catalyses the conversion of 5'-DFUR to 5-FU, the activated form. Murine adenocarcinoma CT26 cells were transfected with human PyNPase cDNA. The engineered transfectants producing PyNPase augmented the response to 5'-DFUR in vitro and in vivo. Animals were administered by means of intraperitoneal (i.p.) injection, and not orally, in order to obtain a better efficiency of absorption. The tumours of the transfected cells nearly all disappeared, even following treatment with quite a small amount of the anticancer agent. The animals injected with the tranfected cells were protected against subsequent challenge with the parental tumour cell line. These findings demonstrate that PyNPase gene transfection increases the sensitivity to 5'-DFUR, and thereby decreases the toxicity of the agent.

Adenocarcinoma↗

PubMed2001

Carcinoembryonic antigen-specific suicide gene therapy of cytosine deaminase/5-fluorocytosine enhanced by the cre/loxP system in the orthotopic gastric carcinoma model.

Tumor-specific gene delivery is crucial to achieving successful effects in suicide gene therapy. Carcinoembryonic antigen (CEA) promoter has been widely used for this purpose, but the expression level of tumor-specific promoters such as CEA promoter is generally low. In the previous study, we used the Cre/loxP system and showed that LacZ expression by the CEA promoter was remarkably enhanced and maintained its specificity using the Cre/loxP regulation system. In this study, the Cre/loxP system was first applied to augmentation of selective expression of the cytosine deaminase (CD) gene as a suicide gene therapy in CEA-producing cells. The double infection with AxCEANCre expressing Cre recombinase under the control of the CEA promoter and AxCALNLCD expressing the CD gene under the control of the CAG promoter by the Cre switching system rendered CEA-producing tumor cells 13-fold more sensitive to 5-fluorocytosine (5-FC) compared with the single infection with AxCEACD expressing CD gene driven by the CEA promoter. The therapeutic efficacy of the enhanced CD/5-FC suicide gene therapy was evaluated in orthotopic implantation models of human gastric carcinoma. Adenovirus vectors (1 x 10(9) plaque-forming units) were administered i.p. into mice three times, and then 5-FC was administered i.p. for the next 10 days. Tumor volume and weight in mice treated with AxCEANCre and AxCALNLCD/5-FC were significantly reduced as compared with those in mice treated not only with Mock (AxCALacZ) but also with AxCEACD/5-FC (P < 0.0001). This beneficial effect on tumor burden was also reflected in the overall survival. The survival periods of the mice treated with AxCEANCre and AxCALNLCD/5-FC were longer than those of mice treated with Mock or AxCEACD/5-FC (P < 0.01). These results suggested that application of the Cre/loxP system could provide a new approach for enhanced selective suicide gene therapy of CD/5-FC for the treatment of advanced gastric carcinoma.

Adenoviridae↗

PubMed2001

Generation of cytotoxic T cell responses to an HLA-A24 restricted epitope peptide derived from wild-type p53.

Mutations in the p53 gene are the most common genetic alterations found in human tumours, and these mutations result in high levels of p53 protein in the tumour cells. Since the expression levels of wild-type p53 in nonmalignant tissue are usually much lower in contrast, the p53 protein is an attractive target for cancer immunotherapy. We tested p53 encoded HLA-A24 binding peptides for their capacity to elicit anti-tumour cytotoxic T lymphocytes (CTL) in vitro. These peptides were in murine p53-derived cytotoxic peptides, which were being presented to CTL by H-2K(d)and H-2K(b)molecules, because the HLA-A24 peptide binding motifs were similar to the H-2K(d)and H-2K(b). For CTL induction, we used CD8(+)T lymphocytes from the peripheral blood mononuclear cells (PBMC) of healthy donors and the peptides from pulsed dendritic cells as antigen-presenting cells. We identified the peptide, p53-161 (AIYKQSQHM), which was capable of eliciting CTL lines that lysed tumour cells expressing HLA-A24 and p53. The effectors lysed C1RA24 cells (p53(+), HLA-A*2402 transfectant), but not their parental cell lines C1R (p53(+), HLA-A,B null cell). These results strongly indicate that the CTL exerts cytotoxic activity in HLA-A24's restricted manner. The identification of this novel p53 epitope for CTL offers the possibility to design and develop specific immunotherapeutic approaches for treating tumours with p53 mutation in HLA-A24-positive patients.

Animals↗

PubMed2001

Mapping the HLA-A24-restricted T-cell epitope peptide from a tumour-associated antigen HER2 / neu: possible immunotherapy for colorectal carcinomas.

HER2 / neu is a potential antigen candidate for immunotherapy because of its correlation to a poor prognosis and high expressions in many kinds of epithelial tumours. Especially in the colorectal carcinomas, the higher expression of HER2 / neu is recognized in metastatic regions as well as in primary sites. Several CTL epitopes restricted by HLA-A2.1 and -A3 were identified so far, however epitopes restricted by HLA-A24, that is one of the most common allele in Japanese and Caucasians, have not been identified. In this paper, we showed identification of a CTL epitope peptide of HER2 / neu restricted by HLA-A24. HLA-A24 binding peptides selected by an analysis based on HLA-A24 binding motifs were determined for their binding affinities to HLA-A24 molecules. The peptide with a sequence of RWGLLLALL (position 8-16) named HE1 showed the highest affinity. We induced CTLs from CD8(+)cells of HLA-A24 healthy donors by stimulation with HE1-pulsed autologous dendritic cells. The CTLs showed cytotoxic activity against not only the peptide-pulsed target cells but also HLA-A24 colorectal tumour cell lines that endogenously overexpressed HER2 / neu. The antigen-specificity was confirmed by cold target inhibition assay using HE1-pulsed target cells. In summary, HER2 / neu peptide, RWGLLLALL, may contribute to the induction of antitumour immunity with the peptide-based immunotherapy for the colorectal carcinomas.

Colorectal Neoplasms↗

PubMed2001

Clinical features and management of hepatic portal venous gas: four case reports and cumulative review of the literature.

HYPOTHESIS: Hepatic portal venous gas (HPVG) has been considered a rare entity associated with a grave prognosis. Since 1978, when Liebman et al reviewed 64 cases of HPVG and reported a mortality of 75%, the number of reported cases has been increasing. DESIGN: Case series. PATIENTS AND METHODS: We reviewed the literature on 182 cases of HPVG in adults, including 4 of our patients, (transplantation and abdominal trauma cases were excluded) and analyzed the cause, pathogenesis, and clinical features. RESULTS: In this series, the underlying clinical events associated with HPVG were bowel necrosis (43%), digestive tract dilatation (12%), intraperitoneal abscess (11%), ulcerative colitis (4%), gastric ulcer (4%), Crohn disease (4%), complications of endoscopic procedures (4%), intraperitoneal tumor (3%), and other (15%). The overall mortality was 39% but varied depending on the underlying disease. CONCLUSIONS: Hepatic portal venous gas is a lethal or curable entity caused by various diseases. The underlying disease associated with HPVG determines the clinical features and prognosis of the patients. The treatment of patients with HPVG should be directed to the underlying disease.

Aged↗

PubMed2001

Complete response of highly advanced gastric cancer with peritoneal dissemination after new combined chemotherapy of S-1 and low-dose cisplatin: report of a case.

TS-1(S-1) has been developed as a new oral anticancer drug based on the biological modulation of 5-fluorouracil. We treated a patient with highly advanced gastric carcinoma with a new combination chemotherapy of S-1 and low-dose cisplatin. Remarkable tumor reduction was observed after two cycles of this therapy in the primary tumor and metastatic lymph nodes, and the ascites disappeared. This was concluded to be a partial response. The only adverse effect was skin pigmentation of the fingers (grade 1), leading to early timing of operation after chemotherapy. The gastric tumor showed evident invasion to the serosa. Lymph nodes around the stomach were swollen. Peritoneal dissemination was also recognized in the omentum and mesocolon. Total gastrectomy with regional lymph node dissection was performed. Disseminated tumors were all resected. Histological examination showed that no tumor cells were detected in the gastric primary lesion, metastatic lymph nodes or disseminated peritoneal tumors, suggesting pathological complete remission. It was suggested that this regimen could be a potent combined therapy for the treatment of patients with highly advanced gastric carcinoma, and it could be useful as neoadjuvant chemotherapy. Further studies are necessary to evaluate the efficacy of this therapy.

Adenocarcinoma↗

PubMed2001

Adenosquamous carcinoma of the pancreas: successful treatment with extended radical surgery, intraoperative radiation therapy, and locoregional chemotherapy.

BACKGROUND: Adenosquamous carcinoma of the pancreas is a rare tumor with an extremely poor survival rate. No obvious evidence that multidisciplinary treatments improves the prognosis and survival has been reported. PATIENT AND RESULTS: A 63-yr-old female with adenosquamous carcinoma of the pancreas underwent extended radical surgery, intraoperative radiation therapy, postoperative intraarterial chemotherapy, and external beam radiation therapy. The patient is alive at 40 mo after surgery with no recurrence. CONCLUSIONS: Multidisciplinary treatments including aggressive surgery, intraoperative radiation therapy, and locoregional chemotherapy might improve the survival of patients with adenosquamous carcinoma of the pancreas to inhibit liver metastasis and local recurrence.

Antineoplastic Agents↗

PubMed2000

In vitro augmentation of antitumor effect in combination with CPT-11 and CDDP for human colorectal cancer.

BACKGROUND AND OBJECTIVES: Irinotecan hydrochloride (CPT-11) is one of the camptothecin analogues that has shown a broad spectrum of strong antitumor effectiveness against various cancers, including colorectal cancer. In order to promote the clinical response of chemotherapy for colorectal cancer using CPT-11, one of the most effective strategies is to use it in combination with other anticancer agents. In the present study, anticancer effects after combining CPT-11 and other antitumor agents were determined by a 3-(4,5-di-methylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay of colorectal cancer cells, especially freshly isolated cancer cells. METHODS: Freshly isolated cancer cells from 20 patients with colorectal cancer and the established colon cancer cell lines were used in this study. The augmentation of the antitumor effectiveness of 7-ethyl-10-hydroxy-CPT (SN-38) was analyzed in combination with other anticancer agents. Furthermore, the antitumor effectiveness using lower concentrations of anticancer agents was measured to understand the mechanism of the augmentation. RESULTS: The percent inhibition of SN-38 in combination with cisplatin (CDDP) and mitomycin revealed a high anticancer effect compared with each anticancer agent alone for freshly isolated rectal cancer. CDDP also had a synergistic effect in combination with SN-38 according to the fractional product concept. At lower than plasma peak concentrations of SN-38, the anticancer effects were augmented in combination with lower concentrations of CDDP for freshly isolated colorectal cancer. This augmentation showed a strong synergistic effect. CONCLUSIONS: These results may be supportive to ongoing clinical studies of chemotherapy by using CPT-11 and CDDP for advanced colorectal cancer.

Adenocarcinoma↗

PubMed2000

Enhanced selective gene expression by adenovirus vector using Cre/loxP regulation system for human carcinoembryonic antigen-producing carcinoma.

Selective gene targeting using the carcinoembryonic antigen (CEA) promoter is useful in gene therapy for gastrointestinal cancer. However, the expression of the CEA promoter is not sufficient. In this study, we tried to enhance CEA promoter activity using the Cre/loxP system. The double infection of CEA-producing cells such as MKN45 and LoVo with AxCEANCre and AxCALNLZ at a total multiplicity of infection (MOI) of 50 achieved 7-fold higher expression level of beta-galactosidase activity than single infection of those cells with AxCEALacZ at 50 MOI. On the other hand, the double infection of CEA-nonproducing cells such as MKN1 and HeLa cells showed a very low expression of beta-galactosidase activity. In the subcutaneous tumor models, the administration of AxCEANCre and AxCALNLZ into the CEA-producing tumor showed stronger expression of the LacZ gene in tumor tissue than that of AxCEALacZ. In the experiment using orthotopic models of CEA-producing gastric cancer, intraperitoneal double administration of AxCEANCre and AxCALNLZ caused evident LacZ gene expression in transplanted gastric tumors, but no LacZ gene expression in the normal stomach or liver. It was confirmed that enhanced tissue-specific gene transduction under control of CEA promoter using the Cre/loxP system was useful not only in vitro, but also in vivo, especially in orthotopic models.

Adenoviridae↗

PubMed2000

Solid and cystic tumor of the pancreas: clinicopathologic and genetic studies of four cases.

BACKGROUND: Solid and cystic tumor (SCT) of the pancreas can be distinguished from other pancreatic neoplasms by its nearly exclusive occurrence in young women, and its favorable prognosis after complete resection. METHODS: We experienced four cases with SCT of the pancreas, and analyzed these tumors by immunohistochemical and electron microscopic studies, as well as genetic analysis of ras oncogene mutation. RESULTS: The presented cases expressed the neuron-specific enolase in two cases, alpha1-antitrypsin and alpha1-antichymotrypsin in two cases, and vimentin in one case, which indicated that this tumor originates from pleuripotential embryonic stem cells. No patients had mutations of K-ras gene in codon 12, and further genetic analysis is required to predict the malignant potential. CONCLUSION: SCT of the pancreas appears to have limited malignant potential and the metastatic ratio is not high, although the tumor has local invasion. Therefore, an aggressive surgical approach seems fully justified.

Adult↗

PubMed2000

[New therapeutic strategy against colon cancer based on a tumor-specific approach].

To develop a new therapy against colon cancer, we investigated two kinds of strategy using a cancer-specific approach. First, we employed the Cre/loxP regulation system to enhance the specific expression by carcinoembryonic antigen (CEA) promotor in CEA-producing tumor cells, and examined whether sufficient enhancement to transcriptional activity of CEA promotor, which maintains its specificity in vitro and in vivo, could be obtained. Next, using dendritic cells pulsed with HLA-A24 epitope peptides of CEA, we performed a Phase I study of active immunotherapy in patients with advanced colon cancer. These results suggest that the newly developed therapy for colon cancer is a promising strategy; however, minor modification may be necessary.

Antigen-Presenting Cells↗

PubMed1999

P-glycoprotein-expressing tumor cells are resistant to anticancer drugs in human gastrointestinal cancer.

The resistance to doxorubicin (DOX) by some tumor cells is mainly due to the effect of P-glycoprotein encoded by the multidrug resistance-1 (mdr1) gene. We tried to prove the correlations between P-glycoprotein expression and the sensitivity for anticancer drugs including DOX and other cytotoxic drugs that are currently used for gastrointestinal cancer patients. We quantified the P-glycoprotein expression by flow cytometry techniques, and the sensitivity for anticancer drugs using a tetrazolium salt, 3-(4,5-di-methylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), assay in highly purified fresh human tumor cells obtained from 25 cancer patients. The inhibition rates were the lowest in DOX and mitomycin C (MMC), compared with other drugs. The most significant correlation between DOX and MMC was seen in the inhibition rates. A significant correlation was also seen between the inhibition rates for DOX and P-glycoprotein expression, whereas only a slight correlation between the sensitivity for MMC and P-glycoprotein expression was observed. We should therefore pay close attention to the effect of P-glycoprotein when treating cancer patients, especially if both the inhibition rates of DOX and MMC are low based on the findings of an MTT assay.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1999

Establishment and analysis of biological characteristics of a human duodenal carcinoma cell line, WDC-1.

BACKGROUND: Duodenal carcinoma is very rare and its culture cell lines have rarely been established. METHODS: Tumor cells separated from a surgically resected primary tumor of duodenal carcinoma were put into culture. The patient was an 81-year-old female and had metastatic lymph nodes. We investigated the biological characteristics of the culture cells including in vitro cell kinetics, karyotype, expression of tumor markers and integrins and tumorigenicity and histology in nude mice. RESULTS: A new cell line, designated WDC-1, was established. This duodenal carcinoma cell line proliferated in a monolayered sheet with a doubling time of 50 h. The histological findings of the xenograft in nude mice were similar to those of the primary tumor. WDC-1 cells produced carcinoembryonic antigen and expressed 1 integrin and very late antigen (VLA)-4d in vitro. CONCLUSIONS: A duodenal carcinoma cell line was established, which is rare and may contribute to progress in understanding the biological features of duodenal cancer.

Adenocarcinoma↗