Utility of synthetic MRI in predicting pathological complete response of various breast cancer subtypes prior to neoadjuvant chemotherapy.

AIM: To evaluate the usefulness of synthetic magnetic resonance imaging (MRI) performed before the initiation of neoadjuvant chemotherapy (NAC) in predicting whether breast cancers can achieve a pathological complete response (pCR) after the completion of NAC. MATERIALS AND METHODS: This retrospective study investigated 37 consecutive patients with 39 breast cancers (pCR: 14, and non-pCR: 25) who underwent dynamic contrast-enhanced (DCE)-MRI and synthetic MRI before the initiation of NAC. Using synthetic MRI images, quantitative values (T1 and T2 relaxation times, proton density [PD] and their standard deviations [SD]) were obtained in breast lesions, before (Pre-T1, Pre-T2, Pre-PD, SD of Pre-T1, SD of Pre-T2, SD of Pre-PD) and after (Gd-T1, Gd-T2, Gd-PD, SD of Gd-T1, SD of Gd-T2, SD of Gd-PD) contrast agent injection. The aforementioned quantitative values and several morphological features that were identified on DCE-MRI were compared between pCR and non-pCR. RESULTS: Multivariate analyses revealed that the SD of Pre-T2 (p=0.038) was significant and was an independent predictor of pCR, with an area under the receiver operating characteristics curve of 0.829. The sensitivity, specificity, and accuracy of the SD of Pre-T2 with an optimal cut-off value of 11.5 were 71.4%, 80%, and 76.3%, respectively. CONCLUSIONS: The SD of Pre-T2 obtained from synthetic MRI was used successfully to predict those breast cancers that would achieve a pCR after the completion of NAC; however, these results are preliminary and need to be verified by further studies.

Considerations on the Factors Influencing Living Kidney Donors' Autonomous Decision-Making: A Systematic Literature Review.

As outcomes of organ transplantation have improved with advances in medicine, managing medical ethics issues has become increasingly more important. Although a basic consensus has been formed on the respect of autonomy in decision-making by prospective donors regarding living kidney transplantation, concrete and practical measures at the clinical site are required to ensure donor autonomy. The aim of the study was to identify elements related to autonomy in the kidney donor decision-making process. METHODS: We systematically collected relevant studies from multiple databases in and out of Japan and conducted qualitative and inductive analyses. RESULTS: The identified elements were categorized into 12 subcategories and then regrouped into the following 4 categories based on the similarity of the contents: donor personality and values, inability to fully understand the implications of donation, possibility of direct pressure on donor's decision-making process, and donor's environment and situation. DISCUSSION: The autonomy-related elements were highly diverse, including obvious pressure upon the donor and their values as well as influences from health care professionals. Some elements had room for change, such as the informed consent procedure, while some elements were unchangeable. Other elements were changeable by intervention, but discussion is required about the appropriateness of the intervention itself. Further, a classification of clinical approach was suggested by the development of an analytical framework using 2 axes of "site where the element arises" and "room for change" based on the practical viewpoint of clinical circumstances.

Different views on treatment decisions by first-year interprofessional healthcare students.

This study explored ethical treatment decisions of healthcare professional students beginning their education. As part of a first-semester modern medicine and bioethics course, 311 students watched and discussed, in interprofessional groups, a video titled Dax's Case: Who Should Decide? regarding the treatment of a life-threatening infectious disease against Dax's wish. The students then discussed and made their decision regarding treating or not. Their decisions, recorded on a worksheet, were classified as "will treat" or "won't treat." Professional groups' decision patterns were compared using the chi-square test. Overall, 151 (71%) opinions from students were classified as "will treat," and 61 (29%) as "won't treat." Nursing students were more likely to decide "won't treat" (in line with Dax's preference); however, the majority of other professions' students favoured treatment (against Dax's wish). Given the students' limited exposure to profession-specific education, our preliminary study supports the notion that healthcare profession students hold different values that align with their chosen profession at the start of their studies.

Real-time time-dependent density functional theory approach for frequency-dependent nonlinear optical response in photonic molecules.

We present ab initio calculations of frequency-dependent linear and nonlinear optical responses based on real-time time-dependent density functional theory for arbitrary photonic molecules. This approach is based on an extension of an approach previously implemented for a linear response using the electronic structure program SIESTA. Instead of calculating excited quantum states, which can be a bottleneck in frequency-space calculations, the response of large molecular systems to time-varying electric fields is calculated in real time. This method is based on the finite field approach generalized to the dynamic case. To speed the nonlinear calculations, our approach uses Gaussian enveloped quasimonochromatic external fields. We thereby obtain the frequency-dependent second harmonic generation beta(-2omega;omega,omega), the dc nonlinear rectification beta(0;-omega,omega), and the electro-optic effect beta(-omega;omega,0). The method is applied to nanoscale photonic nonlinear optical molecules, including p-nitroaniline and the FTC chromophore, i.e., 2-[3-Cyano-4-(2-{5-[2-(4-diethylamino-phenyl)-vinyl]-thiophen-2-yl}-vinyl)-5,5-dimethyl-5H-furan-2-ylidene]-malononitrile, and yields results in good agreement with experiment.

Bicalutamide 80 mg combined with a luteinizing hormone-releasing hormone agonist (LHRH-A) versus LHRH-A monotherapy in advanced prostate cancer: findings from a phase III randomized, double-blind, multicenter trial in Japanese patients.

To compare combination therapy with bicalutamide 80 mg and a luteinizing hormone-releasing hormone agonist (LHRH-A) versus LHRH-A alone in Japanese men with untreated advanced prostate cancer. A total of 205 patients with stage C/D prostate cancer were randomized to either LHRH-A+once-daily oral bicalutamide 80 mg or placebo. Primary study variables have been reported previously. Secondary variables included: time to achieve prostate-specific antigen < or = 4 ng/ml, time-to-treatment failure (TTTF), time-to-disease progression (TTP), overall survival (OS), adverse events and adverse drug reactions. Following combination therapy with bicalutamide 80 mg, there were significant (P<0.001) advantages over LHRH-A alone in terms of TTTF and TTP, but the difference in the interim OS was not statistically significant. First-line combination therapy with bicalutamide 80 mg in Japanese patients with advanced prostate cancer offers significant benefits over LHRH-A alone, with respect to TTTF and TTP. Follow-up for OS continues.

Laparoscopic radical retropubic prostatectomy combined with approaches through a small open incision.

PURPOSE: The laparoscopic technique is now applied to radical prostatectomy. However, even in laparoscopic prostatectomy, we need a small open wound to remove the prostate from the abdomen. We have developed a modified technique of extraperitoneal laparoscopic radical prostatectomy, exploiting this small open wound as a route for surgical manipulations as well. Here, we described our technique and its initial outcomes. PATIENTS AND METHODS: An extraperitoneal retropubic space was developed with finger manipulations through a 3- to 5-cm long suprapubic incision. Three or four trocar ports were set up. A specially designed abdominal wall-lifter was applied to create an endoscopic working space. The surgeons worked using open or endoscopic manipulations through the suprapubic incision or the trocar ports. From October 2000 to August 2001, 11 patients with prostate cancer underwent this surgery. RESULTS: We completed surgery endoscopically without major complications except in one case in which we could not identify a bleeding source. Surgical time ranged from 229 to 469 min. Blood loss ranged from 550 to 3797 ml including urine spilled in the surgical field. Urinary continence returned in 10 cases at 1 to 8 months after surgery. One patient still needed pads at 3 months after surgery. CONCLUSION: Our technique allowed us to avoid insufflation of the abdomen with gas and intraperitoneal surgical intervention that are disadvantages of conventional laparoscopic prostatectomy, offering the same advantages as conventional laparoscopic prostatectomy.

The inorganic and organic characters for predicting bioconcentration on wide variety of chemicals in fish.

The applicability of Fujita's inorganic (i) and organic (o) characters as descriptors for predicting bioconcentration factor (BCF) in fish was investigated with a wide variety of organic chemicals. Among 612 BCF data recently released by National Institute of Technology and Evaluation (NITE), the values for the chemicals with a molecular weight of less than 600 and the 1-octanol/water partition coefficient (log P) of less than six were extracted and analyzed. By applying theoretically derived model equation, a good relationship between these BCF and each Fujita's sigma i: sigma o was established. Statistical analyses and model validations revealed that the estimations of our approach were very excellent. More precise predictions were attained than those by using other published models, especially, for chemicals such as disperse dye having hetero atoms.

[Pneumatosis intestinalis after allogeneic bone marrow transplantation for acute lymphocytic leukemia].

A 45-year-old man was diagnosed as having acute lymphocytic leukemia (ALL) in February 1997. Complete remission was achieved by chemotherapy, and allogeneic BMT from his HLA-identical sister was performed on November 13, 1997. He developed acute GVHD (grade II), but quickly recovered after methyl-PSL pulse therapy. On June 5, 1998--day 202 after BMT--abdominal pain developed. X-ray and CT examinations showed pneumatosis intestinalis, pneumoperitoneum, pneumomediastinum and abdominal free air. We performed oxygen administration and methyl-PSL pulse therapy, and this quickly improved the symptoms. Corticosteroid and chronic GVHD were thought to be the causative factors of pneumatosis intestinalis in this case. Although pneumatosis intestinalis is relatively rare, it is one of the important potential complications that can occur after allogeneic BMT.

Histopathologic analysis of angiogenic factors in localized renal cell carcinoma: the influence of neoadjuvant treatment.

BACKGROUND: This study was conducted in order to clarify whether histopathologic analysis of factor thymidine phosphorylase (TP) and Factor VIII could be a useful predictor of postoperative recurrence in localized renal cell carcinoma. Therefore, the relationship between tumor infiltrated lymphocytes (TIL) and both TP and Factor VIII was studied. METHOD: Of the 71 patients who underwent surgery, 54 patients had no neoadjuvant therapy (group 1), 10 patients were preoperatively administered IFN-gamma (group 2), and the remaining seven patients preoperatively received IFN-gamma and transarterial embolization (group 3). Both TP and Factor VIII immunostaining were performed on formalin-fixed, paraffin-embedded archival tissue from 71 renal cell carcinoma specimens, while TIL immunostaining was performed on frozen sections. Positive immunostaining was quantitatively scored by a computer-assisted digital image analysis. For TIL, positive results were semiquantitatively scored. RESULTS: A significant difference in the recurrence-free rate was recognized for Groups 1, 2 and 3 (P < 0.05). Therefore, the median TP-positive rate (PR), VIII-PR, number of microvessels and positive mean vascular area levels were investigated, between the recurrence cases (n = 6) and the recurrence-free cases (n = 11). Only the TP-PR levels showed a significant difference among them (P = 0.044). In regards to the neoadjuvant cases, a significant correlation was observed between both VIII-PR and CD4 (r = 0.815) as well as between VIII-PR and CD11b (r = 0.756). CONCLUSION: There was no clear evidence that the neoadjuvant treatment would increase the recurrence-free survival in patients with localized renal cell carcinoma. TP-PR might be a predictor of postoperative recurrence in patients with localized renal cell carcinoma.

Genetic heterogeneity of surgically resected prostate carcinomas and their biopsy specimens is related to their histologic differentiation.

BACKGROUND: In human prostate carcinogenesis, many genetic analyses including conventional loss of heterozygosity (LOH) studies and microsatellite LOH analyses using the polymerase chain reaction method have revealed frequent LOH events at specific regions on chromosomes 3p, 7q, 8p, 10q, 16q, 17q, and 18q. METHODS: Using the laser-captured microdissection method, the authors extracted genomic DNA from 23 cases of prostate carcinomas including 59 different lesions and 8 biopsy specimens. Using (32)P-labeled primers, the authors analyzed six microsatellite loci (D3S647, D3S1228, D7S522, D8S137, NEFL, and D10S190) at which frequent LOH events have been reported. RESULTS: Of 10 cases in which the authors found LOH at any of the loci, 8 cases showed a heterogeneous LOH pattern. In four cases, the authors also found replication error (RER) at some of the loci examined. There was no significant relation between histologic differentiation and frequency of LOH or RER events. The overall LOH rate was found to be significantly lower in foci at classification pT2 (1 of 28 foci, 3%) compared with those at classification pT3 (13 of 44 foci, 30%). In pT3 samples, LOH events in extraglandular foci (9 of 23 foci, 39%) tended to be more frequent compared with those in intraglandular foci (8 of 41 foci, 20%). The patterns of LOH events in biopsy specimens correlated well with those in foci from surgical material showing the same histologic characteristics. CONCLUSIONS: Prostate carcinoma is a genetically multicentric carcinoma, and the genetic heterogeneity is well correlated with histologic differentiation. The frequency of LOH events increased according to the degree of tumor progression.

A new type of surgical adhesive made from porcine collagen and polyglutamic acid.

We have developed a new adhesive for surgical use. The new adhesive is made of three components: porcine collagen, poly(L-glutamic acid) and water-soluble carbodiimides (WSC). The optimum concentration of each component was determined by measuring the time required for gel formation in experiments in vitro. Using these optimum concentrations, we applied the adhesive to wounds made on rats. A conventional fibrin glue was used as a control. Measurement of tensile strength and histological examination were performed 5, 7, 10, and 14 days after the operation. The tensile strength of wounds treated with 2.5 mg/mL collagen glue was not significantly different from that of wounds treated with fibrin glue except at 7 days after the operation (p < 0.05 by Student's t-test). Histological examination revealed that the speed of cell infiltration into, and absorption of 2.5 mg/mL collagen glue was slower than for fibrin glue, but faster than for 5.0 mg/mL collagen glue. One of the important advantages of our collagen glue is that the absorption rate of it can be controlled by the collagen concentration. Therefore, it seems to be adequate for sealing air leakage from the lung, which takes a relatively long period for recovery. Moreover it does not contain human serum, and, hence, it requires no blood donation and can be obtained with low cost.

Lack of allelic exclusion and isotype switching in B cell chronic lymphocytic leukemia.

Two rearranged bands of the IgH gene were detected in a case with B cell chronic lymphocytic leukemia (B-CLL). The expressed VH gene was only VH1 with no somatic mutations in IgM and IgD. The expressions of C mu, C delta, and C gamma were detected by reverse transcription of RNA followed by the polymerase chain reaction (RT-PCR). Sequence analysis of the CDR3 regions of each PCR reaction product showed that the sequence of one rearranged allele was identical to those of the expressed VH1 gene, C mu and C delta, and the sequence of another rearranged allele was identical to that of C gamma. However, none of the expressed VH genes was detected in IgG. These findings suggest that this is a case of B-CLL lacking allelic exclusion and undergoing a class switch of one allele with the incomplete expression of the VH gene.

[Influence of erectile dysfunction on daily life and general attitudes towards treatments].

OBJECTIVES: This study investigates the influence of erectile dysfunction (ED) on daily life and the attitude of citizens toward ED treatments. MATERIALS AND METHODS: A mail survey targeting married males and females, aged 30-79, was conducted throughout the nation. The effective responses were 2,034 males and 1,820 females. RESULTS: The ED prevalence rate of male respondents was 29.9% and that of females (indicating the recognition of husband's ED) was 30.1%. For both males and females, the frequency of sexual intercourse and satisfaction about their sexual lives were significantly lower in respondents with ED. 23.6% of males with ED and 16.0% of females whose husbands have ED experienced a negative influence of their married lives. Among male ED sufferers, however, only 4.8% of them had consulted a physician. The reasons cited most often for not consulting a physician were: "no influence on daily life", "not annoyed by ED", and "no interest in sex", Moreover, the barriers to visiting physicians were frequently cited, such as "shyness", "don't know which hospital to go to", and "expensive". With regard to insurance coverage of ED treatment, 80% or more of both men and women say that "it should be reimbursed for all ED patients" or "it should be conditionally reimbursed". CONCLUSIONS: It becomes clear that ED is found at considerable frequency. However, only 4.8% of ED patients had received appropriate treatment at medical facilities. With regard to insurance coverage for ED treatment, it turned out that 80% or more of both men and women supported reimbursement for ED treatment.

Morphometric analysis, at electron microscope level, combined with hormone assay of nonfunctioning adrenocortical adenomas: comparison with aldosterone-producing adenomas.

We performed electron microscopic studies of eight nonfunctioning adrenocortical adenomas (NFA) and nine aldosterone-producing adenomas (APA) obtained from surgical specimens. A comparison of these two types of adenomas was conducted by morphometric analysis of random electron micrographs. The organelles measured included mitochondria (M), smooth-surfaced endoplasmic reticulum (SER), rough-surfaced endoplasmic reticulum (RER), lipid vacuoles (LV), and lysosomes (Ly). The content of steroid hormones, including 17-alpha hydroxyprogesterone (17-OHP), aldosterone (Ald), and other steroid hormones, was measured in adenoma tissue from six NFA and eight APA. The percentages of the areas of the organelles M, SER, and RER per total cell area in the NFA were significantly lower than those in the APA. The average content of Ald in adenoma tissues in APA was markedly higher than that in the NFA, while the mean content of 17-OHP in the NFA was significantly higher than that in APA. In conclusion, NFA are morphometrically characterized by a reduction in organelles such as M, SER, and RER, compared with findings in APA. From the quantitative analysis of steroid hormones, it was suggested that NFA produce more precursor substances with less hormone activity than APA and that steroidgenesis in NFA is shifted to a glucocorticoid pathway, as indicated by the elevated 17-OHP concentration.

[HPLC-separation of racemic cyclohexane-1,2-diamine platinum(II) dimyristates on chiral stationary phases] . / Zur Trennung racemischer Cyclohexan-1,2-diamin-Platin(II)-dimyristate durch HPLC an chiralen stationären Phasen.

In this paper, the stereochemical resolution of racemic cyclohexane-1,2-diamine platinum(II) dimyristates on chiral stationary phases (CSP) is described. These CSP are Pirkle phases chiral column (Sumichiral OA-2500, 3100, 3200, 3300, 4000, 4100). Among them, the Sumichiral OA-2500 column gave the best results. The effects of the temperature and mobile phase composition as well as the hydrophobicity of the analytes on the chromatographic separation are described.

Intrathoracic esophageal replacement with a collagen sponge--silicone double layer tube: evaluation of omental-pedicle wrapping and prolonged placement of an inner stent.

In a previous study, we replaced a 5 cm gap created in the canine intrathoracic esophagus with an artificial esophagus. However, although newly formed esophageal tissue subsequently bridged the gap, mild stenosis occurred, and this seemed to be caused by inadequate regeneration of the skeletal muscle. In the present study, we evaluated whether omental pedicle wrapping (OMPx) of the prosthesis could promote tissue regeneration and whether prolonged retention of the silicone tube within the prosthesis could prevent stenosis. A gap was created in 14 dogs, and the defect was repaired by our prosthesis. OMPx was performed in 5 of the 14 dogs (OMPx group) but not in the rest (control group). The silicone tube was retained for 4 weeks in the control group and for 8 weeks in the OMPx group. All of the dogs in the control group survived for more than 3 months, except for those that were killed. Four dogs in the OMPx group died within 3 months, one caused by perforation at 7 months. Only the thin epithelial and submucosal layer regenerated in the OMPx group. OMPx is not effective for promoting tissue regeneration, and prolonged retention of the silicone tube interrupts epithelial regeneration.

Differential expression of three types of nitric oxide synthase in both infarcted and non-infarcted left ventricles after myocardial infarction in the rat.

In the present report we investigated the differential expression of three types of nitric oxide synthase (NOS) in the left ventricle after myocardial infarction in rats. One, 3, 7, 14, 28 and 56 days (n=6-12 for each group) after ligation of a coronary artery, tissue samples were obtained from infarcted and non-infarcted tissues. The mRNA and protein levels of neuronal (n) NOS, endothelial (e) NOS and inducible (i) NOS were sequentially determined by semi-quantitative reverse transcription-polymerase chain reaction and Western blotting. Progressive left ventricular dilatation and gradual reduction in fractional shortening were confirmed by echocardiography. The expression levels of nNOS were significantly increased 1, 3 and 7 days post-infarct compared to those of sham-operated rats in both the infarcted (P<0.01) and non-infarcted regions (P<0.01). Immunohistochemical analysis showed that nNOS was localized in nerve fibers in the left ventricle and that the number of positive fibers after myocardial infarction had increased compared to that in sham-operated rats. With regard to eNOS, no significant changes in expression levels were detected between infarcted hearts and sham-operated controls. The level of iNOS expression peaked three days post-infarct and then decreased in the infarcted tissue, whereas it increased one day post-infarct, peaked at 14 and 28 days post-infarct and was still elevated in the chronic stage in the ventricular septum. iNOS immunoreactivity was detected in spared cardiomyocytes and macrophages in the infarcted region, and in cardiomyocytes in the ventricular septum. The expressions of three types of NOS were differentially regulated and iNOS produced in the non-infarcted region may contribute to the progression of heart failure after myocardial infarction in rats.

[MALT lymphoma producing IgG-kappa type M-protein].

A 72-year-old woman, who has been administered prednisolone and azathioprine with diagnoses of idiopathic thrombocytopenic purpura (ITP) and autoimmune hepatitis (AIH), underwent a complete medical examination because of monoclonal gammopathy (IgG-kappa). Tumors were found in the ileum and descending colon. Pathological examination of biopsy specimens suggested a diagnosis of marginal zone B-cell lymphoma of the MALT type with a high-grade component. Flow cytometric analysis by two-color staining revealed that the neoplastic B cells expressed CD38, CD19, IgG and kappa, but not CD5 or CD10. There were no abnormal plasma cells in bone marrow smears. The patient achieved complete remission after receiving three cycles of THP-COP chemotherapy, which resulted in a decrease of the IgG level to within the normal range. These findings indicated that monoclonal IgG-kappa might be produced by lymphoma cells. However, the relationship of the immunosuppressive agents to the pathogenesis of the MALT lymphoma remains to be clarified.

Augmented expression of cardiotrophin-1 and its receptor component, gp130, in both left and right ventricles after myocardial infarction in the rat.

Cardiotrophin-1 (CT-1) is a potent cytokine that stimulates the assembly of sarcomeric units in series in cardiomyocytes through gp130 signaling, resulting in myocardial cell hypertrophy. To clarify the role of CT-1 and the gp130-signaling pathway during ventricular remodeling after myocardial infarction, we examined the expression of CT-1 and gp130 in a rat model of myocardial infarction. At 1, 3, 7, 14, 28 and 56 days (n=12 for each group) after ligation of a coronary artery, tissue samples were obtained from infarct tissue, the ventricular septum and the right ventricle. All animals developed large myocardial infarctions, with infarct sizes ranging from 39.8% to 50.3%. Progressive left ventricular dilatation and inadequate hypertrophy of the surviving myocardium were confirmed by echocardiography. CT-1 and gp130 mRNA levels were determined by semiquantitative reverse transcription-polymerase chain reaction using 1 or 5 microg of total RNA followed by Southern blotting. The densitometric analysis of the Southern blots revealed a significant increase in CT-1 and gp130 mRNA levels (P<0.01) compared with those of the sham-operated rats at 1, 3, 7, 14, 28 and 56 days post-infarct in the infarct area, the ventricular septum (non-infarcted area) and right ventricle. The protein levels of CT-1 and gp130, determined by Western blot analysis, were significantly increased (P<0.05) compared with those of sham-operated rats, peaked during the acute stage and declined thereafter in the three regions described above. Immunohistochemical staining showed that CT-1 and gp130-immunoreactivities were detected in cardiomyocytes and fibroblast-like cells and that the intensity of staining was increased at 7 days post-infarct compared with that in sham-operated rats. An augmented CT-1 and gp130 system thus appears to play an important role during ventricular remodeling after myocardial infarction.