Efficacy of 1.2 L polyethylene glycol plus ascorbic acid for bowel preparations.

BACKGROUND: A low-volume polyethylene glycol (PEG) solution that combines ascorbic acid with PEG-based electrolyte solution (PEG-ASC) is gaining mainstream acceptance for bowel preparation due to reduced volume and improved taste. Although several reports showed that bowel preparation with PEG-ASC volume lower than 2.0 L with laxative agents could be an alternative to traditional preparation regimen, the cleansing protocols have not been fully investigated. AIM: To evaluate the cleansing efficacy of 1.2 L PEG-ASC solution comparing with 2.0 L PEG electrolyte (PEG-ELS) for bowel preparations. METHODS: A randomized, single-blinded, open-label, single-center, non-inferiority study was conducted. In total, 312 Japanese adult patients (aged > 18 years) who underwent colonoscopy were enrolled. Patients were randomly allocated to bowel lavage with either 1.2 L of PEG-ASC solution with at least 0.6 L of an additional clear fluid (1.2 L PEG-ASC group) or 2.0 L of PEG-ELS (PEG-ELS group). Then, 48 mg of sennoside was administered at bedtime on the day before colonoscopy, and the designated drug solution was administered at the hospital on the day of colonoscopy. Bowel cleansing was evaluated using the Boston Bowel Preparation Scale (BBPS). The volume of fluid intake and required time for bowel preparation were evaluated. Furthermore, compliance, patient tolerance, and overall acceptability were evaluated using a patient questionnaire, which was assessed using a visual analog scale. RESULTS: In total, 291 patients (1.2 L PEG-ASC group, 148; PEG-ELS group, 143) completed the study. There was no significant difference in successful cleansing, defined as a BBPS score ≥ 2 in each segment, between the two groups (1.2 L PEG-ASC group, 91.9%; PEG-ELS group, 90.2%; 95%CI: -0.03-0.09). The required time for bowel preparation was significantly shorter (164.95 min ± 68.95 min vs 202.16 min ± 68.69 min, P < 0.001) and the total fluid intake volume was significantly lower (2.23 L ± 0.55 L vs 2.47 L ± 0.56 L, P < 0.001) in the 1.2 L PEG-ASC group than in the PEG-ELS group. Palatability, acceptability of the volume of solution, and overall acceptability evaluated using a patient questionnaire, which was assessed by the visual analog scale, were significantly better in the 1.2 L PEG-ASC group than in the PEG-ELS group (7.70 cm ± 2.57 cm vs 5.80 cm ± 3.24 cm, P < 0.001). No severe adverse event was observed in each group. CONCLUSION: The 1.2 L PEG-ASC solution was non-inferior to the 2.0 L PEG-ELS solution in terms of cleansing efficacy and had better acceptability among Japanese patients.

Hand-Foot Syndrome and Post-Progression Treatment Are the Good Predictors of Better Survival in Advanced Hepatocellular Carcinoma Treated with Sorafenib: A Multicenter Study.

OBJECTIVE: To determine the relationship between treatment outcomes and hand-foot syndrome (HFS), and the relationship between survival rate and post-progression treatment after sorafenib therapy. METHODS: The study assessed 314 patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib at 5 general hospitals in Kagawa Prefecture, Japan. RESULTS: At the start of sorafenib therapy, 23.6% of the patients had HCC of a Child-Pugh class other than A. The initial sorafenib dose was 800 mg in 9.2% of the patients and 400 mg in 64.3%. Time to progression was 129 days (95% CI: 87.3-170.7) and the median overall survival (OS) was 392 days (95% CI: 316.0-468.0). The OS of the patients with Child-Pugh class A HCC was significantly better than that of the patients with Child-Pugh class B HCC (p < 0.0001). The survival curves for Child-Pugh class A-5 points and class A-6 points were significantly different, with that for class A-5 points being better (p < 0.0001). A significant difference was observed between the patients who exhibited HFS and those who did not, with the former exhibiting a better survival rate (p < 0.001). In addition, the survival rate of the patients who received post-progression treatment after sorafenib therapy was significantly better than that of the patients who did not (p < 0.001). CONCLUSION: In sorafenib therapy, patients with HFS and those who received post-progression treatment exhibited good OS.

Dietary Starfish Oil Prevents Hepatic Steatosis and Hyperlipidemia in C57BL/6N Mice Fed High-fat Diet.

Starfish oil (SO) is characterized by functional lipids, including n-3 polyunsaturated fatty acid (both in the form of triacylglycerol and in the form of phospholipid), and carotenoids, which may exert beneficial effects on metabolic disorders in obesity-associated diseases. In the present study, the effect of SO on dysregulation of lipid metabolism was examined using C57BL/6N mice treated with high-fat (HF) diet. Mice were fed HF, HF with 2% SO, or HF with 5% SO diet for 8 weeks. Weight gain, blood glucose, serum and hepatic lipid contents, and hepatic fatty acid composition were measured. Fatty acid ß-oxidation activity was monitored by measuring the catabolic rate of 13C-labeled fatty acid, assessed as 13CO2/12CO2 ratio using isotope ratio mass spectrometry (IR-MS). Although there were no differences in body weight or white adipose tissue weight among the test groups, dietary SO reduced blood glucose, and dose-dependently improved hyperlipidemia and decreased hepatic lipid accumulation. Analysis of hepatic fatty acid composition revealed a significant decrease in the ratio of monounsaturated fatty acid to saturated fatty acid, which is attributed to stearoyl-CoA desaturase activity. IR-MS analysis suggested that ß-oxidation activity was enhanced in the mice treated with 5% SO. These results demonstrate that dietary SO improves lipid metabolism measures in HF diet-induced obese mice, suggesting that SO holds promise as an agent for the prevention and treatment of lipid metabolism disorders in the liver.

Prediction of Embolization Area after Conventional Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma Using SYNAPSE VINCENT.

PURPOSE: Transcatheter arterial chemoembolization (TACE) is one of the most effective therapeutic options for hepatocellular carcinoma (HCC) and it is important to protect residual liver function after treatment as well as the effect. To reduce the liver function deterioration, we evaluated the automatic software to predict the embolization area of TACE in 3 dimensions. MATERIALS AND METHODS: Automatic prediction software of embolization area was used in chemoembolization of 7 HCCs. Embolization area of chemoembolization was evaluated within 1 week CT findings after TACE and compared simulated area using automatic prediction software. RESULTS: The maximal diameter of these tumors is in the range 12-42 mm (24.6 ± 9.5 mm). The average time for detecting tumor-feeding branches was 242 s. The total time to detect tumor-feeding branches and simulate the embolization area was 384 s. All cases could detect all tumor-feeding branches of HCC, and the expected embolization area of simulation with automatic prediction software was almost the same as the actual areas, as shown by CT after TACE. CONCLUSION: This new technology has possibilities to reduce the amount of contrast medium used, protect kidney function, decrease radiation exposure, and improve the therapeutic effect of TACE.

Efficacy of probiotic treatment with Bifidobacterium longum 536 for induction of remission in active ulcerative colitis: A randomized, double-blinded, placebo-controlled multicenter trial.

BACKGROUND AND AIM: We conducted a randomized, double-blinded, placebo-controlled trial to investigate the efficacy of Bifidobacterium longum 536 (BB536) supplementation for induction of remission in Japanese patients with active ulcerative colitis (UC). METHODS: Fifty-six patients with mild to moderate UC were enrolled. Three patients had pancolitis, 36 had left-sided colitis, and 17 had proctitis. Patients were randomly treated with 2-3 × 10(11) freeze-dried viable BB536 (28 patients) or placebo (28 patients) for 8 weeks. RESULTS: In total, 63% of patients receiving BB536 showed clinical remission (UC disease activity index [UCDAI] ≤2) at week 8 compared to 52% of those receiving placebo (P = 0.395). We observed a significant decrease of UCDAI scores (3.8 ± 0.4 at baseline to 2.6 ± 0.4 at week 8) in the BB536 group (P < 0.01), whereas there was no significant decrease in the placebo group (P = 0.88). There was also a significant decrease in the Rachmilewitz endoscopic index (EI) and the Mayo subscore at week 8 in the BB536 group, whereas there was no significant decrease in the placebo group. A single patient in the BB536 group complained of a mild side-effect, but no other adverse effects were observed. CONCLUSION: Supplementation with BB536 was well tolerated and reduced UCDAI scores, EI and Mayo subscores after 8 weeks in Japanese patients with mild to moderately active UC.

Initial Experience Performing Percutaneous Ultrasound Examination with Real-Time Virtual Sonography with Color Display.

PURPOSE: We report the efficacy of percutaneous ultrasound (US) examination using a novel real-time virtual sonography (RVS) method that collates multiple Digital Imaging and Communications in Medicine (DICOM) data sources and displays reference images in color. MATERIALS AND METHODS: A total of 7 patients with 9 hepatocellular carcinomas were evaluated. Using the SYNAPSE VINCENT volume analyzer, DICOM data of the portal vein, hepatic vein, tumor, and hepatic segment were isolated from contrast-enhanced computed tomography DICOM data. Each portion of DICOM data was uploaded into an US scanner (HI VISION Ascendus, Hitachi Aloka Medical Ltd., Tokyo, Japan) and unified on a US platform to create a single reference image. Each uploaded portion of DICOM data was assigned a different color. Further, conventional RVS was performed using this information. RESULTS: The maximal tumoral diameter ranged from 6.4 to 15 mm (mean ± SD, 11.0 ± 2.8). DICOM data could be isolated, enabling the display of color RVS in all patients. Color RVS facilitated superior visibility compared with conventional grayscale RVS and facilitated the comprehension of spatial positioning. CONCLUSION: RVS with color display demonstrates utility in increasing operator comprehension of spatial and positional relationships during percutaneous US examination.

Virtual sonography for novice sonographers: usefulness of SYNAPSE VINCENT® with pre-check imaging of tumor location.

PURPOSE: To evaluate the usefulness of a virtual ultrasound (US) imaging device as a tool to assist novice sonographers. MATERIALS AND METHODS: A prospective blinded pilot study was conducted involving patients with liver lesions. Two sonographers and 2 medical doctors with less than 5 years of experience performed US examinations. The time needed to detect liver lesions on US and the success rate for detecting liver lesions with and without using the virtual US imaging device SYNAPSE VINCENT® (Fujifilm Medical Co., Tokyo, Japan) before US examination were evaluated. RESULTS: Thirty-two patients with the following 42 liver lesions were included: liver cyst (n = 24), hemangioma (n = 8), hepatocellular carcinoma (n = 6), and liver metastasis (n = 4). The maximal diameter of these lesions ranged from 0.3 to 1.5 cm (mean ± SD, 0.8 ± 0.4). The average time for detecting liver lesions on US was 47.8 s (range, 7-113) with VINCENT and 112.9 s (range, 14-313) without VINCENT before US examination. There were significant differences in the duration of US examination with and without VINCENT (p = 0.0002, Student's t test). The rates for accurately detecting liver lesions were 100 and 76.2% (16/21) in US beginners with and without VINCENT, respectively. Significantly higher detection rates were found in the US beginners who used VINCENT compared to those who did not use VINCENT (p = 0.047, Fisher's exact test). CONCLUSION: Before US examination, a reference with VINCENT could contribute to the successful detection of liver lesions and could be time-saving for US beginners.

Surgical therapy and chemoradiotherapy for postoperative recurrent esophageal cancer.

BACKGROUND/AIMS: A retrospective analysis of therapeutic modalities used in postoperative recurrent esophageal cancer. METHODOLOGY: Among 43 esophageal cancer patients who underwent esophagectomy between 2003 and 2010, recurrence was found in 15. Best supportive care was given to two patients and another patient was referred to another hospital. The remaining 12 patients were treated by the following modalities: Surgical resection: 2 cases; chemoradiotherapy: 7 cases; chemotherapy: 2 cases; and radiotherapy: 1 case. The median survival time, 1-year survival rates, and response rates were examined. Data from 13 esophageal cancer patients who underwent chemoradiotheray as an initial therapy in the same period were collected and compared with recurrent cases treated with chemoradiotherapy. RESULTS: For all 12 patients, the median overall survival time was 19.5 months, and the 1-year survival rate was 83%. Among 7 chemoradiotherapy patients, the response rate was 57%. The median survival time was 23 months, and the 1-year survival rate was 86%. The response rate of 13 patients receiving chemoradiotherapy as an initial therapy was 69%. The median overall survival time was 12 months and the 1-year survival rate was 54%. CONCLUSIONS: Re-operation and chemoradiotherapy for recurrent esophageal cancer might be as effective as the same treatment used initially.

Significance of renal biopsy in patients with presumed diabetic nephropathy.

AIMS/INTRODUCTION: Patients with diabetic nephropathy (DN) typically show varying degrees of proteinuria and renal impairment. Because these clinical signs are frequently observed in other glomerulopathies, renal biopsy is required to make a definitive diagnosis of DN. We carried out the present study to evaluate the significance of renal biopsy for patients who have been presumptively diagnosed with DN. MATERIALS AND METHODS: A total of 55 patients with type 2 diabetes mellitus (DM), and proteinuria, hematuria and/or renal impairment were enrolled in this study. RESULTS: Renal biopsy showed that just 30 patients (54.5%) were histologically diagnosed with DN. Fasting plasma glucose and glycated hemoglobin levels were associated with the presence of DN, whereas baseline renal function showed no statistically significant relationship to DN. The duration of DM was not associated with the presence of DN. Patients with DN had a higher rate of diabetic retinopathy (DR) than those with non-DN (DN 18 patients vs non-DN three patients, P = 0.00029). DN patients with DR showed a more severe renal histology than those without. CONCLUSIONS: These data suggest that, even for patients with long-term DM, renal biopsy should be carried out in patients with presumed DN. Because treatment options differ between DN and primary glomerulopathies, renal biopsy should especially be considered for presumed DN without DR.

Pdx1 and Ngn3 overexpression enhances pancreatic differentiation of mouse ES cell-derived endoderm population.

In order to define the molecular mechanisms regulating the specification and differentiation of pancreatic ß-islet cells, we investigated the effect of upregulating Pdx1 and Ngn3 during the differentiation of the ß-islet-like cells from murine embryonic stem (ES) cell-derived activin induced-endoderm. Induced overexpression of Pdx1 resulted in a significant upregulation of insulin (Ins1 and Ins2), and other pancreas-related genes. To enhance the developmental progression from the pancreatic bud to the formation of the endocrine lineages, we induced the overexpression express of Ngn3 together with Pdx1. This combination dramatically increased the level and timing of maximal Ins1 mRNA expression to approximately 100% of that found in the ßTC6 insulinoma cell line. Insulin protein and C-peptide expression was confirmed by immunohistochemistry staining. These inductive effects were restricted to c-kit(+) endoderm enriched EB-derived populations suggesting that Pdx1/Ngn3 functions after the specification of pancreatic endoderm. Although insulin secretion was stimulated by various insulin secretagogues, these cells had only limited glucose response. Microarray analysis was used to evaluate the expression of a broad spectrum of pancreatic endocrine cell-related genes as well as genes associated with glucose responses. Taken together, these findings demonstrate the utility of manipulating Pdx1 and Ngn3 expression in a stage-specific manner as an important new strategy for the efficient generation of functionally immature insulin-producing ß-islet cells from ES cells.

Clinicopathological features of 171 cases of primary thyroid lymphoma: a long-term study involving 24553 patients with Hashimoto's disease.

There are few large-scale reports of primary thyroid lymphoma (PTL). This study clinically and pathologically reviewed 171 patients with PTL and 24,553 patients with Hashimoto's disease at Ito Hospital between January 1990 and December 2004, to investigate the clinical features and the treatment outcomes of PTL. The median age of the patients with PTL was 67 years (range, 27-90 years). The pathological diagnosis of PTL patients included diffuse large B-cell lymphoma (DLBCL) (n=74), DLBCL with mucosa-associated lymphoid tissue (MALT) lymphoma (n=13), MALT lymphoma (n=80) and others (n=4). Of the 167 patients with B-cell lymphoma, treatment included combined modality therapy (CMT) (n=95), radiation therapy (RT) alone (n=60) and chemotherapy alone (n=6). Information on treatment was not available in six patients. Information on treatment response was available in 154 patients; 149 patients (97%) responded to treatment. According to the institutional treatment strategy of Ito Hospital, 45 of 54 patients with stage IE disease received RT alone, and 87 of 113 stage IIE patients received CMT. The 5-year overall survival rate was 85% (95% confidence interval, 79-91%). This study demonstrated that PTL showed good response to radiotherapy and chemotherapy and had a favourable prognosis.

Radiation-sensitizing effect of low-concentration docetaxel on human esophageal squamous cell carcinoma cell lines.

Esophageal squamous cell carcinoma (ESCC) is more sensitive to radiation and chemotherapy than other cancers of the digestive system, and combined modality therapy may represent a promising treatment method. The radiation-sensitizing effect of docetaxel on ESCC cell lines was investigated. A colony formation assay was performed in which ESCC cell lines (TE2, TE3) and A431 were exposed to docetaxel (from 1.0×10(-11) to 10(-7) M) for 3 h to determine the concentration of docetaxel that was not able to kill individual cells (i.e., the non-cytocidal concentration). Individual cell lines were then exposed to the non-cytocidal concentration of docetaxel prior to, during, and after irradiation to determine whether the timing of docetaxel administration affected cell survival. In addition, flow-cytometry was performed, and the cell cycle was examined prior to and after docetaxel exposure to assess the mechanism of docetaxel as a radiation sensitizer. Docetaxel exhibited a concentration-dependent cytocidal effect, with a different IC(50) for each cell type. Almost no cytocidal effect was observed at the following docetaxel concentrations: A431, ≤1.0×10(-10) M; TE-2 and TE-3, ≤1.0×10(-9) M. Concurrent treatment with docetaxel and radiation tended to decrease cell survival in all the cell lines compared with docetaxel or radiation alone. Cell survival was lowest when the cells were treated using X-ray irradiation after docetaxel exposure (p<0.05). Flow cytometry revealed that in all three cell lines, docetaxel exposure increased the G2/M cell fraction with a higher increase in the cell line that exhibited the highest radiosensitivity. This study demonstrated that the administration of docetaxel at a non-cytocidal concentration prior to radiotherapy produced a synergistic cell-killing effect in SCC cell lines.

Possible involvement of stem-like populations with elevated ALDH1 in sarcomas for chemotherapeutic drug resistance.

Elevated aldehyde dehydrogenase 1 (ALDH1) has been proposed as one of the possible candidates for a stem cell maker that can be used for the isolation of cancer stem cells from cancers such as leukemia and breast cancer. In the current study, we found that subpopulations with elevated ALDH1 were present in the human sarcoma cell lines, MG63 (osteosarcoma) and HT1080 (fibrosarcoma), using Aldefluor assay. Both ALDH1 positive and negative cell populations were isolated from the MG63 cell line, by cell-sorting using FACSAria. Both subpopulations had a comparable ability to differentiate similarly to the parental MG63, under normal monolayer culture condition. Subpopulations with the ability to form spheres in anchorage-independent, serum-starved conditions showed increased ALDH1 mRNA expression in addition to strong mRNA expression of the stem cell-related genes, such as Nanog, Oct3/4, Stat3 and Sox2, and possessed ability for self-renewal with secondary sphere formation. Sarcosphere cells from the MG63 cell line showed strong chemo-resistance against both doxorubicin and cisplatin compared with monolayer, adherent cells. In conclusion, sphere-forming cells with elevated ALDH1 are a possible candidate for sarcoma stem cells, possessing strong chemo-resistant capacities. Although ALDH1 elevation was not sufficient for representing sarcoma stem cells, the efficient detoxification could contribute to the chemo-resistant properties of the stem-like sphere cells form human sarcoma.

Weekly low-dose docetaxel-based chemoradiotherapy for locally advanced oropharyngeal or hypopharyngeal carcinoma: a retrospective, single-institution study.

PURPOSE: To retrospectively assess the efficacy, toxicity, and prognostic factors of weekly low-dose docetaxel-based chemoradiotherapy for Stage III/IV oropharyngeal or hypopharyngeal carcinoma. METHODS AND MATERIALS: Between 2001 and 2005, 72 consecutive patients with locally advanced oropharyngeal or hypopharyngeal carcinoma were treated with concurrent chemoradiotherapy (CCR; radiation at 60 Gy plus weekly docetaxel [10 mg/m(2)]). Thirty of these patients also received neoadjuvant chemotherapy (NAC; docetaxel, cisplatin, and 5-fluorouracil) before concurrent chemoradiotherapy. Survival was calculated according to the Kaplan-Meier method. The prognostic factors were evaluated by univariate and multivariate analyses. RESULTS: The median follow-up was 33 months, with overall survival, disease-free survival, and locoregional control rates at 3 years of 59%, 45%, and 52%, respectively. Thirty-six patients (50%) experienced more than one Grade 3 to 4 acute toxicity. Grade 3 mucositis occurred in 32 patients (44%), Grade 4 laryngeal edema in 1 (1%). Grade > or =3 severe hematologic toxicity was observed in only 2 patients (3%). Grade 3 dysphagia occurred as a late complication in 2 patients (3%). Multivariate analyses identified age, T stage, hemoglobin level, and completion of weekly docetaxel, but not NAC, as significant factors determining disease-free survival. CONCLUSIONS: Docetaxel is an active agent used in both concurrent and sequential chemoradiotherapy regimens. Mucositis was the major acute toxicity, but this was well tolerated in most subjects. Anemia was the most significant prognostic factor determining survival. Further studies are warranted to investigate the optimal protocol for integrating docetaxel into first-line chemoradiotherapy regimens, as well as the potential additive impact of NAC.

[Assessment of the efficacy, safety and pharmacokinetics of SKG-02 (recombinant human TSH) in postoperative diagnosis of well-differentiated thyroid cancer--a Japanese prospective, controlled, multicenter open-label study].

OBJECTIVE: This study sought to assess the safety, efficacy, impact on hypothyroid symptoms, and pharmacokinetics of SKG-02 (rhTSH, thyrotropin alfa) in the diagnostic follow-up of Japanese patients with well-differentiated thyroid carcinoma (WDTC). METHODS: Ten Japanese adults with WDTC were enrolled into a prospective, multicenter, open-label trial comparing diagnostic whole-body scintigraphy (dxWBS) and serum thyroglobulin (Tg) testing aided by SKG-02 versus these procedures aided by thyroid hormone withdrawal (THW). Patients were their own controls. Variables compared included scan set ability to detect radioiodine uptake by remnant or malignant thyroid tissue, scan set quality, diagnostic sensitivity of dxWBS and Tg testing alone or combined, frequency of hypothyroid signs/symptoms, and adverse events (AEs). SKG-02 pharmacokinetic variables including maximum concentration (Cmax), time to Cmax (Tmax) and the area under the time-concentration curve (AUC) were calculated. RESULTS: In a blinded evaluation by an independent committee of 3 nuclear medicine experts, 70% of SKG-02 dxWBS scan sets were rated "equivalent" (n = 7) or "superior" (n = 0) to their THW counterparts in ability to detect radioiodine uptake in healthy or malignant thyroid tissue. Therefore the study exceeded its primary endpoint of a 60% equivalence/superiority rate. SKG-02 Tg testing identified 3/3 cases of disease. Hypothyroid signs/symptoms were substantially more frequent during THW than during euthyroidism permitted by SKG-02 use. SKG-02 was well-tolerated, with no severe or serious drug-related AEs. Cmax was 240.8 +/- 65.9 microIU/ml, Tmax was 28.75 +/- 14.21 hr after the first SKG-02 injection, and AUC was 11,414 +/- 3,462 microIU hr/ml in 9 patients evaluable for pharmacokinetics. CONCLUSIONS: SKG-02 was safe and effective in the diagnostic follow-up of Japanese patients with WDTC, avoiding hypothyroid morbidity relative to THW. These and the pharmacokinetic findings were similar to those of overseas Phase III studies.

Prediction of PSA bounce after permanent prostate brachytherapy for localized prostate cancer.

BACKGROUND: We aimed to calculate the frequency and features of the development of a prostate-specific antigen (PSA) bounce after prostate brachytherapy alone, to correlate the bounce with clinical and dosimetric factors and to identify factors that predict PSA bounce. METHODS: PSA bounce was evaluated in 86 patients with T1-T2 prostate cancer who underwent radioactive seed implantation using iodine-125 (I-125) without hormonal therapy or external-beam radiation therapy (EBRT) from September 2004 to December 2007. A PSA bounce was defined as a rise of at least 0.4 ng/ml greater than a previous PSA level with a subsequent decline equal to, or less than, the initial nadir. RESULTS: Calculated by the Kaplan-Meier method, the incidence of PSA bounce at a 2-year follow-up was 26%. Median time to the PSA bounce was 15 months. Univariate analysis demonstrated that age, dose received by 90% of the prostate gland (D90), volume of gland receiving 100% of the prescribed dose (V100), and V150 were significantly associated with the PSA bounce, while pretreatment PSA level, Gleason score, pretreatment prostate volume, clinical T stage, and V200 were not. In multivariate analysis, age 67 years or less and D90 more than 180 Gy were identified as independent factors for predicting the PSA bounce (P < 0.05). CONCLUSION: PSA bounce is not a rare phenomenon after prostate brachytherapy. It is more common in younger patients and patients receiving higher doses of radiation.

Converging stereotactic radiotherapy using kilovoltage X-rays: experimental irradiation of normal rabbit lung and dose-volume analysis with Monte Carlo simulation.

PURPOSE: To validate the feasibility of developing a radiotherapy unit with kilovoltage X-rays through actual irradiation of live rabbit lungs, and to explore the practical issues anticipated in future clinical application to humans through Monte Carlo dose simulation. METHODS AND MATERIALS: A converging stereotactic irradiation unit was developed, consisting of a modified diagnostic computed tomography (CT) scanner. A tiny cylindrical volume in 13 normal rabbit lungs was individually irradiated with single fractional absorbed doses of 15, 30, 45, and 60 Gy. Observational CT scanning of the whole lung was performed every 2 weeks for 30 weeks after irradiation. After 30 weeks, histopathologic specimens of the lungs were examined. Dose distribution was simulated using the Monte Carlo method, and dose-volume histograms were calculated according to the data. A trial estimation of the effect of respiratory movement on dose distribution was made. RESULTS: A localized hypodense change and subsequent reticular opacity around the planning target volume (PTV) were observed in CT images of rabbit lungs. Dose-volume histograms of the PTVs and organs at risk showed a focused dose distribution to the target and sufficient dose lowering in the organs at risk. Our estimate of the dose distribution, taking respiratory movement into account, revealed dose reduction in the PTV. CONCLUSIONS: A converging stereotactic irradiation unit using kilovoltage X-rays was able to generate a focused radiobiologic reaction in rabbit lungs. Dose-volume histogram analysis and estimated sagittal dose distribution, considering respiratory movement, clarified the characteristics of the irradiation received from this type of unit.

Epithelial-mesenchymal transition as a potential explanation for podocyte depletion in diabetic nephropathy.

BACKGROUND: Depletion of glomerular podocytes is an important feature of progressive diabetic nephropathy. Although the most plausible explanation for this podocyte depletion is detachment from the glomerular basement membrane after cellular apoptosis, the mechanism is unclear. Fibroblast-specific protein 1 (FSP1; encoded by the S100A4 gene) is a member of the S100 family of calcium-binding proteins and is constitutively expressed in the cytoplasm of tissue fibroblasts or epithelial cells converted into fibroblasts by means of epithelial-mesenchymal transition. STUDY DESIGN: Retrospective cross-sectional analysis. SETTINGS & PARTICIPANTS: 109 patients with type 2 diabetes mellitus, of whom 43 (39%) underwent kidney biopsy. PREDICTOR: Clinical stage (4 categories) and histological grade (5 categories) of diabetic nephropathy. OUTCOME: FSP1 expression in podocytes in urine and glomeruli in kidney biopsy specimens. MEASUREMENTS: Immunohistochemistry, real-time polymerase chain reaction, and in situ hybridization. RESULTS: 38 of 109 patients (35%) were normoalbuminuric, 16 (15%) had microalbuminuria, 8 (7%) had macroalbuminuria, and 47 (43%) had decreased kidney function. Approximately 95% of podocytes in urine sediment were not apoptotic, and 86% expressed FSP1. The number of FSP1-positive podocytes in urine sediment was significantly larger in patients with macroalbuminuria than in those with normoalbuminuria (P = 0.03). Intraglomerular expression of FSP1 occurred almost exclusively in podocytes from patients with diabetes, and the number of FSP1-positive podocytes was larger in glomeruli showing diffuse mesangiopathy than in those showing focal mesangiopathy (P = 0.01). The number also was larger in glomeruli with nodular lesions than in those without nodular lesions (P < 0.001). FSP1-positive podocytes selectively expressed Snail1 and integrin-linked kinase, a known trigger for epithelial-mesenchymal transition. LIMITATIONS: Nonrepresentative study population. CONCLUSIONS: These results suggest that the appearance of FSP1 in podocytes of patients with diabetes is associated with more severe clinical and pathological findings of diabetic nephropathy, perhaps because of induction of podocyte detachment through epithelial-mesenchymal transition-like phenomena.

Treatment with recombinant placental growth factor (PlGF) enhances both angiogenesis and arteriogenesis and improves survival after myocardial infarction.

BACKGROUND: Placental growth factor (PlGF), a homolog of vascular endothelial growth factor, is reported to stimulate angiogenesis and arteriogenesis in pathological conditions. It was recently demonstrated that PlGF is rapidly produced in myocardial tissue during acute myocardial infarction (MI). However, the effects of exogenous PlGF administration on the healing process after MI are not fully understood. The purpose of the present study was to examine whether PlGF treatment has therapeutic potential in MI. METHODS AND RESULTS: Recombinant human PlGF (rhPlGF: 10 microg) was administered continuously for 3 days in a mouse model of acute MI. rhPlGF treatment significantly improved survival rate after MI and preserved cardiac function relative to control mice. The numbers of CD31-positive cells and alpha-smooth muscle actin-positive vessels in the infarct area were significantly increased in the rhPlGF group. Endothelial progenitor cells (Flk-1(+)Sca-1(+) cells) were mobilized by rhPlGF into the peripheral circulation. Furthermore, rhPlGF promoted the recruitment of GFP-labeled bone marrow cells to the infarct area, but only a few of those migrating cells differentiated into endothelial cells. CONCLUSIONS: Exogenous PlGF plays an important role in healing processes by improving cardiac function and stimulating angiogenesis following MI. It can be considered as a new therapeutic molecule.