Prediction of Overall Survival by Thymidine Kinase 1 Combined with Prostate-Specific Antigen in Men with Prostate Cancer.

Thymidine kinase 1 (TK1) is an intracellular enzyme involved in DNA-precursor synthesis. Increased serum TK1 levels are used as a biomarker in various malignancies. We combined serum TK1 with PSA and evaluated its capacity to predict overall survival (OS) in 175 men with prostate cancer (PCa), detected by screening in 1988-1989 (n = 52) and during follow-up (median 22.6 years) (n = 123). TK1 was measured in frozen serum, age was stratified into four groups, and dates of PCa diagnosis and dates of death were obtained from Swedish population-based registries. The median concentration of TK1 and PSA was 0.25 and 3.8 ng/ml. TK1 was an independent variable of OS. In the multivariate analysis, PSA was not statistically significant in combination with age whereas the significance remained for TK1 + PSA. Measured once, TK1 + PSA predicted a difference of up to 10 years (depending on patient subgroup) in OS at a median of 9 years before PCa diagnosis. The TK1 concentration in 193 controls without malignancies did not differ from that of the PCa patients, hence TK1 was likely not released from incidental PCa. Thus, TK1 in the blood circulation may indicate the release of TK1 from sources other than cancers, nonetheless associated with OS.

Micturition problems after bladder distension during hospitalization in Sweden: "I'm not ill, just damaged for the rest of my life".

BACKGROUND: Urinary retention is a common complication following hospital care, which can result in overdistension of the bladder and, at worst, chronic bladder damage and persistent micturition difficulties. OBJECTIVES: The purpose of this study was to explore patients' experiences of micturition problems after bladder distension and their effects on the patients' everyday lives. METHODS: The Swedish Patient Insurance LÖF was used to identify patients from January 2007 to June 2010 who have reported micturition problems after hospital care and have had their injuries classified as avoidable bladder damage due to overdistension. Narrative interviews were conducted with 20 volunteers and analyzed by qualitative content analysis. RESULTS: The micturition problems affected everyday life through constraints (dependence on disposables and access to toilets, clothing restrictions, limitations on social life and career), suffering (pain, infections, impaired sex life, leakage), and concerns for the future (fear of worsening symptoms and fear of losing control with age). Aspects related to having been harmed by the healthcare system were the harm could have been avoided (lack of knowledge, insufficient routines, mistrust), obstacles to overcome when reporting an injury (difficulties in obtaining knowledge about the possibility of reporting an injury, ambivalence toward reporting their healthcare providers), and a wish to improve care (raise awareness, prevent harm to others). DISCUSSION: Bladder distension is a healthcare-related injury that can cause suffering and practical, emotional, and psychosocial problems with a great impact on the life of the person affected and anxiety for the future. The healthcare system must, therefore, raise awareness and improve preventive routines.

A randomised, double-blind, dose-finding, phase II multicentre study of ODX in the treatment of patients with castration-resistant prostate cancer and skeletal metastases.

AIMS: This study aimed to assess the efficacy and safety of ODX, a novel, cytotoxic, bone-targeting drug candidate, in castration-resistant prostate cancer bone metastatic disease. METHODS: Patients with progressive disease were randomised to ten cycles of ODX, intravenous infusion Q2W (3, 6, and 9 mg/kg, respectively). The primary objective was to assess the relative change from baseline in bone alkaline phosphatase (B-ALP) and serum-aminoterminal-propeptide of Type I procollagen (S-P1NP) at 12 weeks. The inclusion criteria selected were broad, and a double-blind design was used to ensure objective recruitment of patients for the assessment of efficacy. None of the patients received bone-protecting agents during the ODX treatment period. RESULTS: Fifty-five 21,20 and 14) patients were randomised to ODX (3, 6 and 9 mg/kg), respectively. The lower number of patients in arm 3 was due to too low a recruitment rate towards the end of the study. The median treatment time were 14, 13 and 14 weeks, respectively. The decrease in B-ALP at 12 weeks in study arms 3, 6 and 9 mg/kg was seen in 6/15 (40%), 8/12 (67%) and 5/12 (42%) patients, respectively, whereas the corresponding numbers for P1NP were 8/15 (53%), 8/12 (67%), and 4/12 (33%), respectively. The median decrease in B-ALP and P1NP at 12 weeks for study arms 3, 6 and 9 mg/kg were 37%, 14% and 43%, respectively, and 51%, 40% and 64%, respectively. The decrease in serum C-terminal telopeptide at 12 weeks was seen in the vast majority of patients and in about one-third of patients in bone scan index. ODX was well tolerated, and no drug-related serious adverse events occurred. There were no significant differences between study arms regarding efficacy and safety. CONCLUSIONS: ODX was well tolerated and demonstrated inhibitory effects on markers related to the vicious cycle in bone at all three doses. The reduction in metastatic burden, assessed with bone scan index, supports this finding. Studies with continued ODX treatment until disease progression are being planned (ClinicalTrials.gov Identifier: NCT02825628).

Preoperative ultrasound monitoring can reduce postoperative bladder distension: a randomized study.

OBJECTIVE: The aim of this study was to explore whether close preoperative ultrasound monitoring starting in the emergency room (ER) could prevent postoperative bladder distension among acute orthopaedic patients. MATERIAL AND METHODS: A randomized controlled trial was conducted at a 650-bed level-2 centre in Sweden. Inclusion criteria were admittance via ER to an orthopaedic ward for acute surgery. Bladder volumes were measured with a portable ultrasound scanner (Bladderscan BVI 3000). In the intervention group, all patients were scanned in the ER and then regularly at the ward at predefined times until surgery. In the control group, no regular scanning was performed before surgery. During surgery, the same procedure was performed for both groups: bladder scanning immediately after arrival to the recovery room and continuous postoperative scanning until voiding. The primary outcome was postoperative bladder distension, defined as a bladder volume ≥500 ml. Secondary outcomes were postoperative urinary tract infection and hospital length of stay. RESULTS: A total of 281 patients completed the study, 141 in the intervention group and 140 in the control group. Postoperative bladder distension was significantly higher in the control group (27.1% vs 17.0%; p = 0.045, 95% confidence interval 4.9-19.8) in the intention-to-treat, per-protocol and as-treated analyses. No statistical difference was found between the intervention group and the control group regarding the secondary outcomes. CONCLUSIONS: Frequent bladder monitoring starting in the ER can reduce postoperative bladder distension among acute orthopaedic patients. A preoperative bladder monitoring protocol should be implemented early in the ER for all patients admitted for acute orthopaedic procedures.

Bipolar transurethral resection of the prostate causes less bleeding than the monopolar technique: a single-centre randomized trial of 202 patients.

OBJECTIVE: To compare bipolar with the conventional monopolar transurethral resection of the prostate (TURP) for blood loss and speed of resection. PATIENTS AND METHODS: In all, 202 consecutive patients from the hospital waiting list were randomized to undergo TURP using either a bipolar system (Surgmaster TURis, Olympus, Tokyo, Japan) or a monopolar system (24 F, Storz, Tübingen, Germany). The blood loss during and after surgery was measured using a photometer. Other variables compared included indices of resection speed and transfusion rate. RESULTS: There were no statistically significant differences in operative duration, resection weight, resection speed or radicality of resection. However, the median blood loss was 235 mL for the bipolar and 350 mL for monopolar TURP (P < 0.001). The decrease in blood haemoglobin concentration during the day of surgery was smaller in the bipolar group (5.5% vs 9.6%P < 0.001). Fewer patients were transfused with erythrocytes (4% vs 11%, P < 0.01), which can be explained by the much lower 75th percentile for blood loss in the bipolar group (at 472 vs 855 mL, respectively). CONCLUSIONS: Bipolar TURP using the TURis system was performed with the same speed as monopolar TURP but caused 34% less bleeding, the difference being greatest (81%) for the largest blood losses. Bipolar TURP also required fewer erythrocyte transfusions than the conventional monopolar technique.

Comparison between normal saline and Ringer's acetate in bipolar transurethral resection of the prostate.

OBJECTIVE: The standard surgical treatment for benign prostatic hypertrophy (BPH) is transurethral resection of the prostate (TURP). The aim of this study was to compare normal saline (NS) (0.9% sodium chloride) and Ringer's acetate (RA) as irrigation fluid with regard to visibility, resection feasibility, coagulation and bleeding in bipolar TURP. MATERIALS AND METHODS: Twenty patients (mean age 70 years) who were diagnosed with BPH were recruited to the study. The first three 3 liter bags of irrigation fluid contained either NS or RA and were administered in a randomized fashion. The surgeon assessed visibility, bleeding, coagulation, resection efficacy and overall outcome after each 3 liter bag on a scale of 1-10. RESULTS: The results disclosed only marginal differences between the two fluids with regard to the recorded parameters. All of the differences lacked statistical significance (p > .05). CONCLUSION: RA can be used as an irrigation fluid in bipolar TURP with no obvious difference in comparison with NS.

Bone-targeted Novel Cytotoxic Polybisphosphonate Conjugate in Castration-resistant Prostate Cancer: A Multicenter Phase 1 Study.

BACKGROUND: Osteodex (ODX) is a cytotoxic bone-targeting polybisphosphonate, intended for treatment of bone metastasis from castration-resistant prostate cancer (CRPC). The primary objective of this study was to describe the tolerability and toxicity of such treatment by defining its maximum tolerated dose (MTD) and dose-limiting toxicity (DLT). PATIENTS AND METHODS: Twenty-eight patients with castration-resistant prostate cancer and confirmed bone metastasis were assigned to seven infusions of ODX every third week, divided in seven ascending dose cohorts. RESULTS: No DLT's were observed and as pre-specified, the highest dose administered was defined as MTD. In total, 206 adverse events (AE) were recorded and 13,6% were classified as treatment-related, while none were serious or severe (SAE). No cumulative toxicity and no renal toxicity were recorded. CONCLUSION: ODX was well tolerated, with few and mild side-effects and with apparent treatment efficacy in the highest dose cohort. Further clinical development is currently in progress.

Degree of vaporization in bipolar and monopolar resection.

PURPOSE: To compare the in vitro degree of vaporization in bipolar and monopolar resection. MATERIALS AND METHODS: Using either a bipolar system or a monopolar system, samples of chicken muscle and lamb kidney were resected in an isolated basin and then desiccated in an incubator. The percentual degree of vaporization for each sample was obtained as a difference between the total fresh weight of the sample and the calculated fresh weights of the resected tissue and remains. RESULTS: Reference samples showed that the water content was 73% in muscle and 77% in kidney. More muscle (mean 52%) than kidney (32%; P<0.0001) tissue was vaporized. The fraction of vaporized tissue was significantly higher in the bipolar technique. In muscle, the differences between monopolar and bipolar were 17% (P<0.05) and 26% (P<0.001), respectively, depending on the type of irrigation used. For kidney, the differences were 27% (P<0.01) and 34% (P<0.01), respectively. Further exploration of the degree of vaporization when using the bipolar resection showed that the choice of loop (P<0.0001), fluid (P<0.03), and tissue (P<0.0001) were all independently associated with the degree of vaporization. CONCLUSIONS: This study indicated that vaporization removes 50% more tissue than the weight of the resected tissue during conventional tissue resection. Bipolar standard loop resection resulted in a significantly higher degree of vaporization in both muscle and kidney than did monopolar technique. Bipolar resection worked satisfactorily in Ringer's acetate.

Complications and clinical outcome 18 months after bipolar and monopolar transurethral resection of the prostate.

PURPOSE: To compare bipolar resection with the conventional monopolar transurethral resection of the prostate (TURP) with respect to peri- and postoperative complications and long-term outcome. PATIENTS AND METHODS: Patients with consecutive benign prostatic hyperplasia needing surgery (n=185) from the hospital's waiting list were randomized to TURP using either a bipolar or a monopolar system. Peri- and postoperative parameters were monitored, complications were registered, and timed micturition/International Prostate Symptom Score (TM/IPSS) forms were collected at 3 and 6 weeks and at 6 and 18 months. RESULTS: Bipolar surgery was followed by a 16% to 20% higher percentage of the patients reporting ongoing improvement (fractional IPSS change >2) at 3 and 6 weeks after the surgery (p<0.05). There were fewer readmissions in the bipolar group than in the monopolar (5 vs. 13, p<0.05). No differences between the groups with respect to hospital stay and catheter duration was recorded. Bipolar and monopolar TURP resulted in marked and sustained improvements of IPSS, bother score, and TM. CONCLUSIONS: Bipolar TURP, using the transurethral resection in saline (TURis) system, resulted in significantly fewer postoperative readmissions, faster postoperative recovery, and equally long-lasting good results in TM/IPSS and bother score, as in monopolar TURP.

Perioperative bladder distension: a prospective study.

OBJECTIVE: Postoperative urinary retention and bladder distension are frequent complications of surgery. The aim of this study was to determine the incidence of perioperative bladder distension in a surgical setting and to identify predisposing factors among patients undergoing common general and orthopaedic procedures. MATERIAL AND METHODS: This was a prospective observational study of 147 adult patients admitted to orthopaedic and surgical departments. Bladder volumes were measured with an ultrasound scanner on three occasions: after emptying the bladder before being transported to the operating theatre, and then immediately before and after surgery. RESULTS: Thirty-three patients (22%) developed bladder distension (>500 ml), eight preoperatively and 25 postoperatively. A total of 21 patients (14%) had a bladder volume >300 ml immediately before surgery. Orthopaedic patients were more likely to develop preoperative bladder distension than surgical patients and had significantly higher postvoid residual volumes. In the binary logistic regression analysis age, gender and time of anaesthesia could not predict bladder distension. Patients undergoing orthopaedic surgical procedures, however, were prone to bladder distension (odds ratio 6.87, 95% confidence interval 1.76 to 26.79, p=0.006). CONCLUSIONS: This study shows that orthopaedic surgical patients are more prone to bladder distension perioperatively. The conventional method of encouraging patients to void at the ward before being transported to the operating theatre does not necessarily mean an empty bladder at the start of the operation.

The patient's choice of androgen-deprivation therapy in locally advanced prostate cancer: bicalutamide, a gonadotrophin-releasing hormone analogue or orchidectomy.

OBJECTIVE: To investigate patient preference for three established androgen-deprivation therapies for locally advanced prostate cancer; the patient's capacity to decide his therapy; the reasons for selecting a certain mode of therapy; and patient satisfaction with the chosen therapy 3 months after initiation. PATIENTS AND METHODS: In all, 150 patients (mean age 75 years, range 57-89) with previously untreated locally advanced prostate cancer from 13 hospitals were consecutively given the chance to choose between the antiandrogenic oral drug bicalutamide, a gonadotrophin-releasing hormone analogue (GnRH) by injection, or surgical orchidectomy. After discussing the nature of their disease the patients took home written information about prostate cancer and the three different treatment options. After 1 week they were assessed using a questionnaire for biographical data, their attitude towards the different treatment alternatives and their choice of therapy. Three months later the patients completed a questionnaire about the treatment they had undergone. RESULTS: Sixty-three patients (42%) chose bicalutamide, 51 (34%) the GnRH analogue and 36 (24%) orchidectomy; 87% of those choosing bicalutamide, 84% GnRH and 94% orchidectomy, respectively, were sure about their choice but 12%, 17% and 3% of the patients, respectively, had some difficulty in deciding. The most important reasons for the therapy chosen were avoidance of injections and surgery, and a lower risk of impotence (bicalutamide), negative attitude to surgery and tablets (GnRH), and avoidance of injections and tablets (orchidectomy). Almost all patients (98%, 98% and 97%, respectively) were satisfied with their choice after 3 months of treatment. CONCLUSION: There are three equally effective forms of androgen deprivation for locally advanced prostate cancer without known metastases. There are major differences among these treatments in the mode of application and the likelihood and impact of side-effects. When patients are fully informed and play an active role in the treatment decision they are satisfied with their decision 3 months later.

S-phase fraction in superficial urothelial carcinoma of the bladder--a prospective, long-term, follow-up study.

OBJECTIVE: To study, in addition to traditional tumor characteristics at diagnosis, the significance of DNA ploidy and S-phase fraction for tumor progression and tumor-related death in superficial carcinoma of the urinary bladder. MATERIAL AND METHODS: Newly detected superficial bladder carcinomas (stage Ta-T1), from 195 consecutive patients were characterized according to stage, grade, tumor size, multiplicity, growth pattern, cytologic evaluation and random mucosal biopsies, as well as DNA ploidy and S-phase fraction as determined by means of DNA flow cytometry. The outcome of disease was evaluated using hospital charts and death certificates. RESULTS: During a median follow-up period of 98 months (range 1-160 months), 28 patients (14%) progressed to muscle-invasive or metastatic disease and 24 (12%) died from disease. In univariate analysis all factors studied, with the exception of the size and number of tumors at diagnosis, were significantly related to progress and tumor-specific survival. In multivariate analysis, however, S-phase fraction was the most significant prognostic factor. When 21 high-risk patients with T1G3 tumors who underwent early cystectomy were excluded, S-phase fraction remained the most important prognostic factor. DNA ploidy failed as an independent predictor of survival. CONCLUSIONS: High S-phase fraction at diagnosis of superficial urothelial carcinoma of the bladder identifies patients at high risk of progression and death from disease.