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Biomedical subjects

Makio Mukai

Publications and source records attributed to Makio Mukai.

At least 19 recordsLinked to original sources
PubMed2006

Accuracy of preoperative prediction of microinvasion of portal vein in hepatocellular carcinoma using superparamagnetic iron oxide-enhanced magnetic resonance imaging and computed tomography during hepatic angiography.

BACKGROUND: Our aim was to diagnose microinvasion of the portal vein in hepatocellular carcinoma from preoperative radiological findings and to construct a scoring system. METHODS: Forty-seven patients (38 men and 9 women; median age, 66.8 years) who underwent hepatic resections for hepatocellular carcinoma were selected retrospectively. Microscopically, 22 had portal vein invasion (PVI) and 25 had no PVI. All patients were examined preoperatively with superparamagnetic iron oxide-enhanced magnetic resonance imaging and computed tomography during hepatic angiography (CTHA). Perilesional enhancement on T1-weighted imaging, tumorous arterioportal (AP) shunt, and corona enhancement (contrast enhancement of the adjacent liver appearing in the late phase of CTHA) were assessed. Relative risk for PVI in terms of clinical and tumor characteristics was also assessed. The relative contribution to PVI was determined by the coefficient of a stepwise logistic regression. Each variable was given a score relative to the coefficient. RESULTS: On univariate analysis, distortion of corona, tumorous AP shunt, and tumor size indicated a higher prevalence of PVI. The PVI predictive score was calculated as: total score = (maximum size in cm) + (T1 ring; + = 1, - = 0) + (tumorous AP shunt; + = 3, - = 0) + (distortion of corona; + = 10, - = 0). The PVI (+) group score was four times that of the PVI (-) group (16 vs 4). At a cutoff score of 10, the sensitivity, specificity, and accuracy were 82%, 84%, and 86%. CONCLUSIONS: Distortion of corona, tumorous AP shunt, and tumor size are good predictors of the risk of PVI. This scoring system is simple and worth using clinically.

Adult↗
PubMed2006

Telomere length, telomerase activity, and expressions of human telomerase mRNA component (hTERC) and human telomerase reverse transcriptase (hTERT) mRNA in pulmonary neuroendocrine tumors.

BACKGROUND: Telomeres are important for chromosome structure and function, protecting them against degradation. However, few studies have examined telomeres in pulmonary neuroendocrine (NE) tumors. METHODS: We investigated deparaffinized sections obtained from 70 primary NE lung tumors [34 typical carcinoids (TCs), 10 atypical carcinoids (ACs), 16 large cell neuroendocrine carcinoma (LCNECs) and 10 small cell lung carcinomas (SCLCs)]. RESULTS: Positive expressions of human telomerase mRNA component (hTERC) and human telomerase reverse transcriptase (hTERT) mRNA were recognized, respectively, in 58% and 74% of TCs, and in 100% and 100% of ACs, LCNECs and SCLCs. Alteration of telomere length was greater in both LCNECs and SCLCs than in TCs. Telomerase activity was detected in LCNECs, but not in TCs. By the reverse-transcriptase polymerase chain reaction (RT-PCR), hTERC mRNA was detected in 100% of LCNECs and TCs examined, while hTERT mRNA was detected in 67% of LCNECs, but not at all in TCs. CONCLUSIONS: These results suggest that alterations in telomere length, telomerase activity, and the expression of hTERT mRNA may (i) play roles in pathogenesis in pulmonary neuroendocrine tumors, and (ii) be a useful tool for differential diagnosis between TCs and LCNECs.

Carcinoma, Neuroendocrine↗
PubMed2006

Chondromodulin-I maintains cardiac valvular function by preventing angiogenesis.

The avascularity of cardiac valves is abrogated in several valvular heart diseases (VHDs). This study investigated the molecular mechanisms underlying valvular avascularity and its correlation with VHD. Chondromodulin-I, an antiangiogenic factor isolated from cartilage, is abundantly expressed in cardiac valves. Gene targeting of chondromodulin-I resulted in enhanced Vegf-A expression, angiogenesis, lipid deposition and calcification in the cardiac valves of aged mice. Echocardiography showed aortic valve thickening, calcification and turbulent flow, indicative of early changes in aortic stenosis. Conditioned medium obtained from cultured valvular interstitial cells strongly inhibited tube formation and mobilization of endothelial cells and induced their apoptosis; these effects were partially inhibited by chondromodulin-I small interfering RNA. In human VHD, including cases associated with infective endocarditis, rheumatic heart disease and atherosclerosis, VEGF-A expression, neovascularization and calcification were observed in areas of chondromodulin-I downregulation. These findings provide evidence that chondromodulin-I has a pivotal role in maintaining valvular normal function by preventing angiogenesis that may lead to VHD.

Aged↗
PubMed2006

Expression of Ets-1 in human clear cell renal cell carcinomas: implications for angiogenesis.

Expression of vascular endothelial growth factor (VEGF) has been reported in renal cell carcinoma (RCC), a highly angiogenic carcinoma. However, little or no information is available on the expression of Ets-1, which is one of the target molecules of VEGF. In the present study, we examined the expression of Ets-1 and VEGF in RCC by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR), and correlations between expression and the microvessel density (MVD) were evaluated. Ets-1 was immunolocalized to carcinoma cells and endothelial cells of the microvessels in clear cell RCC, but not in papillary RCC. Immunohistochemical Ets-1 expression and MVD were significantly higher in clear cell RCC than in papillary RCC. Predominant mRNA expression of Ets-1 in clear cell RCC was confirmed by RT-PCR. The expression of Ets-1 correlated directly with MVD in clear cell RCC. Hypoxic treatment upregulated the mRNA expression of Ets-1 and VEGF in cell lines derived from clear cell RCC, suggesting that hypoxia is a key regulator for these molecules. These results demonstrate the expression of Ets-1 in human clear cell RCC and suggest the possibility that Ets-1 is involved in angiogenesis in clear cell RCC.

Carcinoma, Renal Cell↗
PubMed2006

Syncytiotrophoblastic vesicles in placental intervillous space.

OBJECTIVE: This study was undertaken to investigate the origin and function of vesicles found in the intervillous space. STUDY DESIGN: A retrospective study was performed by using placental sections of different gestational ages. The number of vesicles was counted in each section of gestational age groups. Immunohistochemical staining for beta-human chorionic gonadotropin (beta-hCG) and human placental lactogen (hPL) was conducted to confirm the origin of vesicles. RESULTS: Staining for beta-hCG and hPL was prominent in vesicles separating from syncytiotrophoblast into the intervillous space. The numbers of vesicles were not significantly different in gestational age groups of 42 to 30 weeks and all vesicles disappeared in 9- to 5-week groups. Large vesicles tended to show degeneration and disintegration in the intervillous space. CONCLUSION: The vesicles containing beta-hCG and hPL suggest a different secretory mechanism of syncytiotrophoblast.

Chorionic Gonadotropin, beta Subunit, Human↗
PubMed2006

A case of metacarpal chondrosarcoma of the thumb.

Enchondroma is the most common primary benign bone tumor of the hand. Chondrosarcomas in this location, however, are extremely rare. It often is difficult to make a histological distinction between benign cartilaginous tumors and low-grade chondrosarcomas, because enchondromas at this site often show histological features suggestive of malignancy. However, distinguishing the two conditions is clinically relevant because chondrosarcomas of the hand require prompt and more radical treatments such as ray amputations. On the other hand, Mankin has recently given attention to a less aggressive behavior of chondrosarcomas of the phalanges compared with those of other locations. And also, ray amputation does not cause much functional deficit in the finger but does for the thumb. This is a case report of chondrosarcoma affecting the metacarcal bone of the thumb, treated by en block resection and preserving the function of the thumb by bone graft reconstruction, with reference to the literature.

Bone Neoplasms↗
PubMed2006

Dedifferentiated parosteal osteosarcoma with well-differentiated metastases.

Metastases of dedifferentiated sarcoma usually contain a dedifferentiated component. We report a rare case of dedifferentiated parosteal osteosarcoma (dd-POS) with well-differentiated multiple metastases in a 65-year-old woman with a painful firm mass on her thigh. Radiological examination revealed that the mass arose from the surface of her femur without medullary involvement. Multiple intramuscular metastases were detected in her lower leg on MR imaging. Small subcutaneous palpable masses were identified on her left lower leg, buttock, chest wall and head. An open biopsy and above-the-knee amputation were performed, and the mass on her femur was diagnosed as a dd-POS. However, histological examination on the subcutaneous lesions in her lower leg, buttock and head showed low-grade conventional POS without dedifferentiated components. To the best of our knowledge, this is the first report of a dd-POS with multiple metastases that do not contain any dedifferentiated components.

Aged↗
PubMed2006

Imaging findings of solitary fibrous tumor of the prostate: a case report.

The imaging findings of a solitary fibrous tumor of the prostate are presented. A 35-year-old male presented with urinary retention and was found on transrectal ultrasonography to have a hypoechoic tumor of the prostate, measuring 5.5 cm in size. Magnetic resonance imaging on, the tumor showed low signal intensity on T1-weighted images and heterogeneous mixed signal intensity on T2-weighted images. Gadolinium-enhanced dynamic study showed gradual enhancement from the periphery to the center, and the enhancement is sustained. On immunohistochemistry, the spindle cells of the tumor showed positive staining for CD34 and bcl-2. Although the tumor was labeled as a low-grade malignancy on account of a low mitotic index (MIB-1 index) of about 5%, the patient developed local recurrence of the tumor with bladder wall invasion 12 months later.

Adult↗
PubMed2006

Interim results of sentinel node biopsy during laparoscopic gastrectomy: possible role in function-preserving surgery for early cancer.

INTRODUCTION: Intraoperative detection of sentinel nodes (SNs) has been used clinically to predict regional lymph node (LN) metastasis in patients with breast cancer and malignant melanoma. Intraoperative lymphatic mapping and SN biopsy can potentially be combined with minimally invasive surgery. However, few reports have demonstrated the validity of SN biopsy during laparoscopic gastrectomy. The aim of this study was to investigate the feasibility and accuracy of laparoscopic lymphatic mapping in predicting LN status in patients with gastric cancer. METHODS: A total of 35 patients with gastric cancer diagnosed preoperatively as T1, N0 were enrolled. Endoscopic injection of technetium-99m-radiolabeled tin colloid was completed 16 hours before surgery, and radioactive SNs were identified with a gamma probe intraoperatively. Isosulfan blue dye was injected endoscopically during the operation. Laparoscopy-assisted gastrectomy with LN dissection was performed. All resected LNs were evaluated by routine pathology examination. RESULTS: SNs were detected in 33 (94.3%) of 35 patients. The mean number of SNs was 3.9, and the diagnostic accuracy according to SN status was 97.0% (32/33), as one patient with a false-negative result was observed. The patient with the false-negative specimen was finally diagnosed as having advanced gastric cancer with invasion into the proper muscular layer and severe lymphatic vessel invasion, causing destruction of normal lymphatic flow by the tumor. CONCLUSIONS: Radio-guided SN mapping during laparoscopic gastrectomy is an accurate diagnostic tool for detecting lymph node metastasis in patients with early-stage gastric cancer. Validation of this method requires further studies on technical issues, including indications, tracers, methods of lymph node retrieval, and diagnostic modalities of metastasis.

Adult↗
PubMed2006

Long-term survival after incomplete resection of immunohistochemically diagnosed T0N1 lung cancer: report of a case.

A 63-year-old man who had undergone resection of colon cancer 15 years previously was found to have a right hilar mass on chest X-ray, and an elevated serum carcinoembryonic antigen level. The hilar lymph nodes were resected with the right upper lobe, and the initial diagnosis was colon cancer metastasis to the right hilar lymph nodes. Although the resection was incomplete, and no additional treatment was given, the patient remained free of recurrence for 10 years. This prompted us to reconsider our diagnosis using immunohistochemistry. The resected lymph nodes were found to be positive for thyroid transcription factor 1 (TTF-1) and cytokeratin 7, and negative for surfactant apoprotein (SAP), cytokeratin 20, and napsin A. The neuroendocrine markers and thyroglobulin were also negative. These findings led us to diagnose T0N1 lung cancer. There are reports of patients with clinical T0N1,2 lung cancer having exceptionally good prognoses despite noncurative treatment; however, to our knowledge, this is the first case of a patient with T0N1 lung cancer diagnosed by immunohistochemistry, with a good prognosis despite incomplete resection. In this case, TTF-1 and cytokeratin staining was particularly helpful in the differential diagnosis.

Adenocarcinoma↗
PubMed2006

Operative indications for relatively small (2-5 cm) gastrointestinal stromal tumor of the stomach based on analysis of 60 operated cases.

BACKGROUND: Removal of the primary lesion with a clear operative margin is the standard treatment for gastrointestinal stromal tumor (GIST) of the stomach. However, there are few reports on the operative indications for relatively small GIST. METHODS: Clinicopathologic features and survival data of all 60 patients with GIST of the stomach treated at Keio University Hospital from 1993 to 2004 were analyzed. Laparoscopic wedge resection was used as the primary procedure for tumors between 2 to 5 cm. Tumors larger than 5 cm were resected by laparotomy or laparoscopy-assisted operation. RESULTS: Thirty-five lesions (58.3%) were resected by laparoscopic wedge resection, 3 by laparoscopic operation with a small skin incision and 22 by conventional open procedures. The mean size of the tumors was 42.5 mm, with a range of 18 to 150 mm and a median value of 35.5 mm. All operative margins were clear, but 1 patient had liver metastases at the time of resection of the primary lesion. The median follow-up period was 53 months and the 5-year disease-free survival rate (DFS) was 96.1%. No local recurrence or distant metastasis was encountered in patients with tumors smaller than 4 cm. A statistically significant correlation was observed between tumor size and mitotic count in this cohort (P = .010). Tumors from the intermediate- (n = 14) and high-risk (n = 10) groups as classified by the Risk Assessment Classification showed significantly worse DFS than the low-risk and very low risk group (n = 35) (89.9% vs 100% in 5-year DFS, P = .045). Even among tumors smaller than 3 cm, 2 of 14 cases (14.3%) were classified into the intermediate-risk group. CONCLUSIONS: Although a prospective randomized trial remains to be performed, this study provides additional evidence suggesting that the early removal of GIST, at 5 cm or less in size, provides better DFS than later removal of the tumor at a larger size.

Adult↗
PubMed2006

Unusual hemangioendothelioma of the liver with epithelioid morphology associated with marked eosinophilia: autopsy case.

Vascular neoplasms characterized by epithelioid endothelial cells consist of several different entities from benignity to high-grade malignancy. Because of histological overlap between them, there is substantial difficulty in classifying them correctly. The present patient, a 33-year-old man, presented with hepatomegaly, striking eosinophilia and elevated serum interleukin-5 level. Biopsy and autopsy revealed an unusual epithelioid vascular tumor in the liver, which is histologically distinct from epithelioid hemangioma, epithelioid hemangioendothelioma, or epithelioid angiosarcoma. The tumor cells had vasoformative and partly solid growth with no severe nuclear atypia and very low mitotic activity, and the histological features were similar to those of the entity recognized as hemangioendothelioma of bone. Organs other than the liver, for example the testes and bone, were also involved. This tumor should be considered in the differential diagnosis of severe eosinophilia.

Adult↗
PubMed2006

Maximum tumor diameter is a simple and valuable index associated with the local extent of disease in clinically localized prostate cancer.

BACKGROUND: The present study was undertaken to investigate the association of pathological features, including the total tumor volume (TTV), maximum tumor area (MTA), and maximum tumor diameter (MTD), with the local extent of disease in clinically localized prostate cancer. METHODS: Serial whole sections of the prostate from 164 patients who underwent radical prostatectomy for localized prostate cancer were investigated. The correlations between the indicators of tumor size, including the TTV, MTA, and MTD, and other pathological parameters were evaluated. RESULTS: The MTD, MTA, and TTV were significantly correlated with each other. Multivariate stepwise logistic regression analysis indicated that the Gleason score, perineural invasion, microvascular invasion, and MTD were significant independent parameters associated with extraprostatic disease. CONCLUSION: The histological tumor grade, perineural invasion, microvascular invasion, and tumor size were correlated with the local extent of disease. The MTD, a simple, easy, and inexpensive parameter, is a more significant pathological feature associated with the local extent of disease than the MTA or TTV.

Aged↗
PubMed2006

Primary malignant hepatic pheochromocytoma with negative adrenal scintigraphy.

A 60-year-old male patient with hypertension was referred to our hospital because of insufficient blood pressure control (190/98 mmHg) and to rule out secondary hypertension. A computed tomography scan revealed no adrenal tumor but a large liver mass (5 x 5 cm), and magnetic resonance imaging showed a high signal intensity lesion on the T2-weighted image. Twenty-four hour urinary excretion of catecholamine metabolites was markedly increased, although a 123I-metaiodobenzyl guanidine (MIBG) scintigram failed to show accumulation in the hepatic mass, and no difference was noted between the catecholamine concentration in the tumor-drainage vein and that obtained from the vein draining from the non-tumor area. Liver biopsy did show features compatible with pheochromocytoma (i.e., chromogranin A-positive cells). Transcatheter arterial embolization of the liver tumor was conducted and resulted in a marked (50%) decrease in the 24-h urine normetanephrine excretion. Several metastatic foci were noted in the spinal bone and transcatheter arterial embolization (TAE) was also conducted with successful results. Thus, we experienced a case of primary malignant hepatic pheochromocytoma with negative 123I-MIBG scanning.

3-Iodobenzylguanidine↗
PubMed2006

Evaluation of superparamagnetic iron oxide for MR imaging of liver injury: proton relaxation mechanisms and optimal MR imaging parameters.

PURPOSE: To investigate the proton relaxation mechanisms and the optimal MR imaging parameters in superparamagnetic iron oxide (SPIO)-enhanced MR imaging of liver injury. METHODS: A liver injury model was created in the rat using carbon tetrachloride. The T1 and T2 relaxation effects of SPIO in normal and injured liver were estimated by ex vivo relaxometry. In vivo laser confocal microscopy of the liver was performed to simulate the distribution and clustering of SPIO particles in the hepatic macrophages. SPIO-enhanced MR imaging (1.5T) of normal and diseased rats was performed with variable parameters. The liver specimens were prepared for histopathological examination. RESULTS: Histopathological and laser confocal microscopic findings showed diffuse macrophage distribution but decreased intracellular clustering of SPIO in injured liver. Ex vivo relaxometry showed sustained T1 and T2 relaxation effects of SPIO in liver injury. On MR images obtained with moderate echo time (spin echo [SE] 2000/40 and gradient echo [GRE] 130/9.0/60 degrees), injured liver showed significantly lower decrease in signal-to-noise ratio (SNR) than the normal liver, whereas little difference in SNR was found between the normal and injured liver on heavily T2-(SE 2000/80) and T1-weighted (SE 300/11 and GRE 130/2.0/90 degrees) MR images. CONCLUSION: Pulse sequences with a moderately long echo time (TE) may be more appropriate than heavily T1- or T2-weighted images for distinguishing normal and injured liver in SPIO-enhanced MR imaging because of the maintained T1 and T2 relaxation effect but decreased T2* relaxation effect of SPIO in injured liver.

Animals↗
PubMed2006

Mre11 expression in atypical adenomatous hyperplasia and adenocarcinoma of the lung.

CONTEXT: The Mre11-Rad50-NBS1 complex plays an important role in telomere maintenance. Recently, it has been proposed that alterations in Mre11 function may be contributing factors in the development of some tumors. Moreover, mutations of Mre11 have been demonstrated to cause reduced Mre11 immunostaining. OBJECTIVE: To investigate Mre11 in atypical adenomatous hyperplasia (AAH) and nonmucinous bronchioloalveolar carcinoma (NMBAC), an issue not previously explored. DESIGN: We examined (1) the expression of Mre11 protein in 27 AAHs (9 lesions interpreted as low-grade AAH and 18 as high-grade AAH) and 40 NMBACs (using immunohistochemistry) and (2) Mre11 mRNA expression in 1 high-grade AAH and 6 NMBACs (using reverse transcription polymerase chain reaction). For the analysis of immunoreactivity, the intensity and extent of staining were each scored from 0 to 3. These 2 scores were summed to give in each case a final score of 0 to 6. RESULTS: Scores for Mre11 expression were 5.0 +/- 2.1 for low-grade AAH, 5.4 +/- 1.2 for high-grade AAH, and 5.5 +/- 0.9 for NMBAC, and there was no statistically significant difference among these 3 types of lesions. In the reverse transcription polymerase chain reaction for Mre11 mRNA, polymerase chain reaction products were detected in all samples. CONCLUSIONS: On this basis, we suggest that the part played by Mre11 in telomere maintenance may not be important for the progression of the adenoma-carcinoma (AAH-NMBAC) sequence in the lung, although some role for it in carcinogenesis cannot be completely ruled out.

Adenocarcinoma↗
PubMed2005

LAT1 expression in normal lung and in atypical adenomatous hyperplasia and adenocarcinoma of the lung.

No previous study has investigated neutral large amino acid transporter type 1 (LAT1) in normal lung cells, or in atypical adenomatous hyperplasia(s) (AAH) and nonmucinous bronchioloalveolar carcinoma(s) (NMBAC) of the lung. The authors examined: (1) the levels of LAT1 mRNA/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA in 41 normal lung tissues and 34 NMBAC using semiquantitative reverse transcription-polymerase chain reaction; (2) LAT1 mRNA and protein expressions in 35 normal lung tissues, 34 AAH (11 lesions were interpreted as low-grade AAH and 23 as high-grade AAH), and 43 NMBAC using in situ hybridization and immunohistochemistry; and (2) the association of the incidences of LAT1 mRNA and protein expressions with cell proliferation in these lesions. The level of LAT1 mRNA/GAPDH mRNA (1) tended to be higher in NMBAC (12.0+/-8.1) than in normal lung tissues (1.0+/-0.2), and (2) covered a much wider range (from 0 to 276) in NMBAC than in normal lung tissues (from 0 to 5.8), with six NMBAC having values higher than 7.0, while 5.8 was the highest value detected in normal lung tissues. In peripheral normal lung tissues, LAT1 mRNA and protein were detected in bronchial surface epithelial cells and alveolar macrophages (but not in nonciliated bronchiolar epithelial cells, or in alveolar type I or type II cells). In bronchial surface epithelial cells, LAT1 protein appeared to be of a nodular type, which was considered to be a nonfunctional protein pattern. The incidences of positive expressions for LAT1 mRNA and protein were 54.5 and 27.3% in low-grade AAH, 65.2 and 52.2% in high-grade AAH, and 65.1 and 79.1% in NMBAC, respectively. In the case of LAT1 protein expression, significant differences could be shown between total (low-grade plus high-grade) AAH and NMBAC, and between low-grade AAH and NMBAC. Thus, in terms of the incidence of LAT1 protein expression, high-grade AAH appeared intermediate between low-grade AAH and NMBAC. The Ki-67 labeling index (a cell proliferation score) was significantly higher in those AAH and NMBAC that were LTA1-protein-positive than in their LAT1-protein-negative counterparts. In conclusion, LAT1 expression may increase with the upregulation of metabolic activity and cell proliferation in high-grade AAH and NMBAC.

Adenocarcinoma, Bronchiolo-Alveolar↗