Estimation of post-therapeutic liver reserve capacity using 99mTc-GSA scintigraphy prior to carbon-ion radiotherapy for liver tumors.

BACKGROUND: There is currently no established imaging method for assessing liver reserve capacity prior to carbon-ion radiotherapy (CIRT) for liver tumors. In order to perform safe CIRT, it is essential to estimate the post-therapeutic residual reserve capacity of the liver. PURPOSE: To evaluate the ability of pre-treatment 99mTc-galactosyl human serum albumin (99mTc-GSA) scintigraphy to accurately estimate the residual liver reserve capacity in patients treated with CIRT for liver tumors. MATERIALS AND METHODS: This retrospective study evaluated patients who were performed CIRT for liver tumors between December 2018 and September 2020 and underwent 99mTc-GSA scintigraphy before and 3 months after CIRT, and gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI within 1 month before CIRT were evaluated. The maximal removal rate of 99mTc-GSA (GSA-Rmax) was analyzed for the evaluation of pre-treatment liver reserve capacity. Then, the GSA-Rmax of the estimated residual liver (GSA-RL) was calculated using liver SPECT images fused with the Gd-EOB-DTPA-enhanced MRI. GSA-RL before CIRT and GSA-Rmax at 3 months after CIRT were compared using non-parametric Wilcoxon signed-rank test and linear regression analysis. RESULTS: Overall, 50 patients were included (mean age ± standard deviation, 73 years ± 11; range, 29-89 years, 35 men). The median GSA-RL was 0.393 [range, 0.057-0.729] mg/min, and the median GSA-Rmax after CIRT was 0.369 [range, 0.037-0.780] mg/min (P = .40). The linear regression equation representing the relationship between the GSA-RL and GSA-Rmax after CIRT was y = 0.05 + 0.84x (R2 = 0.67, P < .0001). There was a linear relationship between the estimated and actual post-treatment values for all patients, as well as in the group with impaired liver reserve capacity (y = - 0.02 + 1.09x (R2 = 0.62, P = .0005)). CONCLUSIONS: 99mTc-GSA scintigraphy has potential clinical utility for estimating the residual liver reserve capacity in patients undergoing carbon-ion radiotherapy for liver tumors. TRIAL REGISTRATION: UMIN000038328, https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000043545 .

Hierarchical Elemental Odor Coding for Fine Discrimination Between Enantiomer Odors or Cancer-Characteristic Odors.

Odors trigger various emotional responses such as fear of predator odors, aversion to disease or cancer odors, attraction to male/female odors, and appetitive behavior to delicious food odors. Odor information processing for fine odor discrimination, however, has remained difficult to address. The olfaction and color vision share common features that G protein-coupled receptors are the remote sensors. As different orange colors can be discriminated by distinct intensity ratios of elemental colors, such as yellow and red, odors are likely perceived as multiple elemental odors hierarchically that the intensities of elemental odors are in order of dominance. For example, in a mixture of rose and fox-unique predator odors, robust rose odor alleviates the fear of mice to predator odors. Moreover, although occult blood odor is stronger than bladder cancer-characteristic odor in urine samples, sniffer mice can discriminate bladder cancer odor in occult blood-positive urine samples. In forced-choice odor discrimination tasks for pairs of enantiomers or pairs of body odors vs. cancer-induced body odor disorders, sniffer mice discriminated against learned olfactory cues in a wide range of concentrations, where correct choice rates decreased in the Fechner's law, as perceptual ambiguity increased. In this mini-review, we summarize the current knowledge of how the olfactory system encodes and hierarchically decodes multiple elemental odors to control odor-driven behaviors.

Impact of appendicular and trunk skeletal muscle mass and back extensor strength on sagittal spinal alignment in Japanese women without vertebral fracture.

OBJECTIVES: Progressive and generalized loss of skeletal muscle mass (SMM) and strength are characteristics of sarcopenia. However, the impact of appendicular and trunk SMM and back extensor strength (BES) on spinal sagittal alignment remains unclear. Herein, we investigate the relationship between these factors and spinal sagittal alignment. METHODS: In total, 202 women without vertebral fractures (median age, 66.9 years; interquartile range, 61.4-71.9 years) were analyzed at an orthopedic outpatient clinic. Pelvic incidence (PI), lumbar lordosis (LL), sagittal vertical axis (SVA), and pelvic tilt (PT) were measured on whole spine radiographs. Body mass index (BMI), appendicular and trunk relative SMM index, and BES were also evaluated. These measurements were compared between spinal sagittal alignment groups using the Mann-Whitney U test. Finally, the factors contributing to abnormal alignment were analyzed using multiple logistic regression analysis. RESULTS: BES was significantly lower in all abnormal sagittal alignment groups, as defined by PI-LL (≥ 10°), SVA (≥4 cm), and PT (≥20°) (all P < 0.001). On multivariate analysis, BES was a contributing factor for abnormal PI-LL (P < 0.001), SVA (P = 0.001), and PT (P < 0.001). Conversely, a decrease in appendicular and trunk relative SMM index did not statistically affect abnormal spinal sagittal alignment. CONCLUSIONS: BES was associated with changes in spinal sagittal alignment; however, SMM, which is often used for diagnosing sarcopenia, did not affect spinal sagittal alignment.

Validation set analysis to predict postoperative outcomes by technetium-99m galactosyl serum albumin scintigraphy for hepatectomy.

BACKGROUND: The indocyanine green retention rate at 15 min (ICGR15) is a gold standard parameter of liver function when deciding on the extent of hepatectomy. However, ICGR15 is influenced by several hepatic conditions. To evaluate auxiliary preoperative liver functional reserve, we examined the clinical significance of modified parameters by blood tests and technetium-99m galactosyl human serum albumin (Tc-GSA) scintigraphy. METHODS: We measured liver function parameters, including the hepatic uptake ratio (LHL15) and the blood pool clearance index (HH15) of Tc-GSA and their modified formulae [LHL/HH15, LHL minus HH15, and converted ICGR15 (cICGR15) from a preliminary study] in 229 patients, including 18 with biliary obstruction. RESULTS: The mean values of LHL15/HH15, LHL minus HH15, and cICGR15 were 1.646 ± 0.295, 0.347 ± 0.116, and 13.2 ± 5.3%, respectively. These parameters correlated significantly with other liver functions measured by blood tests except for the bilirubin level (P < 0.05) although the actual ICGR15 level correlated positively with the bilirubin level. The difference of ICGR15 (ICGR15 minus cICGR15) in patients with biliary obstruction tended to be higher in comparison with that in patients without biliary obstruction (P = 0.044). Values of LHL/HH15, LHL minus HH15, and the cICGR15 were not significantly associated with postoperative complications. CONCLUSION: The modified parameters of Tc-GSA were useful for evaluating hepatic function in patients with high bilirubinemia due to biliary obstruction. However, it remains difficult to establish a more reliable parameter as a standard hepatic function test instead of ICGR15.

Significance of the preoperative regional maximal removal rate of technetium-99m-galactosyl human serum albumin in the future remnant liver: a sequential study of regional maximal removal rate of technetium-99m-galactosyl human serum albumin in the whole liver.

BACKGROUND: The relationship between posthepatectomy complications and liver functional parameters was preliminary reported in a pilot study. The present study sequentially evaluated the clinical significance of maximal removal rate of technetium-99m-galactosyl human serum albumin (GSARmax) in the future remnant liver (rGSARmax) in patients to predict posthepatectomy complications. METHODS: Between 2010 and August 2017, GSARmax, rGSARmax, their difference (Dif), and the rGSARmax to GSARmax ratio were examined in 247 additional patients who underwent hepatectomy for liver and biliary diseases. Hepatectomy-related postoperative complications (i.e. long-term ascites, intra-abdominal infection, and hepatic failure) occurred in 73 (29.6%) patients. RESULTS: The median and mean preoperative GSARmax values were 0.477 and 0.498±0.166 mg/min, respectively; rGSARmax values were 0.341 and 0.366±0.145 mg/min, respectively; Dif values were 0.105 and 0.132±0.111 mg/min, respectively; and the rGSARmax to GSARmax ratio values were 0.774 and 0.746±0.177, respectively. Among these, the GSARmax and rGSARmax values were significantly correlated with the liver functional parameters ICGR15, LHL15, HH15, prothrombin activity, serum hyaluronic acid level, and platelet count (all P<0.01). The rGSARmax values were significantly lower in patients with long-term ascites (P<0.05), and the predictive cutoff values of rGSARmax were 0.290 mg/min; however, the multivariate logistic regression analysis showed that rGSARmax was not independently related to long-term ascites. CONCLUSION: When accompanied by other functional liver reserve parameters, rGSARmax seemed to be an alternative liver functional parameter related to ascites.

Prediction of Posthepatectomy Liver Failure Proposed by the International Study Group of Liver Surgery: Residual Liver Function Estimation With 99mTc-Galactosyl Human Serum Albumin Scintigraphy.

PURPOSE: The International Study Group of Liver Surgery (ISGLS) proposed a definition and grading system for posthepatectomy liver failure (PHLF). We evaluated the usefulness of residual liver function estimation using Tc-galactosyl human serum albumin (Tc-GSA) for the prediction of PHLF. METHODS: Patients with liver tumors (n = 136) and scheduled for hepatectomy underwent Tc-GSA scintigraphy. Based on their imaging data, the maximal GSA removal rate (GSA-Rmax)was calculated using multicompartment analysis. We also calculated GSA-Rmax in the predicted residual liver (GSA-RL) whose volume was determined on computed tomography (CT) scans. We compared the age, sex, 15-minute indocyanine green retention rate; albumin, bilirubin, hyaluronic acid, and type 4 collagen levels; the Child-Pugh classification; residual liver volume; residual liver percentage; GSA-Rmax; and GSA-RL in patients with and without PHLF. Univariate and multivariate logistic analyses were used for statistical assessments. RESULTS: Of 136 patients, 17 (12.5%) met the ISGLS criteria for PHLF (ISGLS-PHLF). There was a statistically significant difference in the age, albumin level, Child-Pugh classification, residual liver volume, residual liver percentage, GSA-Rmax, and GSA-RL between patients with and without PHLF. Based on multivariate analysis, GSA-RL and the residual liver volume were significant independent predictors of ISGLS-PHLF (P = 0.004 and P = 0.038, respectively). The odds ratio was 149423 for GSA-RL and 1.003 for the residual liver volume. CONCLUSIONS: GSA-RL calculated using Tc-GSA scintigraphy was the most useful independent predictor for ISGLS-PHLF.

Preoperative maximal removal rate of technetium-99m-galactosyl-human serum albumin of the remnant liver is associated with postoperative tumor relapse in hepatitis C virus-related hepatocellular carcinoma.

BACKGROUND: Prognosis in patients with hepatocellular carcinoma (HCC) is not only influenced by tumor-related factors but also by the background liver functions. The maximal removal rate of technetium-99m-galactosyl human serum albumin (GSA-Rmax) of the remnant liver (rGSA-Rmax) is a useful candidate for predicting the liver function and clarifying the relationship between the remnant liver functional reserve and tumor-free survival in patients who have undergone hepatectomy. PATIENTS AND METHODS: One hundred and sixty-five patients with HCC who underwent curative hepatectomy were divided into three groups of hepatitis B virus (B-HCC; n=42), hepatitis C virus (C-HCC, n=58), and non-B, non-C (NBNC-HCC, n=65). The relationship between rGSA-Rmax and survival was examined by univariate and multivariate analyses. RESULTS: In the C-HCC group, the albumin, or LHL15, level was significantly lower, and alanine aminotransferase, ICGR15, and the prevalence of grade B liver damage were significantly higher than other two groups (P<0.05). GSA-Rmax or rGSA-Rmax was not different between the three groups. Lower GSA-Rmax and rGSA-Rmax were only significantly associated with lower tumor-free survival in the C-HCC group by the univariate analysis (P<0.05) but not significantly by the multivariate analysis. CONCLUSION: GSA-Rmax and rGSA-Rmax reflect the severity of liver dysfunction and furthermore, the lower rGSA-Rmax is useful as a complementary factor to predict the early HCC recurrence after hepatectomy.

Sniffer mice discriminate urine odours of patients with bladder cancer: A proof-of-principle study for non-invasive diagnosis of cancer-induced odours.

Similar to fingerprints, humans have unique, genetically determined body odours. In case of urine, the odour can change due to variations in diet as well as upon infection or tumour formation. We investigated the use of mice in a manner similar to "sniffer dogs" to detect changes in urine odour in patients with bladder cancer. We measured the odour discrimination thresholds of mice in a Y-maze, using urine mixtures from patients with bladder cancer (Stage I) and healthy volunteers (dietary variations) as well as occult blood- or antibiotic drug metabolite-modulated samples. Threshold difference indicated that intensities of urinary olfactory cues increase in the following order: dietary variation < bladder cancer < occult blood < antibiotic drug metabolites. After training with patient urine mixtures, sniffer mice discriminated between urine odours of pre- and post-transurethral resection in individual patients with bladder cancer in an equal-occult blood diluted condition below the detection level of dietary variations, achieving a success rate of 100% (11/11). Furthermore, genetic ablation of all dorsal olfactory receptors elevated the discrimination thresholds of mice by ≥ 105-fold. The marked reduction in discrimination sensitivity indicates an essential role of the dorsal olfactory receptors in the recognition of urinary body odours in mice.

Preoperative regional maximal removal rate of technetium-99m-galactosyl human serum albumin is correlated with liver functional parameters, but did not predict postoperative morbidity.

BACKGROUND: Recently, posthepatectomy complications have been predicted by advances of new liver functional parameters, and the technetium-99m-galactosyl human serum albumin (GSA) liver scintigraphy has been applied widely for this purpose. We evaluated the clinical significance of the regional maximal removal rate (GSA-Rmax) in patients with various liver diseases as predictors of posthepatectomy complications. PATIENTS AND METHODS: Between 2012 and March 2016, we examined 200 patients who underwent hepatectomy for liver and biliary diseases. The patients' background liver conditions included chronic viral liver diseases in 147 patients, normal liver in 44 patients, and others in nine patients. Hepatectomy-related postoperative complications (i.e. long-term ascites, intra-abdominal infection, and hepatic failure) occurred in 69 (35%) patients. A multivariate logistic analysis was carried out to detect the predictive parameters for complications. RESULTS: The median and mean preoperative GSA-Rmax was 0.420 and 0.448±0.148 mg/min, respectively. The GSA-Rmax was significantly correlated with liver functional parameters of ICGR15, LHL15, HH15, platelet count, prothrombin activity, and serum hyaluronic acid level (P<0.01), and was significantly correlated with postoperative total bilirubin level and C-reactive protein level (P<0.05). With respect to patient outcomes, GSA-Rmax was significantly lower in patients with long-term ascites (P<0.05). The predictive cutoff value for posthepatectomy long-term ascites for GSA-Rmax was 0.421 mg/min. However, the multivariate logistic regression analysis identified that a higher serum hyaluronic acid level and a lower platelet count were significant, independent factors, but not lower GSA-Rmax. CONCLUSION: GSA-Rmax is one of the liver functional parameters and is a complementary parameter to predict postoperative hyperbilirubinemia, inflammatory responses, and ascites when Tc-GSA scintigraphy is performed.

Successful transarterial embolization with cellulose porous beads for occipital haemangioma in an infant with Kasabach-Merritt syndrome.

We report a 3-month-old boy with Kasabach-Merritt Syndrome (KMS) with an occipital haemangioma who underwent successful transarterial embolization (TAE) with cellulose porous beads (CPBs). As his response to steroids and coil embolization was inadequate, we performed TAE with CPBs, carefully preventing their migration via dangerous anastomoses. The tumour blush decreased, there were no complications, all coagulation tests were immediately normalized and the tumor size decreased gradually. TAE with CPBs is useful for the treatment of KMS.

Prevalence of sarcopenia in Japanese women with osteopenia and osteoporosis.

Sarcopenia and osteoporosis are both significant health burdens among postmenopausal women. This study examined associations between sarcopenia and osteopenia/osteoporosis in Japanese women and evaluated the prevalence of sarcopenia in women with osteopenia and osteoporosis. A total of 2400 Japanese women aged 40-88 years underwent dual-energy x-ray absorptiometry (DXA) scans of the whole body, lumbar spine, and total hip. Osteopenia and osteoporosis were defined according to World Health Organization criteria using bone mineral density (BMD) of the lumbar spine or hip. Sarcopenia was defined as a relative skeletal muscle index (RSMI) more than 2 standard deviations below the mean for a young adult reference population, calculated as the appendicular skeletal muscle mass (ASM) obtained from whole-body DXA divided by height in meters squared (RSMI = ASM/height(2)). Significant and marginal/moderate positive correlations were observed between RSMI and lumbar spine/total hip BMDs (r = 0.197 and r = 0.274, respectively; p < 0.0001 each). The BMDs of the lumbar spine and total hip showed significant moderate negative correlations with age (r = -0.270 and r = -0.375, respectively; p < 0.0001 each), but RSMI showed no association with age in this population (r = 0.056). When osteopenia/osteoporosis was defined using lumbar spine BMD, prevalences of sarcopenia in subjects with normal BMD, osteopenia and osteoporosis were 10.4, 16.8, and 20.4 %, respectively. When osteopenia/osteoporosis was defined using total hip BMD, the prevalences of sarcopenia in these subjects were 9.0, 17.8, and 29.7 %, respectively. A Chi-square test for independence showed a significant association between sarcopenia and osteopenia/osteoporosis (p < 0.0001). These results indicate that sarcopenia is significantly associated with osteopenia and osteoporosis in Japanese women.

An ultra-high speed Whole Slide Image viewing system.

BACKGROUND: One of the goals for a Whole Slide Imaging (WSI) system is implementation in the clinical practice of pathology. One of the unresolved problems in accomplishing this goal is the speed of the entire process, i.e., from viewing the slides through making the final diagnosis. Most users are not satisfied with the correct viewing speeds of available systems. We have evaluated a new WSI viewing station and tool that focuses on speed. METHOD: A prototype WSI viewer based on PlayStation®3 with wireless controllers was evaluated at the Department of Pathology at MGH for the following reasons: 1. For the simulation of signing-out cases; 2. Enabling discussion at a consensus conference; and 3. Use at slide seminars during a Continuing Medical Education course. RESULTS: Pathologists were being able to use the system comfortably after 0-15 min training. There were no complaints regarding speed. Most pathologists were satisfied with the functionality, usability and speed of the system. The most difficult situation was simulating diagnostic sign-out. CONCLUSIONS: The preliminary results of adapting the Sony PlayStation®3 (PS3®) as an ultra-high speed WSI viewing system were promising. The achieved speed is consistent with what would be needed to use WSI in daily practice.

Urinary continence following laparoscopic radical prostatectomy: Association with postoperative membranous urethral length measured using real-time intraoperative transrectal ultrasonography.

Urinary incontinence is a major complication following radical prostatectomy. The aim of the present study was to assess the association between urinary continence following laparoscopic radical prostatectomy (LRP) and various factors measured using real-time intraoperative transrectal ultrasonography (TRUS). Patients (n=53) with localized prostate cancer underwent LRP in combination with real-time intraoperative TRUS navigation and were evaluated for urinary continence for more than 6 months following LRP. Prostate size, membranous urethral length (MUL) and bladder-urethra angle were measured using real-time intraoperative TRUS immediately before and after surgery. Urinary continence was regained by 4, 15 and 27 patients 1, 3 and 6 months after LRP, respectively. Longer postoperative MUL was significantly correlated with recovery of urinary continence 1, 3 and 6 months after LRP. In addition, an increase in difference between preoperative and postoperative MUL was also associated with superior continence. No correlation was observed between postoperative MUL and the rate of tumor-positive surgical margins. Larger prostate volume was correlated to postoperative continence 6 months after surgery. Shorter operation time and less blood loss resulted in postoperative urinary continence 1 month after LRP. Preoperative MUL, bladder-urethra angle, age and body mass index had no correlation with urinary continence. Postoperative MUL was the most significant factor for early recovery of urinary continence following LRP. These results indicate that preservation of longer urethra during surgery may be recommended without tumor-positive surgical margins.

[Leiomyosarcoma of the scrotum].

A 31-year-old man visited another hospital with a chief complaint of a solid mass in the left scrotum. The diagnosis was a skin cancer of the scrotum, and he was referred to our hospital. We performed surgical resection of the mass, left testis, and bilateral superfical inguinal nodes. Histopathological findings revealed leiomyosarcoma of the scrotum. He is free of disease at 16 months after the operation.

Low circulating serum levels of second mitochondria-derived activator of caspase (Smac/DIABLO) in patients with bladder cancer.

Smac/DIABLO promotes apoptosis by antagonizing inhibitor of apoptosis proteins. The expression of Smac/DIABLO in tissues has been reported in various cancers; however, little is known about circulating levels of Smac/DIABLO. The present study was designed to first determine if Smac/DIABLO can be detected in the serum and then assess whether the circulating levels of Smac/DIABLO are of prognostic significance in patients with bladder cancer. The levels of Smac/DIABLO in the sera of 173 patients with bladder cancer and 36 normal donors were determined by using an enzyme-linked immunosorbent assay. The mean serum level of Smac/DIABLO in patients with bladder cancer was approximately 2-fold lower than that in normal donors. The mean level of serum Smac/DIABLO in patients with muscle-invasive bladder cancer was lower than that in patients with non-muscle invasive cancer. In addition, the mean serum Smac/DIABLO level in patients with T4 muscle-invasive bladder cancer was lower than that in patients with T2 and T3 cancers. The mean serum level of Smac/DIABLO in patients with Grade 3 bladder cancer was lower than that in patients with Grade 1 and Grade 2 cancers. Analysis by Kaplan-Meier revealed that patients with Ta and T1 non-muscle invasive bladder cancer with high level of serum Smac/DIABLO (more than mean value) had a longer post-operative tumor-free interval than those with low level (less than mean value) in the 3-year follow-up. Furthermore, patients with T2-T4 muscle-invasive bladder cancer with high serum Smac/DIABLO level (more than mean value) had a higher post-operative disease-free rate when compared with patients with low level (less than mean value) in the 5-year follow-up. The present study is the first to analyze circulating levels of Smac/DIABLO in the serum. The findings demonstrate that the mean serum level of Smac/DIABLO was downregulated in patients with bladder cancer compared to control healthy individuals, especially high grade muscle-invasive bladder cancer. Noteworthy, lower serum level of Smac/DIABLO predicted early recurrence in patients with bladder cancer. Overall, the findings suggest that measuring the levels of Smac/DIABLO in the serum may be considered a prognostic parameter in patients with bladder cancer. Furthermore, Smac/DIABLO may be a molecular therapeutic target in bladder cancer.

An ultra-high speed whole slide image viewing system.

BACKGROUND: One of the goals for a Whole Slide Imaging (WSI) system is implementation in the clinical practice of pathology. One of the unresolved problems in accomplishing this goal is the speed of the entire process, i.e., from viewing the slides through making the final diagnosis. Most users are not satisfied with the correct viewing speeds of available systems. We have evaluated a new WSI viewing station and tool that focuses on speed. METHOD: A prototype WSI viewer based on PlayStation®3 with wireless controllers was evaluated at the Department of Pathology at MGH for the following reasons: 1. For the simulation of signing-out cases; 2. Enabling discussion at a consensus conference; and 3. Use at slide seminars during a Continuing Medical Education course. RESULTS: Pathologists were being able to use the system comfortably after 0-15 min training. There were no complaints regarding speed. Most pathologists were satisfied with the functionality, usability and speed of the system. The most difficult situation was simulating diagnostic sign-out. CONCLUSIONS: The preliminary results of adapting the Sony PlayStation®3 (PS3®) as an ultra-high speed WSI viewing system were promising. The achieved speed is consistent with what would be needed to use WSI in daily practice.

Utility of transrectal ultrasonography guidance and seven key elements of operative skill for early recovery of urinary continence after laparoscopic radical prostatectomy.

In the present study, we report the utility of transrectal ultrasonography guidance for laparoscopic radical prostatectomy (LRP), and the effect of a novel surgical approach of 'seven key elements of operative skill for the early recovery of urinary continence' ('7 key elements'). Among 170 patients who underwent laparoscopic prostatectomy between July 2007 and June 2010, 72 were treated on the basis of these 7 key elements (group 1), which included the preservation of 1) endopelvic fascia, 2) bladder neck, 3) pelvic nerve, 4) membranous urethra, 5) urethral sphincter and fixation of the organ positioning with 6) bladder neck sling suspension, and 7) restoration of the Denonvilliers' fascia, while the remaining 98 were not (group 2). We compared the data for the two groups with regards to the time taken for recovery of continence, and post-operative course. Application of the 7 key elements led to significantly earlier recovery of continence. In group 1, the number of urinary pads used after surgery was significantly reduced at all of the examined time-points after surgery (1, 3, 6 and 12 months) (p<0.0001). In group 1, more than half of the patients (54%) achieved urinary continence within 3 months, 93% achieved it within 6 months, and all patients had achieved it within 12 months after surgery. However, in group 2, <10% of the patients (8.5%, p<0.0001) achieved continence within 3 months, and 23% (P<0.0001) achieved it within 6 months. Therefore, the results show that the 7 key elements of operative skill with transrectal ultrasonography guidance significantly improve the outcome of LRP, reducing the time required for the recovery of continence.

Cancer death from non-muscle invasive bladder cancer: report of the Japanese Urological Association of data from the 1999-2001 registry in Japan.

OBJECTIVES: Our aim was to clarify the risk factors of cancer death in order to reduce mortality from T1 bladder cancer. METHODS: The Japan registration database (1999-2001) was used for the analysis. Data were collected at least 3years after the initial diagnosis. Cause-specific survival using a Kaplan-Meier survival estimation with the log-rank method was evaluated. Univariate and multivariate analysis using the Cox proportional hazard model was also carried out. The 1997 TNM classification was used for pathological staging, and the 1973 WHO classification was used for pathological grading. RESULTS: There were 76 cancer deaths among a total of 1919 clinical T1 cases. Regardless of the subsequent treatment strategies, non-papillary tumor appearance, non-peduncular tumor stalk, multiple tumors, a tumor size greater than 3cm, positive urinary cytology and pathological grade 3 were found to be statistically significant in cancer death by univariate analysis. By multivariate analysis, non-papillary tumor appearance, positive urinary cytology and a tumor size greater than 3cm were confirmed as significant risk factors. Cancer death cases were found in 47.4% of worst-grade 2 tumors, and in 67.1% of predominantly grade 1 or 2 tumors. CONCLUSION: Non-papillary tumor appearance, positive urinary cytology and a tumor size greater than 3cm should be included to enable the assessment of risk criteria in cancer death from T1 bladder cancer.

Prognostic significance of second mitochondria-derived activator of caspase (Smac/DIABLO) expression in bladder cancer and target for therapy.

Although the expression of Smac/DIABLO has been reported in various cancers, little is known about its clinical significance in bladder cancer. The present study was designed to evaluate the relationship between progression of disease and Smac/DIABLO expression by clinical pathological analysis of patients with bladder cancer. The level of Smac/DIABLO expression was quantified by Western blot analysis using non-fixed fresh frozen tissues derived from patients with bladder cancer. All normal bladders expressed Smac/DIABLO. However, 64/84 (76%) of bladder cancers expressed Smac/DIABLO and 24% were negative. In Ta and T1 superficial bladder cancers, 98% expressed Smac/DIABLO, whereas only 41% expressed Smac/DIABLO in muscle-invasive bladder cancers. Smac/DIABLO expression inversely correlated with the grade of bladder cancer. Patients with Ta and T1 superficial bladder cancer with higher Smac/DIABLO expression had a longer postoperative recurrence-free period than those with lower Smac/DIABLO expression after transurethral resection in the 5-year follow-up. Patients with invasive bladder cancer expressing Smac/DIABLO had a longer postoperative disease-specific survival than those without Smac/DIABLO expression after radical cystectomy in the 5-year follow-up. The cisplatin-resistant T24 bladder cancer line (T24/CDDP) and the adriamycin-resistant T24 line (T24/ADR) showed lower level of Smac/DIABLO expression, compared with the T24 parental line. In conclusion, the present study demonstrates for the first time that Smac/DIABLO expression was downregulated in bladder cancer, especially in high grade muscle-invasive bladder cancer, and that lower Smac/DIABLO expression in bladder cancer predicted a worse prognosis. In addition, the cisplatin-resistant T24/CDDP line and the adriamycin-resistant T24/ADR line expressed lower level of Smac/DIABLO expression. These results suggest that Smac/DIABLO expression in bladder cancer may be used as a prognostic parameter, and that low Smac/DIABLO expression in bladder cancer may be associated with resistance to chemotherapy.

Enhancement of the sensitivity of renal cell carcinoma cells to fas-mediated cytotoxicity and apoptosis by the selective cyclooxygenase-2 inhibitor JTE-522.

BACKGROUND: Cyclooxygenase-2 (COX-2) is a key enzyme involved in the production of prostaglandins and its inhibitors have been shown to induce apoptosis in a variety of cancer cells. We reasoned that combination treatment of renal cell carcinoma (RCC) cells with COX-2 inhibitors and anticancer agents may result in synergistic apoptosis. We examined whether the selective COX-2 inhibitor JTE-522 synergizes with anticancer agents in cytotoxicity and apoptosis against RCC cells. METHODS: The cytotoxicity of the selective COX-2 inhibitor JTE-522 and other anticancer agents against the RCC cell lines and the normal renal cell line was determined by the microculture tetrazolium dye assay. RESULTS: JTE-522 was cytotoxic against the Caki-1 RCC cell line. JTE-522 and anti-Fas monoclonal antibody (CH-11) exhibited a synergistic cytotoxic effect against Caki-1 cells. In contrast, JTE-522 in combination with 5-fluorouracil, adriamycin, cis-diamminedichloroplatinum, or interferon-alpha, all commonly used clinically, resulted in an additive cytotoxic effect. Synergy achieved in cytotoxicity with JTE-522 and CH-11 was shown to be due to apoptosis. CONCLUSIONS: The present study demonstrated that the selective COX-2 inhibitor JTE-522 had a cytotoxic effect on RCC and that synergistic cytotoxicity against RCC was obtained with JTE-522 in combination with anti-Fas monoclonal antibody. These results suggest that selective COX-2 inhibitors in combination with immunotherapy may be useful in treating patients with RCC.