Clomiphene citrate: A potential alternative for testosterone therapy in hypogonadal males.

BACKGROUND: Hypogonadism is a worldwide problem among men causing sexual, physical and mental problems. Testosterone therapy is the first-choice treatment for male hypogonadism, with several side effects, that is, subfertility. Clomiphene citrate (CC) is an alternative off-label therapy for a certain group of hypogonadal males, especially for those with an active or future child wish. There is scarce literature in usage of CC for men with hypogonadism. The aim of this retrospective study was to evaluate the effectiveness and safety of CC for hypogonadal males. METHODS: In this single-centre study, men treated with CC for hypogonadism were evaluated retrospectively. Primary outcome was hormonal evaluation including total testosterone (TT), free testosterone (FT), luteinizing hormone (LH) and follicle stimulating hormone (FSH). Secondary outcomes were hypogonadal symptoms, metabolic and lipid parameters, haemoglobin (Hb), haematocrit (Ht), prostate specific antigen (PSA), side effects, the effect of a trial without medication and potential predictors for biochemical and clinical response. RESULTS: In total, 153 hypogonadal men were treated with CC. Mean TT, FT, LH and FSH increased during treatment. TT increased from 9 to 16 nmol/L, with a biochemical increase in 89% of the patients. In patients who continued CC treatment, an increased level of TT persisted after 8 years of treatment. With CC treatment, 74% of the patients experienced hypogonadal symptom improvement. LH at the lower normal range before CC treatment was predictive for better TT response. During CC therapy, few side effects were reported and no clinical important changes in PSA, Hb and Ht were found. CONCLUSION: Clomiphene citrate is an effective therapy on short and long term, improving both clinical symptoms and biochemical markers of male hypogonadism with few side effects and good safety aspects.

Clomiphene citrate for male infertility: A systematic review and meta-analysis.

BACKGROUND: Male infertility is a prevalent and worldwide problem with various difficulties in treatment. Clomiphene citrate is a selective estrogen receptor modulator and may improve semen quality by stimulating hormone synthesis and spermatogenesis. There is lack of evidence on the efficacy of clomiphene citrate as therapy for male infertility. OBJECTIVES: Therefore, a systematic review and meta-analysis was performed to assess the efficacy of clomiphene citrate on sperm quality in infertile men. METHODS: A search was conducted in the PubMed, EMBASE and Cochrane databases for effectiveness in infertile males treated with clomiphene citrate. Both intervention and observational studies were included. Primary outcome measures were semen parameters (concentration, motility and morphology). Secondary outcomes included hormonal evaluation, pregnancy rate and side effects. Studies were included for meta-analysis if they provided absolute numbers for outcomes before and during treatment with appropriate SD or SE. RESULTS: Total 1799 studies were identified during the search, 18 studies remained for qualitative analysis (n = 731) and 15 studies for meta-analysis (n = 566). Study populations ranged between 11 and 140 participants. Sperm concentration was higher during treatment, with a mean difference 8.38 × 106 /ml (95% confidence interval: 5.17-11.59; p < 0.00001; I2  = 87%). Total sperm motility was higher during treatment, with a mean difference of 8.14% (95% confidence interval: 3.83-12.45; p < 0.00001; I2  = 76%). There was no difference in sperm morphology before and during treatment. Total testosterone, follicle-stimulating hormone, luteinizing hormone and estradiol were higher during clomiphene citrate treatment. During follow-up, no serious adverse effects occurred. In 10 studies, pregnancy rate was reported and yielded a mean of 17% during clomiphene citrate treatment (range: 0%-40%). CONCLUSIONS: Clomiphene citrate increased sperm concentration and motility and could be considered as a safe therapy for improving sperm parameters in infertile males.

Clomiphene citrate for men with hypogonadism: a systematic review and meta-analysis.

BACKGROUND: Male hypogonadism is a clinical and biochemical androgen insufficiency syndrome, becoming more prevalent with age. Exogenous testosterone is first-choice therapy, with several side effects, including negative feedback of the hypothalamic-pituitary-gonadal axis, resulting in suppression of intratesticular testosterone production and spermatogenesis. To preserve these testicular functions while treating male hypogonadism, clomiphene citrate is used as off-label therapy. This systematic review and meta-analysis aimed to evaluate the effectiveness and safety of clomiphene citrate therapy for men with hypogonadism. METHODS: The EMBASE, PubMed, Cochrane databases were searched in May 2021, for effectiveness studies of men with hypogonadism treated with clomiphene citrate. Both intervention and observational studies were included. The Effective Public Health Practice Project Quality Assessment Tool, a validated instrument, was used to assess methodological study quality. The primary outcome measure was the evaluation of serum hormone concentration. Secondary outcomes were symptoms of hypogonadism, metabolic and lipid profile, side effects, safety aspects. RESULTS: We included 19 studies, comprising four randomized controlled trials and 15 observational studies, resulting in 1642 patients. Seventeen studies were included in the meta-analysis, with a total of 1279 patients. Therapy and follow-up duration varied between one and a half and 52 months. Total testosterone increased with 2.60 (95% CI 1.82-3.38) during clomiphene citrate treatment. An increase was also seen in free testosterone, luteinizing hormone, follicle stimulating hormone, sex hormone-binding globulin and estradiol. Different symptom scoring methods were used in the included studies. The most frequently used instrument was the Androgen Deficiency in Aging Males questionnaire, whose improved during treatment. Reported side effects were only prevalent in less than 10% of the study populations and no serious adverse events were reported. CONCLUSION: Clomiphene citrate is an effective therapy for improving both biochemical as well as clinical symptoms of males suffering from hypogonadism. Clomiphene citrate has few reported side effects and good safety aspects.

Psoas hitch procedure in 166 adult patients: The largest cohort study before the laparoscopic era.

Objectives: To present the short-term and long-term outcomes of the psoas hitch procedure in a large cohort with long-term follow-up. Patients and methods: A multicenter, retrospective cohort study was conducted. Patients were included if they had undergone an open psoas hitch procedure with ureteral reimplantation for different types of distal ureteral pathology between 1993 and 2017. Clinical failure was defined as radiologically-proven obstruction of the ureteroneocystostomy and/or post-operative complaints requiring additional surgery. Pre-operative demographic data and post-operative radiological imaging were collected. Complications were categorized as peri-operative, acute (<30 days), and long-term complications. Results: A total of 166 patients had undergone a psoas hitch procedure, with a median follow-up of 15 months (IQR 6-45). Indications for the procedure included intra-operative injury of the ureter during gynecological, urological or general surgery, transitional cell carcinoma of the distal ureter, fistulae, (radiation) fibrosis, and trauma. There was no significant difference in pre- and post-operative estimated glomerular filtration rate. Post-operative complications included urinary leakage, recurrent urinary tract symptoms, recurrent malignancy, and kidney failure. Postoperative imaging was available in 143 patients. Failure of the psoas hitch procedure was seen in 8% (11/143) of the patients. In 55% (6/11) of these patients, radiation fibrosis was the indication for the psoas hitch procedure. Conclusion: This study provides greater insight into the long-term complications of the open psoas hitch procedure in adults. The psoas hitch procedure can be considered a safe procedure for restoring the continuity of the ureter for different types of ureteral pathologies in adult patients. However, patients with a history of radiation therapy causing retroperitoneal fibrosis might be more prone to failure after the procedure.

Consensus statement on tumour bed localization for radiation after oncoplastic breast surgery.

Background: Oncoplastic surgery (ops) is becoming the new standard of care for breast-conserving surgery, leading to some challenges with adjuvant radiation, particularly when accurate tumour bed (tbd) delineation is needed for focused radiation (that is, accelerated partial breast irradiation or boost radiation). Currently, no guidelines have been published concerning tbd localization for adjuvant targeted radiation after ops. Methods: A modified Delphi method was used to establish consensus by a panel of 20 experts in surgical and radiation oncology at the Canadian Locally Advanced Breast Cancer National Consensus Group and in a subsequent online member survey. Results: These are the main recommendations:■ Surgical clips are necessary and should, at a minimum, be placed along the 4 side walls of the cavity, plus 1-4 clips at the posterior margin if necessary.■ Operative reports should include pertinent information to help guide the radiation oncologists.■ Breast surgeons and radiation oncologists should have a basic understanding of ops techniques and work on "speaking a common language."■ Careful consideration is needed when determining the value of targeted radiation, such as boost, in higher-level ops procedures with extensive tissue rearrangement. Conclusions: The panel developed a total of 6 recommendations on tbd delineation for more focused radiation therapy after ops, with more than 80% agreement on each statement. All are summarized, together with the corresponding evidence or expert opinion.

[A chancre instead of cancer]. / Geen kanker, maar een sjanker.

BACKGROUND: Syphilis (lues) is a sexually transmitted infection caused by the spirochete Treponema pallidum. In adolescents, the diagnosis of primary syphilis can be made promptly by taking a sexual medical history and inspecting the glans penis. CASE DESCRIPTION: A 17-year-old male was referred to the paediatric oncology centre for additional diagnostics due to inguinal lymphadenopathy, with a strong suspicion of a malignant lymphoma. None of the physicians took a sexual medical history or investigated the glans penis, as a result of which essential information was lacking. The combination of inguinal lymphadenopathy and the ultrasound findings for the inguinal region made the physicians only consider a malignancy. However, it actually concerned a reactive lymphadenopathy associated with primary syphilis. CONCLUSION: This case demonstrates that a full medical history and thorough physical examination can prevent the need for costly and invasive diagnostics.

Stereotactic image-guided neoadjuvant ablative single-dose radiation, then lumpectomy, for early breast cancer: the SIGNAL prospective single-arm trial of single-dose radiation therapy.

Background and Purpose: Adjuvant whole-breast irradiation after breast-conserving surgery, typically delivered over several weeks, is the traditional standard of care for low-risk breast cancer. More recently, hypofractionated, partial-breast irradiation has increasingly become established. Neoadjuvant single-fraction radiotherapy (rt) is an uncommon approach wherein the unresected lesion is irradiated preoperatively in a single fraction. We developed the signal (Stereotactic Image-Guided Neoadjuvant Ablative Radiation Then Lumpectomy) trial, a prospective single-arm trial to test our hypothesis that, for low-risk carcinoma of the breast, the preoperative single-fraction approach would be feasible and safe. Methods: Patients presenting with early-stage (T < 3 cm), estrogen-positive, clinically node-negative invasive carcinoma of the breast with tumours at least 2 cm away from skin and chest wall were enrolled. All patients received prone breast magnetic resonance imaging (mri) and prone computed tomography simulation. Treatable patients received a single 21 Gy fraction of external-beam rt (as volumetric-modulated arc therapy) to the primary lesion in the breast, followed by definitive surgery 1 week later. The primary endpoints at 3 weeks, 6 months, and 1 year were toxicity and cosmesis (that is, safety) and feasibility (defined as the proportion of mri-appropriate patients receiving rt). Results: Of 52 patients accrued, 27 were successfully treated. The initial dosimetric constraints resulted in a feasibility failure, because only 57% of eligible patients were successfully treated. Revised dosimetric constraints were developed, after which 100% of patients meeting mri criteria were treated according to protocol. At 3 weeks, 6 months, and 1 year after the operation, toxicity, patient- and physician-rated cosmesis, and quality of life were not significantly different from baseline. Conclusions: The signal trial presents a feasible method of implementing single-dose preoperative rt in early-stage breast cancer. This pilot study did not identify any significant toxicity and demonstrated excellent cosmetic and quality-of-life outcomes. Future randomized multi-arm studies are required to corroborate these findings.

Recurrence and mortality after breast-conserving surgery without radiation.

Background: Breast-conserving surgery (bcs) and radiation therapy (rt) are the standard of care for early breast cancer; studies have demonstrated that adjuvant rt confers a protective effect with respect to recurrence, although no randomized trials have shown a survival benefit. Methods: This retrospective cohort study used Ontario data linked through ices to examine patients treated for breast cancer between 1 April 2007 and 31 March 2014. The primary outcome was death or recurrence. Outcomes were compared between patients who did and did not receive rt. Results: The total cohort size was 26,279. The hazard ratios (hrs) for various outcomes were significantly higher for patients who did not receive rt than for patients who did: recurrence or death combined [hr: 2.49; 95% confidence interval (ci): 2.25 to 2.75], recurrence (hr: 2.33; 95% ci: 1.91 to 2.84), and death (hr: 2.28; 95% ci: 2.03 to 2.56). The hr for death was 1.81 (95% ci: 1.65 to 1.99) for patients having stage ii cancer compared with those having stage i disease. The hr for death was 1.97 (95% ci: 1.74 to 2.22) for patients having high comorbidity compared with those having little comorbidity. Conclusions: Adjuvant rt carries a protective effect with respect to recurrence and survival in patients with early-stage breast cancer. That survival benefit has not been appreciated in previous randomized trials and underscores the importance of rt as a component of breast cancer treatment.

Treating benign ureteroenteric strictures: 27-year experience comparing endourological techniques with open surgical approach.

PURPOSE: To compare open surgical anastomotic revision with endourological techniques for the treatment of ureteroenteric strictures in patients with urinary diversions. METHODS: All records of patients treated for ureteroenteric strictures in our clinic between 1989 and 2016 were retrospectively reviewed. In 76 patients, 161 completed procedures were analyzed: 26 open revisions vs. 135 endourological treatments, including balloon dilation, Wallstent and/or laser vaporization. RESULTS: Median follow-up was 34 months. At 60 months, patency rates were 69% (95% CI 52-92%) after open vs. 27% (95% CI 19-39%) after endo-treatment (p = 0.003); median patency duration was 15.5 vs. 5 months, respectively (p = 0.014). Eventually, 15% of patients required open surgery after primary endo-treatment and 21% received endoscopic re-treatment after primary open surgery. Cox regression analysis revealed no confounding factors among the risk factors added to the model. Complication rates were higher after open surgery (27% Clavien 2, 12% Clavien 3-4 vs. 5% Clavien 1-2, 3% Clavien 3, p = 0.528). Median postoperative hospital stay was 14 days (open) vs. 2 days (endo), p < 0.001. Mean estimated glomerular filtration rate improved with + 17 (open) vs. + 8.1 (endo), p = 0.024. Renal function was compromised in 8% of patients in the open surgery group vs. 6% in the endo-treatment group. CONCLUSIONS: In these patients, in terms of patency and patency duration, open surgery was superior to endourology. Nevertheless, endourological treatments offer a safe and less-invasive alternative to delay or avoid open surgery, especially in patients who are unfit for open surgery.

Appropriate treatment receipt after breast-conserving surgery.

Background: Breast-conserving surgery (bcs) and radiation therapy (rt) are the standard of care for early breast cancer, although some women receive ipsilateral mastectomy or adjuvant tamoxifen, both of which can be appropriate alternatives to rt. Objectives of the present study were to determine the proportion of women who are treated appropriately after bcs and to identify factors associated with non-receipt of rt. Methods: This retrospective cohort study used Ontario data linked at the Institute for Clinical and Evaluative Sciences to examine 33,718 patients who received bcs during 2004-2010. Primary outcome was rt receipt. The ipsilateral mastectomy rate and patient, surgeon, and setting variables were measured. Results: Of the study patients, 86.1% received either rt or completion mastectomy; in the cohort less than 70 years of age, 90.8% received rt or completion mastectomy. Among patients less than 70 years of age, 3 risk factors for non-receipt of rt were identified: age less than 46 years, treatment in a non-academic institution, and earlier year of initial bcs. Additionally, in the overall cohort, rt non-receipt was associated with high comorbidity, more than 40 km to the cancer centre, income quintile, and breast care specialization. Conclusions: In Ontario, 90.8% of patients less than 70 years of age are appropriately treated for early breast cancer; approximately 1 in 10 do not receive rt or completion mastectomy. Based on those findings, women less than 46 years of age might be at increased risk of recurrence and death because of incomplete treatment. It also appears that academic centres more effectively treat breast cancer; however, breast cancer care appears to be improving over time in Ontario.

Radiation dose reduction for CT assessment of urolithiasis using iterative reconstruction: A prospective intra-individual study.

OBJECTIVE: To assess the performance of hybrid (HIR) and model-based iterative reconstruction (MIR) in patients with urolithiasis at reduced-dose computed tomography (CT). METHODS: Twenty patients scheduled for unenhanced abdominal CT for follow-up of urolithiasis were prospectively included. Routine dose acquisition was followed by three low-dose acquisitions at 40%, 60% and 80% reduced doses. All images were reconstructed with filtered back projection (FBP), HIR and MIR. Urolithiasis detection rates, gall bladder, appendix and rectosigmoid evaluation and overall subjective image quality were evaluated by two observers. RESULTS: 74 stones were present in 17 patients. Half the stones were not detected on FBP at the lowest dose level, but this improved with MIR to a sensitivity of 100%. HIR resulted in a slight decrease in sensitivity at the lowest dose to 72%, but outperformed FBP. Evaluation of other structures with HIR at 40% and with MIR at 60% dose reductions was comparable to FBP at routine dose, but 80% dose reduction resulted in non-evaluable images. CONCLUSIONS: CT radiation dose for urolithiasis detection can be safely reduced by 40 (HIR)-60 (MIR) % without affecting assessment of urolithiasis, possible extra-urinary tract pathology or overall image quality. KEY POINTS: • Iterative reconstruction can be used to substantially lower the radiation dose. • This allows for radiation reduction without affecting sensitivity of stone detection. • Possible extra-urinary tract pathology evaluation is feasible at 40-60% reduced dose.

Polypoid arteriovenous malformation of the ureter mimicking a fibroepithelial polyp, a case report.

BACKGROUND: Arteriovenous malformations (AVM) of the urinary tract are extremely rare. To the best of our knowledge, only three case of AVM of the ureter have been described in the literature so far. CASE PRESENTATION: We present an additional, fourth case of an AVM of the ureter, clinically presented as asymptomatic haematuria and an obstructive process in the left ureter. Ureteroscopic evaluation revealed a fibroepithelial polypoid-like lesion in the proximal ureter. After biopsy showed a benign lesion, the lesion was treated with the 2-µm continuous wave (cw) thulium laser. Histopathological examination revealed a polypoid laesion caused by a circumscribed arteriovenous malformation. Almost four years after operation the patient remains asymptomatic and free of recurrence. CONCLUSION: Arteriovenous malformations of the urinary tract are extremely rare. We presented a fourth case of a arteriovenous malformation of the ureter.

Reducing Patient Waiting Times for Radiation Therapy and Improving the Treatment Planning Process: a Discrete-event Simulation Model (Radiation Treatment Planning).

AIMS: We analysed the radiotherapy planning process at the London Regional Cancer Program to determine the bottlenecks and to quantify the effect of specific resource levels with the goal of reducing waiting times. MATERIALS AND METHODS: We developed a discrete-event simulation model of a patient's journey from the point of referral to a radiation oncologist to the start of radiotherapy, considering the sequential steps and resources of the treatment planning process. We measured the effect of several resource changes on the ready-to-treat to treatment (RTTT) waiting time and on the percentage treated within a 14 calendar day target. RESULTS: Increasing the number of dosimetrists by one reduced the mean RTTT by 6.55%, leading to 84.92% of patients being treated within the 14 calendar day target. Adding one more oncologist decreased the mean RTTT from 10.83 to 10.55 days, whereas a 15% increase in arriving patients increased the waiting time by 22.53%. The model was relatively robust to the changes in quantity of other resources. CONCLUSIONS: Our model identified sensitive and non-sensitive system parameters. A similar approach could be applied by other cancer programmes, using their respective data and individualised adjustments, which may be beneficial in making the most effective use of limited resources.

The significance of circulating tumor cells in prostate cancer patients undergoing adjuvant or salvage radiation therapy.

BACKGROUND: Following radical prostatectomy, success of adjuvant and salvage radiation therapy (RT) is dependent on the absence of micrometastatic disease. However, reliable prognostic/predictive factors for determining this are lacking. Therefore, novel biomarkers are needed to assist with clinical decision-making in this setting. Enumeration of circulating tumor cells (CTCs) using the regulatory-approved CellSearch System (CSS) is prognostic in metastatic prostate cancer. We hypothesize that CTCs may also be prognostic in the post-prostatectomy setting. METHODS: Patient blood samples (n=55) were processed on the CSS to enumerate CTCs at 0, 6, 12 and 24 months after completion of RT. CTC values were correlated with predictive/prognostic factors and progression-free survival. RESULTS: CTC status (presence/absence) correlated significantly with positive margins (increased likelihood of CTC(neg) disease; P=0.032), and trended toward significance with the presence of seminal vesicle invasion (CTC(pos); P=0.113) and extracapsular extension (CTC(neg); P=0.116). Although there was a trend toward a decreased time to biochemical failure (BCF) in baseline CTC-positive patients (n=9), this trend was not significant (hazard ratio (HR)=0.3505; P=0.166). However, CTC-positive status at any point (n=16) predicted for time to BCF (HR=0.2868; P=0.0437). CONCLUSIONS: One caveat of this study is the small sample size utilized (n=55) and the low number of patients with CTC-positive disease (n=16). However, our results suggest that CTCs may be indicative of disseminated disease and assessment of CTCs during RT may be helpful in clinical decision-making to determine, which patients may benefit from RT versus those who may benefit more from systemic treatments.

Rare case of urinary tract infections and the "forgotten" solution.

This report presents a rare case of recurrent urinary tract infections in a kidney transplant patient. Analysis revealed a ureteral stump calculus 31 years after bilateral nephrectomy which was disintegrated by means of flexible ureteroscopy and holmium laser. In case of unexplained recurrent urinary tract infections and abdominal pain, urolithiasis in the ureteral stumps should be considered.

Angiosarcoma of the prostate: a more frequent finding in the future owing to radiotherapy? A literature review with treatment implications based on a case report.

OBJECTIVE: An increase in the incidence of prostate angiosarcoma may be expected owing to the exponential increase in the use of radiotherapy for prostate carcinoma in recent decades and the possible aetiology of radiation exposure on the development of angiosarcoma in general. The objective of this study was to give an overview of cases in the literature based on a case report of prostate angiosarcoma in a hospital in the Netherlands, and to discuss optimal treatment. MATERIAL AND METHODS: All (related) articles In PubMed/Medline and Embase with possible cases of angiosarcoma were screened on title and abstract. A case of prostate angiosarcoma identified in the authors' institution was included. RESULTS: The literature search yielded 13 cases of prostate angiosarcoma. The earliest six publications lack essential data. Four patients had a history of radiotherapy. The present patient developed angiosarcoma following brachytherapy for prostate cancer. Therapy consisted of radical surgery with or without chemotherapy in five cases. In eight cases curative therapy was not reported or not possible. Mean follow-up was only 1 year. Four patients died within 1 year of diagnosis, irrespective of treatment choice. One patient, treated with a combination of radical surgery and adjuvant chemotherapy, was still alive 36 months after therapy. CONCLUSIONS: The findings confirm that prostate angiosarcoma is mostly radiation induced. This patient is the first case of prostate angiosarcoma after primary brachytherapy. Angiosarcoma may occur more often in the future owing to widespread use of brachytherapy and radiotherapy of the prostate. Current guidelines on management of angiosarcoma suggest radical surgery in local disease as the primary treatment of choice.

Alpha-blockers as medical expulsive therapy for ureteral stones.

BACKGROUND: Urinary stone disease is one of the most common reasons for patients visiting a urology practice, affecting about 5% to 10% of the population. Annual costs for stone disease have rapidly increased over the years and most patients with ureteral colic or other symptoms seek medical care. Stone size and location are important predictors of stone passage. In most cases medical expulsive therapy is an appropriate treatment modality and most studies have been performed with alpha-blockers. Alpha-blockers tend to decrease intra-ureteral pressure and increase fluid passage which might increase stone passage. Faster stone expulsion will decrease the rate of complications, the need for invasive interventions and eventually decrease healthcare costs. A study on the effect of alpha-blockers as medical expulsive therapy in ureteral stones is therefore warranted. OBJECTIVES: This review aimed to answer the following question: does medical treatment with alpha-blockers compared to other pharmacotherapy or placebo impact on stone clearance rate, in adult patients presenting with symptoms of ureteral stones less than 10 mm confirmed by imaging? Other clinically relevant outcomes such as stone expulsion time, hospitalisation, pain scores, analgesic use and adverse effects have also been explored. SEARCH METHODS: We searched the Cochrane Renal Group's Specialised Register to 9 July 2012 through contact with the Trials Search Co-ordinator using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE and EMBASE, handsearching conference proceedings, and searching the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs), comparing alpha-blockers with other pharmacotherapy or placebo on ureteral stone passage in adult patients were included. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study quality and extracted data. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) and 95% CI for continuous outcomes. Reporting bias was investigated using funnel plots. Subgroup analysis was used to explore possible sources of heterogeneity. Sensitivity analysis was performed removing studies of poor methodological quality. MAIN RESULTS: Thirty-two studies (5864 participants) were included. The stone-free rates were significantly higher in the alpha-blocker group (RR 1.48, 95% CI 1.33 to 1.64) when compared to standard therapy. Stone expulsion time was 2.91 days shorter with the use of alpha-blockers (MD -2.91, 95% CI -4.00 to -1.81). Use of alpha-blockers reduced the number of pain episodes (MD -0.48, 95% CI -0.94 to -0.01), the need for analgesic medication (diclofenac) (MD -38.17 mg, 95% CI -74.93 to -1.41) and hospitalisation (RR 0.35, 95% CI 0.13 to 0.97). Patients using alpha-blockers were more likely to experience adverse effects when compared to standard therapy (RR 2.74, 95% CI 1.38 to 5.45) or placebo (RR 2.73, 95% CI 1.50 to 4.96). Most adverse effects were mild of origin and did not lead to cessation of therapy, and several studies reported no adverse events in either the treatment or control group.In 7/32 studies patients and doctors were both blinded. In the other studies blinding was not described in the methods or no blinding had taken place. Two studies described incomplete data and only one study showed a relatively high number of patients who withdrew from the study. These factors limited the methodological strength of the evidence found. AUTHORS' CONCLUSIONS: The use of alpha-blockers in patients with ureteral stones results in a higher stone-free rate and a shorter time to stone expulsion. Alpha-blockers should therefore be offered as part of medical expulsive therapy as one of the primary treatment modalities.

The Wallstent: long-term follow-up of metal stent placement for the treatment of benign ureteroileal anastomotic strictures after Bricker urinary diversion.

OBJECTIVE: To evaluate the long-term follow-up (primary and secondary patency) of metal stent placement in benign ureteroileal anastomotic strictures after Bricker urinary diversion and to compare the failed treatment group with the group of successfully treated patients to search for predisposing factors of stent failure. PATIENTS AND METHODS: For patients treated since 1989 for benign ureteroileal strictures after Bricker urinary diversion with end-to-side anastomosis, we retrospectively collected data on clinical history, stent placement, auxiliary measures and patency rates from a prospectively kept database. RESULTS: In all, 49 patients (mean age 64 years) underwent 56 metal stent procedures. Placement of the stent was possible in all patients. Stent patency without auxiliary treatment remained adequate in 23 cases (primary patency of 41.1%, mean follow-up 37.7 months). A secondary treatment was successfully performed in 11 patients who had stent obstruction, mostly caused by hyperplastic reaction, encrustation, or migration of the stent. The secondary patency rate was 60.7% (mean follow-up 55.8 months), comparable with patency rates of 36-100% described in literature with mostly small patient groups and much shorter follow-up periods. CONCLUSION: To the best of our knowledge we report the largest series of metal stenting in benign ureteroileal anastomotic strictures with the longest follow-up. We show that placement of a metal stent can lead to a permanent de-obstruction in approximately six out of 10 patients with preservation of renal function.

Determination and comparison of radiotherapy dose responses for hepatocellular carcinoma and metastatic colorectal liver tumours.

OBJECTIVE: The purpose of this study was to seek radiation dose responses separately for primary hepatocellular carcinoma (HCC) and metastatic (MET) colorectal liver tumours to establish tumour control probabilities (TCPs) for radiotherapy (RT) of liver tumours. METHODS: The records of 36 HCC and 26 MET colorectal liver tumour patients were reviewed. The median dose per fraction and total dose were 4 Gy (2-10 Gy) and 52 Gy (29-83 Gy) for the HCC group and 3.6 Gy (2.0-13.0 Gy) and 55 Gy (30-80 Gy) for the MET group, respectively. Median tumour diameter was 6.6 cm (3.0-18.0 cm) and 5.0 cm (1.0-13.0 cm) for the HCC and MET groups, respectively. A logistic TCP model was fitted to the response data for each group using the maximum likelihood method. RESULTS: 50% and 90% probabilities of 6-month local control were estimated to be achievable by 2 Gy per fraction equivalent doses (α/ß=10 Gy) of 53 Gy and 84 Gy for the HCC group and 70 Gy and 95 Gy for the MET group, respectively. Actuarial 1-year local control for the HCC and MET groups was 65% (45-85%) and 32% (6-58%), respectively, whereas median time to failure was 543 days (374-711 days) and 183 days (72-294 days), respectively. CONCLUSION: Dose-response relationships were found and modelled for the HCC and MET patient groups, with a higher dose required to control MET tumours. RT offers better local control for HCC than for MET colorectal liver tumours at our institution. ADVANCES IN KNOWLEDGE: An improved understanding of radiation dose-response relationships for primary and MET colorectal liver tumours will help inform future dose prescriptions.