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Hiroki Yamaue

Publications and source records attributed to Hiroki Yamaue.

At least 19 recordsLinked to original sources
PubMed2007

Successful cancer vaccine therapy for carcinoembryonic antigen (CEA)-expressing colon cancer using genetically modified dendritic cells that express CEA and T helper-type 1 cytokines in CEA transgenic mice.

This study was designed to determine whether the vaccination of genetically modified dendritic cells (DCs) simultaneously expressing carcinoembryonic antigen (CEA), granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin 12 (IL-12) can overcome the peripheral T-cell tolerance to CEA and thereby elicit a therapeutic response in CEA transgenic mice. CEA transgenic mice were immunized once by subcutaneous injection with DCs adenovirally transduced with CEA and T helper-type 1 cytokine genes. The cytotoxic activity of spleen cells against CEA-expressing tumors, MC38-CEA, in the mice immunized with DCs expressing CEA (DC-AxCACEA) was higher than that in those immunized with DCs-AxCALacZ (p < 0.0001), and was augmented by the cotransduction with the GM-CSF/IL-12 gene (p < 0.05). The vaccination with DC-AxCACEA/GM-CSF/IL-12 could elicit a more potent therapeutic immunity than the vaccination with DC-AxCACEA in subcutaneous tumor models (p < 0.0001), and 4 of 5 mice showed a complete eradication of the subcutaneous tumors in these vaccination groups. Even in a large tumor model, this vaccination therapy completely eliminated the subcutaneous tumors in all mice. This antitumor activity mostly vanished with the depletion of CD8(+) T cells and NK cells in vivo and was completely abrogated with the depletion of CD4(+) T cells. A histopathological examination showed no evidence of an autoimmune reaction. No other adverse effects were observed. This vaccination strategy resulted in the generation of highly efficient therapeutic immune responses against MC38-CEA in the absence of autoimmune responses and demonstrated no adverse effects, and may therefore be useful for future clinical applications as a cancer vaccine therapy.

Animals↗
PubMed2006

Duodenoportal fistula caused by peptic ulcer after extended right hepatectomy for hilar cholangiocarcinoma.

BACKGROUND: A fistula between the duodenum and the main portal vein near a peptic ulcer is extremely rare, and only two cases of duodenal ulcers have been reported in the past. CASE PRESENTATION: We report a 68-year-old man with a diagnosis of anemia who had a history of extended right hepatectomy for hilar cholangiocarcinoma 20 months previously. The first endoscopic examination revealed a giant peptic ulcer with active bleeding at the posterior wall of the duodenal bulbs, and hemostasis was performed. Endoscopic treatment and transarterial embolization were performed repeatedly because of uncontrollable bleeding from the duodenal ulcer. Nevertheless, he died of sudden massive hematemesis on the 20th hospital day. At autopsy, communication with the main portal vein and duodenal ulcer was observed. CONCLUSION: It should be borne in mind that the main portal vein is exposed at the front of the hepatoduodenal ligament in cases with previous extrahepatic bile duct resection.

Journal Article↗
PubMed2006

Effect of normothermic perfusion using fructose-1,6-bisphosphate for maintenance of liver function during in situ extended hepatectomy by the total hepatic vascular exclusion technique.

BACKGROUND: Recently, hepatic surgery has made remarkable progress, and it is important to use appropriate liver perfusion. We evaluated the effect of normothermic liver perfusion with the addition of fructose-1, 6-bisphosphate (FBP) and oxygenation to maintain liver parenchymal, non-parenchymal, and Kupffer cell function. MATERIALS AND METHODS: The rats were divided into five groups according to the perfusate and continuous perfusion was performed: Control group = 4 degrees C lactate Ringer with 10% glucose (LRG) solution; normothermic group = 25 degrees C LRG solution; normothermic oxygenated group = 25 degrees C oxygenated LRG solution; normothermic FBP group = 25 degrees C LRG solution with addition of 10 mmol/L FBP; normothermic oxygenated FBP group = 25 degrees C oxygenated LRG solution with addition of 10 mmol/L FBP. Parameters under evaluation were oxygen consumption, liver energy level (adenosine triphosphate, total adenine nucleotide), glutathione, lipid peroxide, hyaluronic acid uptake ratio, apoptosis, and histomorphology. Moreover, we studied the effect of FBP and normothermia on Kupffer cells activation in vitro. RESULTS: Liver energy level was lower in the normothermic group than the control group. But, it was improved by oxidation or addition of FBP, and it was satisfactorily maintained up to 120 min in the group with normothermic oxygenated FBP. Hyaluronic acid uptake was maintained highly at all times as measured in normothermic oxygenated FBP group. The uptake of lipopolysaccharide was significantly higher as a result of adding FBP, compared with that in the control group and the normothermic group. Moreover, the apoptotic index in the liver was decreased in normothermic FBP group compared to control group. CONCLUSIONS: The normothermic liver perfusion under additional FBP and oxygenation protects both parenchymal and non-parenchymal cells from reperfusion injury.

Adenosine Triphosphate↗
PubMed2006

Preoperative evaluation of pelvic lateral lymph node of patients with lower rectal cancer: comparison study of MR imaging and CT in 53 patients.

BACKGROUND: Preoperative assessment of the lateral pelvic lymph nodes is important for treatment strategy to patients with lower rectal cancer. MATERIALS AND METHODS: Fifty-three patients with primary lower rectal cancer were preoperatively assessed by spiral computed tomography (CT) and magnetic resonance imaging (MRI) at 1.5 T with a phased-array coil. Preoperative tumor and lymph node stages were compared with the final histological findings. RESULTS: The MRI tumor stage coincided with the histological stage in 36 of 53 patients (68%). The MRI and CT lymph node stage coincided with the histological stage in 33 (62%) and 26 (49%) of 53 patients, respectively. However the accuracy of MRI in detecting the lateral pelvic lymph node involvement was 83%, compared to 77% of CT (p<0.05). CONCLUSIONS: With the use of MRI, the lateral pelvic lymph node involvement can be predicted with high accuracy, allowing preoperative identification of patients who need radiotherapy or extensive surgery to escape recurrence.

Adult↗
PubMed2006

Mesenteric desmoid tumor of the interposed jejunal pouch after total gastrectomy.

BACKGROUND: Desmoid tumor is a rare entity, and most desmoid tumors are located in abdominal wall or extra-abdominal tissues. Occurrence of desmoid tumor in mesentry is extremely rare. CASE PRESENTATION: we report a mesenteric desmoid tumor in a 73-years-old woman who had undergone total gastrectomy reconstructed with jejunal pouch interposition for gastric carcinoma. After 1 year, a tumor was originating from mesentery of the interposed jejunal pouch was identified, and the patient underwent resection of the large mass which was found to invade pancreas. Histological examination revealed desmoid tumor. CONCLUSION: Desmoid tumor is rare, and it was difficult for the differential diagnosis of desmoid tumor or recurrent tumor.

Journal Article↗
PubMed2006

Does postoperative chemotherapy have a survival benefit for patients with pancreatic cancer?

In our study, we investigated whether postoperative chemotherapy improved survival in patients with invasive ductal carcinoma of the pancreas. Between 1987 and 2004, 111 patients underwent pancreatic resection against invasive ductal carcinoma of the pancreas in Wakayama Medical University Hospital. Median survival time (MST) was 19.4 months, 8.6 months, and 7.2 months, in JPS Stage III (UICC Stage IIA and IIB), JPS Stage IVa (UICC Stage IIA and IIB), and JPS Stage IVb (UICC Stage IV), respectively (P < 0.01). The MST of the chemotherapy group was 12 months, and the MST of the non-chemotherapy group was 8.4 months (P < 0.05). Moreover, in JPS Stage IV (UICC Stage IIA, IIB, III, and IV) highly advanced pancreatic cancer, the MST of the chemotherapy group was 10.9 months, and the MST of the group without chemotherapy was 6.6 months (P < 0.01). Since pancreatic cancer is characterized by an aggressive tumor with a high recurrent rate, postoperative chemotherapy is effective for an improvement of survival.

Aged↗
PubMed2006

Indication of hepatopancreatoduodenectomy for biliary tract cancer.

BACKGROUND: The indication for a hepatopancreatoduodenectomy (HPD) in patients with advanced biliary tract cancer is still controversial, because this aggressive surgery might be associated with high mortality and morbidity rates. In this study, we review our experience with HPD for advanced biliary tract cancer, and seek to define the indication for HPD. METHODS: Eleven patients with biliary tract cancer underwent HPD at Wakayama Medical University Hospital between 1986 and 2004. Univariate analysis was used to assess independent variables of the mortality and morbidity associated with HPD. RESULTS: The rates of mortality and morbidity were 18% and 82%, respectively. Univariate analysis showed that the total serum bilirubin level before surgery and the hepatic parenchymal resection of more than two Healey's segments correlated significantly with an increased risk of severe complications (P = 0.044, 0.0152, respectively). The 1-, 2-, and 3-year survival rates were 44%, 33%, and 11%, respectively. CONCLUSIONS: Hepatopancreatoduodenectomy might offer a chance of long survival by yielding a tumor-free margin in selected patients who are able to tolerate such an aggressive operation, but the indication for this aggressive surgery should be carefully considered.

Aged↗
PubMed2006

Surgical management of small gastrointestinal stromal tumors of the stomach.

Small gastrointestinal stromal tumors (GISTs) (< 3 cm) occasionally are found in the stomach during endoscopy. There is no consensus about the surgical management of these small tumors, although this clinical issue is crucial because some of the tumors show unexpected malignant behavior. In this study, we evaluated the clinical management of patients with gastric GISTs who underwent surgical resection. Altogether, 31 patients with gastric GISTs were examined retrospectively. Surgical resection was fundamentally indicated for the patients with gastric GISTs suspected to be malignant by endoscopy or endoscopic ultrasonography (EUS). The malignant grade of the GISTs was evaluated by the mitotic rate, tumor size, and MIB-1 index. EUS was useful for differentiating benign from malignant GISTs; but by limiting the study to patients with small tumors (< 3 cm), the diagnostic value of EUS was not satisfactory for defining the surgical indication. Tumors that were < 50 mm were successfully treated by laparoscopic surgery. Of the 31 patients, 4 had a relapse of the disease, and 1 of those 4 patients had a small tumor (30 mm). All of the recurrences were classified in the high risk category. Surgery is indicated for gastric GISTs that are > or = 20 mm or are suspected to be malignant based on EUS findings. Laparoscopic resection is feasible and is recommended as the treatment of choice for patients with tumors < 50 mm. Risk assessment can be most useful for predicting recurrence.

Aged↗
PubMed2006

Survival in colorectal cancer patients with urinary tract invasion.

PURPOSE: We compared overall survival and disease-free survival in colorectal cancer patients with and without invasion of urinary organs. METHODS: We clarified the potential predictors of the overall and disease-free survivals after surgery, the factors associated with direct tumor invasion of the urinary organs, postoperative complications, recurrence sites, and survival in patients with and without urinary organ resection in 171 patients with Stage III colorectal cancer who underwent surgery, including 23 patients with tumor invasion of the urinary organs and 148 patients without invasion. RESULTS: Old age (65 years or older), rectal cancer, and macroscopic Type 3 and 4 disease were found to be independent poor prognostic factors for the overall and disease-free survivals in all patients. The overall and disease-free survivals in patients with direct tumor invasion of the urinary organs were not shorter than those in patients without invasion. A large extent of tumors located in the cross-sectional circumference of the bowel (> or =72 percent) and a large maximum tumor size (>50 mm) were significant tumor characteristics associated with positive direct tumor invasion of the urinary organs by sigmoid and rectal cancers. Although the local recurrence of patients with tumor invasion of the urinary organs occurred more frequently in patients without invasion, there were no differences in the overall and disease-free survivals between the patients without a urinary organ resection and those with a local resection of urinary bladder or ureter. CONCLUSIONS: The survival of patients with a urinary invasion was not shorter than that of patients without urinary invasion.

Aged↗
PubMed2006

Impact of lymph node metastasis on survival in patients with pathological T1 carcinoma of the ampulla of Vater.

To determine the prognostic factors for patients with pathological T1 (pT1) carcinoma of the ampulla of Vater, 36 consecutive patients with carcinoma of the ampulla of Vater who underwent surgery were retrospectively analyzed in terms of clinicopathological features. The overall 5-year Kaplan-Meier survival in all patients was 50.2%, and the median survival of all patients was 64.0 months. Factors favorably influencing a long-term outcome were the absence of lymph node metastasis (P < 0.0001), the absence of ulcer formation of the tumor (P = 0.0062), and the absence of tumor invasion into the duodenum (P = 0.0025) and the pancreas (P = 0.0098). In a multivariate analysis, lymph node metastasis was the only predictor of survival (P = 0.0023). In the pT1 stage patients, 20% of the patients had lymph node metastasis, and their survival was statistically poor compared to the pT1 patients without lymph node metastasis (P = 0.017). As for survival after the operation, there was no significant difference between pancreatoduodenectomy and pylorus-preserving pancreatoduodenectomy.

Aged↗
PubMed2006

Combination gene therapy of HGF and truncated type II TGF-beta receptor for rat liver cirrhosis after partial hepatectomy.

BACKGROUND: In a cirrhotic liver, the regenerative ability and specific functions are impaired; a hepatic resection increases the possibility of postoperative liver failure. Hepatocyte growth factor (HGF) stimulates liver regeneration, accelerates restoration of hepatic function, and improves fibrosis. A truncated type II transforming growth factor-beta receptor (TbetaTR), which specifically inhibits TGF-beta signaling as a dominant-negative receptor, appears to prevent the progression of liver fibrosis. We demonstrated the therapeutic efficacy of adenovirus-mediated HGF and TbetaTR gene transduction after partial hepatectomy for liver cirrhosis. METHODS: Rats were treated with dimethylnitrosamine for 3 weeks, and they all had severe cirrhosis. After partial hepatectomy (10%), we injected adenovirus expressing bacterial beta-galactosidase (AdLacZ), adenovirus expressing a truncated type II TGF-beta receptor (AdTbetaTR), adenovirus expressing hepatocyte growth factor (AdHGF), or AdTbetaTR + AdHGF into the portal vein, which was followed by an additional 2-week dimethylnitrosamine treatment. RESULTS: On histologic examination, fibrotic tissue had decreased in the livers of the AdTbetaTR + AdHGF-treated rats compared with rats that were treated by AdLacZ, AdTbetaTR alone, and AdHGF alone. Liver function, which included serum levels of alanine aminotransferase, improved significantly in AdTbetaTR + AdHGF-treated rats compared with all other groups. The number of hepatocytes that were positive for proliferating-cell nuclear antigen was greater (P < .05) in AdHGF alone and AdTbetaTR + AdHGF-treated rat livers than in AdLacZ- and AdTbetaTR-treated rats. All AdTbetaTR + AdHGF-treated rats survived >60 days, and AdTbetaTR + AdHGF treatment markedly improved the survival rate after a partial hepatectomy. CONCLUSION: Our results suggest that the combination of HGF and TbetaTR gene therapy may increase the possibility of hepatectomy in a cirrhotic liver by improving fibrosis, hepatic function, and hepatocyte regeneration.

Adenoviridae↗
PubMed2006

Improvement of delayed gastric emptying in pylorus-preserving pancreaticoduodenectomy: results of a prospective, randomized, controlled trial.

OBJECTIVE: To determine if an antecolic or a retrocolic duodenojejunostomy during pylorus-preserving pancreaticoduodenectomy (PpPD) was associated with the least incidence of delayed gastric emptying (DGE), in a prospective, randomized, controlled trial. SUMMARY BACKGROUND DATA: The pathogenesis of DGE after PpPD has been speculated to be related to factors such as inflammation, ischemia, gastric atony, motilin levels, and type of surgical procedure. Previous retrospective studies have shown a lower incidence of DGE after antecolic duodenojejunostomy. A prospective trial is needed. METHODS: Forty patients were enrolled in this trial between May 2002 and April 2004. Just before duodenojejunostomy during PpPD, the patients were randomly assigned to undergo either an antecolic or a retrocolic duodenojejunostomy. RESULTS: DGE occurred in 5% of patients with the antecolic route for duodenojejunostomy versus 50% with the retrocolic route (P = 0.0014). Those with the antecolic route had a significantly shorter duration of postoperative nasogastric tube drainage than did those with the retrocolic route (4.2 days versus 18.9 days, respectively, P = 0.047). By postoperative day 14, all patients with the antecolic route could take solid foods, while only 55% (11 of 20) of the patients with the retrocolic route could take solid foods (P = 0.0007). The length of stay in the hospital was 28 days for the antecolic group versus 48 days for the retrocolic group (P = 0.018). CONCLUSIONS: Antecolic reconstruction for duodenojejunostomy during PpPD decreases postoperative morbidity and length of hospital stay by decreasing DGE. Our data suggest that PpPD with antecolic duodenojejunostomy is a safer operation.

Aged↗
PubMed2006

Early removal of prophylactic drains reduces the risk of intra-abdominal infections in patients with pancreatic head resection: prospective study for 104 consecutive patients.

OBJECTIVE: The aim of this study was designed to determine whether the period of drain insertion influences the incidence of postoperative complications. BACKGROUND DATA: The significance of prophylactic drains after pancreatic head resection is still controversial. No report discusses the association of the period of drain insertion and postoperative complications. METHODS: A total of 104 consecutive patients who underwent pancreatic head resection were enrolled in this study. To assess the value of prophylactic drains, we prospectively assigned the patients into 2 groups: group I underwent resection from January 2000 to January 2002 (n = 52, drain to be removed on postoperative day 8); group II underwent resection from February 2002 to December 2004 (n = 52, drain to be removed on postoperative day 4). Postoperative complications in the 2 groups were compared. RESULTS: The rate of pancreatic fistula was significantly lower in group II (3.6%) than in group I (23%) (P = 0.0038). The rate of intra-abdominal infections, including intra-abdominal abscess and infected intra-abdominal collections, was significantly reduced in group II (7.7%) compared with group I (38%) (P = 0.0003). Eighteen of 52 (34.6%) patients in group I had an inserted drain beyond 8 days, whereas only 2 of 52 (3.7%) patients in group II had an inserted drain beyond 4 days (P = 0.0002). Cultures of drainage fluid were positive in 16 of 52 (30.8%) patients in group I, and in 2 of 52 (3.7%) patients in group II (P = 0.0002). Intraoperative bleeding (> 1500 mL), operative time (> 420 minutes, and the period of drain insertion were significant risk factors for intra-abdominal infections (P = 0.043, 0.025, 0.0003, respectively). The period of drain insertion was the only independent risk factor for intra-abdominal infections by multivariate analysis (odds ratio, 6.7). CONCLUSION: Drain removal on postoperative day 4 was shown to be an independent factor in reducing the incidence of complications with pancreatic head resection, including intra-abdominal infections.

Abdomen↗
PubMed2006

Potential predictors of survival after surgery for colorectal cancer patients with synchronous unresectable liver metastases.

Liver resection has been recognized as the best treatment for patients with colorectal liver metastases, but as a curative resection for multiple and bilobar colorectal liver metastases (MBCLM) it is definitely less effective. We clarify predictors of survival for unresectable MBCLM. Potential predictors of overall survival, and the correlation between tumor marker and survival were evaluated for patients with synchronous unresectable MBCLM, including 6 rectal and 17 colon cancers. In univariate analysis, survival in patients with the following parameters were longer than those without them: number of liver metastases (</=10), without lung metastasis and peritoneal invasion, and with a <1.0 ratio of postoperative CEA/preoperative CEA. In multivariate analysis, the numbers of liver metastases (>10) and a >1.0 ratio of postoperative CEA/preoperative CEA were factors of poor prognosis, and patients with two such factors had an even worse prognosis. There was a tendency for correlation between the ratio of postoperative CEA/pre-operative CEA and survival (R=-0.492, P=0.053; y=17.388-3.733x). Thus, we clarified some of the predictors of survival for MBCLM, and the usefulness of serum CEA.

Adenocarcinoma↗
PubMed2006

The boosting effect of co-transduction with cytokine genes on cancer vaccine therapy using genetically modified dendritic cells expressing tumor-associated antigen.

The T-helper 1 (Th1) immune reaction is most important in dendritic cell (DC)-based immunotherapy. Interleukin 12 (IL-12) and granulocyte macrophage colony-stimulating factor (GM-CSF) play a pivotal role in inducing Th1 and cytotoxic T lymphocyte (CTL) responses. In this study, DCs expressing the natural tumor antigen gp70 of BALB/c-derived CT26 were adenovirally transduced with the IL-12 gene and/or GM-CSF gene, and it was examined whether vaccinations using these genetically engineered DCs can induce strong therapeutic antitumor immunity. Mice were immunized once by subcutaneous (s.c.) injection with genetically modified DCs. The cytotoxic activity of splenocytes against CT26 was assayed in a 51Cr-release assay 14 days after immunization. The therapeutic efficacy of the vaccination was examined in s.c. tumor models. The cytotoxic activity of CTLs against CT26 in mice immunized with DCs expressing gp70 (DC-AxCAgp70) was significantly augmented by co-transduction with the GM-CSF/IL-12 gene (p<0.0001) and remarkably reduced by the depletion of CD4+ or CD8+ cells (p<0.01). The cytotoxic activity against CT26 of the plain spleen cells in mice immunized with DC-AxCAgp70/GM-CSF/IL-12 was significantly higher than that in mice immunized with DC-AxCAgp70 (p<0.0001), and this activity decreased to almost 50% upon the depletion of NK cells. Vaccinations using DC-AxCAgp70/GM-CSF/IL-12 or DC-AxCAgp70/IL-12 could elicit potent therapeutic immunity in s.c. tumor models; tumor-free mice were observed in these vaccination groups. However, there was no significant difference between these two groups. A vaccination therapy using DCs co-transduced with the TAA gene and Th 1-type cytokine genes, especially the IL-12 gene, is ideal for immunotherapy in terms of the activation of DCs, NK cells, CD4+ T cells and CD8+ T cells, and may be useful in the clinical application of a cancer vaccine therapy.

Adenoviridae↗
PubMed2006

The relationship between survival and the expression of dihydropyrimidine dehydrogenase in patients with colorectal cancer.

Dihydropyrimidine dehydrogenase (DPD) is considered to be a key enzyme affecting the prognosis for patients with colorectal cancer. We investigated whether a correlation exists between the expression of DPD and survival in patients with colorectal cancer. The present study was designed to quantify the DPD level using an enzyme-linked immunosorbent assay in tumors and normal tissue specimens obtained from 22 colorectal cancer patients. There were no significant differences in the preoperative features, neither in the intra- and post-operative findings of patients between the high DPD and low DPD groups in tumor tissue. In patients showing an expression of DPD in tumor tissue, the overall survival in the low DPD group tended to be longer than that in the high DPD group (P = 0.076). In contrast, in patients showing an expression of DPD in normal tissue, no significant difference was observed in the overall survival between the high DPD and low DPD groups (P = 0.358). In patients showing an expression of DPD in tumor tissue, the disease-free survival in the low DPD group was longer than that in the high DPD group (P = 0.046), whereas in patients showing an expression of DPD in normal tissue, no significant difference was seen in the disease-free survival between the high DPD and low DPD groups (P = 0.473). There tended to be a correlation between the DPD expression in tumor tissue and that in adjacent normal tissue (R = 0.390, P = 0.073). Based on these findings, we demonstrated the importance of DPD expression in tumor tissue as a prognostic factor in patients with colorectal cancer.

Aged↗