Effects of bisphosphonates on human esophageal squamous cell carcinoma cell survival.

Esophageal squamous cell carcinoma (ESCC) is one of the most malignant cancers in Japan. Anticancer chemotherapy has been useful for ESCC treatment. However, therapeutic options are limited. Recently, bisphosphonates (BPs), which are osteoporosis drugs, have shown anticancer effects in several cancer cell lines, but the effects against ESCC cell lines are unknown. In this study, we examined the cytotoxic effects of BPs and their mechanisms of cytotoxicity in human ESCC cell lines. A first-generation BP (etidronate), two second-generation BPs (alendronate and pamidronate), and two third-generation BPs (risedronate and zoledronate) were used in this study. All BPs, except etidronate, were cytotoxic, as indicated by increased caspase-3/7 activity and numbers of Annexin-fluorescein isothiocyanate positive cells in ESCC cell lines. From cell cycle analysis, G0/G1-phase arrest was observed upon treatment with second- and third-generation BPs. In addition, Cyclin D1 protein expression levels were decreased by second- and third-generation BP treatment. Although squalene and trans, trans-farnesol minimally affected BP cytotoxicity, treatment with geranylgeraniol inhibited BP cytotoxicity almost completely. We concluded that second- and third-generation BPs are cytotoxic to ESCC cell lines as they induce apoptosis and inhibit the cell cycle through mevalonate pathway inhibition. Therefore, BP treatment may be a beneficial therapy in ESCC patients.

Cost analysis of vestibular schwannoma screening with contrast-enhanced magnetic resonance imaging in patients with asymmetrical hearing loss.

BACKGROUND: Vestibular schwannomas are a rare cause of asymmetrical hearing loss, and routine screening with magnetic resonance imaging can be costly. This paper reports results on vestibular schwannoma screening at our institution and compares the cost of screening to a utility of hearing benefit. METHOD: All screening examinations with magnetic resonance imaging performed for asymmetrical hearing loss between 2006 and 2011 were retrospectively reviewed. The cost per new vestibular schwannoma diagnosis was calculated. The cost per patient for those who benefitted from intervention was estimated based on rates of hearing preservation reported in the literature. RESULTS: Forty-five (4.3 per cent) of 1050 screening examinations with magnetic resonance imaging performed for asymmetrical hearing loss were positive for vestibular schwannoma, and the cost per new diagnosis was $11,436. The estimated screening cost per patient for those who benefitted from surgery or radiation was $147,030, while US federal compensation for unilateral hearing loss was $44,888. CONCLUSION: Although we achieved a lower screening cost per new diagnosis than reported in the current literature, there remains disparity between the screening cost per benefitted patient and the 'benefit' of hearing.

Feature stabilized digital x-ray coronary angiograms improve human visual detection in JPEG compressed images.

We evaluate the effect on human visual detection of a display method that stabilizes the motion of the feature of interest in sequential JPEG compressed x-ray coronary angiogram images. At all levels of image compression the feature stabilized display significantly improved performance with respect to the standard display where the artery is moving. In addition, for both the moving artery and stabilized display, human performance with images compressed at 15:1 was not significantly different from performance with the uncompressed images.

Observer performance for JPEG vs. Wavelet image compression of x-ray coronary angiograms.

Development of "filmless" cardiac catheterization laboratories is eminent. The problems of implementing a digital catheterization laboratory involve archiving large amounts of data per procedure and high transfer rates to retrieve previous procedures. Lossy compression can ccommodate these changes, but at the cost of possibly impairing detection of clinically important angiographic features. Our study involves the observer detection and classification of features in clinical images and the effects that JPEG and wavelet compression have on the detectability of these features. We found no significant degradation in human observer performance with 7:1 and 15:1 JPEG compressed images in 6 clinically relevant visual tasks. Human observer performance for wavelet compression degraded significantly for 2 out of 6 tasks at 7:1 compression and 4 out of 6 tasks at 19:1 compression.

The continuous and simultaneous blood flow velocity measurement of four cerebral vessels and a peripheral vessel during cigarette smoking.

There has been no consensus about the acute effect of cigarette smoking on cerebral blood flow, and the continuous change of flow in four cerebral vessel flow with peripheral flow during different kinds of cigarette smoking has not been reported until now. Our results indicate smoking increases the flow of four cerebral vessels almost at the same time and with the same pattern. Many cerebral vessels began to show increases about 10 s after commencement. In most cases, cerebral blood velocity began to decrease between 10 and 20 s after cessation. Blood flow in peripheral vessels decreases after commencement, which is thought to be the effect of nicotine. The effect of high nicotine cigarettes is greater than that of low nicotine cigarettes. Continuous and simultaneous measurement of cerebral vessels by ultrasonic Doppler is though to be the only way to establish the detailed blood flow changes during smoking.

Homologous orthotopic implantation models of pancreatic ductal cancer in Syrian golden hamsters: which is better for metastasis research--cell implantation or tissue implantation?

With a nitrosamine induced hamster pancreatic cancer cell line (HaP-T1), survival time and metastatic rates were compared between orthotopic cell implantation (OCI; n = 5) and orthotopic tissue implantation (OTI; n = 5) models. All the tumors were palpable (100% tumor take) after 1 week in both groups. Hamsters in the OCI group survived 71 +/- 2.17 days (range, 69-75 days), and in the OTI group, 73.8 +/- 4.03 days (range, 58-80 days). After necropsy, spontaneous metastases were noted in 100% of the animals. Direct invasion to adjacent organs was observed in four animals, and liver metastases, in three in the OTI group, which were significantly higher compared with the OCI group. On the other hand, peritoneal dissemination was observed only in the OCI group. Other metastatic sites showed no significant difference between the groups. All the histologically noted metastases had K-ras point mutation confirmed by polymerase chain reaction-restriction fragment length polymorphism (PCR/RFLP) analysis. We conclude that the homologous OTI model may be more useful than the OCI model. The OTI model may contribute to the development of therapeutic strategies in the field of pancreatic cancer research because of the capacity for invasion to adjacent organs, higher liver metastatic rate, and similarity to the clinical picture of the disease.

Automatic correction of biplane projection imaging geometry.

A novel method is presented for correcting errors in measurements of biplane projection imaging geometry without prior identification of corresponding points in the two images. For imaged objects that project onto both images, a constraint equation is obtained that relates weighted integrals along corresponding epipolar lines. The integrals are computed to first order in the angular beamwidth, which is assumed to be small. Starting from measured or estimated values, geometrical parameters are computed iteratively in order to maximize the correlation between epipolar line integrals in the two images. Improvement in the computation of corresponding epipolar lines is demonstrated on images of a wire phantom. The root mean square distance of the epipolar lines from the corresponding reference points is improved from 15 pixel widths to less than 4 pixel widths (1.3 mm). Convergence is demonstrated on phantom images for individual parameter variations up to 70% in relative magnification, a relative shift of the imaging planes by 50 pixels, or a relative rotation of at least 35 degrees around either of two axes. Applicability to clinical images is demonstrated by using a biplane angiogram of a pig to align corresponding points determined from images of a Perspex cube acquired with the same geometry.

Simulating coronary arteries in x-ray angiograms.

Clinical validation of quantitative coronary angiography (QCA) algorithms is difficult due to the lack of a simple alternative method for accurately measuring in vivo vessel dimensions. We address this problem by embedding simulated coronary artery segments with known geometry in clinical angiograms. Our vessel model accounts for the profile of the vessel, x-ray attenuation in the original background, and noise in the imaging system. We have compared diameter measurements of our computer simulated arteries with measurements of an x-ray Telescopic-Shaped Phantom (XTSP) with the same diameters. The results show that for both uniform and anthropomorphic backgrounds there is good agreement in the measured diameters of XTSP compared to the simulated arteries (Pearson's correlation coefficient 0.99). In addition, the difference in accuracy and precision of the true diameter measures compared to the XTSP and simulated artery diameters was small (mean absolute error across all diameters was < or = 0.11 mm +/- 0.09 mm).

Accuracy assessment of layer decomposition using simulated angiographic image sequences.

Layer decomposition is a promising method for obtaining accurate densitometric profiles of diseased coronary artery segments. This method decomposes coronary angiographic image sequences into moving densitometric layers undergoing translation, rotation, and scaling. In order to evaluate the accuracy of this technique, we have developed a technique for embedding realistic simulated moving stenotic arteries in real clinical coronary angiograms. We evaluate the accuracy of layer decomposition in two ways. First, we compute tracking errors as the distance between the true and estimated motion of a reference point in the arterial lesion. We find that noise-weighted phase correlation and layered background subtraction are superior to cross correlation and fixed mask subtraction, respectively. Second, we compute the correlation coefficient between the true vessel profile and the raw and processed images in the region of the stenosis. We find that layer decomposition significantly improves the correlation coefficient.

Subcutaneously inoculated cells and implanted pancreatic cancer tissue show different patterns of metastases in Syrian golden hamsters.

CONTEXT: We studied behavior of the subcutaneously implanted pancreatic tumors and the process of metastasis using syngeneic Syrian golden hamsters. DESIGN: HaP-T1, a cell line derived from nitrosamine-induced pancreatic cancer in Syrian golden hamsters was used for this experiment. Thirty-five animals were divided into two groups: subcutaneous cell inoculation and subcutaneous tissue implantation. The tumor tissue was obtained from subcutaneously implanted cancer cells. One month after implantation, the tumors were resected and studied histopathologically. The animals were followed-up weekly by palpation of the peripheral lymph nodes in order to identify local recurrence. After death, necropsy was performed. Liver, lungs and pancreas specimens were taken for histopathogical study and detection of K-ras point mutation using the PCR/RFLP method. RESULTS: The mean survival time in the subcutaneous cell inoculation group was 151+/-17.5 days, and in the subcutaneous tissue implantation group was 137 +/-12.9 days. During the follow-up, 13 subcutaneously cell inoculated hamsters (86.7%) had right axillary lymph node metastasis while subcutaneously tissue implanted hamsters did not show any palpable lymph nodes. After necropsy, 10 of the 20 subcutaneously tissue implanted animals (50%) showed metastases in the lungs at the histopathological level. However, 16 of the 20 subcutaneously tissue implanted animals (80%) showed K-ras point mutation in the lung specimens. The lungs of the animals of the subcutaneous cell inoculation group did not show any metastases. No metastases were found in the liver or the pancreas in either group. CONCLUSION: This study suggests that homologous subcutaneous cell inoculation and subcutaneous tissue implantation models showed completely different patterns of metastasis. These models may aid further research to clarify the mechanisms of metastasis in pancreatic cancer.

"Return trip" metastases from the liver to the pancreas in Syrian golden hamsters.

In 1889, Paget suggested that metastases resulted only when "seed" (certain tumor cells) and "soil" (specific affinity for certain organs) were matched. We report here, the results of implantation of a hamster nitrosamine-induced pancreatic cancer tissue into the liver in six animals and the resulting metastases to the "primary organ". Survival time and metastatic sites at necropsy were studied. Tumor growth in the primary implantation site was observed in 5 out of 6 hamsters (83.3%) that died of cancer. Survival time ranged from 82 to 199 days. Metastases were found in the splenic lobe of the pancreas in all 5 (100%) successfully-implanted animals. This homologous implantation model of "return trip" in metastasis may be a useful tool for further research about the process of cancer metastasis. Moreover, it may be useful especially in the assessment of the "seed and soil" hypothesis.

The evolution of the concentric lesions of atypical multiple sclerosis on MRI.

We studied a patient with atypical multiple sclerosis (MS) using high field magnetic resonance image scanning and documented the evolution of the lesions from the acute phase to clinical remission. The acute lesions showed the clear concentric structure that is characteristic of Balo's concentric sclerosis on magnetic resonance imaging (MRI). Lesions were enhanced with gadolinium-DTPA (Gd-DTPA). Over a four-month period, the patient recovered clinically, with some evidence of residual intellectual impairment, and the MRI lesions regressed markedly, leaving hypointense areas on T1-weighted images in the corona radiata.

[Feasibility study of quality of life (QOL) instrument in patients with advanced lung cancer].

We have studied the feasibility of the QOL measurement for the group of patients with advanced lung cancer using the QOL questionnaires modified from FLIC (Functional Living Index Cancer). The 16-items instrument showed that the Cronbach's alpha of all categories were over 0.6. as the quality of reliability. Using the principal component method of multivariate analysis, four major factors were identified as a part of the construct validity. We concluded that the QOL of patients with advanced lung cancer under the clinical research setting can be evaluated using this questionnaires even in Japan which has different cultural background from the Western Countries.

Curative resection of orthotopically implanted pancreatic cancer in Syrian golden hamsters.

BACKGROUND: Homologous orthotopic implantation models of pancreatic ductal cancer in Syrian golden hamsters can mimic the clinical features of the disease in humans. However, there have been no studies attempting a surgical approach to this animal model. Our aim was to clarify the possibility of curative resection in these tumor-bearing animals. METHODS: A nitrosamine-induced pancreatic ductal adenocarcinoma cell line, HaP-T1, was used for the experiments. Hamsters underwent two surgeries: first, the cells or the tissue previously grown subcutaneously were implanted into the pancreas, and second, pancreatectomy and splenectomy were performed within the following 4 wk after implantation. Animals were examined until death, when necropsies were performed. Surgically resected and necropsied specimens were studied histopathologically and at the molecular level by detection of K-ras point mutation at codon 12. RESULTS: At the second surgery, the success of implantation was 100%, and the curative resection rate was 75%. After observation for 400 d, 5 of 12 hamsters, which underwent second surgery within 15 d, were still alive. They were sacrificed and were found to be tumor-free. CONCLUSION: Orthotopic homologous implantation model of hamster pancreatic cancer combined with surgical resection may be useful for further research of adjuvant or neoadjuvant therapy for pancreatic carcinoma.

Rapid recovery from anorexia nervosa after a life-threatening episode with severe thrombocytopenia: report of three cases.

We report the cases of three patients with anorexia nervosa (AN) who each recovered rapidly after experiencing a life-threatening episode with severe thrombocytopenia. All three cases were the typical restricting-type of AN, occurring in adolescence. They refused to be admitted to a hospital until their general condition had been severely deteriorated. Their lowest platelet counts were 2.9, 4.6, and 2.3 x 10(4)/mm3, respectively. Apparent hemorrhagic tendencies, such as purpura, gingival and nasal bleeding, and gastrointestinal bleeding were observed. The bone marrow examination showed apparent hypoplasia in two patients. No evidence of disseminated intravascular coagulation or autoantibody to platelets was detected. The platelet counts recovered rapidly by water and nutritional supplementation. The recovery from the AN itself was excellent in all three patients without specific psychotherapy.

Growth inhibition of human pancreatic cancer cell lines by anti-sense oligonucleotides specific to mutated K-ras genes.

About 90% of human pancreatic cancers carry K-ras point mutation, which may play an important role in tumorigenesis. We investigated the inhibitory effects of anti-sense oligonucleotides targeting K-ras point mutation on the growth of cultured human pancreatic cancer cells. Eight human pancreatic cancer cell lines were screened for K-ras codon 12 point mutations by PCR-RFLP analysis and direct sequencing. Then, 3 cell lines with the major types of K-ras point mutation, i.e.,HuP-T1, HuP-T3 and PANC-1, and 1 without mutation, BxPC-3, were used for the experiments. Seventeen mer anti-sense oligonucleotides were designed, targeting the point mutation of K-ras codon 12, and transfected into the cells by the liposome-mediated method. Cell-growth activities were estimated by MTT assay. Levels of K-ras mRNA expression were determined using quantitative RT-PCR, and K-ras p21 protein synthesis was evaluated with Western blotting. Mutation-matched anti-sense oligonucleotides effectively inhibited the growth of these pancreatic cancer cell lines, except for BxPC-3, by suppressing K-ras mRNA expression and K-ras p21 protein synthesis. Moreover, mutation-matched anti-sense oligonucleotides showed stronger anti-proliferative effects than did mutation-mismatched ones. Our results suggest that anti-sense therapy specific to point mutations of K-ras mRNA is a practical approach to selective suppression of tumor growth, with little effect on normal cells.

Psychological stress in middle-aged and aged executives.

Neurotic symptoms were considered to be present in 21.9% of the 210 employees of a company following data analysis from a General Health Questionnaire (GHQ, 60 question items). The results in middle-aged and aged executives were compared. The total GHQ score was > or = 17 in 18/55 executives aged 40 years or above, but in only 9/60 non-executives controls was a significant difference observed (P < 0.05) between executives and non-executives. The scores for three subordinate scales, namely somatic symptoms, anxiety and insomnia, and social dysfunction, were higher in the executives than in the non-executives and showed a significant difference (P < 0.05) in the anxiety and insomnia scale. These results suggest that middle-aged and aged executives are more likely to have neurotic symptoms and more frequently to have anxiety and insomnia than their controls. We would like to apply this method to aid in the prevention, early detection and early management of stress.

Higher cerebral dysfunction in a case with atypical multiple sclerosis with concentric lesions.

A patient with atypical multiple sclerosis (MS) with clear concentric structure was studied using high field magnetic resonance imaging (MRI). This case was considered to be Baló's concentric sclerosis. Magnetic resonance imaging showed diffuse multiple concentric demyelinating lesions in the bilateral centrum semiovales, which finally regressed with the necrotic lesions remaining when the patient was discharged. During his clinical course, he showed some higher cerebral dysfunctions, such as memory disturbance, constructual apraxia and acalculia. He was treated with glycerin, prednisone and rehabilitation; all of which were effective in his recovery. Over a 4 month period, the patient recovered clinically, but some intellectual impairment remained.

Diagnosis of breast calcifications: comparison of contact, magnified, and television-enhanced images.

Matched contact and microfocal-spot-magnified images of 31 breasts, each containing a cluster of microcalcifications within a biopsy-proved benign (n = 21) or malignant (n = 10) lesion, were evaluated. Each matched set consisted of one image magnified 1.5 or 2.0 times by a microfocal spot; one contact film-screen mammogram; and one television-digitized, enhanced, and optically magnified contact film-screen mammogram. Three experienced mammographers and three senior diagnostic radiology residents with 2 weeks of training in mammography interpreted the calcifications. The average area under the receiver-operating-characteristic curve for the experienced mammographers was 0.60 for contact radiographs, 0.61 for the television-digitized images, and 0.69 for the microfocal-spot-magnified radiographs. The less experienced senior residents scored below a random choice, 0.44, for the television-digitized images; 0.51 for contact radiographs; and 0.69 for the microfocal-spot-magnified radiographs. We conclude that when evaluating microcalcifications, radiologists without extensive experience in mammography should not substitute television-digitized and enhanced contact mammograms for microfocal-spot-magnified mammograms; rigorous clinical evaluation is needed before this system is accepted for clinical use.

Comparison of 2048-line digital display formats and conventional radiographs: an ROC study.

Observer performance tests were conducted to compare the effects on diagnostic accuracy of digital hard copy and video display formats versus conventional radiographic film. Digital images were obtained by digitizing conventional chest radiographs to a 2048 x 2048 matrix with a laser film scanner. Three digital display formats were used: laser-printed digital film, a 2048-line video monitor without user interaction, and a 2048-line video monitor with user interaction. Thirty-one posteroanterior chest radiographs, determined by consensus of four thoracic radiologists to contain septal lines (n = 11), parenchymal nodules (n = 7), nodules and septal lines (n = 7), or neither abnormality (n = 6), were used for the study. Images were interpreted by four radiologists in four separate viewing sessions. Diagnostic accuracy was determined by receiver-operating characteristic analysis for each observer with each viewing technique. No statistical differences in diagnostic accuracy, determined by the area under the receiver-operating-characteristic curve, were found between the analog film, the digital film, and the two video digital display formats. This preliminary study suggests that 2048-line digital displays may be an acceptable alternative to the traditional lightbox viewing method for the perception of these two abnormalities commonly seen on chest radiographs.