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.

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.

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.

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.

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.

[Neuroendocrine differentiation in adenocarcinoma of the prostate during hormonal treatment : a case report].

A case of neuroendocrine (NE) differentiated prostate cancer is reported herein, which was progressed with NE differentiation during hormonal treatment in adenocarcinoma of the prostate. A 65-year-old man was admitted to our department with increased serum prostate specific antigen (PSA) (150 ng/ml). A prostate biopsy was performed and histological examinations indicated poorly differentiated adenocarcinoma with a Gleason score of 5 + 4 = 9. Further examinations showed metastases to systemic bones. The clinical stage was T3bN0M1b and hormonal therapy using leuprorelin was started. Eighteen months after hormonal therapy, the serum PSA level declined to 1.702 ng/ml. He subsequently experienced edema in his legs. Computed tomography (CT) demonstrated enlargement of the prostate and swelling of multiple pelvic lymph nodes. Immunohistochemical examination of a re-biopsy specimen revealed a neuroendocrine carcinoma. The neuron-specific enolase (NSE) level was 50.9 ng/ml. The treatment measure was changed from hormonal therapy to combination chemotherapy comprising cisplatin (CDDP) and irinotecan (CPT-11). Pelvic radiotherapy (50 Gy) was then performed. Two courses of the chemotherapy resulted in a great reduction of the tumor volume. However, he had liver metastases 3 months later. His condition worsened rapidly and he died at 8 months after definite diagnosis.

Recent advances in molecular targeted therapy for metastatic renal cell carcinoma.

Advanced renal cell carcinoma (RCC) is resistant to chemotherapy and radiotherapy. Immunotherapy is relatively effective against RCC. However, the response rate is approximately 15-20%. Therefore, new therapeutic approaches are necessary. Recently, molecular mechanisms responsible for the proliferation of RCC are identified, and molecular targeted therapy is developed. Bevacizumab, sorafenib, sunitinib, axitinib, temsirolimus, everolimus are promising molecular targeted therapeutic agents for metastatic RCC, and will be used widely in clinics in the near future. In addition, combination therapy with molecular targeted therapy and other therapies including immunotherapy may also be developed soon.

Post-chemotherapy nerve-sparing retroperitoneal lymph node dissection for advanced germ cell tumor.

OBJECTIVE: To report our experience with post-chemotherapy nerve-sparing retroperitoneal lymph node dissection (RPLND) for advanced germ cell tumor (GCT). METHODS: Between 1994 and 2008, 92 patients with advanced GCT underwent RPLND after multiple treatments with systemic chemotherapy at our institution. A nerve-sparing RPLND was carried out in 78 patients (84.8%; median age 32 years). Of them, 19 had a seminoma and 59 had a non-seminoma. RESULTS: Lumbar splanchnic nerves controlling ejaculatory function were macroscopically preserved during RPLND. Bilateral and unilateral lumbar splanchnic nerves were preserved in 40 patients and 38 patients, respectively. Sixty-five patients could be evaluated for ejaculation. Fifty-four patients (83.1%) achieved antegrade ejaculation with a median postoperative interval of 3 months (range: 1-10 months). Twenty-eight patients (28/30: 93.3%) and 26 patients (26/35: 74.3%) undergoing bilateral and unilateral nerve-sparing RPLND had antegrade ejaculation, respectively (P = 0.041). Only two patients (2.6%) had mediastinal and retroperitoneal recurrences during a median follow-up of 42 months (range: 1-138 months), respectively. However, these patients were cured by chemotherapy and surgery. CONCLUSIONS: Post-chemotherapy nerve-sparing RPLND preserves ejaculatory function in the majority of patients with advanced GCT without increasing the risk of local recurrence.

Clinical outcome of tumor recurrence for Ta, T1 non-muscle invasive bladder cancer from the data on registered bladder cancer patients in Japan: 1999-2001 report from the Japanese Urological Association.

OBJECTIVE: To characterize the clinical outcome in a large contemporary series of Japanese patients with newly diagnosed Ta, T1 non-muscle invasive bladder cancer who underwent transurethral bladder tumor resection with or without intravesical chemotherapy or Bacillus Calmette-Guérin (BCG) therapy. METHODS: We developed a database incorporating newly diagnosed non-muscle invasive bladder cancer data and outcomes from a Japanese bladder cancer registry between 1999 and 2001 and identified a study population of 3237 consecutive patients who had complete data based on pathological features. Median patient age was 69.9 years. RESULTS: The 1-year, 3-year, and 5-year overall recurrence-free survival rates were 77.0%, 61.3%, and 52.8%, respectively. In multivariate analyses, the multiplicity of bladder tumors, tumor size greater than 3 cm, pathological stage T1, tumor grade G3, and the absence of adjuvant intravesical instillation were independent risk factors for tumor recurrence. Overall, 1710 patients (52.8%) received intravesical instillation; chemotherapy in 1314 (76.8%) and BCG treatment in 396 (23.2%). In patients treated with intravesical chemotherapy in which an anthracycline chemo-agent was used in 90.5% of the cases, multivariate analyses demonstrated that male gender, multiple bladder tumors, a tumor size greater than 3 cm, and pathological stage T1 were associated with tumor recurrence. CONCLUSIONS: The accumulation and analysis of data from the Japanese National Bladder Cancer Registry made it possible to determine the clinical characteristics, management trends, and survival rates for the period studied. Further study with a dataset created from longer follow-up data would be warranted to analyze tumor progression and disease survival.

Bladder cancer develops 6 years earlier in current smokers: analysis of bladder cancer registry data collected by the cancer registration committee of the Japanese Urological Association.

OBJECTIVES: It is generally recognized that cigarette smoking is the most important risk factor for bladder cancer. The present study was undertaken to examine the relationships between smoking history of bladder cancer patients and the age of onset of bladder cancer and tumor characteristics. METHODS: The present study examined the data for 5959 cases (4728 males and 1231 females) collected in the bladder cancer database of the Japanese Urological Association from 1999 to 2001. Patients were divided by smoking history into three categories as current non-smokers, current smokers and unknown smoking history. Relationship between smoking history and the age at diagnosis of bladder cancer, gender, T stage, grade, tumor size, tumor number and initial symptoms was analyzed. RESULTS: In both males and females the onset of bladder cancer is about 6 years (6.1 years in males and 5.9 years in females) earlier for current smokers than for current non-smokers. At the time of diagnosis, tumor stage was significantly higher in the current smokers group. The current smokers group tended to have larger tumor size. CONCLUSIONS: The finding of 6-year-earlier onset of bladder cancer among current smokers is of great importance to both health care and medical economics. It is essential to make people better informed concerning the need to quit smoking.

Anti-gout agent allopurinol exerts cytotoxicity to human hormone-refractory prostate cancer cells in combination with tumor necrosis factor-related apoptosis-inducing ligand.

Allopurinol has been used for the treatment of gout and conditions associated with hyperuricemia for several decades. We explored the potential of allopurinol on cancer treatment. Allopurinol did not expose cytotoxicity as a single treatment in human hormone refractory prostate cancer cell lines, PC-3 and DU145. However, allopurinol drastically induced apoptosis of PC-3 and DU145 in combination with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which is a promising candidate for anticancer agent but its efficacy is limited by the existence of resistant cancer cells. We examined the underlying mechanism by which allopurinol overcomes the resistance of prostate cancer cells to TRAIL. Allopurinol up-regulated the expression of a proapoptotic TRAIL receptor, death receptor 5 (DR5). Allopurinol increased DR5 protein, mRNA, and promoter activity. Using DR5 small interfering RNA (siRNA), we showed that allopurinol-mediated DR5 up-regulation contributed to the enhancement of TRAIL effect by allopurinol. Furthermore, we examined the mechanism of allopurinol-mediated DR5 up-regulation. DR5 promoter activity induced by allopurinol was diminished by a mutation of a CAAT/enhancer binding protein homologous protein (CHOP)-binding site. In addition, allopurinol also increased CHOP expression, suggesting that allopurinol induced DR5 expression via CHOP. Allopurinol possesses the activity of a xanthine oxidase (XO) inhibitor. We used XO siRNA instead of allopurinol. XO siRNA also up-regulated DR5 and CHOP expression and sensitized the prostate cancer cells to TRAIL-induced apoptosis. Here, we show the novel potential of allopurinol in cancer treatment and indicate that the combination of allopurinol with TRAIL is effective strategy to expand the TRAIL-mediated cancer therapy.

[Squamous cell carcinoma of the renal pelvis with elevation of G-CSF in the serum: a case report].

A 67-year-old man was admitted with left renal pelvic tumor. He had a leukocytosis of 26,500/mm3 (neutrophils: 81.7%) in the peripheral blood, but with no obvious focus of infection. Moreover, the serum granulocyte-colony stimulating factor (G-CSF) and squamous cell carcinoma antigen (SCC) were elevated. Abdominal enhanced computed tomography (CT) and left retrograde pyelography showed left renal pelvic cancer T4N0M0. He received neoadjuvant chemotherapy (M-VAC: cisplatin + methotrexate + vinblastin + doxorubicin, TN: paclitaxel + nedaplatin). After neoadjuvant chemotherapy, left nephroureterectomy was performed because of normalization of the serum SCC and G-CSF. Histological examination revealed squamous cell carcinoma of the renal pelvis. He is alive with no evidence of disease for 4 years.