Biomedical subjects

Shuji Takiguchi

Publications and source records attributed to Shuji Takiguchi.

At least 19 recordsLinked to original sources

PubMed2006

Prediction of peritoneal metastasis in advanced gastric cancer by gene expression profiling of the primary site.

Peritoneal metastasis is the most common cause of tumour progression in advanced gastric cancer. Clinicopathological findings including cytologic examination of peritoneal lavage have been applied to assess the risk of peritoneal metastasis, but are sometimes inadequate for predicting peritoneal metastasis in individuals. Hence, we tried to construct a new prediction system for peritoneal metastasis by using a PCR-based high throughput array with 2304 genes. The prediction system, constructed from the learning set comprised of 30 patients with the most informative 18 genes, classified each case into a 'good signature group' or 'poor signature group'. Then, we confirmed the predictive performance in an additional validation set comprised of 24 patients, and the prediction accuracy for peritoneal metastasis was 75%. Kaplan-Meier analysis with peritoneal metastasis revealed significant difference between these two groups (P=0.0225). By combining our system with conventional clinicopathological factors, we can identify high risk cases for peritoneal metastasis more accurately.

Aged↗

PubMed2006

A prospective trial for avoiding cervical lymph node dissection for thoracic esophageal cancers, based on intra-operative genetic diagnosis of micrometastasis in recurrent laryngeal nerve chain nodes.

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the usefulness of intra-operative genetic diagnosis of RN node micrometastasis in the decision-making of 3FL for thoracic esophageal cancers. METHODS: Eighty-nine patients with middle and lower thoracic esophageal cancer were enrolled in a prospective study, in which 3FL was performed when RN node metastasis was revealed by intra-operative histological examination and/or genetic analysis using real-time RT-PCR assay. For other cases, 2FL was performed. RESULTS: Of the 89 patients, 3FL was performed for 33 patients and 2FL for 56 patients. In the 3FL group, RN node metastasis was both histologically and genetically positive in 19 patients, histologically negative and genetically positive in 11, and histologically positive and genetically negative in 3, with cervical node metastasis being detected in 7, 3, and 0 patients, respectively. In the 2FL group, only one patient had cervical node recurrence during the follow-up period. The post-operative survival in this study was equivalent to that of the historical controls (3-year survival rates 63.9% vs. 52.3%, P = 0.1513) of 66 3FL patients when 3FL was the first choice for thoracic esophageal cancers. CONCLUSIONS: Intra-operative histological and genetic diagnosis of RN node metastasis may help avoid unnecessary cervical node resection. A Phase III trial should be done.

Aged↗

PubMed2006

Expression of hepatoma-derived growth factor is correlated with lymph node metastasis and prognosis of gastric carcinoma.

PURPOSE: Hepatoma-derived growth factor (HDGF) is a unique nuclear/growth factor and might play an important role in the development and progression of carcinomas. In the present study, association of HDGF expression with recurrence and prognosis of gastric carcinoma was examined. PATIENTS AND METHODS: HDGF expression in 317 patients with gastric carcinoma (233 males and 84 females) with ages ranging from 26 to 81 years (median, 60 years) was analyzed by immunohistochemistry. Samples with >90% of tumor cells to express positive immunoreactivity similar to or stronger than that in endothelial cells both for nucleus and cytoplasm were regarded as HDGF index level 2, and others as HDGF index level 1. RESULTS: One hundred and eighty-two cases showed level 1 HDGF expression, whereas 135 cases showed level 2 HDGF expression. Patients with level 2 expression showed higher rates of proximal tumor location (P < 0.0001), large tumor size (P < 0.0001), infiltrative tumor growth (P < 0.0001), presence of vascular and lymphatic invasion (P < 0.0001 for both), presence of lymph node metastasis (P < 0.0001), deep tumor invasion (P < 0.0001), and poorer disease-free and overall survival (P < 0.0001 for both) compared to those with level 1 expression. Multivariate analysis revealed HDGF expression level as an independent prognosticator for disease-free and overall survival. CONCLUSION: HDGF expression level was shown to be a prognostic factor for gastric carcinoma.

Adult↗

PubMed2006

Overexpression of hypoxia-inducible factor-1 alpha in gastric adenocarcinoma.

BACKGROUND: The transcriptional factor hypoxia-inducible factor 1alpha (HIF-1alpha) controls angiogenesis and metabolism by upregulating hypoxia-induced genes, such as the vascular endothelial growth factor (VEGF) gene and the glucose transporter (GLUT-1) gene. In addition to its regulation by oncogenes or tumor suppressor genes such as HER2, p53, VHL, and PTEN, overexpression of HIF-1alpha is induced by hypoxia. Increased HIF-1alpha expression is associated with malignant potential, and with patient prognosis and response to chemoradiotherapy in some cancer types. METHODS: We investigated the association between HIF-1alpha expression and clinicopathological characteristics, including the expression of VEGF and p53 proteins, in gastric cancer. Furthermore, we analyzed the impact of HIF-1alpha, VEGF, and p53 protein expression on resistance to chemotherapy in advanced gastric cancer. RESULTS: Among 146 specimens from patients with gastric adenocarcinoma, 89 (61.0%), 52 (35.6%), and 102 (69.9%) were positive for HIF-1alpha, p53, and VEGF expression, respectively. The increased expression of HIF-1alpha protein correlated significantly with the increased expression of p53 (P < 0.0001) and VEGF (P = 0.0007). However, overexpression of these proteins was not associated with prognosis or clinicopathological status, with the exception of infrequent distant metastases. Furthermore, overexpression of these proteins was not associated with chemosensitivity in these patients with gastric cancer. CONCLUSION: Our results indicate that overexpression of HIF-1alpha correlates significantly with p53 and VEGF protein expression in patients with gastric cancer; however, this overexpression shows no association with clinicopathological status, patient prognosis, or chemosensitivity.

Adenocarcinoma↗

PubMed2006

Clinical significance of class III beta-tubulin expression and its predictive value for resistance to docetaxel-based chemotherapy in gastric cancer.

Docetaxel, one of the most effective anticancer drugs for gastric cancer, targets beta-tubulin, the major protein in mitotic spindles. Eight isotypes of beta-tubulin, with tissue and organ-specific expression, have been identified in mammalian cells. We examined class III beta-tubulin expression in gastric cancer and assessed its relationship with sensitivity to docetaxel-based chemotherapy. A total of 115 paraffin-embedded gastric tumors were analyzed by immunohistochemistry for class III beta-tubulin expression. Twenty patients with advanced gastric cancer received preoperative docetaxel-based chemotherapy. Their biopsied specimens, obtained by endoscopy before chemotherapy were examined for class III beta-tubulin expression. The relationship between expression and chemosensitivity was assessed. Forty-two (36.4%) of 115 cases were confirmed to be positive for class III beta-tubulin expression. There was no association between clinicopathological status and prognosis. Among the patients positive for class III beta-tubulin expression, only 16.7% showed no response to chemotherapy, while 64.3% responded to the chemotherapy in the negative group. Our results suggest that class III beta-tubulin is a simple and useful predictive marker for the clinical response to docetaxel-based chemotherapy in gastric cancer.

Adult↗

PubMed2006

[A phase I study of combination chemotherapy using TS-1 and weekly paclitaxel for advanced gastric cancer].

The safety of chemotherapy combining TS-1 and weekly paclitaxel for the treatment of unresectable and recurrent gastric cancer was evaluated in this study. Paclitaxel was administered by intravenous drip infusion at a starting dose (level 1) of 50 mg/m2 on days 1, 8, and 15. TS-1 was administered orally at a dose of 40 mg/m2twice a day for 2 weeks (days 1-14) followed by 2 weeks rest. A total of 9 patients were enrolled in this study. Two out of 6 patients treated with level 1 suffered from leukocytopenia and neutropenia, which were determined as dose-limiting toxicity (DLT). Three patients were treated with level 2, in which the dose of paclitaxel was increased up to 60 mg/m2. One of 3 patients suffered from grade 3 diarrhea and one patient from grade 4 leukocytopenia, eutrocytopenia, anemia, and stomatitis, which were determined as DLT. According to these results,level 1 of this regimen was recommended as a safe treatment for gastric cancer patients. A phase II study will be performed to evaluate the efficacy of the combination chemotherapy.

Adult↗

PubMed2005

Prediction of recurrence in advanced gastric cancer patients after curative resection by gene expression profiling.

The prognosis of patients with advanced gastric cancer remains unfavorable. Even after curative resection, 40% of patients with advanced gastric cancer die of recurrence. Conventional clinicopathlogic findings are sometimes inadequate for predicting recurrence in individuals. Hence, we tried to construct a new diagnostic system, which predicts recurrence in patients with advanced gastric cancer after curative resection based on molecular analysis. Gastric cancer progression is a function of multiple genetic events that may affect the expression of large number of genes. We performed gene expression profiling with 2,304 genes in 60 advanced gastric cancer patients who underwent curative resection using a PCR array technique, a high-throughput quantitative RT-PCR technique. The diagnostic system, which was constructed from the learning set comprised of 40 patients with the most informative 29 genes, classified each case into a good-signature or poor-signature group. Then, we confirmed the predictive performance in an additional test set comprised of 20 patients, and the prediction accuracy for recurrence was 75%. Kaplan-Meier analysis revealed significant difference between the good-signature and the poor-signature group (p = 0.0125). Especially in patients with smaller tumor (< or = 5 cm), less developed LN metastasis (N(0,1)), or earlier stage (stages I and II), the prediction accuracy was high (88.9%, 84.6%, or 81.8%, respectively). Our diagnostic system based on systematic analysis of gene expression profiling can predict the recurrence at clinically meaningful level. By combining our system with conventional clinicopathologic factors, we can improve the prediction of recurrence in patients with advanced gastric cancer who underwent curative surgery.

Aged↗

PubMed2005

Correlation between histological effects on the main tumors and nodal status after chemoradiotherapy for squamous cell carcinoma of the esophagus.

BACKGROUND AND OBJECTIVES: Although the histological effectiveness of preoperative chemoradiotherapy against the main tumor is reported to be the strongest prognostic factor for patients with esophageal cancer, it remains unknown whether such chemoradiotherapy is equally effective against metastatic lymph nodes. METHODS: We studied 103 consecutive patients with esophageal cancer, who were given preoperative chemoradiotherapy followed by surgery. The histological effectiveness against the main tumor of the chemoradiotherapy was correlated with lymph mode metastasis and other clinico-pathological factors. RESULTS: The histological effectiveness against the main tumor was grade 3 in 26 patients, grade 2 in 49 and grade 1 in 28. The number of pathological node-negative patients was 21 (80.8%), 19 (38.8%), and 7 (25.0%) in those having grade 3, 2, and 1 responses of their main tumors, respectively. The average number of pathological metastatic lymph nodes was 0.19, 1.4, and 4.4 in patients with grade 3, 2, and 1 responses, respectively. Endoscopic biopsy after the chemoradiotherapy could not accurately diagnose the pathological complete response (CR) of the main tumors, with a high false negative rate (60.9%). CONCLUSIONS: The effects of chemoradiotherapy against main tumors significantly correlated with nodal status. Most patients with main tumors of pathological CR are node-negative. Patients with a grade 2 response have at most a few positive nodes. Surgery would be most beneficial for such patients.

Adult↗

PubMed2005

A simple technique for performing laparoscopic purse-string suturing during circular stapling anastomosis.

An esophagojejunostomy using a circular stapler requires the fixing of an anvil at the esophageal stump. When this placement procedure is laparoscopically performed, purse-string suturing is difficult, and there is a risk of loosening when a conventional needle driver is used. We herein present a simple but effective technique for performing laparoscopic purse-string suturing of the esophageal stump using a semiautomatic suturing device called the Endostitch. Gastrointestinal anvil placement was laparoscopically performed for 10 patients who underwent an esophagojejunostomy following a total gastrectomy. After the lumen of the esophagus was expanded using bowel forceps, the Endostitch was used to place approximately 12 encircling purse-string sutures. An anvil was positioned with support of the esophageal wall at three points with forceps. The Endostitch was used for the ligation with a sufficient degree of tension applied by extracorporeally pulling the sutures through the abdominal wall. The time for placement of the anvil averaged approximately 8 min. The ring formation following anastomosis was favorable in all patients. As a result, we consider our technique to be simple but very effective.

Anastomosis, Surgical↗

PubMed2005

High incidence of thrombosis of the portal venous system after laparoscopic splenectomy: a prospective study with contrast-enhanced CT scan.

OBJECTIVE: The aims of this prospective study were to investigate the true incidence of portal or splenic vein thrombosis (PSVT) after elective laparoscopic splenectomy using contrast-enhanced computed tomography (CT) scan, and outcome of anticoagulant therapy for PSVT. SUMMARY BACKGROUND DATA: Although rare, thrombosis of the portal venous system is considered a possible cause of death after splenectomy. The reported incidence of ultrasonographically detected PSVT after elective open splenectomy ranges from 6.3% to 10%. METHODS: Twenty-two patients underwent laparoscopic splenectomy (LS group), and 21 patients underwent open splenectomy (OS group). Preoperative and postoperative helical CT with contrast were obtained in all patients, and the extent of thrombosis was investigated. Prothrombotic disorder was also determined. RESULTS: PSVT occurred in 12 (55%) patients of the LS group, but in only 4 (19%) of the OS group. The difference was significant (P = 0.03). Clinical symptoms appeared in 4 of the 12 LS patients. Thrombosis occurred in the intrahepatic portal vein (n = 9), extrahepatic portal vein (n = 2), mesenteric veins (n = 1), proximal splenic vein (n = 4), and distal splenic vein (n = 8). Prothrombotic disorder was diagnosed in 1 patient. Anticoagulant therapy was initiated once the diagnosis was established, and complete recanalization, except for distal splenic vein, was observed without any adverse event. Patients with splenomegaly were at high risk of PSVT. CONCLUSIONS: PSVT is a more frequent complication of laparoscopic splenectomy than previously reported but can be treated safely following early detection by CT with contrast.

Aged↗

PubMed2005

A mouse model of early-stage peritoneal metastasis: optimal RT-PCR-based method for detection of peritoneal micrometastases.

The presence of peritoneal micrometastasis in the abdomen is a poor prognostic factor in advanced gastric cancer. However, there is no standardized method for detection of peritoneal micrometastases. The aim of this study was to establish an animal model mimicking early phase peritoneal dissemination of advanced gastric cancer and then to use this model to compare the sensitivity and specificity of reverse transcription-polymerase chain reaction (RT-PCR) with peritoneal lavage fluid, randomly collected omentum with or without milky spots stained with activated carbon particles for detection of disseminated cancer cells. MKN-45-EGFP gastric cancer cells (1 x 10(3), 5 x 10(3) and 1 x 10(4)) were injected intraperitoneally into 4-week-old female BALBc nu/nu mice on day 0. Mice were sacrificed at 7 or 14 days postinjection. Peritoneal seeding was assessed by fluorescence stereomicroscopy. The sensitivities of RT-PCR with peritoneal lavage fluid, omentum with or without milky spots, were compared. Peritoneal seeding was confirmed in 8 of 10 mice injected with 1 x 10(4) MKN-45-EGFP cells by fluorescence stereomicroscopy. On days 7 and 14, the rate of the detection of CEA mRNA was 0, 50.0, and 87.5% in the omentum, omentum with milky spots and peritoneal lavage fluid, respectively. On days 7 and 14, the average level of CEA mRNA was 0, 51113+/-28225, and 3556+/-2842 in the omentum, omentum with milky spots and peritoneal lavage fluid, respectively. Molecular diagnosis using peritoneal lavage fluid is more sensitive than that using the omentum.

Animals↗

PubMed2004

Preoperative intraperitoneal chemotherapy for patients with serosa-infiltrating gastric cancer.

BACKGROUND AND OBJECTIVES: Serosa-infiltrating gastric cancer poses a high risk for peritoneal recurrence. This study examined the feasibility and efficacy of preoperative intraperitoneal (i.p.) chemotherapy for such cancer. METHODS: Patients with serosa-infiltrating tumors, diagnosed by conventional examinations as well as by staging laparoscopy, were enrolled in this study. Those with unresectable T4 tumors, visible peritoneal metastasis or distant organ metastasis were excluded. Twenty-five eligible patients received preoperative i.p. chemotherapy, which consisted of i.p. injection of 20 mg of mitomycin C on day 1 and 10 mg of cisplatin for 5 days, followed by surgery. RESULTS: Of the 25 patients, 24 underwent gastrectomy with lymph node dissection and 1 underwent palliative gastrojejunostomy. The curability of the surgery was curability A in 6, B in 16, and C in 3. Preoperative T stages (T3 in 21 and T4 in 4) were downstaged postoperatively (T1 in 1, T2 in 10, T3 in 11, and T4 in 3). The 1- and 2-year overall survival was 83.3 and 51.3%, respectively. The median survival time was 24.4 months. The toxicity of the preoperative treatment was tolerable and no serious postoperative complication was seen. CONCLUSIONS: Preoperative i.p. chemotherapy seems to be a safe and effective therapy for serosa-infiltrating gastric cancer. Randomized clinical trials comparing preoperative i.p. chemotherapy followed by surgery and surgery alone are needed.

Adenocarcinoma↗

PubMed2004

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↗

PubMed2004

Application of molecular diagnosis for detection of peritoneal micrometastasis and evaluation of preoperative chemotherapy in advanced gastric carcinoma.

BACKGROUND: In advanced gastric cancer, peritoneal recurrence is the main cause of death after curative surgical resection. The aim of this report was to describe a novel approach for quantitative genetic diagnosis using peritoneal lavage for the identification of patients at high risk for peritoneal recurrence and for evaluation of the clinical response to intraperitoneal chemotherapy in advanced gastric cancer. METHODS: Nineteen patients with advanced gastric cancer who underwent staging laparoscopy and intraperitoneal chemotherapy before surgical resection or systemic chemotherapy between June 1999 and September 2001 were enrolled in this study. All peritoneal lavage specimens, collected at both staging laparoscopy and gastrectomy, were subjected to real-time quantitative genetic diagnosis. RESULTS: The reverse transcriptase polymerase chain reaction (RT-PCR) values decreased in 8 cases, stabilized as negative in 5, and increased in 6 during therapy. Patients whose RT-PCR values diminished and were ultimately negative survived except for one, and all but one patient whose values increased during treatment died of recurrence. CONCLUSIONS: Quantitative evaluation of genetic changes can provide accurate, useful information on the effects of preoperative intra-abdominal chemotherapy and overall prognosis for patients with advanced gastric cancer.

Adenocarcinoma↗

PubMed2004

Rapid genetic diagnosis with the transcription-reverse transcription concerted reaction system for cancer micrometastasis.

BACKGROUND: Detection of cancer micrometastases is required for improvement of cancer therapy. The aim of this study was to establish a rapid and practical genetic assay to detect micrometastasis in gastric cancer and to assess its clinical significance with respect to prognosis. METHODS: A novel RNA amplification system with transcription-reverse transcription concerted reaction (TRC) was introduced for quantitative detection of cancer-specific carcinoembryonic antigen messenger RNA. The sensitivity and quantitative aspects of the assay were assessed with the full-length carcinoembryonic antigen messenger RNA, a gastric cancer cell line (MKN-45), and metastatic lymph nodes obtained from patients with gastric cancer. Peritoneal lavage fluid specimens that were collected from gastric cancer surgery were subjected to the assay, and the clinical significance of the results was examined for prediction of recurrence and survival. RESULTS: The quantification, sensitivity, and reproducibility of the assay with the TRC reaction were equal to those of quantitative reverse transcriptase-polymerase chain reaction with LightCycler. The most important advantages of the assay were its simplicity and rapidity. Molecular diagnosis of peritoneal lavage fluid by the TRC reaction significantly correlated with depth of invasion, peritoneal metastasis, clinical stage, overall survival, and peritoneal recurrence-free survival. CONCLUSIONS: Molecular diagnosis of peritoneal lavage fluid with the TRC reaction could be a useful prognostic indicator for peritoneal recurrence and survival. Because the TRC reaction is more rapid and simpler than reverse transcriptase-polymerase chain reaction as a format for detecting RNA sequences, it may enhance the genetic diagnosis of cancer micrometastasis and may improve cancer therapy.

Biomarkers, Tumor↗

PubMed2004

[Weekly administration of paclitaxel as a second-line chemotherapy for advanced and recurrent gastric cancer].

Chemotherapy with TS-1 has recently become the first-line chemotherapy for recurrent and unresectable gastric cancer in Japan. Therefore, the establishment of a second-line chemotherapy is needed for cases that show resistance and aberrant effect to TS-1. In this study, 7 patients were treated with weekly administrations of paclitaxel after TS-1 treatment. We assessed the therapeutic effect and feasibility of chemotherapy with weekly administration of paclitaxel. Our results showed that weekly administration of paclitaxel could be a promising regimen as a second-line chemotherapy after TS-1.

Aged↗

PubMed2004

[Cases of postoperative hepatic metastasis from gastric cancer in which hepatic arterial infusion chemotherapy with 5-FU, adriamycin and cisplatin was performed after TS-1 chemotherapy].

The prognosis of patients with hepatic metastasis of gastric cancer is poor, and standard therapies for patients are not established. Here we present two cases of hepatic metastasis from gastric cancer. In both cases, no other organ metastasis except the liver was confirmed, in which hepatic arterial infusion chemotherapy with 5-FU, adriamycin and cisplatin (FAP) were performed because TS-1 chemotherapy was not an effective chemotherapy. Case 1: An 80-year-old man had distal gastrectomy for type 2 gastric cancer (Stage II) in January 2001. A liver S8 metastatic recurrence was discovered in the 18th month post operation. After chemotherapy with TS-1 for 5 courses, a hepatic arterial infusion treatment was performed for 7 courses. The effect was PR, but the treatment was canceled because of a catheter obstruction. The patient is living without recurrence. Case 2: This case was a 73-year-old man who had distal gastrectomy for type 0 IIc gastric cancer (Stage IA) in May 1999. Multiple hepatic metastases recurred in the 32nd month post operation. After chemotherapy with TS-1 for 2 courses, a hepatic arterial infusion treatment was performed for 10 courses. The effect was CR, but a peritoneal recurrence was discovered, and a systemic chemotherapy was performed. The patient is living without recrudescence of hepatic metastasis. The hepatic arterial infusion chemotherapy with FAP was effective for gastric cancer patients with liver metastasis because TS-1 chemotherapy was not an effective chemotherapy. It is necessary to consider combined chemotherapy in addition to systemic chemotherapy.

Aged↗

PubMed2004

[Two cases of advanced and recurrent gastric cancer treated with the combination of chemotherapy and radiation].

Recently, new promising anti-tumor agents such as TS-1, taxanes, and CPT-11 have been approved for gastric cancer treatment. These agents showed a better response and may contribute to a patient's survival and quality of life. However, there are cases with advanced and recurrent gastric cancer that are resistive or tolerant to these agents. We report two cases in which the patients had suffered symptomatic local recurrence during the chemotherapy. Consequently, they had been treated with radiotherapy in order to improve their clinical status. We also discuss the significance of radiotherapy in gastric cancer.

Antineoplastic Combined Chemotherapy Protocols↗