Selective Suppression of Cell Growth and Programmed Cell Death-Ligand 1 Expression in HT1080 Fibrosarcoma Cells by Low Molecular Weight Fucoidan Extract.

Low molecular weight fucoidan extract (LMF), prepared by an abalone glycosidase digestion of a crude fucoidan extracted from Cladosiphon novae-caledoniae Kylin, exhibits various biological activities, including anticancer effect. Various cancers express programmed cell death-ligand 1 (PD-L1), which is known to play a significant role in evasion of the host immune surveillance system. PD-L1 is also expressed in many types of normal cells for self-protection. Previous research has revealed that selective inhibition of PD-L1 expressed in cancer cells is critical for successful cancer eradication. In the present study, we analyzed whether LMF could regulate PD-L1 expression in HT1080 fibrosarcoma cells. Our results demonstrated that LMF suppressed PD-L1/PD-L2 expression and the growth of HT1080 cancer cells and had no effect on the growth of normal TIG-1 cells. Thus, LMF differentially regulates PD-L1 expression in normal and cancer cells and could serve as an alternative complementary agent for treatment of cancers with high PD-L1 expression.

Induction of apoptosis by low-molecular-weight fucoidan through calcium- and caspase-dependent mitochondrial pathways in MDA-MB-231 breast cancer cells.

Fucoidan, a fucose-rich polysaccharide extracted from brown seaweed, has antitumor, anticoagulant, antiviral, anti-inflammatory, and antibacterial activities. Several studies have shown that a fucoidan treatment of cancer cells induced cytotoxicity and apoptosis and inhibited angiogenesis and invasion. We investigated in the present study the effect of low-molecular-weight fucoidan (LMWF) on apoptosis in estrogen receptor-negative MDA-MB-231 human breast cancer cells. The LMWF treatment of MDA-MB-231 cells was associated with the activation of caspases and mitochondrial dysfunction, including dissipation of the mitochondrial membrane potential (ΔΨm), alteration of Ca(2+) homeostasis, cytochrome c release, and decreased expression of antiapoptotic Bcl-2 family proteins. Understanding the molecular events that mediated LMWF-induced MDA-MB-231 cell death will contribute to a more rational approach to cancer chemotherapy.

Fucoidan extract enhances the anti-cancer activity of chemotherapeutic agents in MDA-MB-231 and MCF-7 breast cancer cells.

Fucoidan, a fucose-rich polysaccharide isolated from brown alga, is currently under investigation as a new anti-cancer compound. In the present study, fucoidan extract (FE) from Cladosiphon navae-caledoniae Kylin was prepared by enzymatic digestion. We investigated whether a combination of FE with cisplatin, tamoxifen or paclitaxel had the potential to improve the therapeutic efficacy of cancer treatment. These co-treatments significantly induced cell growth inhibition, apoptosis, as well as cell cycle modifications in MDA-MB-231 and MCF-7 cells. FE enhanced apoptosis in cancer cells that responded to treatment with three chemotherapeutic drugs with downregulation of the anti-apoptotic proteins Bcl-xL and Mcl-1. The combination treatments led to an obvious decrease in the phosphorylation of ERK and Akt in MDA-MB-231 cells, but increased the phosphorylation of ERK in MCF-7 cells. In addition, we observed that combination treatments enhanced intracellular ROS levels and reduced glutathione (GSH) levels in breast cancer cells, suggesting that induction of oxidative stress was an important event in the cell death induced by the combination treatments.

Fucoidan extract induces apoptosis in MCF-7 cells via a mechanism involving the ROS-dependent JNK activation and mitochondria-mediated pathways.

BACKGROUND: Fucoidan extract (FE), an enzymatically digested compound with a low molecular weight, is extracted from brown seaweed. As a natural compound with various actions, FE is attractive, especially in Asian countries, for improving the therapeutic efficacy and safety of cancer treatment. The present study was carried out to investigate the anti-tumor properties of FE in human carcinoma cells and further examine the underlying mechanisms of its activities. METHODOLOGY/PRINCIPAL FINDING: FE inhibits the growth of MCF-7, MDA-MB-231, HeLa, and HT1080 cells. FE-mediated apoptosis in MCF-7 cancer cells is accompanied by DNA fragmentation, nuclear condensation, and phosphatidylserine exposure. FE induces mitochondrial membrane permeabilization (MMP) through loss of mitochondrial membrane potential (ΔΨm) and regulation of the expression of Bcl-2 family members. Release of apoptosis-inducing factor (AIF) and cytochrome c precedes MMP. AIF release causes DNA fragmentation, the final stage of apoptosis, via a caspase-independent mitochondrial pathway. Additionally, FE was found to induce phosphorylation of c-Jun N-terminal kinase (JNK), p38, and extracellular signal-regulated kinase (ERK) 1/2, and apoptosis was found to be attenuated by inhibition of JNK. Furthermore, FE-mediated apoptosis was found to involve the generation of reactive oxygen species (ROS), which are responsible for the decrease of ΔΨm and phosphorylation of JNK, p38, and ERK1/2 kinases. CONCLUSIONS/SIGNIFICANCE: These data suggest that FE activates a caspase-independent apoptotic pathway in MCF-7 cancer cells through activation of ROS-mediated MAP kinases and regulation of the Bcl-2 family protein-mediated mitochondrial pathway. They also provide evidence that FE deserves further investigation as a natural anticancer and cancer preventive agent.

Can anti-infective drugs improve the infection-related symptoms of patients with cancer during the terminal stages of their lives?

BACKGROUND: Appropriate use of anti-infective drugs is essential in clinical practice. No evidence-based guidelines or protocols have been published on the appropriate use of anti-infective drugs in patients receiving palliative care as yet. METHODS: The medical records, which included the demographic data of patients, anti-infective drug use, bacteriologic findings, symptoms, and hematologic findings were reviewed retrospectively to determine the potential factors that contribute to symptom improvement of patients in terminal phase. RESULTS: Seventy-one patients (64%) who received anti-infective drugs and had a total of 326 episodes of infection were assessed. Symptom improvement was seen in 33.1%. A total of 22.6% of episodes were started on anti-infective drugs during the last week of life and the symptom improvement in these episodes was 9.2%. Symptom improvement was hardly observed when the anti-infective drug was administered during the last week of life. The association between the decrease in the C-reactive protein (CRP) levels, the decrease of the leukocyte count, reduction of fever, and symptom improvement was determined. The decrease of CRP levels was 42.4%; leukocyte, 56.7%; and reduction of fever was 28.4%. The symptom improvement of individual treatment history was also investigated. The symptom improvement of the group who took positive treatment such as chemotherapy, radiotherapy, surgery, and catheter placement was significantly lower than that of no-treatment group. CONCLUSIONS: Active cancer treatment probably induces the symptoms related to infection and the use of anti-infective drugs. Unnecessary and excessive treatment should be avoided, and the symptoms should be managed with consideration of the patient's state of mind in order to improve the quality of life of terminally ill patients.

Quantitative detection of micrometastases in pelvic lymph nodes in patients with clinically localized prostate cancer by real-time reverse transcriptase-PCR.

PURPOSE: Routine pathologic examination can miss micrometastatic tumor foci in the lymph nodes of patients with prostate cancer, resulting in confusion during tumor staging and clinical decision-making. The objective of this study was to clarify the significance of micrometastases in pelvic lymph nodes in patients who underwent radical prostatectomy for prostate cancer. EXPERIMENTAL DESIGN: The expression of prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) in 2,215 lymph nodes isolated from 120 patients with clinically localized prostate cancer was assessed by a fully quantitative real-time reverse transcriptase-PCR. We regarded specimens in which either PSA or PSMA mRNAs were positive as proof of the "presence of micrometastasis." Immunohistochemical staining of lymph node specimens with an antibody against PSA was also done. RESULTS: Pathologic examinations detected tumor cells in 29 lymph nodes from 11 patients, and real-time reverse transcriptase-PCR further identified micrometastasis in 143 lymph nodes from 32 patients with no pathologic evidence of lymph node involvement. The presence of micrometastatic cancer cells was confirmed by immunohistochemical staining in 61 lymph nodes from 17 patients with pathologically negative lymph nodes. The presence of micrometastases was significantly associated with other conventional prognostic variables, including serum PSA value, pathologic stage, Gleason score, and tumor volume. Biochemical recurrence was detected in 32 patients, 17 of whom were negative for lymph node metastasis by pathologic examination (including 4 patients with pathologically organ-confined disease), but were diagnosed as having micrometastasis. Biochemical recurrence-free survival rate in patients without micrometastasis was significantly higher than in those with micrometastasis irrespective of the presence of pathologically positive nodes. Furthermore, only the presence of micrometastasis was independently associated with biochemical recurrence regardless of other factors examined. CONCLUSIONS: These findings suggest that approximately 30% of clinically localized prostate cancers shed cancer cells to the pelvic lymph nodes, and that biochemical recurrence after radical prostatectomy could be explained, at least in part, by micrometastases in pelvic lymph nodes.

Clinicopathological features of recurrence after radical cystectomy for patients with transitional cell carcinoma of the bladder.

BACKGROUND: The objective of this study was to investigate the clinicopathological features of recurrent transitional cell carcinoma (TCC) of the bladder in patients who had previously undergone radical cystectomy. MATERIALS AND METHODS: This study included 124 patients who underwent radical cystectomy for transitional cell carcinoma (TCC) of the bladder in our institution. Several clinicopathological factors were analyzed to characterize differences between patients with and without disease recurrence, and determined predictive factors for disease recurrence using multivariate analysis. We further analyzed prognostic parameters that affect survival after disease recurrence was diagnosed. RESULTS: Of the 124 patients, 24 (19.5%) developed recurrence, and the median time to recurrence was 9.5 months (range, 1-44 months). The 5-year recurrence-free survival in these 124 patients was 75.6%. The incidence of disease recurrence was significantly associated with gender, pathological stage, lymph node metastasis, lymphatic invasion and blood vessel invasion. Multivariate analysis identified gender, pathological stage and lymph node metastasis as independent predictors of disease recurrence following radical cystectomy. After disease recurrence, the 1-year cancer-specific survival of the 24 patients was 16.7%; that is, 23 of the 24 patients had died of progressive recurrent diseases, while the remaining 1 who survived had developed recurrence in the upper urinary tract. CONCLUSIONS: These findings suggest that careful follow-up should be performed after radical cystectomy for TCC of the bladder considering gender, pathological stage and nodal involvement; however, once recurrent disease develops, the prognosis of such patients is extremely poor. Therefore, it would be potentially important to establish a multimodal therapeutic approach targeting recurrent TCC of the bladder.

Clinical outcome of combined immunotherapy with low-dose interleukin-2 and interferon-alpha for Japanese patients with metastatic renal cell carcinoma who had undergone radical nephrectomy: a preliminary report.

BACKGROUND: The objective of this study was to evaluate the clinical outcome of combined immunotherapy with interferon-alpha (IFN-alpha) and low-dose interleukin-2 (IL-2) for Japanese patients with metastatic renal cell carcinoma (RCC) who had undergone radical nephrectomy. METHODS: This study included 13 patients who were diagnosed as having metastatic RCC following radical nephrectomy. These patients received a subcutaneous injection of IFN-alpha (6 x 10(6) IU per day) three times per week and an intravenous injection of IL-2 (1.4 x 10(6) IU per day) twice per week. Tumor response was evaluated every 16 weeks, and as a rule, this weekly regimen was repeated 50 times in patients with evidence of objective response or stable disease. RESULTS: One of the 13 patients dropped out because of severe toxicity; hence, 12 patients were evaluable, with a median follow-up period of 18 months after the start of this combined therapy. Six patients (50.0%) achieved objective responses, with 1 complete response (CR), while only 2 (16.7%) demonstrated progressive disease. The median duration of response in the 6 responders was 13.5 months. Toxicity associated with this combined immunotherapy was limited to WHO grade 1 or 2 in these 12 patients. All patients were alive at last follow-up, and 2 remain disease-free after 1 additional patient showed a CR following surgical resection of the remaining metastatic disease. CONCLUSION: Our preliminary experience suggests that long-term, repeated treatment with IFN-alpha and low-dose IL-2 is feasible in Japanese patients with metastatic RCC who have undergone radical nephrectomy. Although it will be necessary to accumulate data from a larger number of patients with a longer follow-up period, the combined immunotherapy tested in this study may become the preferred therapy for Japanese patients with metastatic RCC.

Is a limited lymphadenectomy targeting obturator nodes alone an adequate procedure for Japanese men undergoing radical prostatectomy?

BACKGROUND: The objective of the present study was to investigate the significance of pelvic lymphadenectomy during radical prostatectomy in Japanese men with prostate cancer. METHODS: A total of 178 consecutive patients who underwent radical prostatectomy and standard pelvic lymphadenectomy targeting the external iliac nodes and obturator fossa for clinically localized prostate cancer were studied. The median observation period of this series was 18 months (range: 3-36 months). RESULTS: Lymph node metastases were detected in 13 patients; that is, positive nodes were located in the external iliac nodes alone in seven patients, the obturator fossa alone in four patients, and both external iliac nodes and obturator fossa in two patients. Of these 13 patients, all of the seven with more than one positive node demonstrated biochemical recurrence, whereas five of the six with single node involvement remained without signs of biochemical recurrence. Furthermore, a single positive node was located in the external iliac region in five of the six patients. When a group at high-risk for lymph node metastasis was defined as those meeting more than two of the following three criteria: (i) pretreatment serum prostate specific antigen value > or = 20 ng/mL; (ii) biopsy Gleason sum > or = 8; or (iii) percentage of positive biopsy core > or = 50%, the incidence of lymph node metastasis was 24.5% in the high-risk group and 0.8% in the low-risk group. CONCLUSIONS: These findings suggest that limited dissection of the obturator node alone may not be sufficient for Japanese men undergoing radical prostatectomy; therefore, we recommend performing standard pelvic lymphadenectomy targeting both the external iliac nodes and the obturator fossa for patients at high-risk of lymph node involvement.

Clinical outcome of maximum androgen blockade using flutamide as second-line hormonal therapy for hormone-refractory prostate cancer.

OBJECTIVES: To investigate the efficacy of maximum androgen blockade (MAB) using flutamide as second-line hormonal therapy for advanced hormone-refractory prostate cancer (HRPC). PATIENTS AND METHODS: The study included 55 patients with HRPC who were treated with MAB using flutamide (375 mg daily) as second-line hormonal therapy. All patients had previously received bicalutamide combined with either surgical or medical castration as first-line hormonal therapy, which failed. The effect of the second-line therapy was evaluated by serum prostate-specific antigen (PSA) level alone, and the response defined as a decrease of >50% from the baseline PSA at the start of second-line therapy. RESULTS: On initiating second-line hormonal therapy there was a reduction in the PSA level in 25 of the 55 patients (45%), among whom 12 (22%) were regarded as responders, while the PSA level continued to increase in the remaining 30 (55%). The median (range) duration of the PSA response was 6 (1-13) months. During the observation period there were no severe side-effects from the second-line MAB therapy. Patients without bone metastases or whose disease progressed >1 year after first-line therapy had a significantly higher incidence of PSA response to second-line therapy, despite no significant effect of other factors examined on the PSA response to second-line therapy. Furthermore, the cause-specific survival in responders to second-line therapy was significantly better than that in nonresponders; however, multivariate analysis showed that no factors, including response to second-line therapy, could be used as independent predictors of cause-specific survival. CONCLUSIONS: MAB using flutamide as second-line hormonal therapy can give a comparatively favourable PSA response with no severe side-effects; therefore, this therapy may be suitable for patients with HRPC after primary MAB using bicalutamide has failed, particularly in those with no bone metastases or whose disease has progressed for >1 year after first-line therapy.

Significance of the percentage of prostate needle biopsy cores with cancer as a predictor of disease extension in radical prostatectomy specimens in Japanese men.

OBJECTIVES: To evaluate the significance of the percent of positive biopsy cores (PPBC) with cancer, which has been shown to be one of the most useful predictors of prostate cancer extension in patients undergoing radical prostatectomy. MATERIALS AND METHODS: This study included 120 patients who underwent radical prostatectomy for prostate cancer without any neoadjuvant therapies. All of these patients were diagnosed by random prostate biopsy targeting 8 cores; that is, standard sextant cores and 2 additional cores from the bilateral anterior lateral horns. We evaluated the appropriate cut-off points of PPBC for predicting disease extension according to the number of biopsy cores. Based on these criteria, multivariate analysis was then performed to determine whether PPBC could be an independent factor differentiating organ-confined disease from extraprostatic disease. RESULTS: The most suitable PPBC cut-off value using findings targeting 8 cores for predicting disease extension was 37.5%. If PPBC was calculated based on the outcome of standard sextant cores alone, it is most appropriate to use 33.3% as the cut-off point. Multivariate analysis showed that PPBC calculated based on the standard sextant cores and percent of cancer in the biopsy set could be used as independent factors predicting disease extension irrespective of other biopsy-associated factors. CONCLUSIONS: For predicting disease extension, it may be useful to calculate PPBC based on the outcomes of standard sextant biopsy cores alone even if additional cores were taken, and that PPBC calculated in such a way may be the strongest preoperative predictor of prostate cancer extension in Japanese men scheduled for radical prostatectomy.

A comparison of the biological features between prostate cancers arising in the transition and peripheral zones.

OBJECTIVES: To investigate differences in the biological features of prostate cancer according to the zonal origin. PATIENTS AND METHODS: Among 172 consecutive patients who had a radical prostatectomy (RP), the study included 124 diagnosed as having either transition zone (TZ) or peripheral zone (PZ) cancer, defined according to whether there was > 70% of the cancer area in the TZ or PZ, respectively. The clinicopathological features were then compared between these groups. In addition, the RP specimens were stained immunohistochemically with antibodies to Ki-67, Bcl-2, matrix metalloproteinase-2 (MMP-2), MMP-9 and vascular endothelial growth factor (VEGF). RESULTS: Twenty-four patients were diagnosed as having TZ cancer and the remaining 100 as having PZ cancer. Prostate specific antigen (PSA) values in patients with TZ cancer were significantly higher than in those with PZ cancer. Tumour volume in TZ cancer was significantly greater than that in PZ cancer, but there was no significant difference in biochemical recurrence-free survival between the groups. Immunohistochemistry showed that despite there being no differences in Bcl-2 and VEGF expression between TZ and PZ cancers, there was significantly greater expression of Ki-67, MMP-2 and MMP-9 in PZ than TZ cancers. CONCLUSIONS: Despite there being no significant difference in biochemical recurrence-free survival after RP between patients with TZ and PZ cancers, there was less cell proliferation and biomarker levels related to invasive potential in TZ than in PZ cancers.

Clinical outcome of oral uracil/tegafur (UFT) therapy for patients with hormone refractory prostate cancer.

There is no standard therapeutic strategy for advanced hormone refractory prostate cancer after the initial hormonal therapy fails. The objective of this study was to retrospectively evaluate the clinical outcome of the oral anticancer agent, uracil/tegafur (UFT) for patients with hormone refractory prostate cancer. This study included 68 patients with hormone refractory prostate cancer treated by oral administration of UFT (300-600 mg/day). All patients had previously received maximum androgen blockade (MAB) which failed. In this series, response was defined as more than 50% decrease from the baseline prostate specific antigen (PSA) value at the start of second line therapy. Upon initiating administration of UFT, a reduction in PSA value was observed in 41 of the 68 patients (60.3%), among whom 13 (19.1%) were regarded as responders; however, PSA value continued to increase in the remaining 27 (39.7%). Median duration of PSA response was 7 months (range 1-22 months). During the observation period, there were no severe side effects due to UFT administration, but 7 patients transiently presented appetite loss. Patients without bone metastasis at the initial diagnosis or whose serum PSA value at the start of UFT therapy was less than 2.0 ng/ml showed a significantly higher incidence of PSA response to UFT; however, other factors examined had no significant impact on PSA response to UFT. Furthermore, cause-specific survival in responders to UFT therapy was significantly better than that in non-responders. These findings suggest that administration of UFT after the failure of initial MAB therapy can achieve a comparatively favorable PSA response without severe side effects; therefore, it may be worthy to consider administering UFT to patients with hormone refractory prostate cancer.

Detection of micrometastases in pelvic lymph nodes in patients undergoing radical cystectomy for locally invasive bladder cancer by real-time reverse transcriptase-PCR for cytokeratin 19 and uroplakin II.

PURPOSE: The objective of this study was to clarify the significance of micrometastases in pelvic lymph nodes in patients who underwent radical cystectomy for bladder cancer. EXPERIMENTAL DESIGN: We included 40 patients with locally invasive bladder cancer who underwent radical cystectomy and pelvic lymphadenectomy. Expression of cytokeratin 19 (CK19), uroplakin II (UP II), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in 760 lymph nodes were assessed by a fully quantitative real-time reverse transcription-PCR (RT-PCR) assay. The quantification value of CK19 or UP II mRNA was described as each value relative to GAPDH mRNA. In this study, we regarded specimen in which either CK19 or UP II mRNA was positive as "presence of micrometastasis." RESULTS: Routine pathologic examinations detected tumor cells in 29 lymph nodes from six patients. Real-time RT-PCR identified positive expression of CK19 and UP II mRNAs in 49 lymph nodes from 10 patients and 98 lymph nodes from 16 patients, respectively. Of 633 lymph nodes from 34 patients with no pathologic evidence of nodal involvement, 13 nodes from five patients and 58 nodes from 10 patients were diagnosed as positive for CK19 and UP II mRNAs expression, respectively, by real-time RT-PCR. Presence of micrometastases was significantly associated with other conventional prognostic variables, including pathologic stage and microvascular invasion. Disease recurrence was occurred in eight patients, among whom four patients were negative for lymph node metastasis by routine pathologic examination and diagnosed as having micrometastasis by real-time RT-PCR assay. Furthermore, cause-specific survival rate in patients without micrometastasis was significantly higher than that in those with micrometastasis, irrespective of the presence of pathologic-positive nodes. CONCLUSIONS: Approximately 30% of locally invasive bladder cancer shed cancer cells to pelvic lymph nodes, and disease recurrence after radical cystectomy could be explained, at least in part, by micrometastases in pelvic lymph nodes.

Limited value of perineural invasion in radical prostatectomy specimens as a predictor of biochemical recurrence in Japanese men with clinically localized prostate cancer.

The objective of this study was to determine whether the presence of perineural invasion (PNI) in radical prostatectomy specimens could be a useful prognostic parameter in Japanese men with prostate cancer. Between January 1995 and September 2003, 202 Japanese men underwent radical retropubic prostatectomy for prostate cancer without any neoadjuvant therapies prior to surgery. We retrospectively analyzed the relationship between PNI in radical prostatectomy specimens and other prognostic factors, and also assessed the significance of PNI in biochemical recurrence after radical prostatectomy. The presence of PNI was significantly related to clinical stage, pathological stage, Gleason score, seminal vesicle invasion, lymph node metastasis and tumor volume, but not pretreatment serum prostate specific antigen value. During the observation period, biochemical recurrence occurred in 20 patients (3 in patients without PNI and 17 in those with PNI), and the biochemical recurrence-free survival rate in patients with PNI was significantly lower than that in patients without PNI. In addition to-PNI, pathological stage, seminal vesicle invasion, lymph node metastasis and tumor volume were significantly associated with the biochemical recurrence-free survival rate; however, among these five factors, only seminal vesicle invasion was an independent predictor of biochemical recurrence on multivariate analysis. Despite a significant association between several prognostic parameters, PNI was not an independent predictor of biochemical recurrence; therefore, it may not provide an additive effect to consider the presence of PNI in predicting the prognosis of Japanese men who underwent radical prostatectomy if there are other conventional parameters available.

Prognostic significance of vascular invasion in patients with bladder cancer who underwent radical cystectomy.

BACKGROUND: The objective of this study was to determine whether vascular invasion (i.e. lymphatic and blood vessel invasion) could be a useful prognostic predictor in patients with locally invasive transitional cell carcinoma (TCC) of the bladder who underwent radical cystectomy. METHODS: This series included 114 consecutive patients undergoing radical cystectomy for primary TCC of the bladder between November 1989 and July 2003. Several clinicopathological characteristics of these patients were analyzed, focusing on the association between vascular invasion and disease recurrence after radical cystectomy. RESULTS: Lymphatic and blood vessel invasions were detected in 55 (48.2%) and 33 (29.8%) specimens, respectively. Lymphatic invasion was significantly associated with pathological stage, tumor grade, lymph node metastasis, blood vessel invasion and disease recurrence, whereas blood vessel invasion was significantly related to pathological stage, lymph node metastasis, lymphatic invasion and disease recurrence. Recurrence-free survival in patients with lymphatic invasion was significantly lower than that in those without lymphatic invasion, and a similar significant difference in recurrence-free survival was observed between patients with and without blood vessel invasion. However, multivariate analysis using the Cox proportional hazards model showed that only pathological stage and lymph node metastasis could be used as independent predictors for disease recurrence after radical cystectomy. CONCLUSIONS: Despite a significant association between several prognostic parameters, vascular invasion was not an independent predictor of disease recurrence; therefore, if there are other conventional parameters available, there might not be any additional advantage to considering the presence of vascular invasion when predicting the prognosis of patients undergoing radical cystectomy for TCC of the bladder.

Prediction of potentially insignificant prostate cancer in men undergoing radical prostatectomy for clinically organ-confined disease.

BACKGROUND: The objectives of the present study were to characterize, according to tumor significance, the clinicopathological features of patients with prostate cancer who underwent radical prostatectomy, and to determine useful parameters for predicting insignificant disease before surgery. METHODS: In this series, we included 195 patients who underwent radical prostatectomy for clinically organ-confined prostate cancer at our institution between January 1999 and November 2003. Several clinicopathological factors were analyzed, focusing on whether the largest tumor volume in radical prostatectomy specimens was >/=0.5 cm(3) or <0.5 cm(3), which is the criterion defined to distinguish insignificant cancer from significant cancer. RESULTS: Potentially insignificant cancer was detected in 28 of 195 patients (14.4%). There were significant differences between patients with insignificant disease and those with significant disease in serum prostate specific antigen (PSA) as well as all biopsy parameters, with the exception of biopsy Gleason score. Furthermore, final pathological examination demonstrated that these two patient groups showed significant differences in Gleason score and the incidence of extraprostatic disease extension. Pearson's correlation analysis showed that tumor volume in the prostatectomy specimens was significantly associated with serum PSA and all biopsy parameters; however, each of the correlations was comparatively weak. There was no single parameter that could viewed as a useful predictor of tumor significance. The best model for predicting insignificant tumor was the combined use of biopsy Gleason score <7 and percent of positive biopsy core (PPBC) <15%; however, the further addition of serum PSA <10 ng/mL to these two parameters failed to enhance the predictive value of cancer significance. CONCLUSIONS: These findings indicate that clinicopathological findings suggesting favorable features are well observed in patients with potentially insignificant prostate cancer compared to those with significant prostate cancer, and the combination of a biopsy Gleason score <7 and PPBC <15% might be useful as a predictor of insignificant disease.

Intussusception of the bladder neck does not promote early restoration to urinary continence after non-nerve-sparing radical retropubic prostatectomy.

BACKGROUND: The objectives of the present study were to investigate whether buttressing sutures, which prevent the bladder neck from pulling open as the bladder fills, can promote earlier recovery from urinary incontinence after radical retropubic prostatectomy (RRP) and to identify possible risk factors associated with urinary incontinence after RRP. METHODS: The present study included 72 patients who underwent non-nerve-sparing RRP without neoadjuvant therapy between January and December 2003. Among these 72 patients, intussusception of the bladder neck was performed in 24 who consented to this procedure. In the present series, continence was defined as the absence of any need to use sanitary pads or diapers. Continence was evaluated by a patient interview 1, 3 and 6 months after RRP. RESULTS: There were no significant differences in clinicopathological characteristics between patients with and without intussusception of the bladder neck. The percentage of continent patients 1, 3 and 6 months after RRP was 34.7%, 63.9% and 95.8%, respectively, and there were no significant differences in continence between the two groups at any time point. Among several factors examined, only bladder neck preservation was an independent predictor of recovery from urinary incontinence 1 and 3 months after RRP. CONCLUSIONS: These findings suggest that it would be important to preserve the bladder neck for early return to continence after non-nerve-sparing RRP; however, intussusception of the bladder neck may not offer significant improvement in earlier return of urinary control.

Prognostic significance of insulin-like growth factor (IGF) binding protein-2 to IGF-binding protein-3 ratio in patients undergoing radical cystectomy for invasive transitional cell carcinoma of the bladder.

OBJECTIVES: To analyse the prognostic significance of insulin-like growth factor binding protein-2 (IGFBP-2) and IGFBP-3 in patients having a radical cystectomy for invasive bladder cancer. PATIENTS AND METHODS: Tissue samples of invasive bladder cancer were obtained from 97 patients who had radical cystectomy. The expression of IGFBP-2 and IGFBP-3 mRNAs in these samples was measured by real-time reverse transcription-polymerase chain reaction (RT-PCR), and the findings analysed in relation to clinicopathological factors. RESULTS: During the observation period, 31 patients (group A) developed disease recurrence, while the remaining 66 (group B) had no evidence of recurrence. The expression level of IGFBP-2 mRNA was significantly higher in group A than in B, while IGFBP-3 mRNA expression was significantly lower in group A than in B, and there was a significant difference in the relative expression ratio of IGFBP-2 to IGFBP-3 (BP-2/BP-3 ratio) between the groups. Recurrence-free survival in patients with an elevated BP-2/BP-3 ratio was significantly lower than in those with a normal ratio. Multivariate analysis indicated that an elevated BP-2/BP-3 ratio, but not IGFBP-2 and IGFBP-3 mRNA levels, was an independent predictor of disease recurrence. CONCLUSIONS: These findings suggest that the BP-2/BP-3 ratio measured by real-time RT-PCR could be useful for predicting disease recurrence in patients who have had a radical cystectomy for invasive bladder cancer.

Preoperative prediction of final pathological features is not improved by the free-to-total prostate-specific antigen ratio in Japanese men with clinically localized prostate cancer.

BACKGROUND: The objective of the present study was to determine whether the percentage of free/total prostate-specific antigen (f/tPSA) in patients scheduled to undergo radical prostatectomy for clinically localized prostate cancer can preoperatively predict organ-confined versus extraprostatic disease. METHODS: Serum levels of fPSA and tPSA were measured in 97 patients with clinically organ-confined disease before they underwent radical prostatectomy. The relationships of tPSA, f/tPSA and the pathological stage of the prostatectomy specimens were analyzed. Furthermore, the ability of f/tPSA to predict the pathological features was compared with those of tPSA and systematic biopsy findings. RESULTS: Organ-confined and extraprostatic extension diseases were present in 51 and 46 men, respectively. tPSA in patients with extraprostatic diseases was significantly higher than that in those with organ-confined diseases; however, there was no significant difference in f/tPSA between these two groups. There was also a significant difference in tPSA levels at each pathological stage, while f/tPSA did not parallel the pathological stage. Furthermore, there was no additional information concerning the extent of prostate cancer obtained when f/tPSA was combined with tPSA or with the percent of positive biopsy cores, which is the most significant predictor of the extent of prostate cancer among factors associated with systematic biopsy. CONCLUSION: f/tPSA could not predict the final pathological features in patients with clinically localized prostate cancer before radical prostatectomy. Moreover, the predictive value provided by tPSA or systematic biopsy findings was not improved by combined analysis with f/tPSA.