SU-D-217BCD-02: Online Angular Tube Current Modulation in X-Ray Computed Tomography: Can Tube Current Be Modulated Appropriately?

PURPOSE: In X-ray computed tomography (CT), X-rays are significantly less attenuated in the anteroposterior direction and more in the lateral direction. Therefore, the tube current should be adjusted within one gantry rotation using angular tube current modulation (TCM). The aim of this study was to evaluate whether online angular TCM could reduce radiation dose appropriately. METHODS: A 128-detector dual-source CT (SOMATOM Definition Flash; Siemens Healthcare, Erlangen, Germany) and an online TCM system (CARE Dose 4D; Siemens Healthcare) were used. Dose profiles were acquired using the CT Dose Profiler (RTI Electronics, Molndal, Sweden) and an elliptical cylindrical phantom (MHT; Kyoto Kagaku, Kyoto, Japan) for helical CT scans with and without TCM. In addition, absorbed dose distributions within a single section were acquired using an anthropomorphic phantom (RANI 10; The Phantom Laboratory, Salem, NY) and radiophotoluminescent glass dosimeters (RPLDs) (GD- 302M; Chiyoda Technol, Tokyo, Japan) for helical CT scans with and without TCM after placing RPLDs within all holes of one section and pasting them around the section. A graph of each absorbed dose distribution was drawn using graphing software (ORIGIN 8.6; OriginLab, Northampton, MA). RESULTS: The acquired dose profiles suggested that online angular TCM could adjust the tube current in near-real time according to the attenuation measured from the previous projection. The profiles gradually stabilized because the tube current was adjusted properly. The absorbed doses were low and the distributions were stable with TCM compared with those without TCM. CONCLUSIONS: In X-ray CT, an online angular TCM can reduce radiation dose effectively by adjusting tube current within one gantry rotation in near-real time.

Comparison between 3-D and z-axis automatic tube current modulation technique in multidetector-row CT.

In this study, the 3-D automatic tube current modulation (3-D ATCM) technique was compared with the z-axis ATCM technique on multidetector-row CT. Absorbed dose measurements were performed by inserting an ion chamber into the phantoms, and objective image noise shown as the standard deviation of CT value in Hounsfield units was measured on the obtained images. The ratio of absorbed doses with 3-D ATCM technique to z-axis ATCM technique was 94.7% using an elliptical cylinder phantom with an inner cylinder phantom and 96.3% using an elliptical cylinder phantom without an inner cylinder phantom. Differences in objective noise between the 3-D ATCM technique and z-axis ATCM technique were within a tolerable range compared with the setting noise index. Therefore, the 3-D ATCM technique effectively optimises the radiation dose, while maintaining an appropriate image quality compared with z-axis ATCM technique.

Development of a cone angle weighted three-dimensional image reconstruction algorithm to reduce cone-beam artefacts.

OBJECTIVES: Image reconstruction from cone-beam projections collected along a single circular source trajectory is commonly done using the Feldkamp algorithm, which performs well only with a small cone angle. In this report, we propose an algorithm to reduce cone-beam artefacts by increasing the cone angle by several fold to achieve satisfactory image quality at the same radiation dose. METHODS: To examine the factors involved in the occurrence of cone-beam artefacts, a microspheres-phantom was arranged longitudinally at different positions and a computer simulation was performed. Due to differences in projection angle, data projected onto the detector surface were projected along trajectories shown as different periodic functions depending on the distance and position from the mid-plane position. Therefore, projection along several detector channels based on different projection data resulting from different periodic functions is considered responsible for the increase in cone-beam artefacts associated with an increase in the distance of reconstruction planes from the mid-plane position. Our recommended algorithm to reduce such artefacts features a change in weighting with respect to projection data obtained at different projection angles, three-dimensional back-projection of corrected projection data. RESULTS: Numerical phantom simulation and real human head origin study (a prototype cone-beam CT) showed that the effect of the reduction in cone-beam artefacts of an object located at the edges was markedly enhanced at reconstruction planes at positions further from the mid-plane position. CONCLUSION: We propose a projection angle weight-based algorithm to increase the cone angle by several fold to achieve satisfactory image quality at the same radiation dose. These findings confirmed that this algorithm reduces cone-beam artefacts and generates high-quality reconstruction images.

Immunohistochemical detection of the 150-kDa oxygen-regulated protein in bladder cancer.

OBJECTIVE: To investigate the relationship between the expression of the 150-kDa oxygen-regulated protein (ORP150, which functions as a molecular chaperone in the endoplasmic reticulum for the folding and trafficking of newly synthesized proteins) and the aggressiveness of bladder cancer, and the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs), as the former is a secreting protein through the endoplasmic reticulum and the latter are closely involved in tumour invasion. MATERIALS AND METHODS: Thirty-nine cystectomy specimens, comprising 12 superficial (pT1) and 27 invasive (pT2-pT4) tumours, were immunohistochemically analysed using antibodies against ORP150, VEGF, MMP-1, MMP-2 and MMP-9. Staining was scored from 0 to 3, according to the ratio of positively staining cells. RESULTS: Staining was positive (score 1-3) for ORP150 in 10 of 12 superficial and 25 (93%) of the invasive tumours, with a significantly higher staining score for stage T4 than stage T1 tumours. The trend was the same for the staining score of MMP-2, and there was a significant correlation between ORP150 and MMP-2 expression. CONCLUSIONS: The expression of ORP150 was common in bladder cancer, with a tendency for greater expression in higher stages. The significant correlation between ORP150 and MMP-2 expression suggests that ORP150 acts as a molecular chaperone for MMP-2 secretion and thus tumour invasion.

[A case of plasmacytoma involving adrenal gland].

We report a case of extramedullary plasmacytoma involving the right adrenal gland. A 52-year-old male was introduced under diagnosis of right adrenal tumor which was found incidentally by computerized tomography in a health check up. Laboratory data showed the presence of M protein and elevation of monoclonal lambda type IgG. It was a hormonally non-active tumor involving the adrenal area. Extramedullary plasmacytoma was confirmed by histological analysis of the resected specimen after laparoscopic right adrenalectomy. Extramedullary plasmacytoma is an uncommon neoplasm and occurs most frequently in the upper respiratory tract and is fairly rare in the adrenal area.

Antitumor effect of reduction of 150-kDa oxygen-regulated protein expression in human prostate cancer cells.

Heat shock proteins (HSPs)/stress proteins are molecular chaperones that are induced by various environmental and physiological stimuli. Evidence of the relations between the expression of HSPs and the regulation of cell growth or transformation has accumulated. The 150-kDa oxygen-regulated protein (ORP150), a new member of HSP family, functions as a molecular chaperone in the endoplasmic reticulum. We have examined whether transduced antisense ORP150 cDNA reduces tumorigenicity and angiogenicity. Relations between these stress proteins and cancer and possibilities for anticancer gene therapy are described.

Clinical approach to renal study incidental to 99mTc-MDP bone scintigraphy.

In order to investigate the feasibility of the assessment of renal function with 99mTc-MDP, we compared renographical images, renogram patterns and the glomerular filtration rate (GFR) obtained by means of a modified Gates' method and 200 MBq of 99mTc-MDP with those obtained by means of 99mTc-DTPA. Because 19 of 20 patients had malignant tumors in the genitourinary tract, there was no difference between the two tracers in identifying a parenchymal defect corresponding to renal cancer. Of eight patients with hydronephrosis, four had a defect or decreased uptake with a dilated pelvis, whereas the other four had marked radioisotope retention in the renal pelvis or the whole kidney on serial images. There was also no difference between the two tracers in identifying hydronephrosis. Of 38 paired renograms 35 showed the same renogram patterns with both tracers. Of three patients with different renogram patterns, two had hydronephrosis. In 20 patients including three patients with bone metastasis, total GFR and split GFR obtained with both tracers correlated with a correlation coefficient of r = 0.920 (p < 0.001) and r = 0.944 (p < 0.001), respectively. Excluding bone metastasis from the analysis, a linear-regression analysis showed excellent agreement between the two measurements with a correlation coefficient of r = 0.960 (p < 0.001) and r = 0.963 (p < 0.001), respectively. The linear regression equations were Y = 1.009X - 0.111 and Y = 1.034X - 0.714, respectively. In conclusion, 99mTc-MDP can be used as a supplement to evaluate renal function incidental to the survey of bone metastases in patients with malignant tumor.

Characteristics of acoustic noise in echo-planar imaging.

Characteristics of the acoustic noise generated by magnetic resonance imagers of different systems and performance levels were studied when operating in echo-planar imaging (EPI) sequence. Continuous equivalent A-weighted sound pressure levels (Leq) and peak impulse sound pressure levels (Lpeak) during EPI were measured in 12 clinical super-conducting MRI systems (0.5-1.5 T). Sound pressure levels and frequency spectra of EPI were compared with those of nine different pulse sequences. EPI sound pressure levels differed among institutions (Leq = 94.2 +/- 2.7 dBA. Lpeak = 109.1 +/- 3.5 dB), but these were within permissible noise exposure levels. Sound pressure levels during EPI were not significantly different from those during other pulse sequences. However, compared to other pulse sequences. EPI had a significantly greater proportion of acoustic noise in the high octave-frequency band. Single-shot EPI had relatively higher frequency noise and greater Leq than multishot EPI, but the difference in Leq decreased when the number of slices in multishot EPI was increased.

[A case of adrenal pheochromocytoma with contralateral adrenocortical adenoma].

A case of a pheochromocytoma in the right adrenal gland and adrenocortical adenoma in the left adrenal gland of a 58-year-old male is reported. The patient was incidentally found to have a right adrenal tumor by ultrasonographic study. A computerized tomographic (CT) study and magnetic resonance image (MRI) study revealed bilateral adrenal tumors. The sizes of the right tumor and left tumor were 2.5 x 3.5 cm and 1.2 x 1.0 cm, respectively. The intensity of each tumor was different on T2-weighted MRI. 131I-MIBG scintigram showed the uptake of right adrenal gland. The existence of pheochromocytoma was confirmed by the elevated levels of catecholamines. We performed venous sampling to be certain whether the patient had unilateral or bilateral pheochromocytoma. As a result, bilateral adrenal pheochromocytoma was diagnosed. Therefore, we performed bilateral adrenalectomy. However, histopathological examination revealed right pheochromocytoma and left non-functioning adrenocortical adenoma.

Long-term exposure of tumor necrosis factor alpha causes hypersensitivity to androgen and anti-androgen withdrawal phenomenon in LNCaP prostate cancer cells.

BACKGROUND: One of the mechanisms through which prostate cancers relapse during anti-androgen therapy may involve adaptation to low concentrations of androgen induced by anti-androgen therapies. Recent studies from our laboratory have reported that tumor necrosis factor-alpha (TNFalpha) is secreted from prostate cancer epithelial cells and LNCaP cells. We hypothesized that TNFalpha changes androgen-sensitivity in LNCaP cells. METHODS: We cultured LNCaP cells for more than 3 months in the presence of 50 ng/ml TNFalpha and established TNFalpha-resistant LNCaP cells (LN-TR2). Sensitivity to androgen was examined by the cell proliferation assay. We also transfected LNCaP and LN-TR2 cells with a luciferase reporter plasmid driven by prostate-specific antigen (PSA) promoter and compared PSA promoter activity. Nuclear localization of AR protein that binds to target genes was also examined by Western blotting. RESULTS: LN-TR2 cells had increased sensitivity to dihydrotestosterone (DHT) (i.e., proliferation and PSA promoter activation) than LNCaP cells. Total AR mRNA and AR protein levels were decreased in LN-TR2 cells. However, LN-TR2 cells demonstrated increased levels of nuclear AR compared to LNCaP cells. At 1 nM DHT, the anti-androgen bicalutamide stimulated LN-TR2 and inhibited LNCaP proliferation. CONCLUSIONS: Long-term exposure of TNFalpha causes hypersensitivity to DHT in LNCaP and this was associated with increased nuclear AR protein. Furthermore, hypersensitivity to androgen caused anti-androgen withdrawal phenomenon in the presence of DHT although bicalutamide itself did not stimulate LNCaP proliferation without androgen. This result may be one possible mechanism for the anti-androgen withdrawal phenomenon.

[Prospects for molecular research in urological oncology: bladder cancer].

This report consists of a description of our research findings relating to the mechanism of cancer metastasis and target molecules for early diagnosis or cancer therapy. First, we investigated the significance of metastasis-related genes expressed to various extents in three human bladder cancer cell lines using two in vivo models. The relationship between the gene expression pattern and the behavior of cancer cells implicated a loss of E-cadherin expression as a critical factor in facilitating the progression of bladder cancer. Second, we examined the expression of human telomerase reverse transcriptase (hTERT) mRNA in voided urine samples in patients with bladder cancer. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed a higher positive rate as compared with cytological examination, suggesting that the expression of hTERT in urine samples may be a useful diagnostic marker for bladder cancer. Finally, we searched for a molecule to which antisense can be applied as a treatment modality. The 150 kDa oxygen regulated protein (ORP 150), a kind of heat shock proteins, functions as a molecular chaperone in the endoplasmic reticulum. We demonstrated that the adenoviral-mediated antisense ORP150 cDNA transfer resulted in the suppression of vascular endothelial growth factor (VEGF) expression and tumor growth in vivo. In addition, the significant correlation between ORP150 and matrix metalloproteinase 2 (MMP-2) expression was observed in bladder cancer, suggesting that ORP150 functions as a molecular chaperon to MMP-2 secretion for tumor invasion. Anti-sense ORP150 may therefore have a potentially stronger antitumor effect because of its multitargeting capability as a molecular chaperone.

[A case of chromophobe cell renal carcinoma].

We report a case of chromophobe cell renal carcinoma. A 27-year-old male suffered from right flank pain and gross hematuria. Drip infusion pyelography and ultrasonographic examination revealed a right renal mass and it was diagnosed as renal oncocytoma by needle biopsy of the right kidney. He was referred to our hospital for the operation and right radical nephrectomy was performed. The cut surface of the tumor was beige in color. The cytoplasm of the tumor cells stained positively for colloidal iron and showed a negative reaction for Vimentin. From these results, this tumor was given a diagnosis of chromophobe cell renal carcinoma.

Demethylating reagent 5-azacytidine inhibits telomerase activity in human prostate cancer cells through transcriptional repression of hTERT.

Telomerase activation is thought to be a critical step in cellular immortality and oncogenesis. Several reagents including differentiation-inducing and antineoplastic agents are known to inhibit telomerase activity, although the molecular mechanisms through which they inhibit telomerase activity remain unclear. Demethylating reagents have recently been used as potential antineoplastic drugs for some types of cancers including those of the prostate. In the present study, we examined the effect of the demethylating reagent 5-azacytidine (5-aza-CR) on telomerase activity using cells of two prostate cancer cell lines, DU-145 and TSU-PR1. 5-aza-CR treatment significantly reduced telomerase activity in TSU-PR1 cells, but not in DU-145 cells, although growth inhibition was observed to a similar extent in both cell lines. Reverse transcription-PCR analyses revealed that inhibition of telomerase activity was accompanied by down-regulation of telomerase catalytic subunit (hTERT) mRNA expression. Transient expression assays showed that 5-aza-CR repressed the transcriptional activity of the hTERT promoter and that the E-box within the core promoter was responsible for this down-regulation. Western blot analyses revealed that 5-aza-CR reactivated p16 expression and repressed c-Myc expression in TSU-PR1 cells but not in DU-145 cells. Overexpression of p16 in TSU-PR1 cells led to significant repression of c-Myc transcription. These findings suggest that 5-aza-CR inhibits telomerase activity via transcriptional repression of hTERT, in which p16 and c-Myc may play a key role.

[Correlation between expression of metastasis-related genes and lymph node metastasis in testicular cancer].

To investigate the factors related to lymph node metastasis of testicular germ cell tumors, we first established a seminoma orthotopic model with lymph node metastasis in SCID mice by inoculating small fragments from subcutaneous xenografts. Second, we compared the expression patterns of metastasis-related genes of the seminoma xenografts and of the TCam-2 cells which were established as a seminoma cell line from a primary testicular seminoma. Third, we immunohistochemically analyzed human germ cell tumors (25 seminomas, 17 nonseminomas) using monoclonal antibodies to CD34, VEGF, VEGF-C, Flt-4, MMP-2 and E-cadherin. Testicular seminoma xenografts grew in 32/32 (100%) of the inoculated mice, of which 15 (47%) developed macroscopic metastasis to the renal hilar lymph node. Circulating tumor cells were detectable by using a PCR assay for the human beta-globin gene in 25/32 (78%) mice, although metastatic foci were not histologically evident in the visceral organs, including lungs, liver, kidneys and spleen. This may reflect the lymphophilic characteristics of the seminoma cells used. Regarding mRNA expression of metastasis-related genes, an increased expression of MMP-2 and VEGF compared with that in the s.c. xenografts was demonstrated by RT-PCR assay in the testicular seminoma xenografts. In addition, uPAR, MMP-1, MMP-2, MT1-MMP and MT3-MMP showed a a stronger expression and PAI-2 a weaker expression in the seminoma xenografts than did TCam-2 cells. These results suggest a higher metastatic potential of the seminoma xenografts, especially testicular xenografts, as compared with TCam-2 cells. In the immunohistochemical study, a significant correlation was found between MMP-2 expression and lymph node metastasis, which is compatible with the results for the metastasis-related gene expression from the seminoma xenografts.

[Renal cell carcinoma recurrence in the mediastinum lymph node 19 years after nephrectomy: a case report].

A 62-year-old male, who had undergone right nephrectomy to treat renal cancer 19 years earlier, was recently referred to our hospital to receive a detailed examination and treatment of mediastinal lymph node swelling. Biopsy of the swollen lymph nodes allowed a diagnosis of renal cell carcinoma (alveolar type, clear cell subtype, GI) to be made. The pathological features of his tumor were consistent with those of the renal tumor resected 19 years previously. Because there was a high probability of further growth of the swollen mediastinal lymph nodes and consequent high probability of compression of the superior vena cava, we performed mediastinal lymph node excision. Immediately after surgery, prophylactic interferon therapy was started. To date, five cases (including the present case) in which renal tumors recurred more than 15 years after surgical treatment have been reported in Japan.

A human seminoma xenograft model with regional lymph node metastasis.

PURPOSE: To establish a seminoma orthotopic model with lymph node metastasis to investigate the factors related to the lymphophilic behavior of seminoma cells. MATERIALS AND METHODS: Testicular seminoma xenografts were established by the inoculation of small fragments from subcutaneous (s.c.) xenografts that had previously been established in severe combined immunodeficient (SCID) mice with a supraclavicular lymph node metastasis from a human seminoma. Hematologic dissemination of tumor cells was analyzed by polymerase chain reaction (PCR) amplification of the human beta-globin gene. Xenograft messenger RNA levels of metastasis-related genes were examined by reverse transcription (RT)-PCR. RESULTS: Testicular seminoma xenografts grew in 32/32 (100%) of the inoculated mice, of which 15 mice (47%) developed macroscopic metastasis to the renal hilar lymph node. Circulating tumor cells and tumor cell shedding in the lung and liver were detectable by PCR assay in 25/32 (78%), 32/32 (100%), and 27/32 (84%) mice, respectively, although metastatic foci were not histologically evident in these organs. Increased expression of matrix metalloproteinase-2 (MMP-2), membrane-type 3 matrix metalloproteinase (MT3-MMP) and vascular endothelial growth factor (VEGF), and reduction in expression of plasminogen activator inhibitor-2 (PAI-2) were demonstrated by RT-PCR assay in the testicular xenografts as compared with the s.c. xenografts. CONCLUSIONS: This model mimics the lymphophilic behavior of seminoma and may help in elucidating the molecular mechanism of tumor spread via the lymphatics.

Dominant role of E-cadherin in the progression of bladder cancer.

PURPOSE: To elucidate factors with a role in the progression of bladder cancer. MATERIALS AND METHODS: One invasive (T24) and two superficial (RT4 and KK47) human bladder cancer cell lines, which express metastasis-related genes, were used. Cells were intravenously inoculated into chick embryos to evaluate metastatic potential to the liver. An orthotopic model with severe combined immunodeficiency mice was also used to investigate both histological appearance and changes in metastasis-related gene expression. Finally, gene expression patterns in a clinical setting were compared between superficial and invasive bladder cancers. RESULTS: In culture condition metastasis-related genes, including matrix metalloproteinases, urokinase-type plasminogen activator, and integrins alpha2 and alpha3 were continually expressed in T24 but only slightly or not at all in RT4 and KK47, respectively. The expression pattern of the metastasis-related genes in vitro reflected the characteristics of the original tumors. Liver metastasis in chick embryos was demonstrated not only with T24 cells, but also with RT4 cells in which enhanced expression of metastasis-related genes was induced. In the orthotopic model, histological appearances were in accordance with the characteristics of the original tumors, although enhanced gene expression was notable with RT4. Expression of E-cadherin by Western blotting was demonstrated only with RT4 under these experimental conditions. Furthermore, predominant E-cadherin mRNA expression was found in superficial and not in invasive human primary bladder cancers; expression of other genes was similar in the two groups. Dominant expression of E-cadherin in superficial tumors was confirmed by immunohistochemical analysis. CONCLUSIONS: These results implicate loss of E-cadherin expression as a critical factor in facilitating the progression of bladder cancer.

Detection of human telomerase reverse transcriptase messenger RNA in voided urine samples as a useful diagnostic tool for bladder cancer.

Activation of telomerase and stabilization of telomeres are thought to be required for cellular immortality and oncogenesis. Telomerase activity is detected in >90% of various cancers, including urothelial cancers. Of the three subunits comprising telomerase complex, human telomerase reverse transcriptase (hTERT) is a rate-limiting determinant of the enzymatic activity of telomerase. In the present study, spontaneously voided urine specimens from 33 patients with bladder cancer and 26 without bladder lesions were examined for the expression of hTERT mRNA, and the usefulness of detecting hTERT mRNA in urine samples for screening of bladder cancer was evaluated. RT-PCR analysis revealed that approximately 80% of urinary sediments from patients with bladder cancer expressed hTERT mRNA, regardless of clinical stage or pathological grade, whereas only 4% of sediments from patients without urothelial lesions did. Interestingly, hTERT mRNA expression was observed, even in some urine samples from bladder cancer patients with negative urinary cytology. These findings suggest that the expression of hTERT in urine sample may be a useful diagnostic marker for bladder cancer.

A chick embryo model for metastatic human prostate cancer.

OBJECTIVE: To establish a suitable experimental model of bone and liver micrometastases from human prostate cancer for evaluating antitumor agents. METHODS: PC-3 cells, an androgen-independent prostate cancer cell line, were inoculated into the chorioallantoic membrane vein of 10-day-old chick embryos (10(6) cells/egg). The polymerase chain reaction product for the human beta-globin gene in chick embryo femur and liver was quantified at various time points after inoculation, when immunohistochemical staining was done for Ki-67 antigen and cytokeratin. The antitumor effect of suramin was evaluated using the model, as was regional blood flow after thallium injection. RESULTS: Micrometastases were identified in bone and liver 1 day after inoculation and grew to form established metastatic foci in all embryos. Suramin showed significant antitumor effect for liver metastases, but not for those in bone where blood flow was relatively low. CONCLUSION: The chick embryo system provides a highly reproducible model for bone and liver micrometastases from human prostate cancer, suitable for evaluating antineoplastic agents at an early stage of the metastatic process.

Induction of necrosis by zinc in prostate carcinoma cells and identification of proteins increased in association with this induction.

Zinc exhibits inhibitory effects on apoptosis, and a deficiency in this metal generally causes this type of cell death to occur. In the present study, we found that exposure to zinc results in necrosis of prostate carcinoma cells. When zinc acetate was added to LNCaP or PC-3 cells in monolayer culture, they began to detach from the culture dishes, and viability was lost after 4-8 h. Most of the cell death was found to be due to necrosis as determined by double staining with fluorescein-isothiocyanate-labeled annexin V and ethidium bromide, and by detection of hypodiploid cells. Associated with the induction of necrosis was an increase in low molecular-mass proteins, identified by HPLC analysis to be thymosin beta10, parathymosin and GAGE in LNCaP cells, and thymosin beta4, parathymosin and metallothionein in PC-3. The time course of the increase of thymosin beta10 in LNCaP cells and thymosin beta4 in PC-3 cells was consistent with that of appearance of cell detachment and dead cells. These results indicate that zinc can induce necrosis and suggest that production of proteins including beta-thymosins is involved in induction of processes leading to cell detachment.