Clinical decision making in prostate cancer care-evaluation of EAU-guidelines use and novel decision support software.

Keeping up to date with the latest clinical advances in prostate cancer can be challenging. We investigated the impact of guideline use on quality of treatment decisions as well as the impact of a novel, CE-certified clinical decision support tool (Siemens AIPC software) on the amount of time clinicians spend on decision-making in a multicenter setting. Ten urologists assessed ten clinical cases (screening and localized prostate cancer) in three settings: without support, using a digital version of the EAU guidelines, and with the AIPC tool, resulting in 300 clinical decisions. Comparison involved time spent, decision correct- and completeness. Using AIPC compared to digital guidelines led to a significant reduction of expenditure of time at a per case level (3.57 min and 0:14 min, p < 0.01) and for overall time per urologist (39.45 min and 02:20 min, p < 0.01). Decision options without guidelines support, online guideline usage and usage of AIPC were complete in 61%, 80% and 100%, respectively (p < 0.01). Decision making without guidelines support, online guideline usage and usage of AIPC was correct including all options in 28%, 66% and 100%, respectively (p < 0.01).Clinical decision support systems have the potential to reduces decision-making time and to enhance decision quality.

The Success and Evolution of a Urological "Boot Camp" for Newly Appointed UK Urology Registrars: Incorporating Simulation, Nontechnical Skills and Assessment.

BACKGROUND: Urological training has dramatically changed in recent years. Training durations are shorter and a drive toward consultant led care has reduced trainees experience. Within the UK, approximately 50 registrars annually embark on a 5-year Urology training programme, with variable levels of basic urological experience. OBJECTIVE: To describe a simulation programme aimed at delivering the knowledge and skills necessary to safely and effectively start working as a registrar in Urology by intensive training with a 1:1 faculty to delegate ratio. DESIGN, SETTING, AND PARTICIPANTS: Our course content mirrors the UK training syllabus for junior Urology registrars. We delivered 8 modules over a 4-day programme with a fifth day of assessments. Delegates level of urological knowledge, operative competency and confidence pre-, immediately post-training and at 3-months postcourse were assessed. Objective delegate and faculty feedback was also collected. Technical skills modules include; inguinoscrotal surgery, ureteroscopy, transurethral resection, urodynamics, and Botox administration as well as basic reconstructive and laparoscopic operative skills. "Nontechnical" skills included simulated ward round, out-patient, and emergency scenarios. RESULTS: Feedback from delegates and faculty members has been overwhelmingly positive. We have used this feedback to tailor the content of the course for following years. An increased knowledge level (based on mean examination scores [precourse 55.5%, postcourse 70.1%]) and operative competency was observed in all skills assessed (transurethral resection of the prostate, transurethral resection of bladder tumor, Ureteroscopy, laparoscopic skills, and instrument assembly). Operative confidence was increased immediately and at 3-months postcourse. CONCLUSIONS: Our "boot camp" course provides a realistic introduction and foundation to begin Urological practice. Being delivered at the beginning of the training scheme, prior to intensive patient exposure, registrars are in an optimum position to develop their newly acquired knowledge and skills to enhance training and intends to improve patient safety and satisfaction.

Heat shock protein expression independently predicts clinical outcome in prostate cancer.

Heat shock proteins (hsps) occupy a central role in the regulation of intracellular homeostasis, and differential expression of individual hsps occurs in a broad range of neoplastic processes. This study was performed to test the hypothesis that the particular patterns by which individual hsps become specifically modulated in human prostate cancers are correlated with behavioral phenotype and hence may be of value in determining the most appropriate clinical management of individual patients. Monoclonal antibodies specific for each hsp protein were used to assess expression of hsp27, hsp60, and hsp70 in formalin-fixed, paraffin wax-embedded, archival tissue specimens of early prostatic adenocarcinomas (pT1-2N0M0) removed at radical prostatectomy (n = 25) and in advanced cancers (n = 95) identified at transurethral resection of prostate (TURP). These findings were compared with similar data from control prostates (n = 10) removed at primary cystectomy for urinary bladder neoplasia not involving the prostate and also at TURP for benign prostatic hyperplasia (n = 50). Western blotting of whole cell lysates derived from established human prostatic epithelial cell lines PNT2, LNCaP, DU145, and PC3 was compared with expression of hsps by the primary human tissues. This study found that early in situ neoplastic transformation of normal prostatic epithelium was consistently associated with loss of hsp27 expression and that the level of hsp27 expression by individual prostate cancers was correlated with their Gleason grade. In advanced cancers, hsp27 expression was invariably associated with poor clinical outcome (P = 0.0001). Data from cell lines supported the primary tissue findings, with elevated hsp27 expression only in aggressive malignant cell lines and androgen-insensitive cell lines. Expression of hsp60 was significantly increased in both early and advanced prostate cancer when compared with nonneoplastic prostatic epithelium (P < 0.0001), as well as in malignant prostate cancer cell lines. Expression of hsp70 was unaltered in early prostate cancers when compared with nonneoplastic prostatic epithelium but showed a diminished expression in morphologically advanced cancers (P = 0.0029). No consistent correlation was found between levels of hsp60 or hsp70 expression and phenotypic behavior of individual primary prostatic cancers. Thus, patterns of hsp expression have been confirmed to be specifically and consistently modulated in both early and advanced human prostate cancers. Whereas absence of hsp27 is a reliable objective marker of early prostatic neoplasia, reexpression of this protein by an individual invasive prostatic carcinoma invariably heralds poor clinical prognosis. Because this protein has been shown to alter the balance between proliferation and apoptosis, understanding the mechanism(s) by which individual hsps regulate intracellular homeostasis may assist in explaining some key processes that occur during evolution of human prostate cancers. We suggest that hsp27 expression provides novel diagnostic and prognostic information on individual patient survival which, if obtained at the time of primary diagnosis, would assist in determining tumor-specific management strategies. Development of techniques to therapeutically modulate hsp27 expression raises the possibility of novel targeted approaches to regulate this homeostatic mechanism, thus allowing better control over tumor cell proliferation and hence patient survival.

Human decidua is a target tissue for bradykinin and kallikrein: phosphoinositide hydrolysis accompanies arachidonic acid release in uterine decidua cells in vitro.

The endocrine and intracellular mechanisms regulating prostaglandin precursor release in the uterine decidua during labor are unknown. This in vitro study investigates a potential role for a kallikrein-kinin system in the activation of phospholipid hydrolysis and arachidonic acid release in human decidua cells. Primary cultures of human decidua cells were prelabeled with [3H]inositol or [14C]arachidonic acid to monitor phosphoinositide hydrolysis and prostaglandin precursor release, respectively. Bradykinin (100 nmol/L) stimulated a rapid release of arachidonic acid (within 2 min) associated with an increase in inositol trisphosphate which was detectable after 20 s. Protein kinase C activation by phorbol ester enhanced arachidonic acid release in response to both bradykinin and the Ca++ ionophore A23187 but inhibited bradykinin-stimulated phosphoinositide hydrolysis. Epidermal growth factor also enhanced arachidonate release in response to both bradykinin and A23187. Kallikrein stimulated both phosphoinositide hydrolysis and arachidonic acid release in decidua cells. Kallikrein action was inhibited by the kallikrein protease inhibitor aprotinin and D-Arg[Hyp3Thi5,8,D-Phe7] bradykinin, a B2 receptor antagonist. Bradykinin also stimulated prostaglandin F2 alpha production in both primary decidua cell cultures and fibroblasts in the presence of interleukin-1 beta. These findings are consistent with a mediatory role for bradykinin in the action of kallikrein on decidua cells and suggest that inositol phospholipid hydrolysis is instrumental for arachidonic acid release in response to bradykinin in these cells. This study supports a novel role for a kallikrein-kinin system in the human uterine decidua.

Periurethral abscess complicating male gonococcal urethritis treated by surgical incision and drainage.

Gonococcal urethritis in a heterosexual male complicated by periurethral abscess and its treatment with antibiotics and surgical drainage is presented.

Functional results of pyeloplasty in patients with ante-natally diagnosed pelvi-ureteric junction obstruction.

OBJECTIVE: To assess the outcome after pyeloplasty in children with an ante-natal diagnosis of hydronephrosis, shown on post-natal renography to be due to pelvi-ureteric junction (PUJ) obstruction, and in particular to review the outcome of those who had initially been managed expectantly. PATIENTS AND METHODS: Between 1984 and 1995, 321 patients were diagnosed as having PUJ obstruction, after investigating ante-natal hydronephrosis. Of these, 47 had undergone pyeloplasty and also had a normal contralateral kidney; 26 patients had early pyeloplasty because of impaired function and 21 underwent surgery after a period of expectant management. Renal function was assessed renographically before and at least one year after surgery. RESULTS: Relative renal function was stabilized in those patients who underwent early pyeloplasty (mean differential function 28.1% before and 32.7% after surgery). In patients who underwent pyeloplasty after a period of expectant management, the mean relative function decreased from 44.8% initially to 30.5% before surgery; this recovered to 37.5% at the post-operative reassessment, representing a statistically significant loss of function (P < 0.01). CONCLUSION: In patients born with PUJ obstruction and impaired renal function, pyeloplasty failed to significantly improve function. Possibly because of cortical loss. In patients with ante-natal PUJ obstruction managed expectantly there is a small but significant risk of a modest loss of renal function.

Testicular microlithiasis needs long-term surveillance.

We present a case of testicular microlithiasis in which testicular biopsy failed to predict the development of a testicular tumour.

Vesicoureteric angulation: a modified method for placement of a double J stent.

In the past few years, retrograde placement of ureteral stents by urologists has been popularized in support of extracorporeal shock wave lithotripsy and various endoscopic procedures. It is occasionally difficult to advance a double pigtail stent in patients with angulated vesicoureteric junctions. We present a simple and safe technique for placement of ureteral stents in these patients.

Retrograde endoureteropyelotomy with the holmium:YAG laser. Initial experience.

OBJECTIVE: To evaluate the safety and efficacy of the holmium:YAG laser in the management of pelviureteric junction (PUJ) obstruction. PATIENTS AND METHODS: Between November 1994 and February 1996, 8 patients with 5 primary and 3 secondary PUJ obstructions underwent retrograde ureteroscopic holmium:YAG laser endopyelotomy. A 320- to 365-micron (Slimline, Coherent) fibre was used to deliver the laser energy. A posterolateral endopyelotomy was performed under visual monitoring. All patients had a ureteral stent left in place postoperatively for 6 weeks and a renogram was performed after 3 months. The mean follow-up was 12.4 months (3-24 months). RESULTS: Almost bloodless, accurate and layered division of the PUJ was easily performed. The average procedure time was 37.5 min. Our overall success rate was 87.5%. CONCLUSION: The holmium:YAG laser is a safe, reliable laser with adequate coagulative properties and precise cutting abilities. This allows a 'bloodless' operative field for controlled, accurate and safe endoscopic division of the PUJ.

Transurethral incision of the prostate using the holmium:YAG laser: a catheterless procedure.

PURPOSE: Transurethral incision of the prostate is a well established technique for relieving bladder outflow obstruction caused by prostate glands less than 30 gm. We present data showing that the holmium:YAG laser can prevent postoperative catheterization without compromising the outcome of surgery. MATERIALS AND METHODS: We prospectively followed 100 men an average of 62 years old with symptomatic bladder outflow obstruction and a benign prostate gland less than 30 gm. clinically in whom serum prostate specific antigen was less than 4 microg./l. They were assessed using International Prostate Symptom Score, urinary flow rate, post-void residual estimation and sexual function questionnaires preoperatively, and 6 weeks, and 1 and 2 years postoperatively. With the patient under general anesthesia a single incision was made from the ureteral orifice to the verumontanum and out to fat using holmium:YAG laser energy transmitted through a 400 nm. fiber sheathed in a ureteral catheter. RESULTS: A total of 97 patients voided without postoperative catheterization. Average International Prostate Symptom Score decreased from 19.2 to 3.7 at 6 weeks and it remained improved at 2 years (average 3.5). Reciprocal results were achieved with improvement in average urinary flow rate from 9.79 to 19.23 and 18.27 ml. per second at 6 weeks and 2 years, respectively. Residual urine measurement decreased from 133.6 ml. preoperatively to 27 and 10 ml. at 6 weeks and 2 years, respectively. All 77 patients potent preoperatively remained so, although retrograde ejaculation developed in 8. CONCLUSIONS: The holmium:YAG laser allows transurethral prostatic incision to be performed without the need for postoperative catheterization while maintaining efficacy.

Ureteroscopic holmium lasertripsy for ureteric stones. Initial experience.

The clinic benefits of the Holmium: YAG laser include a pronounced haemostatic effect, fibreoptic delivery system and a wide range of power-setting options. We review our initial experience in treating 48 patients with ureteric stones. Stones were located in the upper, middle and lower ureter in 27%, 21% and 52% of patients respectively. The Holmium laser successfully fragmented all calculi and there were no major complications. We have found the Holmium laser to be a safe, effective and reliable alternative for the management of urolithiasis.

Ureteroscopic endopyelotomy with the Holmium:YAG laser. mid-term results.

OBJECTIVE: Various modalities ranging from acucise balloon to endoincision with electrocautery, cold knife, and lasers have been used to treat ureteropelvic junction obstruction (UPJO). We assessed the intermediate effectiveness of endopyelotomy with the holmium(Ho):YAG laser. PATIENTS AND METHODS: Between November 1994 and May 1998, 20 patients with 16 primary and 4 secondary symptomatic UPJO were treated. All patients were evaluated clinically and radiologically before and after the procedure at 3 months, and yearly thereafter. The mean follow-up was 34 months (12-38 months). RESULTS: A total of 22 procedure were performed on 20 patients with an average operating time of 44.3 min and mean hospital stay of 1.9 days. All patients were stented after the procedure for 6 weeks. Complication included urinoma (1) and guidewire fracture in 1 patient. 15 patients had a successful outcome determined by a diuretic renography and/or Whitaker test. Three patients with poor preoperative renal function (<25%) had an unsatisfactory outcome. There were 2 failures and they were treated with nephrectomy (1) and open pyeloplasty (1). CONCLUSIONS: A controlled, precise, safe and almost 'bloodless' endopyelotomy can be performed with the holmium laser. Success rate tends to be poor in patients with poor renal function.

A role for phosphoinositide hydrolysis in human uterine smooth muscle during parturition.

Phosphoinositide hydrolysis is thought to be important in regulating a variety of intracellular signals, including Ca++ and prostaglandins, both of which have been implicated in the action of oxytocin during uterine smooth muscle contraction. We investigated the in vitro effect of oxytocin and various other uterotonic agents on phosphoinositide hydrolysis in gestational myometrium by measuring the production of inositol phosphates in tissue explants prelabeled with 3H-inositol. Oxytocin caused significant increases in all three inositol phosphates in myometrium at 3 minutes. Stimulation of inositol monophosphate production was sustained for 30 minutes and was dose dependent, with a half-maximal effect around 2 X 10(-8) mol/L. Platelet activating factor and alpha-adrenergic agonists also stimulated myometrial phosphoinositide hydrolysis, but carbachol prostaglandins E2 and F2 alpha had no effect. Vasopressin had greater efficacy than oxytocin for stimulating hydrolysis in gestational myometrium. Furthermore, in contrast to vasopressin, oxytocin had no effect on inositol phosphate production in nongestational myometrium. Oxytocin also stimulated arachidonic acid release and prostaglandin E2 and F2 alpha production in gestational myometrium. The hydrolysis of phosphatidylinositol by myometrium homogenates showed a precursor-product relationship for the production of diacylglycerol, monoacylglycerol, and arachidonic acid, indicative of a sequential action of phospholipase C and diacylglycerol lipase. These data demonstrate the potential for certain uterotonic agonists to use inositol lipid signaling to mobilize free arachidonic acid for prostaglandin production and to release intracellular Ca++ during excitation-contraction coupling.

Massive peri-renal haemorrhage from ruptured renal artery aneurysm in the presence of normal renal function.

A 65-year-old man presented acutely with a large right peri-nephric haematoma as seen on a CT scan. Intravenous urography demonstrated normal function. An arteriogram later revealed a 1 cm renal artery tributary aneurysm, which was successfully embolized.

Emphysematous cystitis.

A case of emphysematous cystitis in a diabetic female is described. Its presentation is non-specific and the prognosis depends on then degree of aggressiveness at presentation. Early diagnosis and aggressive medical and surgical management of gas-forming organisms are vital.

Xanthogranulomatous pyelonephritis with bilateral nephrocutaneous fistulae.

This case report describes a patient with bilateral nephrocutaneous fistulae and xanthogranulomatous pyelonephritis. Contralateral involvement of the psoas muscle is a rare occurrence and has not been previously documented.

Daycase transurethral incision of the prostate using the holmium: YAG laser: initial experience.

OBJECTIVE: To ascertain whether the holmium: YAG laser can be used for transurethral incision of the prostate (TUIP), without the need for post-operative catheterization. PATIENTS AND METHODS: The study comprised 100 men with symptomatic bladder outlet obstruction and clinically benign glands (< 30 g). The International Prostate Symptom Score (IPSS), flow rates and post-void residual urine volume were measured before and 6 weeks after surgery. The first 22 patients were admitted overnight for observation, but the remaining 78 patients were discharged on the day of the procedure, once they had successfully voided. RESULTS: Ninety-seven men voided successfully on the day of the procedure. The mean IPSS, flow rate and residual urine volume were all significantly improved at the time of review. Six patients developed a urinary tract infection post-operatively and eight men reported retrograde ejaculation. CONCLUSION: The holmium: YAG laser facilitates a bloodless TUIP thus avoiding catheterization, allowing the procedure to be carried out as a day case.

Detailed tissue expression of bcl-2, bax, bak and bcl-x in the normal human pancreas and in chronic pancreatitis, ampullary and pancreatic ductal adenocarcinomas.

BACKGROUND: The aim of this study was to evaluate expression of the bcl-2 family of apoptosis regulating proteins in normal and diseased human pancreatic tissues. METHOD: Expression of bcl-2, bax, bcl-x, bak and p53 was determined in formalin-fixed paraffin wax-embedded archival specimens of normal pancreatic tissue (n = 7), chronic pancreatitis (n = 7), pancreatic ductal adenocarcinoma (n = 23) and ampullary cancer (n = 7) by immunohistochemistry using specific antibodies. RESULTS: In normal pancreas and chronic pancreatitis tissues, bcl-2, bax and bcl-x were predominantly expressed in ductal epithelial cells while p53 was not detected. In pancreatic ductal adenocarcinoma and ampullary cancer, bcl-2 was not detected compared with expression seen in normal acini (p < 0.01), minor (p < 0.001) and major ducts (p < 0.01), bax expression was reduced with respect to minor ducts (p < 0.01) but no different from normal acini or major ducts. bak and bcl-x were more strongly expressed in malignant epithelia compared with acini and major ducts but reduced when compared with minor ducts (p < 0.01). Overexpression of p53 was identified in 11 (48%) of 23 pancreatic adenocarcinomas and 4 (57%) of 7 ampullary cancers. Differential survival of individual patients was predicted by the relative level of bcl-x expression but not bax or bak, such that strong expression of bcl-x was associated with a median postoperative survival of 171 days when compared with 912 days for diminished expression (p < 0.001) of bcl-x. CONCLUSION: Pancreatic and ampullary cancer are associated with absent bcl-2 expression. bax, bak and bcl-x expression was reduced compared with normal minor ducts whilst bak and bcl-x expression was increased when compared with major ducts. bcl-x expression correlates with survival following resection and may represent a potential prognosis marker.

Risk-adjusted analysis of surgeon performance: a 1-year study.

A 1-year prospective analysis was undertaken of all non-day-case general surgery in a district general hospital. Using the Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity (POSSUM) scoring system 3004 patients were assessed. From the predictions of mortality and morbidity so obtained, a quality measure, the ratio of observed to expected numbers of deaths and complications (O:E ratio) was determined for each surgeon, both overall and within specialty zones. The present study demonstrates the serious hazard in using 'raw' uncorrected mortality and morbidity statistics to compare surgeon performance. Mortality rates varied from 1.0 to 4.9 per cent whereas O:E ratios ranged from 0.83 to 1.06; morbidity rates varied from 5.3 to 12.6 per cent with O:E ratios 0.86-1.02. Great misunderstanding may result from the publication of surgeon or hospital 'league tables'. The present study demonstrates a technique that might allow surgeon performance to be monitored adequately and accurately.