Biomedical subjects

Mitsuru Koizumi

Publications and source records attributed to Mitsuru Koizumi.

15 recordsLinked to original sources

PubMed2006

The relative use of eight collagenous and noncollagenous markers for diagnosis of skeletal metastases in breast, prostate, or lung cancer patients.

The present study was sought to assess the relative use of eight biomarkers for the detection of bone metastases in cancer forms frequently spreading to the skeleton. Participants were 161 patients with either breast, prostate, or lung cancer. The presence and extent of bone metastases was assessed by imaging techniques (computer tomography and/or magnetic resonance imaging) and Technetium-99m scintigraphy. Serum or urinary level of the bone resorption markers (alphaalphaCTX, betabetaCTX, NTX, and ICTP), formation marker (BSAP), and osteoclastogenesis markers (osteoprotegerin, RANKL, and TRAP5b) was measured by commercially available immunoassays. When assessed on a group basis, all biomarkers, except for osteoprotegerin and RANKL, were significantly elevated in patients compared with those without bone metastases (P<0.05). Biomarkers had greater diagnostic value in breast and prostate cancer patients, yet alphaalphaCTX, NTx, and ICTP were able to discriminate lung cancer patients with or without bone metastases (P<0.05). Strong linear associations were seen between the extent of skeletal infiltration and levels of the different biomarkers, except for osteoprotegerin and RANKL. Furthermore, all biomarkers (except for osteoprotegerin and RANKL) were indicative at the early stage of skeletal involvement (one to five metastases). When expressing sensitivity as the percentage increase in biomarker level relative to patients without bone metastases, alphaalphaCTX showed the largest relative increases at each stage of the metastatic disease. These results suggest that closer monitoring of cancer patients with serial measures of biomarkers might facilitate the timely diagnosis of skeletal metastases.

Adult↗

PubMed2006

Alpha CTX as a biomarker of skeletal invasion of breast cancer: immunolocalization and the load dependency of urinary excretion.

We recently showed that increased urinary excretion of the cross-linked, nonisomerized form of the C-telopeptide of collagen type I (alphaalphaCTX) could be a sensitive indicator of the presence of bone metastases in breast cancer patients. The present study was sought to investigate (a) the localization of alphaCTX epitopes in the proximity of a bone metastasis and (b) the relationship between number of metastases and the urinary excretion of alphaalphaCTX. Adjacent bone sections from breast cancer patients were stained for the presence of tumor cells (anti-cytokeratin antibody), osteoclasts (TRAcP activity), and alphaCTX (anti-alphaCTX antibody). The association between the extent of metastatic bone disease and urinary excretion of alphaalphaCTX measured with ELISA was assessed in 90 breast cancer patients (45 with bone metastasis and 45 without bone metastasis). Immunohistochemistry revealed accumulation of TRAcP-positive osteoclasts and intense staining for alphaCTX epitopes in the proximity of cytokeratin-positive bone metastasis. Areas of alphaCTX staining showed unstructured bone tissue under polarized light. In addition, there was a significant linear association between the number of bone metastases and the urinary levels of alphaalphaCTX in breast cancer patients with metastatic bone disease, independent of age and body mass index (r = 0.56, P < 0.001). The estimated relative increases in alphaalphaCTX associated with the presence of one, two, or three metastases are 38%, 57%, and 81%, respectively. Taken into account the 17% intraindividual variation of the assay, alphaalphaCTX could be a sensitive biochemical marker for the close monitoring of cancer patients aiming the facilitation of early metastasis detection.

Biomarkers, Tumor↗

PubMed2006

[Diagnostic imaging of skeletal metastases].

Metastases to bone (skeletal metastases) are the most frequent malignant bone tumor. Skeletal metastases can be classified three types;osteolytic, osteoblastic and mixed type. These types depend on the nature of primary cancer. Because imaging studies visualize bone defect and bone formation, these abnormalities can be seen differently depend on the methods to use. In addition, effective therapy to skeletal metastases alters the image. Information of primary cancer and what kinds of treatment have been performed are essential to a diagnosis of skeletal metastasis.

Bone Neoplasms↗

PubMed2006

[Diagnostic imaging of skeletal metastases].

Skeletal metastases are the most frequent in malignant bone tumor. Vast majority of skeletal metastases are encountered in middle-aged to elderly persons. Skeletal metastases should be included in differential diagnosis of bone lesion in elderly persons. In this mini-review, clinical features are mainly discussed and some recent advances are also described. They are 1) mechanisms of skeletal metastasis, 2) vicious cycle (what happens in the process of osseous metastasis progression), 3) frequency, site and number of skeletal metastases, 4) osseous response to metastatic tumor, 5) diagnostic imaging of skeletal metastasis, 6) bone metabolic markers in osseous metastasis, and 7) complications.

Aged↗

PubMed2004

Improved detection of axillary hot nodes in lymphoscintigraphy in breast cancer located in the upper lateral quadrant with additional projection imaging.

BACKGROUND: Sentinel node (SN) biopsy has been becoming a standard method for early stage breast cancer. Scintigraphic image of SN helps the biopsy procedure. It is reported that the scintigraphic detection rate is not 100%. The value of taking additional projection view in SN detection was assessed in breast cancer patients. PATIENTS AND METHODS: Consecutive 114 breast cancer patients with upper lateral quadrant tumor were included in this study. After injection of 99mTc-phytate, scintigram was taken at the projection of anterior oblique (AO) 30 degrees view and an additional AO 60 degrees view. Images were evaluated visually. RESULTS: In 7 of 114 patients, an axillary hot node was hidden on the activity at the injected site on AO 30 degrees view, and was visualized on AO 60 degrees view. In 17 of 114 patients, the axillary hot node was seen as a hump from the injected activity, and was separate on AO 60 degrees view. In 90 of 114 patients, the axillary hot node was separately seen on AO 30 degrees view. CONCLUSION: Multi-directional views are helpful to depict the axillary sentinel nodes that are concealed behind the injected radioactivity.

Axilla↗

PubMed2004

99mTc-labeled mannosyl-neoglycoalbumin for sentinel lymph node identification.

99mTc-labeled mannosyl-neoglycoalbumin (NMA) was prepared and evaluated as a radiopharmaceutical for sentinel lymph node (SLN) identification, since 99mTc-labeled human serum albumin (HSA) rapidly cleared from injection sites. NMA was conjugated with 6-hydrazinopyridine-3-carboxylic acid (HYNIC) and reacted with [99mTc](tricine)2 to prepare [99mTc](HYNIC-NMA)(tricine)2. After subcutaneous injection of [99mTc](HYNIC-NMA)(tricine)2 from murine foot pad, radioactivity levels in the popliteal and lumbar lymph nodes, the injection site and other tissues were compared with those of [99mTc](HYNIC-HSA)(tricine)2 and 99mTc-labeled colloidal rhenium sulfate ([99mTc]colloid). [99mTc](HYNIC-NMA)(tricine)2 demonstrated significantly higher radioactivity levels in the popliteal lymph node, the SLN in this model, than did [99mTc](HYNIC-HSA)(tricine)2 and [99mTc]colloid at 0.5, 1, and 6 h post-injection. [99mTc](HYNIC-NMA)(tricine)2 showed a dose-dependent decrease in the popliteal accumulation while the radioactivity levels in the blood, liver and spleen increased with an increase in the molar dose of NMA. [99mTc]colloid registered a decrease in the radioactivity levels in the popliteal lymph node, blood, liver, and spleen with dilution. However, the radioactivity levels at the injection site increased with dilution of [99mTc] colloid. Both [99mTc](HYNIC-NMA)(tricine)2 and [99mTc](HYNIC-HSA)(tricine)2 showed the radioactivity levels at the injection site similar each other. These findings indicated that an addition of a macrophage binding function to 99mTc-labeled HSA provided high and selective accumulation of the radioactivity in the SLN without affecting the elimination rate from the injection site. Such characteristics render [99mTc](HYNIC-NMA)(tricine)2 attractive as a radiopharmaceutical for SLN identification. This study also demonstrated that the number of non-radiolabeled colloidal particles and the molar dose of mannosylated compounds play a crucial role in the SLN accumulation.

Albumins↗

PubMed2004

Radioguided sentinel node detection in breast cancer patients: comparison of 99mTc phytate and 99mTc rhenium colloid efficacy.

BACKGROUND: Radioguided sentinel node biopsy (SNB) of breast cancer patients has become a standard method for detecting early stage breast cancer. However, no standard radiopharmaceutical exists. METHODS: 99mTc rhenium colloid or 99mTc phytate SNB was used to aid detection in breast cancer patients. For each radiopharmaceutical, 100 patients were examined. The following points were compared: (1) scintigraphic detection rate of axillary sentinel nodes (detectability and number when detectable) and internal mammary sentinel nodes; (2) the number of nodes detected scintigraphically and the number detected during surgery; (3) sensitivity, specificity, accuracy, negative predictive value, and positive predictive value for axillary sentinel nodes. RESULTS: Axillary sentinel nodes of patients were biopsied using either 99mTc rhenium or 99mTc phytate. The number of axillary nodes surgically removed from patients given 99mTc rhenium was 2.28+/-1.08 (mean+/-SD), and the number of axillary nodes surgically removed from patients given 99mTc phytate was 1.68+/-0.82. Some patients given 99mTc rhenium showed a spill-over of radioactivity from sentinel nodes. Concordance of scintigraphically detected nodes and surgical removed nodes was superior for 99mTc phytate compared to that with 99mTc rhenium, with a statistically significant difference. The sensitivity and negative predictive value was superior with 99mTc phytate compared to that with 99mTc rhenium, even though no statistical difference was detectable. However, visualization of internal mammary nodes was superior with 99mTc rhenium. CONCLUSION: In breast cancer patients, 99mTc phytate is a better choice for the detection of axillary SNB than 99mTc rhenium colloid. However, 99mTc rhenium colloid is a better choice for the detection of internal mammary nodes.

Adult↗

PubMed2003

Bone metabolic markers in bisphosphonate therapy for skeletal metastases in patients with breast cancer.

The use of bisphosphonates for skeletal metastasis of breast cancer is now well established. Although clinical judgement for treating skeletal metastasis is based on symptoms and imaging studies, accurate or quantitative means are few. Various bone metabolic markers have been developed and these were evaluated in patients with metastasis to bone. Bone metabolic markers, especially resorption markers, have been shown to be a good tool for the monitoring the response to therapy for skeletal metastasis. This is also true for bisphosphonate treatment for skeletal metastasis. Bone metabolic markers are produced by different mechanisms. There are some different classes of resorption markers; tartrate-resistant acid phosphatase (TRAP) is secreted by osteoclast, N- and C-terminal cross-linking telopeptide of type I collagen (NTx and CTx) are the degradation the products of type I collagen, mainly produced by cathepsin K, and pyridinoline cross-linked carboxyl-terminal telopeptides of type I collagen (I CTP) is also a degradation product of type I collagen, by matrix metalloproteases. Even though bone resorption markers are a good tool to monitor response to bisphosphonate therapy, there remains the question of which class of bone resorption markers is best suited to the task.

Antineoplastic Agents↗

PubMed2002

Predictors of successful hepatic resection: prognostic usefulness of hepatic asialoglycoprotein receptor analysis.

To test the clinical usefulness of hepatic asialogycoprotein receptor analysis in liver surgery, we have conducted univariate and multivariate analysis for the detection of cirrhotic patients and prediction of morbidity after hepatic resection. Liver scintigraphy using technetium 99m-labeled asialoglycoprotein analog (TcGSA), ICG test, and CT hepatic volumetry were undertaken in 158 surgical patients including 111 who underwent hepatic resection. Hepatic functional parameters including Child-Pugh score, indocyanine green retention at 15 minutes (ICG-R15), clearance index (HH15), receptor index (LHL15), receptor concentration ([R]0), total hepatic receptor amount (R0) and hepatic parenchymal volume (HPV) were compared among patients with normal, cirrhotic, and non-cirrhotic damaged liver. Preoperative hepatic functional parameters, resected parenchymal fraction (RPf), operative blood loss, and total receptor amount of the remnant liver (R0-remnant) were compared between patients with and without signs of postoperative liver failure. All parameters but HPV were significantly different among patients with normal, cirrhotic, and noncirrhotic damaged liver. The multivariate analysis selected two significant (p <0.05) parameters, [R]0 and Child-Pugh score for the detection of liver cirrhosis. Of the 111 patients who underwent resection, 14 developed transient signs of postoperative liver failure. Of the parameters tested, presence of liver cirrhosis, LHL15, R0, intraoperative blood loss, and R0-remnant were significantly different between patients with and without signs of postoperative liver failure (p <0.05). The multivariate logistic regression analysis selected only R0-remnant as a significant (p = 0.022) parameter for the prediction of liver failure. The morbidity rate in patients with R0-remnant under 0.05 mmoles was 100%, and the rate decreased in inverse proportion to R0-remnant. In conclusion, combining the ASGP-R concentration ([R]0) and the Child-Pugh score best detected liver cirrhosis in surgical candidates. Cirrhotic patients and patients with a low R0-remnant are at higher risk for postoperative liver failure. The present study confirms the usefulness of hepatic asialogycoprotein receptor analysis in liver surgery.

Adult↗

PubMed2002

Can initial prostate specific antigen determinations eliminate the need for bone scans in patients with newly diagnosed prostate carcinoma? A multicenter retrospective study in Japan.

BACKGROUND: The objective of the current study was to assess rigorously whether serum prostate specific antigen (PSA) determination can eliminate the need for bone scans in Japanese patients with newly diagnosed prostate carcinoma with serum PSA levels < or = 10 ng/mL. METHODS: A retrospective assessment of 1294 patients with newly diagnosed, untreated prostate carcinoma was conducted at the authors' institutions. All patients underwent a bone scan, serum PSA measurement, and core needle biopsy of the prostate. The receiver operating characteristic curve for identifying a positive bone scan based on serum PSA levels and a decision tree were analyzed to determine the expected 10-year cumulative cost and disease specific survival rate. Two competing strategies were used: PSA alone and PSA plus baseline bone scan. For the PSA-alone strategy, a baseline bone scan was performed only when the patient had a serum PSA level > 10 ng/mL. RESULTS: The proportion of positive bone scans in patients with serum PSA levels < or = 10.0 ng/mL was 1.33%. The area under the receiver operating characteristic curve was 0.870. Patients with a Gleason Grade > or = 3 tumors or with a Gleason score > or = 7 had a higher proportion of positive bone scans. The 10-year disease specific survival rates with the PSA-alone strategy and the PSA-plus-bone-scan strategy were the same. The PSA-alone strategy was minimally cost effective, with a savings of $16.00 (U.S.) in the cumulative net cost per patient over the PSA-plus-bone-scan strategy. CONCLUSIONS: The current results suggest that baseline bone scans can be eliminated in patients with newly diagnosed prostate carcinoma in Japan who have serum PSA levels < or = 10 ng/mL. Apparently, it is possible to omit baseline bone scans for patients with a Gleason Grade < or = 2 tumors or with a Gleason score < or =6.

Adult↗

PubMed2002

Bone metabolic markers as gauges of metastasis to bone: a review.

Currently, imaging techniques are the leading methods used to diagnose of metastasis to bone. However, these techniques are expensive, expose patients to toxic and radioactive compounds, and monitor response to treatment poorly; these drawbacks have prompted the search for alternative screening methods. Therefore, bone metabolic markers have been evaluated as possible methods to diagnose and monitor the development and progression of metastatic bone disease. Although bone metabolic markers are often grouped as either resorption or formation markers, studies have revealed that each marker has its own biologic meaning and clinical relevance. Recent milestones in the use of bone metabolic markers as screening methods for metastatic bone disease and as evaluation methods for treatment response are shown in the following lists. 1. Bone metabolic marker measurements provide insight into mechanisms of metastasis to bone. 2. Although promising data have been reported, bone metabolic markers are not yet considered to be reliable screening methods for metastasis to bone. 3. Bone metabolic markers are reliable indicators of response to both conventional and bisphosphonate therapies. 4. Preliminary results indicate bone metabolic markers might be an independent prognostic factor in patients whose tumors metastasize to bone. 5. New or refined assays for bone metabolic markers are expected to improve the sensitivity and specificity of bone metabolic marker use in diagnosing and monitoring metastasis to bone.

Biomarkers, Tumor↗

PubMed2002

Indications for sentinel lymph node biopsy in patients with breast cancer: retrospective and simulation analyses.

BACKGROUND: The disease status of axillary lymph nodes at diagnosis is the most powerful predictor of prognosis for patients with breast cancer. Axillary lymph node dissection (ALND) has been the standard treatment. Recently, lymphatic mapping and sentinel lymph node biopsy (SNB) have been suggested as alternatives to ALND. However, a clear indication for SNB has not yet been established. The goal of this study was to determine which patients might best benefit from the SNB method. METHODS: A retrospective study compared the relationship of age, menopausal status, tumor size group, histology and clinical evaluation of nodes to histological axillary lymph node status in 5892 consecutive Japanese breast cancer patients who underwent ALND. A simulation analysis with reported SNB sensitivity and specificity was carried out. RESULTS: Clinical lymph node evaluation was the most relevant factor to predict axillary nodal status. However, even patients with no clinical nodal involvement (N0) showed only 71% axillary nodal negativity. Tumor group based on tumor size and histology also related to axillary nodal status. The simulation analysis revealed that of patients with negative lymph node probability, more than 66% were good candidates for SNB. CONCLUSION: The clinically negative node (N0) is the most important indication for SNB. Therefore, the candidates for SNB should be picked from the patients with N0. When no histological information is available, patients whose tumor is 20 mm or smaller are candidates for SNB. When histological information is available, the SNB indication extends to patients whose type of tumor has histologically good prognosis or a low probability of having nodal involvement, regardless of tumor size.

Adult↗

PubMed2002

Metabolic gaps in bone formation may be a novel marker to monitor the osseous metastasis of prostate cancer.

PURPOSE: Although skeletal metastasis is a common complication associated with prostate cancer, assessment of the response of osseous metastasis to therapy is still difficult. To remedy this situation a study of bone formation metabolic markers gaps in patients with prostate cancer and osseous metastasis was done to determine these gaps as clinical markers for the efficacy of therapy against osseous metastasis. MATERIALS AND METHODS: The activities of the bone formation markers amino terminal propeptide of type I procollagen (PINP), bone alkaline phosphatase (BAP) and osteocalcin (OC) were measured in 57 and 60 patients with prostate cancer without and with osseous metastasis, respectively. Of the 60 patients with osseous metastasis serial measurements were performed in 31. The status of osseous metastasis at the time of marker measurement was categorized, and the BAP-to-PINP, OC-to-PINP and OC-to-BAP ratios were calculated. RESULTS: The BAP-to-PINP ratio did not change. However, the OC-to-PINP and OC-to-BAP ratios were significantly different depending on osseous metastasis status. The ratios were high in patients with no osseous metastasis or with metastasis shrinkage (improvement) but low in those in whom metastases were growing and/or spreading (progression). Cutoff levels of OC-to-PINP and OC-to-BAP ratios were determined by comparing ratios with clinical judgment on the response to treatment in all patients. When these cutoffs were applied to the 31 patients, the OC-to-PINP ratio agreed with clinical judgment in 29 (94%) and the OC-to-BAP ratio agreed in 28 (90%). CONCLUSIONS: Different bone formation markers seem to be sensitive clinical markers for judging the response to therapy of prostate cancer metastasized to bone.

Aged↗

PubMed2002

[Not Available].

Explore the source record for details and available documents.

Journal Article↗

PubMedDate not supplied

Comparison of serum bone resorption markers in the diagnosis of skeletal metastasis.

BACKGROUND: There are several bone resorption markers which are generated by different mechanisms. The serum level of 3 different bone resorption markers in cancer patients with or without skeletal metastasis was compared to see whether the markers exhibit clinically significant differences useful for metastatic screening. PATIENTS AND METHODS: Serum bone metabolic markers were measured in 75 cancer patients with and 201 cancer patients without skeletal metastasis. The 3 bone resorption markers, N-terminal cross-linked telopeptide of type I collagen (NTx), pyridinoline cross-linked carboxy-terminal telopeptides of type I collagen (ICTP) and tartrate-resistant acid phosphatase type 5b (TRAP 5b), and two bone formation markers, procollagen type I C-terminal peptide (PICP) and procollagen type I N-terminal peptide (PINP), were measured in the single sample. Each marker serum level was compared with the menopausal and the osseeous metastatic status assessed using Soloway's method for each patient. RESULTS: Bone resorption marker serum levels, except for ICTP, were about 16% larger in postmenopausal patients than in premenopausal patients. All 3 bone resorption marker serum levels were 3-4 times greater in patients with extensive skeletal metastasis (extent of disease III; EOD = III) than in patients with no osseous metastasis. Although ROC analysis indicated each bone resorption marker had a similar sensitivity and specificity regarding the ability to detect osseous metastasis, some differences were detectable. The T-score of TRAP 5b was elevated, but not significantly so, in patients with a small bone metastatic burden (EOD = I). In contrast, although the T-score of NTx was not elevated in patients with a small metastatic burden (EOD = I), it was significantly elevated in patients with extensive osseous metastasis (EOD = III). CONCLUSION: Three bone resorption markers with different generation mechanisms showed a difference in menopause and osseous metastasis status. The level of ICTP was not elevated in postmenopausal patients, but the levels of NTx and TRAP 5b. In osseous metastasis, even though not statistically significant, TRAP 5b increased in patients with a small bone metastatic burden and NTx increased in patients with extensive bone metastatic burden.

Acid Phosphatase↗