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Biomedical subjects

Takayuki Asao

Publications and source records attributed to Takayuki Asao.

At least 19 recordsLinked to original sources

Matrilsin expression is a useful marker of submucosal invasion and lymph node metastasis in early stage signet ring cell carcinoma of the stomach.

BACKGROUND: Matrilysin (MMP-7) is considered to play an important role in tumor progression and metastasis. The aim of this study was to examine the MMP-7 expression of early-stage undifferentiated gastric carcinoma, and to investigate differences between gastric signet ring cell (SIG) and other undifferentiated carcinomas (non-SIG). METHODS: Immunohistochemical staining of MMP-7 was performed using specimens from 150 patients with early-stage gastric undifferentiated carcinomas (76 SIG, 74 non-SIG). RESULTS: SIG had a larger proportion of mucosal-confined carcinoma and a lower rate of lymphatic invasion than non-SIG (P < 0.05). The incidence of the positive expression of MMP-7 in submucosal SIG was significantly higher than that of mucosal SIG (P < 0.01). In contrast, MMP-7 expression was frequently found in mucosal non-SIG, suggesting an apparent difference in the invasiveness between mucosal SIG and non-SIG. The larger the size of the mucosal SIG, the more frequently MMP-7 positive expression was demonstrated (P < 0.05). There was a significant correlation between MMP-7 positive expression and lymph node metastasis of early SIG (P < 0.05). CONCLUSION: Early SIG revealed less invasiveness than non-SIG in terms of clinicopathologic features and MMP-7 expression. Preoperative estimation of the MMP-7 expression might be useful as a predictor of submucosal invasion and lymph node metastasis in early SIG.

Adult↗

Living-related liver transplantation for multiple liver metastases from rectal carcinoid tumor: a case report.

A 42-year-old woman was admitted to our hospital because of multiple liver tumors detected by ultrasonography. Colonoscopy revealed submucosal tumor in the rectum, which was considered the primary lesion. Endoscopic mucosal resection followed by histopathological examination revealed that the tumor was carcinoid. The resected margin of the tumor was positive for malignant cells. Two courses to transcatheter arterial chemotherapy for liver metastasis were ineffective. Accordingly, the rectal tumor and metastatic lymph nodes were surgically resected. One month after the operation, she received liver transplantation (left lateral segment and caudate lobe) from her son. No recurrent lesion has been observed at two years after the liver transplantation. Liver transplantation should be considered as a treatment option even in advanced case of carcinoid metastasis to the liver. We also discuss the literature on liver transplantation for metastatic carcinoid tumor.

Adult↗

Sentinel lymph node mapping with technetium-99m colloidal rhenium sulfide in patients with gastric carcinoma.

BACKGROUND: The objective of this study was to determine, with the use of technetium-99m colloidal rhenium sulfide, whether the concept of sentinel lymph nodes (SLNs) is applicable to gastric cancers. METHODS: Fifty-nine gastric cancer patients underwent radical gastrectomy and SLN mapping with an intraoperative hand-held gamma probe. After surgery, each transected lymph node was measured for radioisotope (RI) activities by a well-type scintillation counter. RESULTS: SLNs were detectable in 57 (96%) of 59 patients. The sensitivity, specificity, and diagnostic accuracy were calculated to be 83.3%, 100%, and 92.9%, respectively. Sensitivity was 100% in the T1 group, 91.6% in the T2 group, and 62.5% in the T3 group. When RI activities were measured with a well-type scintillation counter, every metastatic non-SLN was found to be situated in the same lymphatic basin as the SLNs. CONCLUSION: The SLN concept is applicable to patients with early gastric cancer (T1). SLN mapping is suitable for identifying the lymphatic basin in cases of gastric cancer.

Adenocarcinoma↗

The synchronization of chemotherapy to circadian rhythms and irradiation in pre-operative chemoradiation therapy with hyperthermia for local advanced rectal cancer.

PURPOSE: The therapeutic and adverse effects of pre-operative chrono-chemoradiation with local hyperthermia for patients with rectal adenocarcinoma were evaluated. MATERIALS AND METHODS: Pre-operative radiation therapy of a total dose of 40 Gy (n = 10) or 50 Gy (n = 19) on the whole pelvis and hyperthermia once a week during the radiation therapy for 1 h were performed for patients with T2-T4 rectal adenocarcinoma. Chemotherapy consisted of 5-FU (250 mg m-2 per day) and LV (25 mg m-2 per day) administered by continuous infusion in the night for 5 days a week in the second and fourth weeks of radiation. RESULTS: Grade 3+ toxicities were seen only in two patients (6.9%). A significant down staging was seen in 41.4% of all cases and 52.6% of cases with a radiation dose of 50 Gy. Of the patients who had received surgical resection of a tumour, three (11.1%) had no residue pathologically in the specimen and eight (29.6%) had microscopic lesions. CONCLUSIONS: These results yielded a high response rate with minimal toxicities for advanced low-rectal adenocarcinoma. The administration of 5-FU during the sleeping time before irradiation might have an advantage not only as a chronotherapy but also as a radiation sensitizer.

Adenocarcinoma↗

A phase I radioimmunolocalization trial of humanized monoclonal antibody huA33 in patients with gastric carcinoma.

In order to determine the in vivo characteristics of huA33, an open label dose escalation biopsy-based phase I clinical trial and radioimmunolocalization study were conducted with a complement determinant region-grafted humanized monoclonal antibody against the A33 antigen in patients with gastric carcinoma. Thirteen patients were entered onto one of four dose levels (1.0, 2.0, 5.0 or 10.0 mg/m(2)). Patients with locally advanced (UICC-TNM [International Union Against Cancer-tumor, node, metastasis] stage over 2 but resectable at clinical diagnosis) gastric carcinoma received a single infusion of (131)I-huA33 1 week prior to surgery. Adverse events were monitored, and imaging studies with gamma camera plus ex vivo scintigraphy of the resected specimen, biodistribution study by dosimetry analysis of the biopsied and resected tissues, and immunohistochemical analysis were carried out and evaluated. No dose-limiting toxicity was observed during the trial. Therefore, the maximum tolerated dose was not reached. Although cancer tissues with + intensity and <25% extent by immunostaining in biopsied frozen sections did not show positive imaging or postoperative dosimetry findings, cancers with ++ or +++ intensity or wide (>25%) extent by frozen and paraffin sections in the biopsied specimen showed positive ex vivo tumor images and positive antigen expression in resected gastric cancer specimens, and the biodistribution analysis showed tumor uptake of (131)I-huA33. In conclusion, humanized monoclonal antibody huA33 demonstrated selective localization to gastric cancer that expressed A33 antigen strongly. These excellent targeting characteristics of huA33 indicate potential for targeted therapy of advanced gastric cancer that is refractory to cytotoxic therapy, and could also be exploitable for curatively resected early gastric cancer in an adjuvant setting.

Aged↗

The soluble form of human leukocyte antigen class I antigen causes apoptosis on hepatocellular carcinoma cell lines.

A soluble form of human leukocyte antigen class I antigen (sHLA-I) has been reported to cause apoptosis on cytotoxic T cells and inhibit killer activity of natural killer cells via killer-cell inhibitory receptors. However, its effect on cancer cells has not yet been elucidated. We examined the direct effect of sHLA-I on human liver cancer cell lines, HepG2, HLE and HLF. The effects of sHLA-I on cell growth, DNA synthesis, and apoptosis induction were evaluated. To elucidate the mechanisms, cDNA expression arrays were also examined. sHLA-I caused cell growth inhibition, resulting in apoptosis on human hepatocellular carcinoma, dose-dependently. In this process, caspase-3 was activated. sHLA-I also inhibited in vivo growth of hepatocellular carcinoma in severe combined immunodeficient mice. sHLA-I caused apoptosis on human hepatocellular carcinoma.

Alternative Splicing↗

Prognostic significance of combined expression of MUC1 and adhesion molecules in advanced gastric cancer.

The objective of the present study was to evaluate the combination of MUC1 and the status of adhesion molecules in advanced gastric cancers as a possible predictor of patient survival. Two hundred and two paraffin-embedded specimens of gastric carcinoma were examined by immunohistochemical staining using monoclonal antibodies against MUC1 mucin, E-cadherin and beta-catenin. The expression of MUC1 was considered positive if at least 10% of the neoplastic cells were stained. E-cadherin and beta-catenin were classified into four groups. Only a membranous pattern, which was stained as strongly as normal epithelial cells, was judged as normal. The absent pattern (loss of staining), cytoplasmic pattern (cytoplasmic staining with loss of membranous expression), and heterogeneous pattern (cytoplasmic staining with preservation of membranous expression) were considered abnormal. There was a significant relationship between MUC1-positive expression and abnormal expression of E-cadherin (P=0.017). The cancer with abnormal E-cadherin expression or MUC1-positive expression increased, indicating that the cancer invasion was deep. Survival analysis of the outcome revealed that the survival time for those with abnormal E-cadherin/MUC1-positive expression was shorter than for those with other expression patterns. Multivariate analysis revealed that patients with abnormal E-cadherin/MUC1-positive expression had a poorer prognosis with significance (P<0.0001). In conclusion, abnormal E-cadherin/MUC1-positive expression pattern in advanced gastric cancer is an independent unfavorable prognostic marker.

Antigens↗

18F-fluorodeoxyglucose positron emission tomography: useful technique for predicting malignant potential of gastrointestinal stromal tumors.

The malignant potential of gastrointestinal stromal tumors (GISTs) is difficult to diagnose before surgery because the diagnoses are based on tumor diameter and mitotic index. The progression of small GISTs is always observed because they do not seem to have malignant potential. 18F-Fluorodeoxyglucose (FDG)-positron emission tomography (PET) is a useful technique for assessing tumor activity. The objective of this study was to determine if FDG-PET is useful for predicting the malignant potential of gastric GISTs. Ten patients diagnosed with gastric GISTs participated. FDG-PET was performed on all of them before tumor resection. A whole-body image was initiated 40 minutes after the injection of 275 to 370 MBq FDG. FDG uptake was assessed by a standardized uptake value. All tumors had FDG uptake. There was a significant correlation between the FDG uptake and both the Ki67 index and the mitotic index but not the tumor diameter. The FDG uptake and malignant potential of gastric GISTs had a significant correlation. FDG-PET may be of considerable value for predicting the malignant potential of gastric GISTs before surgery. A gastric GIST with a high FDG uptake should be regarded as having malignant potential.

Adult↗

Laparoscopy-assisted gastrectomy for early gastric cancer in young and elderly patients.

Open gastric surgery in elderly patients is associated with higher morbidity and mortality rates than those reported among younger individuals. Therefore, minimally invasive surgery may have a larger impact on the elderly compared to the younger age group. The objective of this study was to evaluate the experience of laparoscopy-assisted distal gastrectomy (LADG) in patients with early gastric cancer and compare the results in patients 70 years of age and older to those in patients younger than 70 years of age. From January 1998 to October 2004, a total of 103 patients underwent LADG. Of these patients, 30 who were older than 70 years were compared with 73 who were younger. Preoperative co-morbidity, operative results, postoperative outcomes, and survival were analyzed. Furthermore, as a standard control of this study, we reviewed 54 distal gastrectomy cases with open surgery (open distal gastrectomy; ODG) in the same term with the same background factors, categorized into elder (n = 16) and younger (n = 38). The mean age of the elderly patients was 75 years in the LADG group. A significantly higher proportion of elderly patients had concurrent diseases in both groups. Blood loss was significantly less in the elderly than in younger patients undergoing LADG, and it was less in the LADG group than in the ODG group. The overall 5-year survival rates in the LADG group were not significantly different between elderly and younger patients. Laparoscopy-assisted distal gastrectomy is a safe and effective treatment for early gastric cancer in the elderly. Therefore, chronological age alone should not be considered a contraindication in selecting patients for LADG.

Adenocarcinoma↗

Laparoscopic assisted distal gastrectomy for early gastric cancer: Five years' experience.

BACKGROUND: Laparoscopic assisted gastrectomy is being reported increasingly as the treatment of choice for early gastric cancer. However, no reports concerning the prognosis of patients who have undergone laparoscopic assisted distal gastrectomy (LADG) for early gastric cancer or data comparing the results to those obtained after open gastric surgery are yet available. METHODS: A retrospective study was performed comparing laparoscopic assisted and open distal gastrectomies for early gastric cancer. Eighty-nine patients who underwent LADG were compared to 60 who underwent conventional open distal gastrectomy (DG) in terms of pathologic findings, operative outcome, complications, and survival. RESULTS: There were no significant differences between LADG and DG in operation time (209 vs 200 minutes), complication rate (9% vs 18%), and 5-year survival rate (98% vs 95%). There were differences between LADG and DG with regard to blood loss (237 vs 412 mL), number of lymph nodes (19 vs 25), postoperative stay (17 vs 25 days), and the duration of epidural analgesia (2 vs 4 days) ( P < .05 each). CONCLUSIONS: For properly selected patients, LADG can be a curative and minimally invasive treatment for early gastric cancer.

Early Diagnosis↗

Videoscopic thyroidectomy with fine needle-type apparatuses: an approach that does not leave a scar on the neck or anterior chest.

A total videoscopic operation with constant CO(2) gas insufflation is ideal for performing a scarless thyroidectomy because the skin incisions at the surgical ports are made far from the neck in the axillar area. However, there are many difficulties associated with the performance of a videoscopic thyroidectomy when approaching pneumo-subcutaneously from distant ports, because the instruments are inserted tangentially toward the thyroid gland from a distant port and their range of manipulation is limited. The devices and surgical techniques used for a videoscopic thyroidectomy that does not leave a scar on the anterior chest or neck were developed. Fine needle-type cautery and forceps that could access directly to the thyroid gland from the neck were used to support the forceps. A CO(2) reservoir bag connected to the CO(2) insufflation tube contributed to the safer manipulation by the creation of a stable operation space during emitting smoke from coagulation device. A silicon ring stopper was useful to prevent dislodging of the ports. In conclusion, videoscopic neck surgery would be easier using these new devices and techniques and would produce better cosmetic results than video-assisted and conventional neck surgeries.

Adult↗

alpha1-acid glycoprotein fucosylation as a marker of carcinoma progression and prognosis.

BACKGROUND: Serum alpha1-acid glycoprotein (AGP), an acute-phase protein secreted by the liver, carries alpha(1,3)-fucosylated structures on its 5 highly branched, N-linked sugar chains. METHODS: Serum AGP levels in patients with various types of malignancies (n=214 patients) were measured using an enzyme-linked immunosorbent assay with anti-AGP antibody. To investigate glycoforms that differed in their degree of branching and extent of fucosylation, serum AGP samples were analyzed by crossed affinoimmunoelectrophoresis (CAIE) with concanavalin A, and Aleuria aurantia lectin (AAL), and anti-AGP antibody. RESULTS: A significant difference (P <0.001) in serum AGP levels was observed in preoperative patients compared with levels in the healthy control group, but the levels in individual patients did not reflect their clinical status. Conversely, it was found not only that the patterns of AGP glycoforms differed widely in the patient group compared with the healthy control group, but they also changed depending on each patient's clinical status. Furthermore, AGP glycoforms seemed to be appropriate markers of disease progression and prognosis according to follow-up studies of 45 patients during prolonged preoperative and postoperative periods. CONCLUSIONS: Patients with advanced malignancies who had AGP glycoforms that contained highly fucosylated triantennary and tetraantennary sugar chains for long periods after surgery were likely to have a poor prognosis. However, patients who had AGP glycoforms without such changes were expected to have a good prognosis.

Biomarkers, Tumor↗

Inactivation of 14-3-3sigma by hypermethylation is a rare event in colorectal cancers and its expression may correlate with cell cycle maintenance at the invasion front.

In many kinds of cancers, 14-3-3sigma, one of the cell cycle negative regulator, is inactivated by hypermethylation of the gene. In colorectal cancers, this study revealed that the hypermethylation of the 14-3-3sigma gene was an uncommon event and 14-3-3sigma expression was kept even in established colorectal cancer cell lines. Immunohistochemical study using surgical materials showed the expression of 14-3-3sigma was localized at the deep peripheral area of the tumor, so-called invasion front. According to the results of Ki-67 and cyclin B1 immunohistochemistry, 14-3-3sigma-positive cases maintained higher proliferative activity compared to 14-3-3sigma-negative cases at IF. However, a significant correlation between 14-3-3sigma expression and proliferative activity in CRC cells remains to be unsolved.

14-3-3 Proteins↗

Evaluation of 18F-2-deoxy-2-fluoro-D-glucose positron emission tomography for gastric cancer.

Positron emission tomography (PET) with (18)F-2-deoxy-2-fluoro-D-glucose (FDG) has been investigated as a means of detecting certain primary tumors and their metastatic disease in recent years. The aim of this study was to compare the performance of FDG-PET and operative assessment with formal pathologic staging. Altogether, 85 patients had undergone surgical treatment for gastric cancer with curative intent, with FDG-PET preoperatively. The results using FDG-PET were compared with those using computed tomography (CT); they were also correlated with the pathologic findings. For quantitative analysis, the regional tumor uptake was measured by the standard uptake value (SUV) using a region of interest technique. Using FDG-PET, the primary tumor was visualized in 75.2% of patients. A comparison of the FDG uptake and the clinicopathologic findings showed that there was a significant association between FDG uptake and the depth of invasion, the size of the tumor, and lymph node metastasis. FDG-PET scans had less accuracy for diagnosing locoregional lymph nodes than CT because of a significant lack of sensitivity (23.3% vs. 65.0%). The survival rate for patients with high FDG uptake (SUV > 4) was significantly lower than that for those with low FDG uptake (SUV < 4) ( p < 0.05). FDG-PET was successful in detecting the primary gastric cancer lesion but not for finding early-stage gastric cancers. Detection of nodal metastasis also was not possible by FDG-PET. However, FDG-PET appears to provide important additional information concerning the aggressiveness of the tumor and the prognosis in patients with gastric cancer.

Adult↗

Postoperative functional evaluation of jejunal interposition with or without a pouch after a total gastrectomy for gastric cancer.

BACKGROUND: The objective of this study was to compare the motility of a gastric substitute after jejunal interposition without a pouch and jejunal interposition with a pouch and to evaluate the relationship of both methods with nutritional outcome. METHODS: Twelve patients with gastric cancer treated by total gastrectomy and reconstruction with jejunal interposition without a pouch (J-I) and 14 patients treated by total gastrectomy and reconstruction with jejunal interposition with a pouch (J-P) were investigated in regard to the motor activity of the interposed jejunum and changes in body weight and dietary intake. RESULTS: Phase III of the interposed jejunum without a pouch was observed over a 3-month follow-up, but phase III of the interposed jejunum with a pouch was not observed in any patient within 3 months of surgery. In the fed state, the motor activity of the interposed jejunum without a pouch increased significantly in patients within 12 months of follow-up, but in the interposed jejunum with a pouch, it did not. The amount of food consumed by the J-I group was significantly greater than that consumed by the J-P group. CONCLUSIONS: This study demonstrates that the interposed jejunum with a pouch shows marked disturbances from the motor pattern of a normal jejunum during the fasting and fed states. These motor abnormalities may be responsible for insufficient food intake of the J-P group.

Body Weight↗

Evidence for segmental bile drainage by hepatic portoenterostomy for biliary atresia: Cholangiographic, hepatic venographic, and histologic evaluation of the liver taken at liver transplantation.

BACKGROUND: The result of hepatic portoenterostomy for biliary atresia (BA) has improved, but there are some patients who experience worsened liver function in the long term after one decrease in jaundice owing to portoenterostomy. However, the cause of the liver dysfunction in the long term has not been clearly ascertained. METHODS: Five patients (5 to 28 years of age) with BA underwent liver transplantation (LT) because of liver dysfunction after successful portoenterostomy. To clarify the cause of liver dysfunction occurring in the long term, the authors performed a cholangiogram, hepatic venogram, and macroscopic/microscopic examination of the liver just after LT. RESULTS: (1) Macroscopically, the liver could be divided into 3 areas, the hypertrophic, atrophic, and intermediate, with findings between those of the hypertrophic and atrophic areas. (2) The divided areas clearly corresponded to the liver segments. Segment IV was the hypertrophic area in all patients, but segments VI and VII were the atrophic areas in 4 of the 5 patients. (3) Based on the cholangiographic and microscopic findings, the hypertrophic area had near-normal structure with bile ducts. The atrophic area had severe fibrosis and contained only a few bile ducts in the intralobular spaces of liver. CONCLUSIONS: It seems that segmental bile drainage must have been established by hepatic portoenterostomy in some patients and that some postoperative patients might have worsened liver function in the long-term follow-up period accompanied with progression of fibrosis and impaired bile drainage. These pathologic changes occur in each liver segment.

Adolescent↗

Mucin phenotypic expression in early signet ring cell carcinoma of the stomach: its relationship with the clinicopathologic factors.

Gastric early-stage signet ring cell carcinoma (SIG) has been reported to have a lower rate of lymph node metastasis and a higher rate of favorable prognosis than other histological types. However, the development and progression mechanisms of early-stage SIG (early SIG) are controversial. This study examined the correlation between the mucin phenotype of early SIG and its clinicopathologic factors, particularly for the sake of less invasive surgery. Sixty-nine early SIGs were studied immunohistochemically with gastric mucin (M1 and MUC6) and intestinal mucin (MUC2). SIGs were classified into gastric (G), intestinal (I), gastrointestinal (GI), or unclassified (U) type. The intramucosal spreading patterns of SIG were investigated and then classified as either expansive or infiltrative. SIGs were classified into G-type (59.4%) and GI-type (40.6%). Neither the I- nor the U-type was observed. The GI-type expression correlated with the depth of tumor invasion in SIGs (P < 0.05). In contrast, there was no increase in GI-type expression in relation to tumor size. Intramucosal infiltrative growth correlated with intestinal metaplasia (IM) of background mucosa of SIGs (P < 0.01). There was no significant correlation between phenotypes and intramucosal spreading pattern. In conclusion, the GI-type expression of SIG is a clinically useful factor for predicting submucosal invasion. The findings of SIG surrounded with IM revealed the need to exercise great care in determining the surgical margin.

Aged↗