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Tomoo Tajima

Publications and source records attributed to Tomoo Tajima.

At least 19 recordsLinked to original sources
PubMed2004

Prophylactic hepatic arterial infusion chemotherapy for the prevention of liver metastasis in patients with colon carcinoma: a randomized control trial.

BACKGROUND: The liver is the most frequent site of recurrence after curative resection in patients with colon carcinoma. For liver metastasis, a high response rate can be achieved with hepatic arterial infusion (HAI) chemotherapy. In the current study, the authors administered 5-fluorouracil (5-FU) as adjuvant chemotherapy by HAI to patients with colon carcinoma without liver metastases and studied its effects on recurrence in the liver and survival. METHODS: A total of 316 patients with preoperative Stage II or Stage III colon carcinoma (according to the 1997 revision of the International Union Against Cancer TNM staging system) were randomly assigned to receive surgery plus 3-week continuous HAI of 5-FU or surgery alone. There were 305 eligible patients, of whom the 119 patients assigned to the HAI arm actually received 5-FU. The primary endpoint was disease-free survival, whereas the secondary endpoints were overall survival and liver metastasis-free survival. Analysis was by intent to treat. RESULTS: There were no significant differences noted in morbidity between the two treatment arms. During the follow-up period (median, 59.0 months), the incidence of liver metastasis was significantly decreased in the HAI arm whereas there were no significant differences reported between the 2 arms with regard to the frequency of metastasis at other sites. In the HAI arm, the risk ratio for recurrence was 0.40 (95% confidence interval [95% CI], 0.24-0.64; P=0.0002), the risk ratio for death was 0.37 (95% CI, 0.21-0.67; P=0.0009), and the risk ratio for liver metastasis was 0.38 (95% CI, 0.22-0.66; P=0.0005). These differences were found to be significant only for patients with Stage III disease. Toxicities were mild. CONCLUSIONS: A schedule of 3-week HAI of 5-FU given as adjuvant chemotherapy to patients with Stage III colon carcinoma appeared to contribute to a significant decrease in the frequency of liver metastases and was associated with an improved survival rate.

Adenocarcinoma↗
PubMed2004

Immunohistochemical evaluation of hormone receptors in breast cancer: which scoring system is suitable for highly sensitive procedures?

To evaluate hormone receptors immunohistochemically, standardized staining procedures and scoring systems are required. The authors previously reported that highly sensitive procedures affected basic factors for technical validation. The aim of the present study was to show the characteristics of scoring systems for highly sensitive procedures. To examine how highly sensitive procedures enhance the staining intensity and increase the positive cell population, two different staining methods were compared. To evaluate scoring systems, three systems--cell counting score, modified immunoreactive score, and H score--were compared using the same samples stained by an autostaining system. It was found that the highly sensitive procedure increased the positive cell population, especially in breast cancers with a low enzyme immunoassay (EIA) level of less than 100 fmol/mg, and strengthened the staining intensity. This enhancement led to a correlation in a logarithmic curve rather than a linear correlation by all three scoring systems. The results showed that scoring systems including a factor of staining intensity did not have an absolute advantage because boosted staining intensity by highly sensitive procedure did not reflect EIA value or protein contents accurately. To the authors' knowledge, there is no report discussing the nonlinear correlation between biochemical and immunohistochemical assay by highly sensitive procedures; however, it is important to select a scoring system and threshold based on nonlinear correlation.

Breast Neoplasms↗
PubMed2004

[Improving the surgeon's image: introduction].

The number of medical students who aspire to become surgeons has been decreasing in recent years. With a vicious spiral in the decreasing number and the growing deterioration of surgeons' working conditions, there is fear of deterioration of surgical care and subsequent disintegration of overall health care in Japan. The purpose of this issue is to devise a strategy for improving surgeons' image and their working conditions to attract future medical students. However, we cannot expect a quick cure for the problem of the decreasing number of applicants for surgery since this issue is deeply related to many fundamental problems in the health care system in Japan. The challenge for surgical educators in coming years will be to solve the problem of chronic sleep deprivation and overwork of surgery residents and to develop an efficient program to meet the critical educational needs of surgical residents. To solve this problem it is necessary to ensure well-motivated surgical residents and to develop an integrated research program. No discussion of these issues would be complete without attention to the allocation of scarce medical resources, especially in relation to financial incentives for young surgeons. The authors, who are conscientious representatives of this society, would like to highlight these critical problems and issues that are particularly relevant to our modern surgical practice, and it is our sincere hope that all members of this society fully recognize these critical issues in the Japanese health care system to take leadership in improving the system. With the demonstration of withholding unnecessary medical conducts we may be able to initiate a renewal of the system and eventually to fulfill our dreams of Japan becoming a nation that can attract many patients from all over the world. Furthermore, verification of discipline with quality control and effective surgical treatment is needed to avoid criticism by other disciplines for being a self-centered field. The Japanese Surgical Society appears to be the only medical society that is capable of leading a revolution in the health care system of this country with its autonomy and self-discipline. It is timely for the Japanese Surgical Society to consider a modification of its stated mission by adding "to improve the care of the surgical patient" as dictated by the American College of Surgeons.

Attitude of Health Personnel↗
PubMed2003

Risk of lymph node and distant metastases in patients with early invasive colorectal cancer classified as Haggitt's level 4 invasion: image analysis of submucosal layer invasion.

PURPOSE: Tumor invasion in patients with early invasive colorectal cancer has been classified into four levels proposed by Haggitt. Level 4 invasion into the submucosa has been defined as a risk factor for lymph node metastasis; however, the false-positive rate remains high. This study was designed to determine risk factors for lymph node and distant metastases in addition to Haggitt's Level 4 invasion. METHODS: Seventy-one of 142 patients with submucosa-invasive colorectal cancer underwent intestinal resection as an initial surgical treatment between 1975 and 2000. The subjects of this study were 65 of these 71 patients, all of whom were diagnosed as having Haggitt's Level 4 invasion. The depth, width, and area of submucosal invasion were measured with an image analyzer. RESULTS: Lymph node metastasis was noted in 11 (16.9 percent) of the 65 patients. There were no significant differences in the depth or area of submucosal invasion between node-positive and node-negative patients. However, the width of submucosal invasion was significantly greater in node-positive than in node-negative patients (P = 0.001). When 5-mm-wide submucosal invasion was used as an indicator for intestinal resection, 37 patients were found to have indications for bowel resection, and 11 (29.7 percent) of the 37 had lymph node metastases. Distant metastasis was noted in five patients (7.7 percent). The depth, width, and area of submucosal invasion in patients with distant metastasis did not differ significantly from those without distant metastasis. CONCLUSION: Although further prospective investigation is required, the positive predictive value increases from 17 to 30 percent when the width of submucosal invasion is added to Haggitt's Level 4 as an indicator for bowel resection.

Adenocarcinoma↗
PubMed2003

Sentinel lymph node detection with Tc-99m tin colloids in patients with esophagogastric cancer.

BACKGROUND: The aim of this study was to determine by radioisotope use whether the sentinel lymph node concept is applicable to esophagogastric cancers. In addition, we examined radioactivities of hot nodes and compared them with the sensitivity of a gamma probe. METHODS: The subjects were 44 patients, 23 with esophageal cancer and 21 with gastric cancer. The day before surgery, patients underwent endoscopic submucosal injection of 184 MBq of Tc-99m tin colloids into sites surrounding the tumor. Radioisotope activities of lymph nodes dissected at surgery were measured with a well-typed gamma detector and each lymph node was categorized as a hot or cold node. Histopathology of the lymph nodes was examined by hematoxylin and eosin staining. Radioisotope activities and histopathological results were compared to determine whether radioisotope flow reflects lymphatic flow to regional lymph nodes. The sensitivity of a gamma probe was measured in a laboratory study and the relation between the radioisotope activities of hot nodes and the detection sensitivity of the gamma probe was examined. RESULTS: Histopathological examination revealed lymph node metastasis in 18 of the 44 patients. In 15 of these 18 patients, metastatic foci were recognized in at least one hot node. Subsequent analysis was performed on the 36 patients in whom tumor invasion was confined to the muscle layer and in whom endoscopic clippings had not been applied. Lymph node metastases were observed in 12 of these 36 patients. In these 12 patients, at least one hot node was positive for metastasis. The laboratory study revealed that the gamma probe was able to detect radioisotope activities of >/=0.02 micro Ci. Thirty-two of 63 (51%) esophageal cancer hot nodes and 16 of 86 (19%) gastric cancer hot nodes showed radioisotope activities below the detection sensitivity of the gamma probe. CONCLUSION: The sentinel lymph node concept is applicable to patients with esophageal and gastric cancers; however, further studies are necessary to identify hot nodes accurately using gamma probes.

Colloids↗
PubMed2003

Combination of trastuzumab and vinorelbine in metastatic breast cancer.

BACKGROUND: Since the clinical introduction of trastuzumab (Herceptin) for metastatic breast cancers that overexpress human epidermal growth factor receptor 2 (HER2), this anticancer agent has played an important role in breast cancer treatment. We examined the effects of trastuzumab and vinorelbine (Navelbine) as a second- or third-line therapy in 24 patients whose HER2-positive tumors did not respond to or relapsed after administration of trastuzumab alone or in combination with taxane. METHODS: Trastuzumab was administered at 2 mg/kg (loading dose 4 mg/kg) once weekly and vinorelbine at 25 mg/m(2) once weekly. The median treatment duration was 118.5 days (range, 22-351 days). RESULTS: The response rate was 42% (95% confidence interval (CI): 22%-63%). The adverse events of NCI-CTC grade 3 or above consisted of neutropenia in three patients; other adverse events, including vasculitis, generalized fatigue, anemia and thrombocytopenia, were grade 1 or 2. All adverse events were reversible after treatment withdrawal and were easily manageable. CONCLUSION: A combination of trastuzumab and vinorelbine can be safely administered on an outpatient basis, and is useful in the treatment of patients with HER2-overexpressing metastatic breast cancer.

Adult↗
PubMed2003

Immunohistochemical evaluation of hormone receptor for routine practice of breast cancer: highly sensitive procedures significantly contribute to the correlation with biochemical assays.

Immunohistochemical evaluation of hormone receptors for breast cancer has been performed parallel to biochemical assays. Recently, immunohistochemistry has tended to substitute the biochemical method in Japan. To clarify the factors concerned and problems to be resolved, we reviewed our evaluation system for hormone receptors by immunohistochemistry from 1990. A total of 861 breast cancer samples were examined by immunohistochemistry and biochemistry. In 3 main periods, phase 1 (1990-1993), phase 2 (1995-1998), and phase 3 (1999-2001), increasing sensitivity of the immunohistochemical method was provided by commercially available staining systems and shown to range from 83.6% (phase 1) to 92.0% (phase 3). The highly sensitive procedures of the antigen retrieval and peroxidase-conjugated polymer method are main contributing factors. The authors examined how these procedures influenced the distribution of positive cell population; concordance rate, including sensitivity and specificity; cutoff points; and evaluation categories. The correlation between biochemistry and immunohistochemistry was extensively studied in the 1980s and 1990s. In reference to the progress achieved in the United States and United Kingdom to control the current situation in Japan, it should be recognized that recently developed, highly sensitive procedures boost the immunoreactivity, which will affect the basic factors for technical validation.

Breast Neoplasms↗
PubMed2003

Heterogeneous gene alterations in primary breast cancer contribute to discordance between primary and asynchronous metastatic/recurrent sites: HER2 gene amplification and p53 mutation.

The aim of the present study was to clarify differences in genetic events between primary breast cancers and asynchronous metastatic/recurrent lesions, by examining HER2 gene amplification and p53 mutation. The subjects were 44 breast cancer patients with asynchronous metastasis or recurrence. Synchronous metastases were excluded. HER2 overexpression and gene amplification were examined using immunohistochemistry and fluorescent in situ hybridization (FISH). P53 point mutation was examined by immunohistochemistry, laser-captured microdissection, PCR-single-strand conformation polymorphism, and a direct sequencing method. Immunohistochemistry showed that, for HER2, p53, ER and PgR, discordance rates between primary and recurrent tumor were 2 (4.5%), 1 (2.3%), 7 (15.9%) and 10 (22.7%), respectively. Two primary tumors with discordant HER2 overexpression were composed of at least two populations of carcinoma cells, with and without HER2 gene amplification. Distribution of HER2 gene amplification was consistent with protein overexpression. Corresponding recurrent tumors consisted of carcinoma cells without HER2 gene amplification. Of 6 recurrent tumors in which the primary carcinoma had a p53 point mutation, 3 tumors had identical mutations, 1 tumor had a different point mutation, and 2 tumors had no mutation. It was suspected that the latter 3 recurrent tumors comprised a minor component of the primary tumor. In the present study, we examined a large series of asynchronous recurrent tumors. A limited number of these tumors showed discordance between primary and recurrent tumors. Detailed observations revealed that cell populations present in recurrent tumors were also present in the primary tumors, although they comprised a minor component of the primary tumor. Heterogeneity of the primary tumor apparently contributed to discordance.

Breast Neoplasms↗
PubMed2003

[Prospects for standardization of surgical treatment for breast cancer].

Surgical treatment of breast cancer in general guided cancer surgery in the direction of extensive radical operations until two decades ago. More recently, the trend has been toward conservative, less-extensive surgery. Moreover, breast cancer has become a model case for establishing standardization of surgical care of cancer. The Japanese Breast Cancer Society issued "Guidelines for Breast-Conserving Therapy" in 1999, and the Clinical Research Group for Establishing Guidelines for Standardized Diagnosis and Treatment for Breast Cancer became active in 2002 under the auspices of the Ministry of Health, Welfare and Labor. There are several areas of controversy in terms of surgical care in breast cancer. Examples are yet-immature breast-conserving surgery which is performed with wide variations (15-90%) depending upon the institution, and sentinel lymph node biopsy which must await long-term results before being recognized as standard care. The installation of expensive diagnostic devices indispensable for standardized surgical care might not be necessary at each institution, and it must be noted that postoperative follow-up policies practiced in Japan differ greatly from those recommended by the American Society of Clinical Oncology. Despite the anticipated difficulties, a consensus on what constitutes standardized surgical treatment for breast cancer might be easily reached among breast cancer surgeons. However, it may be somewhat difficult to popularize the standardized surgical treatment among ordinary general surgeons in Japan, since there is a wide disparity in the level of clinical care offered by individual physicians and healthcare institutions. Standardization of medical care guided by the government is mainly designed to reduce healthcare costs, which is instrumental in eliminating unnecessary medical interventions and may in turn shed light on valuable medical care advances. This may be the moment for the Japanese Surgical Society and its members who practice life-saving surgery to lead a genuine national medical reformation.

Breast Neoplasms↗
PubMed2003

Gastrointestinal cytomegalovirus infection in collagen diseases.

Cytomegalovirus infection of the gastrointestinal tract is a rare serious complication in patients with collagen diseases receiving immunosuppressive agents. We report 3 such cases diagnosed by endoscopy followed by proper treatment. The patients include 38 and 53 years old females with systemic lupus erythematosus. They presented epigastric pain after pulse steroid therapy and combination therapy with steroids and cyclophosphamide, respectively. Their endoscopical findings were multiple small gastric erosions. The other patient was a 60-year-old female with polymyositis who developed rectal bleeding after steroid and imuran therapy. Her endoscopical finding was a discrete, irregular rectal ulcer. The diagnosis of all the patients was confirmed by biopsies of those lesions showing giant cell inclusion bodies and positive staining with anti- cytomegalovirus -antibodies. All patients were treated properly with ganciclovir. We should always keep in mind of a cytomegalovirus infection of the gastrointestinal tract in a patient with collagen disease receiving immunosuppressive agents.

Adult↗
PubMed2003

[A case of advanced gastric cancer with multiple liver metastases responding to TS-1 and CDDP].

A 44-year-old male presented to our hospital with abdominal pain. The upper endoscopy revealed advanced gastric cancer. On the abdominal CT, there was evidence of multiple, massive liver metastases. After total gastrectomy, the patient was treated with daily oral administration of 120 mg TS-1 for 4 weeks followed by 2 weeks' rest and 6 weekly infusions of 10 mg CDDP in an intra-hepatic artery as 1 cycle. On the follow-up CT, the liver metastases had decreased significantly both in size and number after 2 cycles. The current case suggests that TS-1 and CDDP may have a potent therapeutic efficacy in cases of advanced gastric cancer with multiple liver metastases.

Administration, Oral↗
PubMed2002

The in vivo development of human T cells from CD34(+) cells in the murine thymic environment.

There is increasing evidence that human hematopoietic stem cells can develop into lymphocytes expressing T cell surface markers in the organ culture of murine embryonic thymic lobes. If human T cells with functional maturity are inducible from human stem cells in the mouse, it may be a useful model to investigate human T cell development and the human immune response in vivo. To approach this, we produced a hybrid cluster of murine fetal thymic epithelial cells and human cord blood-derived CD34(+) cells (hu/m cluster) using reaggregate thymic organ culture, and subsequently implanted it under the kidney capsule of NOD/SCID mice. The implanted hu/m cluster grew in volume under the kidney capsule and contained increased numbers of CD4(+)CD8(+)cells as well as CD4 or CD8 single-positive cells with low CD1a expression. These lymphocytes were also shown to possess activity for producing IL-2 and IL-4. Characteristics similar to human T cells also developed in the thymus of newly established mice lacking NK activity from NOD/SCID mice. These results indicate that functionally mature T cells can develop in vivo from human hematopoietic progenitors in the murine environment composed of thymic epithelial cells.

Animals↗
PubMed2002

Evaluation of esophageal cancer by positron emission tomography.

BACKGROUND: A retrospective study was performed to determine the indications for positron emission tomography (PET) using [(18)F]fluorodeoxyglucose (FDG) in patients with esophageal cancer, including those with early cancer, and to investigate whether the tumor-to-normal ratio (T/N ratio) could be used as a substitute for the standardized uptake value (SUV). METHODS: Thirty-six patients were included in the study. Thirty-one patients who had 36 biopsy-proven lesions (35 squamous cell carcinomas and one small cell carcinoma) underwent PET study prior to treatment. PET images were evaluated visually and the relationship between the depth of invasion and the PET findings were examined in 22 lesions of 19 patients from whom specimens were obtained from the primary tumor by surgery or endoscopic mucosal resection. PET results were also compared with computed tomography (CT) and endoscopic ultrasonography (EUS) for detection of regional lymph node metastases in 18 patients who underwent extended lymph node dissection. Five patients underwent PET studies for the detection of recurrence and the PET findings were compared with their CT findings. The T/N ratio and the SUV were calculated for 20 primary tumors. RESULTS: Among the 15 tumors that were pT1b or greater, all 15 were positive on PET and all seven of the lesions confined to the mucosa (Tis or T1a) were negative. The sensitivity, specificity and accuracy of detecting nodal involvement were, respectively, 37.5, 96.1 and 88.3% by CT, 30.8, 88.5 and 81.0% by EUS and 41.7, 100 and 92.2% by PET. More sites of recurrence were detected by PET than by CT. There was no statistically significant correlation between the SUV and the T/N ratio. CONCLUSIONS: PET imaging can detect primary esophageal cancer with a depth of invasion of T1b or greater, but Tis and T1a tumors are undetectable. PET seems to be more accurate than CT or EUS for diagnosing lymph node metastasis. The T/N ratio cannot be used as a substitute for the SUV.

Adult↗
PubMed2002

[The sentinel navigation surgery: current review and future perspective].

Sentinel node navigation surgery (SNNS) is a new technology that provides accurate nodal staging with minimal morbidity, and potentially debilitating side effects of lymph node dissection can be eliminated in those patients that are node negative. SNNS seems feasible in early breast cancer patients with clinically negative nodes and the capacity for its application in patients with cancer in the gastrointestinal tract has been suggested. There are, however, still open questions regarding technical performance of sentinel node surgery, and determining how well SNNS compares to routine lymph node dissection will require long-term prospective randomized trial for each type of surgical tumor. With more intensive examination of biopsied sentinel nodes, the necessity of elucidating the biologic nature of micrometastases has risen to the surface.

Breast Neoplasms↗
PubMed2002

[Breast cancer].

The HER2/neu protein is thought to be a unique and useful target for antibody therapy of cancers overexpressing the HER2/neu gene. The recombinant humanized anti-HER2 monoclonal antibody, trastuzumab(Herceptin) has recently been available for clinical use in Japan. In this paper, the details of this novel biologic agent are reviewed in conjunction with the results of the clinical trials for breast cancer.

Antibodies, Monoclonal↗
PubMed2002

[Trastuzumab (Herceptin)].

The HER 2/neu protein is thought to be a unique and useful molecular target for antibody therapy of cancers overexpressing the HER 2/neu gene. The recombinant humanized anti-HER 2 monoclonal antibody trastuzumab (Herceptin) has been available for clinical use in metastatic breast cancer in Japan since June 2001. Some breast cancer patients have responded to trastuzumab alone. A phase III study showed significant efficacy of combination use with paclitaxel compared with paclitaxel alone. Trastuzumab has some toxicities including infusion reaction and cardiotoxicity. It is very rare that infusion reaction manifests lethally. Although trastuzumab should not be concurrently used with an anthracycline, cardiotoxicity was also identified in patients treated with trastuzumab alone. The cumulative dose of anthracycline has not yet been identified as a risk factor, but patients who have received a high cumulative dose should be treated with special caution. In this article, the details of this novel biologic agent are reviewed from basic and clinical studies.

Animals↗
PubMed2002

[Herceptin and its therapeutic strategy in patients with breast cancer overexpressing HER2].

Herceptin (trastuzumab) is a recombinant humanized murine monoclonal antibody that recognizes HER2/neu cell-surface receptors and has been shown to be active both in combination with adriamycin (epirubicin)/cyclophosphamide or taxanes and as a single agent, either in the 1st or 2nd/3rd line treatment of women with metastatic breast cancer with HER2 overexpression by IHC or gene amplification by FISH. Preliminary results of Herceptin with other agents such as vinorelbine, cisplatin and various hormonal agents are also promising, and these combinations warrant further clinical exploration. Large-scale multicenter trials including a European and an international study in adjuvant setting have started for high-risk women with HER2 overexpressing breast cancer, with total planned recruitment of nearly 10,000 women.

Antibodies, Monoclonal↗