EAU-ESMO consensus statements on the management of advanced and variant bladder cancer-an international collaborative multi-stakeholder effort: under the auspices of the EAU and ESMO Guidelines Committees†.

BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial. OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management. DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts before voting during a consensus conference. SETTING: Online Delphi survey and consensus conference. PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus). RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these, 33 (28%) statements achieved level 1 consensus and 49 (42%) statements achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease and the evolving role of checkpoint inhibitor therapy in metastatic disease. CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time where further evidence is available to guide our approach.

Associations between functional polymorphisms in the NFκB signaling pathway and response to anti-TNF treatment in Danish patients with inflammatory bowel disease.

Antitumor necrosis factor-α (TNF-α) is used for treatment of severe cases of inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). However, one-third of the patients do not respond to the treatment. Genetic markers may predict individual response to anti-TNF therapy. Using a candidate gene approach, 39 mainly functional single nucleotide polymorphisms (SNPs) in 26 genes regulating inflammation were assessed in 738 prior anti-TNF-naive Danish patients with IBD. The results were analyzed using logistic regression (crude and adjusted for age, gender and smoking status). Nineteen functional polymorphisms that alter the NFκB-mediated inflammatory response (TLR2 (rs3804099, rs11938228, rs1816702, rs4696480), TLR4 (rs5030728, rs1554973), TLR9 (rs187084, rs352139), LY96 (MD-2) (rs11465996), CD14 (rs2569190), MAP3K14 (NIK) (rs7222094)), TNF-α signaling (TNFA (TNF-α) (rs361525), TNFRSF1A (TNFR1) (rs4149570), TNFAIP3(A20) (rs6927172)) and other cytokines regulated by NFκB (IL1B (rs4848306), IL1RN (rs4251961), IL6 (rs10499563), IL17A (rs2275913), IFNG (rs2430561)) were associated with response to anti-TNF therapy among patients with CD, UC or both CD and UC (P ⩽ 0.05). In conclusion, the results suggest that polymorphisms in genes involved in activating NFκB through the Toll-like receptor (TLR) pathways, genes regulating TNF-α signaling and cytokines regulated by NFκB are important predictors for the response to anti-TNF therapy among patients with IBD. Genetically strong TNF-mediated inflammatory response was associated with beneficial response. In addition, the cytokines IL-1ß, IL-6 and IFN-γ may be potential targets for treating patients with IBD who do not respond to anti-TNF therapy. These findings should be examined in independent cohorts before these results are applied in a clinical setting.

Should cavitation in proximal surfaces be reported in cone beam computed tomography examination?

AIM: A clinical study was done to assess the clinical diagnostic accuracy of cone beam computed tomography (CBCT) in detecting proximal cavitated carious lesions in order to determine whether cavitation should be reported when a CBCT examination is available. MATERIALS AND METHODS: 79 adjacent proximal surfaces without restorations in permanent teeth were examined. Patients suspected to have carious lesions after a visual clinical and a bitewing examination participated in a CBCT examination (Kodak 9000 3D, 5 × 3.7 cm field of view, voxel size 0.07 mm). Ethical approval and informed consent were obtained according to the Helsinki Declaration. Radiographic assessment recording lesions with or without cavitation was performed by two observers in bitewings and CBCT sections. Orthodontic separators were placed interdentally between two lesion-suspected surfaces. The separator was removed after 3 days and the surfaces recorded as cavitated (yes/no), i.e. validated clinically. Differences between the two radiographic modalities (sensitivity, specificity and overall accuracy) were estimated by analyzing the binary data in a generalized linear model. RESULTS: For both observers, sensitivity was significantly higher for CBCT than for bitewings (average difference 33%, p < 0.001) while specificity was not significantly different between the methods (p = 0.19). The overall accuracy was also significantly higher for CBCT (p < 0.001). CONCLUSION: CBCT was more accurate in detecting cavitation in proximal surfaces than bitewing radiographs; therefore a CBCT examination performed for other clinical applications should also be assessed for proximal surface cavities in teeth without restorations, and when detected, this pathology must be part of the dentist's report.

Fluctuations in sedation levels may contribute to delirium in ICU patients.

BACKGROUND: Delirium in patients admitted to the intensive care unit (ICU) is a serious complication potentially increasing morbidity and mortality. The aim of this study was to investigate the impact of fluctuating sedation levels on the incidence of delirium in ICU. METHODS: A prospective cohort study of adult patients at three multidisciplinary ICUs. The Richmond Agitation and Sedation Scale (RASS) and the Confusion Assessment Method for the ICU were used at least twice a day. RESULTS: Delirium was detected at least once in 65% of the patients (n = 640). Delirious patients were significantly older, more critically ill, more often intubated, had longer ICU stays, and had higher ICU mortality than non-delirious patients. The median duration of delirium was 3 days (interquartile range: 1;10), and RASS was less than or equal to 0 (alert and calm) 91% of the time. The odds ratio (OR) for development of delirium if RASS changed more than two levels was 5.19 when adjusted for gender, age, severity of illness, and ICU site and setting. Continuous infusion of midazolam was associated with a decrease in delirium incidence (OR: 0.38; P = 0.002). CONCLUSIONS: Fluctuations in sedation levels may contribute to development of delirium in ICU patients. The risk of developing delirium might be reduced by maintaining a stable sedation level or by non-sedation.

Time to diagnosis and mortality in colorectal cancer: a cohort study in primary care.

BACKGROUND: The relationship between the diagnostic interval and mortality from colorectal cancer (CRC) is unclear. This association was examined by taking account of important confounding factors at the time of first presentation of symptoms in primary care. METHODS: A total of 268 patients with CRC were included in a prospective, population-based study in a Danish county. The diagnostic interval was defined as the time from first presentation of symptoms until diagnosis. We analysed patients separately according to the general practitioner's interpretation of symptoms. Logistic regression was used to estimate 3-year mortality odds ratios as a function of the diagnostic interval using restricted cubic splines and adjusting for tumour site, comorbidity, age, and sex. RESULTS: In patients presenting with symptoms suggestive of cancer or any other serious illness, the risk of dying within 3 years decreased with diagnostic intervals up to 5 weeks and then increased (P=0.002). In patients presenting with vague symptoms, the association was reverse, although not statistically significant. CONCLUSION: Detecting cancer in primary care is two sided: aimed at expediting ill patients while preventing healthy people from going to hospital. This likely explains the counterintuitive findings; but it does not explain the increasing mortality with longer diagnostic intervals. Thus, this study provides evidence for the hypothesis that the length of the diagnostic interval affects mortality in CRC patients.

Empirical support for a reclassification of eating disorders NOS.

OBJECTIVE: To explore the empirical support for a reclassification of the eating disorders NOS (EDNOS) category. METHODS: In a cross-sectional design eight specific subgroups of EDNOS were compared to anorexia nervosa (AN) and bulimia nervosa (BN) on interview-based data and questionnaire measures. The sample consisted of 965 patients in the age 13-54 years admitted to treatment for an eating disorder. RESULTS: According to the DSM-IV 176(18%) presented with AN, 290(30%) with BN and 499(52%) with EDNOS. Of all EDNOS cases 34% could be reclassified as AN or BN. Three specific subgroups emerged as separate diagnostic entities. A heterogeneous subgroup of 122 patients (13% of all) was proposed as 'true' EDNOS. Implications of the results on the DSM-V are discussed. CONCLUSIONS: The results support a broader definition of AN and BN and suggest subgroups of EDNOS as separate diagnostic entities. This results in a substantial reduction of the heterogeneous EDNOS group.

Trans-diagnostic outcome of eating disorders: A 30-month follow-up study of 629 patients.

OBJECTIVE: To assess the 30-month outcome and predictors of outcome in a cohort of patients with any eating disorder (ED). METHOD: A naturalistic design was used to determine time to remission, predictors of remission, relapse, diagnostic cross-over and mortality of 629 patients. RESULTS: At follow-up (FU) 312 patients attended, 42% obtained full remission and 72% partial remission. No differences were found between diagnostic groups for adolescents. Adult patients with anorexia-like eating disorder not otherwise specified-anorexia nervosa (EDNOS-AN) had the poorest outcome. Bulimia-like EDNOS was the most frequent relapse diagnosis. Bingeing/purging behaviour predicted a poorer outcome for individuals with bulimic disorders. Desired low BMI predicted a poorer outcome for individuals with anorexia. Comorbid personality disorder was a common predictor of a worse outcome. CONCLUSION: Adults with EDNOS-AN had the poorest prognosis. Bulimic symptoms emerged frequently during FU regardless of diagnosis. Remission rates and outcome predictors were similar to previous findings.

Cancer-associated fibroblasts of the prostate promote a compliant and more invasive phenotype in benign prostate epithelial cells.

Reciprocal interactions between prostate epithelial cells and their adjacent stromal microenvironment not only are essential for tissue homeostasis but also play a key role in tumor development and progression. Malignant transformation is associated with the formation of a reactive stroma where cancer-associated fibroblasts (CAFs) induce matrix remodeling and thereby provide atypical biochemical and biomechanical signals to epithelial cells. Previous work has been focused on the cellular and molecular phenotype as well as on matrix stiffness and remodeling, providing potential targets for cancer therapeutics. So far, biomechanical changes in CAFs and adjacent epithelial cells of the prostate have not been explored. Here, we compared the mechanical properties of primary prostatic CAFs and patient-matched non-malignant prostate tissue fibroblasts (NPFs) using atomic force microscopy (AFM) and real-time deformability cytometry (RT-FDC). It was found that CAFs exhibit an increased apparent Young's modulus, coinciding with an altered architecture of the cytoskeleton compared with NPFs. In contrast, co-cultures of benign prostate epithelial (BPH-1) cells with CAFs resulted in a decreased stiffness of the epithelial cells, as well as an elongated morphological phenotype, when compared with co-cultures with NPFs. Moreover, the presence of CAFs increased proliferation and invasion of epithelial cells, features typically associated with tumor progression. Altogether, this study provides novel insights into the mechanical interactions between epithelial cells with the malignant prostate microenvironment, which could potentially be explored for new diagnostic approaches.

Sex steroids modulate alpha 1-adrenoceptor-stimulated Ca2+ elevation in human cultured prostatic stromal cells.

BACKGROUND: Benign prostatic hyperplasia is an age- and androgen-dependent condition of urethral compression caused by prostatic contractility and glandular enlargement. In this study we investigate whether testosterone, dihydrotestosterone and estradiol modulate the ability of human cultured prostatic stromal cells (HCPSCs) to respond to the adrenoceptor agonists, noradrenaline (30 microM) and phenylephrine (100 microM), the protein kinase C activating phorbol ester, phorbol diacetate (PDA, 10 microM), and the L-type Ca(2+) channel activator, (-)-Bay K8644 (Bay K, 10 microM) with elevations of intracellular Ca(2+) ([Ca(2+)](i)). METHODS: Cells were loaded with the Ca(2+) sensitive fluorophore, FURA-2AM (10 microM) and changes in intracellular Ca(2+) determined before and 8-12 min after ligand addition. RESULTS: Compared to steroid-free (SF) controls, the incubation of HCPSC with testosterone (30 and 300 pM) significantly increased responses to both noradrenaline and phenylephrine. Responses to Bay K were significantly reduced between 30 nM to 300 pM but responses to PDA were not greatly affected. Compared to SF the addition of estradiol (E(2), 100 pM) did not affect responses to phenylephrine. The concomitant addition of dihydrotestosterone (DHT) and E(2) (to give ratios from 1:1 to 1,000:1) elevated the responses to noradrenaline and phenylephrine at the extreme ranges. Responses to PDA and Bay K generally increased as DHT:E(2) approached unity. CONCLUSIONS: These results indicate that sex steroids modulate the activities of HCPSCs through the regulation of both receptors and signal transduction processes.

Testosterone- and phorbol ester-stimulated proliferation in human cultured prostatic stromal cells.

Prostatic stromal proliferation may be commonly associated with the development of benign prostatic hyperplasia. In this study, we investigate the role of testosterone and protein kinase C in stimulating cultured stromal cell proliferation. Testosterone increased the uptake of [(3)H]-thymidine into the human cultured prostatic stromal cells, this was reduced by the protein kinase C inhibitors, bisindolylymaleimide (10 nM) and myristoylated protein kinase C inhibitor (mPKCi, 20 microM), but not by Gö 6983 (1 microM) or Gö 6976 (1 microM). Cells responded to the addition of the PKC activators phorbol 12,13 dibutyrate (PDB), phorbol 12,13 diacetate (PDA), 12-deoxyphorbol 13-acetate (DPA) and 12-deoxyphorbol 13-tetradecanoate (DPT) with proliferation (order of potency DPT> or =PDB>>PDA=DPA). The DPT-stimulated proliferative response was inhibited after cells were electroporated with PKCalpha antisense, but not mismatch oligonucleotides (8 microM). These results indicate that PKCalpha is involved in the proliferative response of human cultured prostatic stromal cells.

Protein kinase G activation of K(ATP) channels in human-cultured prostatic stromal cells.

In this study, we identify and investigate the role of protein kinase G (PKG) in cells cultured from human prostatic stroma. Cells were used for immunocytochemistry, contractility or K(+) fluorescent imaging studies. All cultured prostatic stromal cells showed PKG immunostaining. Phorbol 12,13 diacetate (PDA, 1 microM) elicited contractions from human-cultured prostatic stromal cells that could be blocked by both the L-type Ca(2+) channel blocker, nifedipine (3 microM), and the protein kinase C inhibitor, bisindolylmaleimide (1 microM). The nitric oxide donor, sodium nitroprusside (SNP, molar pIC(50) 5.16+/-0.17) and the cGMP-phosphodiesterase inhibitor, zaprinast (50 microM), inhibited PDA (1 microM)-induced contractions. The PKG activator beta-phenyl-1, N(2)-ethenoguanosine-3',5'-cyclic monophosphate (PET-cGMP, molar pIC(50) 6.96 +/- 0.25) also inhibited PDA (1 microM)-induced contractions. Glibenclamide (10 microM) and Rp-8-Br-cGMPS (5 microM), but not iberiotoxin (100 nM) or Rp-cAMP (5 microM), reversed this inhibition. In human-cultured prostatic stromal cells loaded with the K(+) fluorescent indicator, 1,3-Benzenedicarboxylic acid, 4,4'-[1,4,10,13-tetraoxa-7,16-diazacyclooctadecane-7,16-diylbis(5-methoxy-6,2-benzofurandiyl)]bis-, tetrakis [(acetyloxy) methyl] ester (PBFI), PET-cGMP (300 nM) caused a reduction in intracellular K(+) that was blocked by glibenclamide (10 microM) and Rp-8-Br-cGMPS (5 microM), but not by iberiotoxin (100 nM). These data are consistent with the hypothesis that, in human-cultured prostatic stromal cells, PKG inhibits contractility through the activation of K(ATP) channels.

The metaplastic effects of estrogen on mouse prostate epithelium: proliferation of cells with basal cell phenotype.

The exogenous administration of estrogens to male mice alters the hypothalamic-pituitary-gonadal axis and reduces androgen levels, leading to a regression of the prostatic epithelium. As well, a specific direct response to estrogens is the induction of epithelial squamous metaplasia. The aims of this study were to identify the process by which the prostatic epithelium is transformed in intact adult male mice using the synthetic estrogen, diethylstilbestrol. A comparison of the effects of diethylstilbestrol in the three lobes revealed a hierarchy of response, with the anterior lobe being the most responsive, the dorsolateral lobe less responsive, and the ventral lobe the least responsive. The effect of castration was used to distinguish between the epithelial responses to estrogen administration and androgen deprivation. The results demonstrate that transformation of the epithelium involved proliferation of cells with a basal cell phenotype, the onset of cytokeratin 10 expression, up-regulation of progesterone receptor expression, and loss of the cell cycle inhibitor, p27(Kip1) expression; none of these changes was observed after castration. Mice lacking functional estrogen receptor alpha failed to respond, demonstrating a requirement for estrogen receptor alpha in the epithelium and/or stroma to mediate the proliferative response to estrogen in the prostate gland.

How many patients are needed? Variation and design considerations in bone histomorphometry.

In osteoporosis research, bone histomorphometry plays an important role in documenting the biological effects and possible side-effects of new drug treatments. To ensure that the study is properly scaled, it is important to be concerned with the risk of type II error; that is, the risk of failing to detect a real difference. We therefore calculated the necessary sample size in bone histomorphometric studies according to a specified difference of 15% between two groups. The calculations were based on variance components estimated from three different studies: women with a distal fracture of the forearm (n = 22); patients with pituitary insufficiency (n = 21); and patients with primary hyperparathyroidism (n = 21). Using a significance level of 0.05 and a risk of type II error of 0.20, the statistical power of two different designs was compared: a single biopsy design comparing the responses in two groups after the treatment; and a paired biopsy design in which individual differences (posttreatment minus baseline) were calculated before the comparison of the two groups. We found that the mineral apposition rate, wall thickness, and erosion depth are statistically powerful indices that, in the single biopsy design, require no more than n = 25 in each group to detect differences of 15% between the groups. Bone volume, erosion surface, osteoid surface, mineralizing surface, and activation frequency need group sizes of 100-600 individuals to find a 15% difference to be statistically significant. However, the effect of bisphosphonate treatment, for instance, is large enough to reduce the group size to 20 individuals concerning activation frequency. The remodeling balance reaches extreme group sizes of several thousand for a 15% difference to be statistically significant, but for a 5 microm (approximately 150%) improvement, about 100 individuals are required in the single biopsy design. An analysis of the components of variance showed that the variation between individuals is small and often negligible compared with the variation within individuals, and sample sizes needed for the paired biopsy design are therefore larger than those for the single biopsy design. In conclusion, the most cost-effective histomorphometric study design within a randomized clinical trial appears to be a single biopsy design comparing posttreatment biopsies with scaling performed according to the statistical power of the indices of interest.

A1 and A2A adenosine receptor modulation of alpha 1-adrenoceptor-mediated contractility in human cultured prostatic stromal cells.

1. This study investigated the possibility that adenosine receptors modulate the alpha(1)-adrenoceptor-mediated contractility of human cultured prostatic stromal cells (HCPSC). 2. The nonselective adenosine receptor agonist, 5'-N-ethylcarboxamido-adenosine (NECA; 10 nm-10 microm), and the A(1) adenosine receptor selective agonist, cyclopentyladenosine (CPA; 10 nm-10 microm), elicited significant contractions in HCPSC, with maximum contractile responses of 18+/-3% and 17+/-2% reduction in initial cell length, respectively. 3. In the presence of a threshold concentration of phenylephrine (PE) (100 nm), CPA (1 nm-10 microm) caused contractions, with an EC(50) of 124+/-12 nm and maximum contractile response of 37+/-4%. The A(1) adenosine receptor-selective antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX 100 nm) blocked this effect. In the presence of DPCPX (100 nm), NECA (1 nm-10 microm) inhibited contractions elicited by a submaximal concentration of PE (10 microm), with an IC(50) of 48+/-2 nm. The A(2A) adenosine receptor-selective antagonist 4-(2-[7-amino-2-[furyl][1,2,4]triazolo[2,3-alpha][1,3,5,]triazin-5-yl amino]ethyl)phenol (Zm241385 100 nm) blocked this effect. 4. In BCECF-AM (10 microm)-loaded cells, both CPA (100 pM-1 microm) and NECA (100 pm-10 microm) elicited concentration-dependent decreases in intracellular pH (pH(i)), with EC(50) values of 3.1+/-0.3 and 6.0+/-0.3 nm, respectively. The response to NECA was blocked by Zm241385 (100 nm; apparent pK(B) of 9.4+/-0.4), but not by DPCPX (100 nm). The maximum response to CPA was blocked by DPCPX (100 nm), and unaffected by Zm241385 (100 nm). 5. NECA (10 nm-10 microm) alone did not increase [(3)H]-cAMP in HCPSC. In the presence of DPCPX (100 nm), NECA (10 nm-10 microm) caused a concentration dependent increase in [(3)H]-cAMP, with an EC(50) of 1.2+/-0.1 microm. This response was inhibited by Zm241385 (100 nm). CPA (10 nm-10 microm) had no effect on cAMP, in the presence or absence of forskolin (1 microm). 6. These findings are consistent with a role for adenosine receptors in the modulation of adrenoceptor-mediated contractility in human prostate-derived cells.

Obstetric factors, urbanization and psychosis.

BACKGROUND: Epidemiologic evidence as early as the 1930s has suggested urbanization is linked to schizophrenia, either by place of admission, place of upbringing, or, more recently, place of birth. In the past decade, obstetric complications have been implicated in the etiology of schizophrenia. METHODS: With appropriate protections for anonymity, the files of the Danish Medical Birth Register were linked with the files of the Danish Psychiatric Case Register. The linkage produced 132 cases of schizophrenia and 69 cases of affective psychosis, who were born in 1973 or later, who entered a Danish psychiatric hospital before 1994. Controls were drawn from a 10% sample of the Medical Birth Register. Analysis was by logistic regression. RESULTS: The risk of hospitalization for schizophrenia was 4.20 times higher (95% CI=2.4-7.4) for those born in Copenhagen versus those born in rural areas of Denmark, and a linear relationship was demonstrated between urbanization of birthplace and risk. There was no difference in risk of hospitalization for affective psychosis for those born in Copenhagen versus rural areas. Obstetric complications had a moderate sized relationship to schizophrenia, but the relationship of urban birth to schizophrenia was unaffected by adjustment for obstetric complications. CONCLUSION: Urban birth is a strong risk factor for schizophrenia, not mediated by obstetric complications, which deserves further exploration.

Obstetric complications in women with schizophrenia.

It is not known whether schizophrenic women have increased incidence of complications during pregnancy and delivery. Data from the Danish Medical Birth Register were used to compare 2212 births to 1537 schizophrenic women in Denmark with a random sample of all deliveries in Denmark during 1973-1993 (122931 births to 72742 women). The schizophrenic women had fewer antenatal care visits. They were at lower risk of pre-eclampsia, but tended to have lower Apgar scores. There were no other differences in the incidence of specific complications such as placenta previa, placental abruption, and abnormal fetal presentation. Schizophrenic women were at increased risk of interventions such as Cesarean section, vaginal assisted delivery, amniotomy, and pharmacological stimulation of labor. There were no important differences between the deliveries to schizophrenic women who gave birth before and after their first admission to a psychiatric department. These results show no evidence that schizophrenic women have a greater frequency of specific obstetric complications than non-schizophrenic women. Nevertheless, they are at increased risk for interventions during delivery.

Radical prostatectomy for pathologic stage C prostate cancer: influence of pathologic variables and adjuvant treatment on disease outcome.

A retrospective analysis was performed on 1,035 patients with pathologic Stage C prostate cancer treated with bilateral pelvic lymphadenectomy and radical retropubic prostatectomy. Of these patients, 661 received no immediate adjuvant treatment, 131 adjuvant radiotherapy only, and 103 postoperative adjuvant orchiectomy only. Overall crude survival at five, ten, and fifteen years was 91 percent, 68 percent, and 46 46 percent, respectively. Cause-specific survival was 96 percent, 81 percent, and 66 percent and overall nonprogression survival was 78 percent, 56 percent, and 48 percent at five, ten, and fifteen years, respectively. Patients with margin-positive and residual disease, high-grade tumors, large tumor bulk, and seminal vesicle involvement were more likely to receive adjuvant treatment. However, both univariately and multivariately, only tumor grade and increasing tumor volume correlated significantly with cause-specific survival and local and systemic progression. Adjuvant treatment significantly decreased local, systemic, and overall progression but did not improve cause-specific or crude survival. Orchiectomy and radiation appeared to demonstrate similar efficacy in controlling local recurrences: five-year local recurrence-free survival in this retrospective analysis was > 95 percent for both treatments compared with 84 percent for those without adjuvant treatment.

Homologous blood transfusion in patients with prostate cancer: no effect on tumor progression or survival.

OBJECTIVE: To determine the effect of perioperative blood transfusions in patients with prostate cancer who underwent radical prostatectomy, we analyzed 1,785 patients with a follow-up of five years or more who were treated during a twenty-one-year period (1966 to 1987). METHODS: Patients were divided into three groups according to the number of units transfused during the perioperative period: group 1, 0 units (n = 440), group 2, 1 to 2 units (n = 746), and group 3, 3 or more units (n = 599). RESULTS: With univariate analysis, no statistically significant differences were found among the three groups in overall survival rate (71%, 75%, and 71% at ten years; p = 0.48), cause-specific survival rate (89%, 88%, and 86% at ten years; p = 0.36), or progression-free survival rate (61%, 68%, and 68% at ten years; p = 0.83). Adjusting for tumor grade, pathologic stage, and hormonal therapy using the Cox statistical model, we found no significant association between the blood-use group and overall survival rate (p = 0.45), cause-specific survival rate (p = 0.17), or progression-free survival rate (p = 0.34). The estimated relative risk and 95 percent confidence interval associated with blood transfusion (three or more units versus none) were as follows: 1.03 and 0.76 to 1.38 for total mortality, 1.56 and 0.95 to 2.56 for cause-specific death, and 1.20 and 0.91 to 1.57 for disease progression, respectively. CONCLUSIONS: According to these findings, withholding homologous blood transfusion, except for infectious precautions, should not be based on the suspicion that it can accelerate death from cancer in patients who undergo radical prostatectomy for prostate cancer.

Gyrus bipolar electrovaporization vs transurethral resection of the prostate: a randomized prospective single-blind trial with 1 y follow-up.

The Gyrus system uses bipolar electrocautery with saline irrigation to vaporize prostatic tissue and is compared to transurethral resection of the prostate (TURP) in a randomized prospective study with 1 y follow-up. Outcomes measured were fluid absorption, blood loss, period of catheterization, hospital stay, symptom scores, quality of life, flow rates, and post-void residual volumes at 3, 6, and 12 months. All measured parameters were similar, although re-catheterization rates were higher (30% vs 5%) in the Gyrus group. Clot evacuation rates were higher in the TURP group (19% vs 0%). The Gyrus device is safe and produces results that are similar to TURP at 1 y.