Toshinao Takenouchi

Transperineal ultrasound-guided 12-core systematic biopsy of the prostate for patients with a prostate-specific antigen level of 2.5–20 ng/ml in Japan

BackgroundThe aim of this study was to investigate the cancer detection rate in patients with a prostate-specific antigen (PSA) level of 2.5 to 20 ng/ml, using transperineal ultrasound-guided systematic biopsy of the prostate.MethodsThree hundred consecutive patients with PSA levels of 2.5 to 20 ng/ml underwent transperineal ultrasound-guided 12-core systematic biopsy of the prostate.ResultsProstate cancer was detected in 108 of the 300 patients (36.0%). The cancer detection rates in patients with total PSA levels of 2.5–4.0, 4.01–10.0 and 10.01–20.0 ng/ml were 18.2%, 31.0%, and 50.0%, respectively. The cancer detection rates in patients with prostate volumes of less than 30 cc and over 50 cc were almost 50%, and 13.3%, respectively. The cancer detection rate in patients with a PSA density (PSAD) of less than 0.10 ng/ml per cc was only 5.6%, and no prostate cancer was detected in patients with a free-to-total PSA ratio (% f PSA) over 40%.ConclusionWe demonstrated a high prostate cancer detection rate by the transperineal ultrasound-guided 12-core systematic biopsy method in patients with PSA levels of 2.5 to 20 ng/ml. Accordingly, if the number of core biopsies is further increased overall, except in patients with a large prostate volume, and if the indication for biopsy is decided based on the PSAD and %f PSA, then the cancer detection rate by the present method may be further improved, with fewer unnecessary biopsies.

Establishment of a cell line from a human giant cell tumor of bone

A cell line (CG-1) was established from a specimen of a 21-year-old woman with giant cell tumor of bone. Inverted-phase microscopic analysis showed that the cultured cells were spindle-shaped in appearance. Multinucleated giant cells and macrophagelike round cells characterizing the histology of giant cell tumor of bone were not found. It is believed that the spindle-shaped cells were the neoplastic element of this tumor, because they were cultured more than 40 passages over the course of one year and subsequent cytogenetic analysis with a G-band technique showed constant loss of chromosomes 14 and 19. The cell line was found to produce several cytokines: M-CSF, IFN-gamma and TNF-alpha, as demonstrated by Western blotting analysis. These cytokines are known to show chemotactic, differentiation-inducing, and activating effects on macrophages. Because it has been recently reported in the literature that there are many infiltrated macrophages in giant cell tumor of bone, and because multinucleated giant cells are formed by fusion of macrophages, the newly established cell line may prove a useful system in studying the nature of giant cell tumor of bone.

PIVKA-II-producing advanced gastric cancer

We describe the case of a 68-year-old man with primary advanced adenocarcinoma of the stomach, who displayed extremely high plasma levels of protein induced by vitamin K antagonist (PIVKA)-II (15 600 mAU/ml) and normal levels of alphafetoprotein (AFP) (4 ng/ml). Ultrasonography and dynamic computed tomography ruled out hepatocellular carcinoma (HCC) or liver metastasis. After preoperative chemotherapy, pancreatico-spleno total gastrectomy with D2 lymphadenectomy was performed. Postoperatively, plasma levels of PIVKA-II returned to within the normal range (29 mAU/ml). Microscopic examination revealed stomach adenocarcinoma showing various histological types, such as moderately to poorly differentiated mucinous adenocarcinoma, but hepatoid differentiation of gastric adenocarcinoma was not detected. Localization of PIVKA-II and AFP within tumor cells was demonstrated by immunohistochemical staining using monoclonal antibodies. These results indicate that tumor cells from gastric cancer may produce PIVKA-II. Some cases of PIVKA-II- and AFP-producing advanced gastric cancer with liver metastasis have been reported, but this is the first report of gastric cancer without liver metastasis producing PIVKA-II alone.

Longterm survival after surgical removal of solitary brain metastasis from osteosarcoma

The prognosis of osteosarcoma with brain metastasis is very poor. We report a 14-year-old girl with osteosarcoma of the right distal femur who is alive and free of disease 6 years after the craniotomy and irradiation for brain metastasis. This longterm survival is attributed to the absence of active pulmonary metastasis at the onset of brain metastasis and the complete removal of the brain metastasis by craniotomy. Patients without active pulmonary metastasis at the onset of brain metastasis may achieve longterm survival. In such patients, it would be worthwhile to perform craniotomy aggressively.

Establishment and characterization of a human malignant fibrous histiocytoma cell line.

Malignant fibrous histiocytoma is the most frequent soft tissue sarcoma. However, the pathogenesis still remains unclear, because there are very few human malignant fibrous histiocytoma cell lines available for precise cellular study. In this study, a human malignant fibrous histiocytoma cell line (MMF-1) was established from the pulmonary metastatic lesion of a 55-year-old man with malignant fibrous histiocytoma. Human cell line MMF-1 and its heterotransplanted tumor had almost the same characteristics as the original tumor morphologically and immunohistochemically. This cell line is expected to be a useful for studying the pathogenesis of malignant fibrous histiocytoma. The cloned cell lines (MMF-2 and MMF-3) also consisted of spindle-shaped, polygonal, and multinucleated giant cells, meaning that the fibroblast-like cells, histiocyte-like cells, and multinucleated giant cells seen in malignant fibrous histiocytoma were derived from a single tumor cell. Human cell line MMF-1 produced inflammatory cytokines, such as tumor necrosis factor-alpha, macrophage colony-stimulating factor, interleukin-8, and monocyte chemotactic and activating factor, that might be involved in the morphogenesis of malignant fibrous histiocytoma. Furthermore, the results of the analysis of human cell line MMF-1 suggested that malignant fibrous histiocytoma originated from a poorly differentiated fibroblast.

Evaluation of mandibular invasion by head and neck cancers using 99mTc-methylene diphosphonate or 99mTc-hydroxymethylene diphosphonate and 201Tl chloride dual isotope single photon emission computed tomography

Whether a patient with head and neck cancer has mandibular invasion or not is important in determining the method of resection surgery. But, no modality is adequately reliable when used alone in the evaluation of mandibular invasion. Therefore, to more accurately diagnose mandibular invasion in head and neck cancer, we used a new modality, namely,99mTc methylene diphosphonate (MDP) or 99mTc hydroxymethylene diphosphonate (HMDP) and201Tl chloride dual isotope single photon emission computed tomography (Tc/T1 SPECT). The aim of this study is to disclose the usefulness of Tc/Tl SPECT in the assessment of mandibular invasion by head and neck cancers.99mTc-MDP or -HMDP SPECT (Tc SPECT)s and201T1 chloride SPECT (Tl SPECT)s were performed in 34 patients with suspected mandibular involvement of head and neck cancer. Thirty of 34 cases underwent both Tc/Tl SPECT and CT examination. Tc/Tl SPECT fusion images were obtained using the Automatic Registration Tool (ART, TOSHIBA, Japan) system. In the diagnosis of mandibular invasion on Tc/Tl SPECT fusion images, a problem was that the range of Tc and Tl uptake was changed by the condition of display used in the reconstruction and expression of the images. Then, prior to clinical evaluation, to reveal the most appropriate upper window level for display, a phantom study was performed. In a clinical study, the upper window level was set at 40 or 50%, which were verified to be the proper values in the preliminary study. The diagnostic accuracy obtained using Tc SPECT, Tc/Tl SPECT and CT was compared with the histopathological findings. Tc/Tl SPECT at 40 and 50% upper window level had higher specificity, accuracy, and positive predictive value (73.3%, 85.3%, 81.8%) than Tc SPECT alone (21.4%, 67.6%, 64.5%) and higher sensitivity and negative predictive value (94.7%, 91.7%) than CT (70.6%, 72.2%) for detecting mandibular invasion. Tc/Tl SPECT was a useful diagnostic procedure for the assessment of mandibular invasion by head and neck cancers.

Extraosseous accumulation of bone scanning agents in malignant brain tumors: Comparison to semi-quantitative evaluation with 99mTc SPECT/201Tl SPECT and histological findings

Although201Tl chloride (Tl) SPECT has been used in the differential diagnosis between recurrence of malignant brain tumor and necrosis after treatment, it is not generally recognized as a definite modality to distinguish them. We conducted a preliminary study using Tl SPECT and99mTc-MDP or99mTc-HMDP (Tc) SPECT because it has been said that extraosseous accumulation was caused by calcium deposits in necrotic tissues. In our study, for the purposes of clarifying the mechanism of extraosseous uptake and the correlation between extraosseous accumulation of bone-scanning agent and tumor viability in malignant brain tumors, we compared whether Tc uptake was correlated with the histopathological findings and further performed semi-quantitative evaluation between Tc SPECT and Tl SPECT. The correlation coefficients between the ratio of tumor to normal skull count obtained from Tc SPECT (Tc-T/N) and those of tumor to normal brain count (T/N) and to normal scalp count (T/S) both obtained from Tl SPECT were calculated. Using contrast enhanced CT (CECT) or contrast enhanced MRI (CE-MRI), 8 of 10 cases showed intensely ring-enhanced tumor with necrotic lesion. Histopathologically, 7 of 8 cases whose tumor had been resected before treatment had necrosis with increased vascularity or bleeding. Of the remaining 2 cases one case, malignant lymphoma had only hypervascularity by biopsy, while the other one was excluded for resection after treatment. Three of these 8 cases whose CE-CT or CE-MRI showed necrotic lesions exhibited Tc and Tl accumulations in the area corresponding to necrosis. In contrast, 2 showed no Tc nor Tl uptake. Tc-T/N had no significant correlation with any of early-, delayed-T/N or T/S. In conclusion, there was no significant correlation between Tc and Tl uptakes by malignant brain tumors in semiquantitative evaluation.

Expression of functional molecules in non-Hodgkin's lymphoma. Correlation with bone marrow involvement and serum LDH value.

It is well known that non Hodgkins lymphoma (NHL) cells express various antigens which are normally involved in a variety of functions. In addition, NHL is diverse in its proliferative capacity. To investigate the relation between these factors and the clinical picture, 45 cases of NHL were studied by immunohistochemistry using snap‐frozen materials obtained before therapy. Reactivities with 27 monoclonal antibodies were examined and the results were correlated with clinical findings. The expression of surface μ and CAM‐1 in B‐NHLs and CD25 in T‐NHLs were significantly associated with bone marrow involvement. B‐NHLs without expression of CD21(B2) and T‐NHLs with CD25 were seen more frequently in cases with a LDH value of over 500 units/ml. The positivity rate of Ki‐67 on B‐NHLs was correlated with serum LDH value, NHL histologic classification, and overall survival. These data indicate that immunophenotyping and determination of the proliferative capacity of NHL are of value not only for confirmation of the histopathologic classification of the tumor but also for assessment of clinical behavior.

Semi-quantitative assessment of oral cavity squamous cell carcinoma using 201Tl SPECT for evaluating effectiveness of preoperative radiotherapy

The aim of this study is to reveal the usefulness of semi-quantitative assessment using201 Tl chloride (Tl) single photon emission computed tomography (SPECT) (Tl SPECT) to evaluate the effectiveness of radiotherapy in 15 patients with oral cavity squamous cell carcinma (SCC). Fifteen patients were diagnosed with SCC by biopsy. All 15 patients enrolled in this study were planned to undergo preoperative radiotherapy with or without chemotherapy using carboplatin (CBDCA) and received reduction operation. Tl SPECTs were performed 15 minutes after intravenous administration of 111 MBq201T1 chloride. Regions of Interest (ROI) were set up around tumor (T), and non-lesion (N) at the part of contralateral scalp at the height of the cerebellum. The ratios of mean counts in ROI of the tumor to those in non-lesion were measured as pre- and post-treatment T/N ratios (pre T/N, post T/N). Furthermore, reduction rate (RR) was obtained by calculating [(pre T/N - post T/N)/(pre T/ N)] x 100%. Each parameter (pre T/N, post T/N, and RR) was compared to histopathological grade of surgical specimen based on the Oboshi and Shimosato classification (grade I-IV). RR showed significantly higher values in grade III and IV than in grade I and II (p = 0.0008). In conclusion, semi-quantitative assessment using Tl SPECT, especially calculating RR, is useful to evaluate the effectiveness of preoperative radiotherapy.

Correlation between angiogenesis and reduction ratio measured using201Tl chloride single photon emission computed tomography in patients with oral cavity squamous cell carcinoma

Objective: The aim of this study is to examine the correlation between tumor angiogenesis and response to preoperative radiotherapy evaluated using201T1 single photon emission computed tomography (Tl SPECT) in oral cavity squamous cell carcinoma (SCC).Methods: Tl SPECTs before and after preoperative radiotherapy were obtained from 11 patients diagnosed with SCC in oral cavity. Regions of interest were set around the tumor and scalp respectively, and the ratio of mean counts in the tumor to those in the scalp was calculated (T/N). Immunohistochemical staining for investigating microvessel density of pre-treatment biopsy specimen was performed using CD31 monoclonal antibody. We compared microvessel density with semi-quantitative parameters obtained using Tl SPECT (T/N at pre-an post-treatment, reduction ratio) and prognosis.Results: The subgroup with higher microvessel density showed a significantly higher reduction ratio than the one with lower microvessel density. Regarding prognosis, the subgroup with locoregional recurrent disease exhibited a significantly higher microvessel density than the one without recurrence.Conclusions: In SCC of the oral cavity, there was a significant correlation between microvessel density and response to preoperative radiotherapy. Namely, it was revealed that change of201Tl uptake after preoperative radiotherapy correlated with tumor angiogenesis of oral cavity SCC.