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Introduction: Liver fibrosis and cirrhosis are one of the critical complications in Fontan patients. However, there are no well-established non-invasive and quantitative techniques for evaluating liver abnormalities in Fontan patients. Intravoxel incoherent motion diffusion-weighted imaging with MRI is a non-invasive and quantitative method to evaluate capillary network perfusion and molecular diffusion. The objective of this study is to assess the feasibility of intravoxel incoherent motion imaging in evaluating liver abnormalities in Fontan children., Materials and Methods: Five consecutive Fontan patients and four age-matched healthy volunteers were included. Fontan patients were 12.8 ± 1.5 years old at the time of MRI scan. Intravoxel incoherent motion imaging parameters (D, D*, and f values) within the right hepatic lobe were compared. Laboratory test, ultrasonography, and cardiac MRI were also conducted in the Fontan patients. Results of cardiac catheterization conducted within one year of the intravoxel incoherent motion imaging were also examined., Results: In Fontan patients, laboratory test and liver ultrasonography showed almost normal liver condition. Cardiac catheter and MRI showed good Fontan circulation. Cardiac index was 2.61 ± 0.23 L/min/m2. Intravoxel incoherent motion imaging parameters D, D*, and f values were lower in Fontan patients compared with controls (D: 1.1 ± 0.0 versus 1.3 ± 0.2 × 10-3 mm2/second (p = 0.04), D*: 30.8 ± 24.8 versus 113.2 ± 25.6 × 10-3 mm2/second (p < 0.01), and f: 13.2 ± 3.1 versus 22.4 ± 2.4% (p < 0.01), respectively)., Conclusions: Intravoxel incoherent motion imaging is feasible for evaluating liver abnormalities in children with Fontan circulation.

Purpose: Prostate cancer (PCa) may be a multifocal or bilateral disease. A single positive biopsy core is usually associated with indolent PCa, and doctors may choose to perform active surveillance or focal therapy. We investigated the correlation between finding a single positive biopsy core and the pathological outcome after radical prostatectomy (RP)., Methods: Data from the Michinoku Japan Urological Cancer Study Group database including pre- and post-operative information, on 1928 consecutive patients with PCa treated with RP alone at four institutions was used. Among them, 503 patients with a single positive core PCa were followed up, and the clinical and pathological parameters influencing prognosis were analyzed., Results: Of the 503 patients, 258 (51.3%) had pathological findings ≥ pT2c and 160 (32%) had an undergraded Gleason Score (GS) based on their biopsy findings. A total of 112 patients (39.5%) with clinical T1c developed bilateral tumors (pT2c-T3). The rate of developing pT3 tumors in the single positive core group was significantly higher than that of the multiple positive core group. Moreover, there was no significant difference in the number of pT3b patients between the single and multiple positive core PCa groups., Conclusions: Based on analysis of radical prostatectomy specimens, positive core PCa can lead to clinically significant disease, with considerable rates of pT3. For patients with PCa and a positive prostate biopsy core, definitive therapy such as RP should be considered.

The newly developed radioisotope-free technique based on magnetic nanoparticle detection using a magnetic probe is a promising method for sentinel lymph node biopsy. In this study, a novel handheld magnetic probe with a permanent magnet and magnetic sensor is developed to detect the sentinel lymph nodes in breast cancer patients. An outstanding feature of the probe is the precise positioning of the sensor at the magnetic null point of the magnet, leading to highly sensitive measurements unaffected by the strong ambient magnetic fields of the magnet. Numerical and experimental results show that the longitudinal detection length is approximately 10 mm, for 140 μg of iron. Clinical tests were performed, for the first time, using magnetic and blue dye tracers-without radioisotopes-in breast cancer patients to demonstrate the performance of the probe. The nodes were identified through transcutaneous and ex-vivo measurements, and the iron accumulation in the nodes was quantitatively revealed. These results show that the handheld magnetic probe is useful in sentinel lymph node biopsy and that magnetic techniques are widely being accepted as future standard methods in medical institutions lacking nuclear medicine facilities.

The aim of the present study was to assess the cost-effectiveness of extended pelvic lymph node dissection (ePLND) compared to neoadjuvant chemohormonal therapy using gonadotropin-releasing hormone agonist/antagonist and estramustine. We retrospectively analyzed data within Michinoku Urological Cancer Study Group database containing 2971 PC patients treated with radical prostatectomy (RP) at four institutes between July 1996 and July 2017. We identified 237 and 403 high-risk patients who underwent RP and ePLND (ePLND group), and neoadjuvant chemohormonal therapy followed by RP and limited PLND (neoadjuvant group), respectively. The oncological outcomes and cost-effectiveness were compared between groups. Medical cost calculation focused on PC-related medication and adjuvant radiotherapy. Biochemical recurrence-free and overall survival rates in the neoadjuvant group were significantly higher than those in the ePLND group. Significantly higher number of patients progressed to castration-resistant PC in the ePLND group than in the neoadjuvant group. Background-adjusted multivariate Cox regression analysis using inverse probability of treatment weighting (IPTW) revealed that neoadjuvant chemohormonal therapy independently reduced the risk of biochemical recurrence after RP. The 5-year cost per person was significantly higher in the ePLND group than in the neoadjuvant group. Although the present study was retrospective, neoadjuvant chemohormonal therapy followed by RP as a concurrent strategy has potential to improve oncological outcome and cost-effectiveness.

Resolving the immunogenicity of cells derived from induced pluripotent stem cells (iPSCs) remains an important challenge for cell transplant strategies that use banked allogeneic cells. Thus, we evaluated the immunogenicity of mouse fetal neural stem/progenitor cells (fetus-NSPCs) and iPSC-derived neural stem/progenitor cells (iPSC-NSPCs) both in vitro and in vivo. Flow cytometry revealed the low expression of immunological surface antigens, and these cells survived in all mice when transplanted syngeneically into subcutaneous tissue and the spinal cord. In contrast, an allogeneic transplantation into subcutaneous tissue was rejected in all mice, and allogeneic cells transplanted into intact and injured spinal cords survived for 3 months in approximately 20% of mice. In addition, cell survival was increased after co-treatment with an immunosuppressive agent. Thus, the immunogenicity and post-transplantation immunological dynamics of iPSC-NSPCs resemble those of fetus-NSPCs.

Human induced pluripotent stem cells (iPSCs) are promising in regenerative medicine. However, the risks of teratoma formation and the overgrowth of the transplanted cells continue to be major hurdles that must be overcome. Here, we examined the efficacy of the inducible caspase-9 (iCaspase9) gene as a fail-safe against undesired tumorigenic transformation of iPSC-derived somatic cells. We used a lentiviral vector to transduce iCaspase9 into two iPSC lines and assessed its efficacy in vitro and in vivo. In vitro, the iCaspase9 system induced apoptosis in approximately 95% of both iPSCs and iPSC-derived neural stem/progenitor cells (iPSC-NS/PCs). To determine in vivo function, we transplanted iPSC-NS/PCs into the injured spinal cord of NOD/SCID mice. All transplanted cells whose mass effect was hindering motor function recovery were ablated upon transduction of iCaspase9. Our results suggest that the iCaspase9 system may serve as an important countermeasure against post-transplantation adverse events in stem cell transplant therapies., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

The optimal treatment for high-risk prostate cancer (Pca) remains to be established. The current guidelines recommend extended pelvic lymph node dissection (e-PLND) for selected intermediate- and high-risk patients treated with RP. However, the indications, optimal extent, and therapeutic benefits of e-PLND remain unclear. The aim of this study was to assess whether e-PLND confers an oncological benefit for high-risk Pca compared to neoadjuvant luteinizing hormone-releasing hormone and estramustine (LHRH + EMP). The Michinoku Urological Cancer Study Group database contained the data of 2403 consecutive Pca patients treated with RP at four institutes between March 2000 and December 2014. In the e-PLND group, we identified 238 high-risk Pca patients who underwent RP and e-PLND, with lymphatic tissue removal around the obturator and the external iliac regions, and hypogastric lymph node dissection. The neoadjuvant therapy with limited PLND (l-PLND) group included 280 high-risk Pca patients who underwent RP and removal of the obturator node chain between September 2005 and June 2014 at Hirosaki University. The outcome measure was BRFS. The 5-year biochemical recurrence-free survival rates for the neoadjuvant therapy with l-PLND group and e-PLND group were 84.9 and 54.7%, respectively (P < 0.0001). The operative time was significantly longer in the e-PLND group compared to that of the neoadjuvant therapy with l-PLND group. Grade 3/4 surgery-related complications were not identified in both groups. Although the present study was not randomized, neoadjuvant LHRH + EMP therapy followed by RP might reduce the risk of biochemical recurrence.

Background: Liposarcoma is one of the most common soft tissue sarcomas found in adults. It has a predilection for retroperitoneal space. Renal cell carcinoma is the most common tumor of the kidney., Case Presentation: Concurrent retroperitoneal liposarcoma and renal cell carcinoma were found in a 34-year-old Japanese man. The renal tumor was first detected by ultrasonography, it was confirmed by computed tomography, which also identified a presumptive retroperitoneal liposarcoma, and the tumors were further assessed with magnetic resonance imaging. The patient was treated by surgical resection of retroperitoneal liposarcoma and left nephrectomy and has been disease-free for 10 years., Conclusions: The concomitant occurrence of a renal tumor and a primary primary liposarcoma is rare. The major factors promoting a good prognosis in this case were the favorable histology and the small size of the tumors.

The efficacy and safety of degarelix, a luteinizing hormone-releasing hormone(LH-RH)antagonist, in patients with prostate cancer(PCa)were evaluated in a phase II, open-label, multicenter clinical trial. In this trial, a total of 13 patients were accrued at the Yamagata Prefectural Central Hospital from 2007 to 2008. The median age was 80 years(range, 65-85 years), and clinical stages were T1c, T2, T3, and T4 in 1, 4, 6, and 2 patients, respectively. Nodal(N)status was N0 in 9 patients and N1 in 4 patients. Distant metastases were absent(M0)in 12 patients and present(M1b)in 1 patient. The median prostate- specific antigen(PSA)level was 29.1 ng/mL(range, 6.3-427 ng/mL). All but one patient, who died of an unrelated cause, received a monthly dose(80 or 160mg)of degarelix for 12 months and were followed-up for 3 years. The PSA level declined in all patients. One patient died of an unrelated cause during the phase II trial. After completion of the phase II trial, 5 patients were treated with combined and rogen blockade(CAB)(leuprolide plus anti-androgen therapy), 2 patients were treated with single-agent leuprolide, 2 patients received single-agent bicalutamide, and 1 patient was followed-up without additional treatment. Radical prostatectomy was performed in 2 patients. Among the 5 patients treated with CAB, 2 died of metastatic cancer. CAB was effective in suppressing PSA levels in 3 patients. In 1 patient with T3aN1M1b PCa, colon cancer with lung metastases was detected during the follow-up period. Treatment with chemotherapy for colon cancer was effective in suppressing PSA levels for 12 months. In 1 patient with cT3aN1M0 PCa, the PSA level declined to <0.02 ng/mL, and a reduction in size of the prostate gland and metastatic lymph nodes was observed. This effect persisted for 3.5 years after the completion of the 12-month degarelix regimen, and no additional treatment was required.

The objective of this article is to reduce the preparation time for oral anticancer drugs, reduce the exposure to drug preparations, and develop drug preparation equipment without external drug leaks in a closed state. In the newly developed closed oral drug preparation device, a 10 mL disposable syringe that was replaced with one projection for crushing tablets and a no-processing 30 mL disposable syringe were connected to a three-way stopcock. Using this instrument, Endoxan(®) tablets (principal components: cyclophosphamide) were crushed and suspended in water in a closed state. The drug was prepared to suspension and flowed out via a feeding tube by switching the handle of the three-way stopcock. To assess human exposure to cyclophosphamide, a high-performance volatile organic compound-solvent desorption passive sampler was attached to the preparer's mouth to collect air drifting in the vicinity, and cyclophosphamide levels were subsequently measured by liquid chromatography with tandem mass spectrometry. Using the developed drug preparation equipment, Endoxan(®) tablets were suspended in a closed state. According to liquid chromatography with tandem mass spectrometry analysis, the exposure of the preparer to cyclophosphamide was greatly reduced when using the developed device; cyclophosphamide was detected in only two of the five samples, though only at trace levels. The closed oral drug preparation device may permit the preparation and administration of toxic drugs to patients while greatly reducing the risk of occupational exposure among health-care workers and caregivers.

Objectives: To determine cyclophosphamide exposure to preparers during tablet crushing and subsequent handling by analyzing indoor air collected using a high-performance volatile organic compounds-solvent desorption (VOC-SD) passive air sampler., Methods: The passive sampler was taped to the mask over the mouth of the preparer and indoor air was collected during crushing and preparation of cyclophosphamide tablets (Endoxan®). After collection, the carbon molecular sieve adsorbent of the passive sampler was placed in a centrifuge tube, and 1 mL of carbon disulfide was used to elute cyclophosphamide from the adsorbent. Liquid-liquid extraction with 1 mL of water was performed, and the aqueous phase was used as the test solution. Cyclophosphamide concentration was determined by liquid chromatography with ultraviolet and tandem mass spectrometry detection., Results: Cyclophosphamide concentration was detected in the range of 7.6-157.7 ng/sampler. Our results showed that low-level exposure occurred near the mouth of the preparer, which could present risks for long-term exposure, especially if combined with multiple toxic drug exposures., Conclusion: The anticancer drug monitoring methodology described here is a simple exposure assessment that can be used to ensure the safety of hospital pharmacy tablet preparers. Furthermore, since the anticancer drug exposure risk is very high for preparers, preparation should be in hood or with face mask.

The identification of the sentinel lymph nodes that cause tumor metastasis is important in breast cancer therapy. The detection of magnetic fluid accumulating in the lymph nodes using a magnetic probe allows surgeons to identify the lymph nodes. In this study, we carried out numerical simulations and experiments to investigate the sensitivity and basic characteristics of a magnetic probe consisting of a permanent magnet and a small magnetic sensor. The measured magnetic flux density arising from the magnetic fluid agreed well with the numerical results. In addition, the results helped realize an appropriate probe configuration for achieving high sensitivity to magnetic fluid. A prototype probe detected magnetic fluid located 30 mm from the probe head.

A simple, rapid and sensitive method termed dispersive liquid-liquid microextraction (DLLME) combined with gas chromatography-mass spectrometry (GC/MS) was developed for the determination of tricyclic antidepressants (TCAs) in human urine sample. An appropriate mixture of methanol (disperser solvent), carbon tetrachloride (extraction solvent), and acetic anhydride (derivatization reagent) was injected rapidly into human urine sample. After extraction, the sedimented phase was analyzed by GC/MS. The calibration curves obtained with human urine were linear with a correlation coefficient of over 0.99 in the range of 2.0/5.0-100 ng mL(-1). Under the optimum conditions (carbon tetrachloride: 10 μL, methanol: 150 μL), the detection limits and the quantification limits of the tricyclic antidepressants were 0.5-2.0 ng mL(-1) and 2.0-5.0 ng mL(-1), respectively. The average recoveries of TCAs were 88.2-104.3%. Moreover, the inter- and intra-day precision and accuracy was acceptable at all concentrations. The results showed that DLLME is applicable to the determination of trace amounts of TCAs in human urine sample., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Objective: Increased understanding of cytokines and their associated proteoglycans will contribute to the investigation of the formation of nasal polyps. Recently, some studies have suggested that syndecan-1 ectodomains are shed in response to low respiratory infection, but no studies regarding nasal and paranasal diseases have been reported. Transforming growth factor-beta (TGF-beta) is involved in the regulation of nasal polyps, especially in processes crucial to the initiation, maintenance, and resolution of inflammatory responses. In the nasal mucosa and nasal polyps, we analyzed the expression of syndecan-1, which readily promotes infection, and TGF-beta, which plays a role in syndecan-1 activity., Methods: Fifteen patients who underwent turbinectomy for the treatment of nasal obstruction and seventeen patients with nasal polyps who underwent nasal endoscopic sinus surgery were included in this study. The localization of syndecan-1 and TGF-beta in the nasal mucosa and nasal polyps was investigated by immunohistochemistry, and mRNA transcript levels of syndecan-1 and TGF-beta were examined using quantitative real-time PCR., Results: Immunohistochemical staining revealed that the expression of syndecan-1 in the nasal mucosa and nasal polyps was co-localized with TGF-beta. The mean mRNA expression values for syndecan-1 and TGF-beta were higher in nasal polyps compared to the nasal mucosa., Conclusions: This is the first report showing expression of syndecan-1 in the nasal mucosa and nasal polyps. In nasal polyps, syndecan-1 expression may be increased by an unknown mechanism, permitting infection and inducing larger nasal polyps. We hypothesize that the accumulation of TGF-beta, which is involved in the pathophysiological development of nasal polyps, may result in a change in the binding properties of syndecan-1 at inflammatory sites., (Copyright 2009 Elsevier Ireland Ltd. All rights reserved.)

To clarify the efficacy and indication of hepatectomy in gastric cancer metastasis to the liver, we studied 26 liver metastases patients undergoing hepatectomy. The cumulative 5-year survival rations were 25.3%. A survival analysis showed that prognoses of patients n(-) or T2 group were statistically better than other group. Three patients underwent a repeat liver resection from gastric metastasis and survived for about thirty months. There was an example using chemotherapy which made a liver tumor removal operation possible to the patient who had multiple liver metastases. In conclusion, liver resection is a beneficial option and multimodal therapy including a repeat liver resection and systemic chemotherapy, may be important for improving the prognosis of patients with liver metastases from gastric cancer.

We used a new tactile sensor to measure the elastic properties of skin in patients with systemic sclerosis or Raynaud's phenomenon. The sensor consists of a piezoelectric vibrator with vibration pickup to measure frequency changes when the sensor is placed on the skin. The mean frequency change at the skin surface of the proximol third phalanx in patients with systemic sclerosis was significantly lower than in age- and sex-matched controls. The results in systemic sclerosis patients were statistically correlated to the Modified Rodnan Skin Thickness Score. This technique was also used to measure the therapeutic efficacy of salpogrelate, a new specific serotonin receptor antagonist. A greater mean frequency change was seen after treatment. We conclude that this new tactile sensor is useful for quantitatively measuring skin sclerosis and may help determine the efficacy of therapeutic treatments.

An 85-year-old man had a 2 vessel coronary disease. Preoperative echogram showed the lateral femoral circumflex artery (LFCA) had enough diameter and length. We performed coronary artery bypass grafting (OPCAB) with the left internal thoracic artery (LITA) and LFCA. Postoperative coronary angiogram showed that the LFCA bypass graft was patent and supplied sufficient blood to the anastomosed vessel.

We investigated the reason for the absence of the long-wavelength PSI Chl a fluorescence at -196 degrees C in the cyanobacterium Gloeobacter violaceus using two methods: p-nitrothiophenol (p-NTP) treatment and time-resolved fluorescence spectra. The p-NTP treatment showed that PSII Chl a fluorescence was specifically affected in a manner similar to that for Synechocystis sp. PCC 6803 and spinach chloroplasts, although there were no components modified by the p-NTP treatment, indicating an absence of the long-wavelength PSI Chl a fluorescence. The time-resolved fluorescence spectra with a time resolution of 1.3 ps and spectral resolution of 1.0 nm gave no indication of the presence of the long-wavelength PSI fluorescence in the wavelength region between 700 nm and 760 nm, indicating that a very fast energy transfer among Chl a molecules could not account for the absence of the long-wavelength PSI fluorescence. From these data, it seems that the absence of the long-wavelength PSI fluorescence is due to a lack of the formation of a component responsible for the fluorescence at -196 degrees C, which may originate from a difference in the amino acid sequence. We discuss the significance of this phenomenon and interpret our findings in terms of the evolution of cyanobacteria.

The function of Epstein-Barr virus (EBV)-specific cytotoxic T cells is disturbed in rheumatoid arthritis (RA) patients but the mechanism for this disturbance has remained unknown. In a recent study searching for the causative gene of X-linked lymphoproliferative syndrome, the gene possibly linked to EBV-specific cytotoxic T cells or NK cell-mediated cytotoxic activity to EBV-infected cells was discovered, and its product is now referred to as signaling lymphocytic-activation molecule-associated protein (SAP) or Src homology 2 domain-containing protein (SH2D1A). In the present study, we attempted to investigate the involvement of the SAP gene in RA using a quantitative real-time PCR; the expression level of SAP transcripts in peripheral leukocytes or T cells was examined for patients with RA. The expression level of SAP transcripts in peripheral leukocytes of 21 RA patients was significantly lower than that of 13 normal individuals (P = 0.0007), four patients with palindromic RA, 11 with inactive systemic lupus erythematosus (SLE) or 17 with chronic renal diseases. The decreased expression of SAP transcripts in RA patients was also observed in peripheral CD2(+) T cells compared with normal individuals. There was no mutation in the coding region of SAP cDNAs derived from peripheral leukocytes of five RA patients. The decreased expression of SAP transcripts in peripheral leukocytes or T cells of RA patients might lead to the failure of the immune system to eliminate the EBV-infected synovial lining cells in joints of RA patients. Our findings have suggested that decreased expression of the SAP gene might be involved in the onset or progress of RA.

The small guanosine triphosphatases (GTPases) Cdc42 and Rac1 regulate E-cadherin-mediated cell-cell adhesion. IQGAP1, a target of Cdc42 and Rac1, was localized with E-cadherin and beta-catenin at sites of cell-cell contact in mouse L fibroblasts expressing E-cadherin (EL cells), and interacted with E-cadherin and beta-catenin both in vivo and in vitro. IQGAP1 induced the dissociation of alpha-catenin from a cadherin-catenin complex in vitro and in vivo. Overexpression of IQGAP1 in EL cells, but not in L cells expressing an E-cadherin-alpha-catenin chimeric protein, resulted in a decrease in E-cadherin-mediated cell-cell adhesive activity. Thus, IQGAP1, acting downstream of Cdc42 and Rac1, appears to regulate cell-cell adhesion through the cadherin-catenin pathway.

A male patient with severe aplastic anemia was admitted for bone marrow transplantation. While waiting for a donor, high doses of methylprednisolone, anabolic steroid and granulocyte colony stimulating factor were given without response. Deferoxamine was administered for prophylaxis of hemochromatosis because of high level of ferritin. Acute right lower abdominal pain and pyrexia developed. A diagnosis of acute appendicitis was made and appendectomy was performed. The histopathological examination of the resected appendix revealed necrotizing hemorrhagic appendicitis with numerous hyphae of Mucorales. Though anti-fungal agent (amphotericin B) administration was continued, he subsequently developed ileo-cecal abscess and eventually died due to myoglobinuric nephropathy caused by extensive necrosis of the iliopsoas muscle. Autopsy revealed dissemination of hyphae of Mucorales in lungs, kidneys, large vessels and muscle of the bilateral lower limbs. Systemic vascular invasion and embolization of fungal hyphae were also observed. However, culture of exudate sampled from ileocecum yielded no Mucorales. It was emphasized that antemortem diagnosis and effective anti-fungal treatments are essential for the management of intestinal mucormycosis. The relation ship between mucormyocosis and deferoxamine was also discussed.

The patient, a 36-year-old male, was admitted with massive hemoptysis. He had two gunshot wounds in the right lateral abdomen and supraclavicular fossa. His chest X-ray showed right tension hemothorax. Emergency thoracotomy and laparotomy were performed. Massive bleeding from the right pulmonary artery (A4+5), lacerations in the diaphragm and injuries of the liver were found. We performed right middle lobectomy, S3 segmentectomy and plication of the diaphragm and liver. He was discharged uneventfully.

We reviewed cerebral angiograms studied between May 1985 and December 1992 focusing on unruptured incidental intracranial aneurysms. In a total of 605 cases of cerebral angiograms except for patients with SAH, 43 patients (7.1%) were found to have unruptured aneurysms. In the 72 patients with headache, 11 patients (15.3%) were found to have unruptured aneurysms. This high frequency of unruptured aneurysms in headache patients is significant as a factor showing that headache may be due to unruptured aneurysms. The result of this observation is that as a screening study for headache patients, cerebral angiography may be required in spite of the invasive and high-risk method. But we think that MR angiography is, at present, a useful screening study only for detecting cerebral aneurysms with a diameter of over 5mm, and which are considered to need an operation.