Data on urothelial malignancies and UTUC were searched using the following keywords: urinary tract cancer; urothelial carcinomas; upper urinary tract, carcinoma; renal pelvis; ureter; bladder cancer; chemotherapy; ureteroscopy; nephroureterectomy; adjuvant treatment; instillation; recurrence; risk factors; and survival. References were weighted by a panel of experts AbstractText: Owing to the rarity of UTUC, there are insufficient data to provide strong recommendations ...
Abstract: BackgroundCisplatin-based combination chemotherapy is the standard treatment for advanced urinary tract cancer (aUTC) but 50% of patients are ineligible for cisplatin according to recently published criteria. We used a multinational database to study patterns of chemotherapy utilization in patients with aUTC and determine their impact on survival.Patients and MethodsThis was a retrospective study of patients with: UTC ...
Studies are mixed regarding the efficacy of antibiotic prophylaxis for UTI prevention... develop and evaluate an evidence-based protocol that reduces unnecessary antibiotic use while avoiding an increase in UTI AbstractText: A clinic antibiogram was created based on all urology ... effectively risk stratifies patients before cystourethroscopy, decreasing the use of antibiotics without increasing rates of symptomatic UTI Keyword: Antibiotic Prophylaxis.
... either chemotherapy (eight and three, respectively) or study drug (none and four, respectively) AbstractText: We noted no survival benefit in men with metastatic castration-resistant prostate cancer with the addition of custirsen to cabazitaxel and prednisone treatment. Cabazitaxel and prednisone remains the standard of care for patients with metastatic castration-resistant prostatecancer progressing after docetaxel chemotherapy AbstractText: OncoGenex Pharmaceuticals.
... resulted in antibiotic treatment AbstractText: To prevent excessive use of antibiotics, dipslide possibly supported by a combination of nitrite and leukocyte esterase tests can be used. Trained frontline health care professionals correctly diagnosed E. coli UTI and negative urine cultures, which would help preventing antibiotic misuse. In addition, regular screening for antibiotic resistance would improve correct treatment Keyword: E. coli.
BACKGROUND: Endometrial cancer is one of the most common gynaecological cancers in the world. Rates of endometrial cancer are rising, in part because of rising obesity rates. Endometrial hyperplasia is a precancerous condition in women that can lead to endometrial cancer if left untreated. Endometrial hyperplasia occurs more commonly than endometrial cancer. Progesterone tablets currently used to treat women with endometrial hyperplasia are associated with adverse effects in up to 84% of women. The levonorgestrel intrauterine device (Mirena Coil, Bayer HealthCare Pharmaceuticals, Inc., Whippany, NJ, USA) may improve compliance, but it is invasive, is not acceptable to all women, and is associated with irregular vaginal bleeding in 82% of cases. Therefore, an alternative treatment for women with endometrial hyperplasia is needed. Metformin, a drug that is often used to treat people with diabetes, has been shown in some human studies to reverse endometrial hyperplasia. However, the effectiveness and safety of metformin for treatment of endometrial hyperplasia remain uncertain.
OBJECTIVES: To determine the effectiveness and safety of metformin in treating women with endometrial hyperplasia.
SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), PubMed, Google Scholar, OpenGrey, Latin American Caribbean Health Sciences Literature (LILACS), and two trials registers from inception to 10 January 2017. We searched the bibliographies of all included studies and reviews on this topic. We also handsearched the conference abstracts of the European Society of Human Reproduction and Embryology (ESHRE) 2015 and the American Society for Reproductive Medicine (ASRM) 2015.
SELECTION CRITERIA: We included randomised controlled trials (RCTs) and cross-over trials comparing metformin (used alone or in combination with other medical therapies) versus placebo or no treatment, any conventional medical treatment, or any other active intervention for women with histologically confirmed endometrial hyperplasia of any type.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for eligibility, extracted data from included studies, and assessed the risk of bias of included studies. We resolved disagreements by discussion or by deferment to a third review author. When study details were missing, review authors contacted study authors. The primary outcome of this review was regression of endometrial hyperplasia histology (with or without atypia) towards normal histology. Secondary outcome measures included recurrence of endometrial hyperplasia, progression of endometrial hyperplasia to endometrial cancer, hysterectomy rate, abnormal uterine bleeding, health-related quality of life, and adverse effects during treatment.
MAIN RESULTS: We included three RCTs in which a total of 77 women took part. We rated the quality of the evidence as very low for all outcomes owing to very serious risk of bias (associated with poor reporting, attrition, and limitations in study design) and imprecision.We performed a meta-analysis of two trials with 59 participants. When metformin was compared with megestrol acetate in women with endometrial hyperplasia, we found insufficient evidence to determine whether there were differences between groups for the following outcomes: regression of endometrial hyperplasia histology towards normal histology (odds ratio (OR) 3.34, 95% confidence interval (CI) 0.97 to 11.57, two RCTs, n = 59, very low-quality evidence), hysterectomy rates (OR 0.91, 95% CI 0.05 to 15.52, two RCTs, n = 59, very low-quality evidence), and rates of abnormal uterine bleeding (OR 0.91, 95% CI 0.05 to 15.52, two RCTs, n = 44 , very low-quality evidence). We found no data for recurrence of endometrial hyperplasia or health-related quality of life. Both studies (n = 59) provided data on progression of endometrial hyperplasia to endometrial cancer as well as one (n = 16) reporting some adverse effects in the metformin arm, notably nausea, thrombosis, lactic acidosis, abnormal liver and renal function among others.Another trial including 16 participants compared metformin plus megestrol acetate versus megestrol acetate alone in women with endometrial hyperplasia. We found insufficient evidence to determine whether there were differences between groups for the following outcomes: regression of endometrial hyperplasia histology towards normal histology (OR 9.00, 95% CI 0.94 to 86.52, one RCT, n = 16, very low-quality evidence), recurrence of endometrial hyperplasia among women who achieve regression (OR not estimable, no events recorded, one RCT, n = 8, very low-quality evidence), progression of endometrial hyperplasia to endometrial cancer (OR not estimable, no events recorded, one RCT, n = 13, very low-quality evidence), or hysterectomy rates (OR 0.29, 95% CI 0.01 to 8.37, one RCT, n = 16, very low-quality evidence). Investigators provided no data on abnormal uterine bleeding or health-related quality of life. In terms of adverse effects, three of eight participants (37.5%) in the metformin plus megestrol acetate study arm reported nausea.
AUTHORS' CONCLUSIONS: At present, evidence is insufficient to support or refute the use of metformin alone or in combination with standard therapy - specifically, megestrol acetate - versus megestrol acetate alone, for treatment of endometrial hyperplasia. Robustly designed and adequately powered randomised controlled trials yielding long-term outcome data are needed to address this clinical question.
Oncology (7), Endocrine Disorders (1), Anti-Obesity and Weight Loss (1) Endometrial Hyperplasia (21), Endometrial Carcinoma (7), Uterine Hemorrhage (3), more mentions
... under-treatment of resistant infections AbstractText: To characterize risk factors for antibiotic-resistant community urine isolates using routine record-linked health data AbstractText: Within the NHS ... previous hospitalizations, antibiotic exposure and resistant (any antibiotic) or MDR (≥1 antibiotic from ≥3 categories) urinary isolates were quantified using multivariable logistic regression AbstractText: Of 40 984 ...
... 2004, and is now standard of care for late stage disease. Recent clinical studies demonstrated that patients with metastatic castration-sensitive disease, and possibly those with high-risk localized prostate cancer also benefit from docetaxel administration, expanding the role of chemotherapy in the prostatecancer treatment landscape. Another taxane, cabazitaxel, is approved for post-docetaxel metastatic castration-resistant prostate cancer.
AbstractText: To characterize antibiotic regimens utilized for bacteremic Enterobacteriaceae urinary tract infections and assess treatment failure associated with intravenous-only compared ... failure in patients who received intravenous-only antibiotics versus intravenous/oral antibiotics for the treatment of bacteremic urinary tract infections (intravenous-only 3.8% [95% CI: 1.0-9.4%] failure; intravenous ...
... TEAE) was similar in the tasquinimod and placebo arms (97.2% versus 94.3%, respectively), whereas severe TEAEs (NCI-CTC Grade 3-5) incidence was higher in the tasquinimod group (50.7% versus 27.1%) AbstractText: Randomized trials testing new drugs as maintenance can be successfully conducted after chemotherapy in castrate-resistant prostatecancer.
Oncology (5) Prostatic Neoplasms (4), Neoplasms (1), more mentions
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... classes were significantly associated with xerostomia and salivary gland hypofunction AbstractText: Medication use was significantly associated with xerostomia and salivary gland hypofunction in older adults. The risk of dry mouth was greatest for drugs used for urinary incontinence. Future research should develop a risk score for medication-induced dry mouth to assist with prescribing and medication management Keyword: dry mouth.
Urology (1) Xerostomia (4), Urinary Incontinence (1), more mentions
BACKGROUND: In the COU-AA-302 study (NCT00887198), abiraterone acetate plus prednisone (AAP) significantly improved outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC) versus prednisone alone. Baseline clinical parameters predicting that treatment response could help inform clinical decisions were explored.
OBJECTIVE: To identify patients who derive the greatest clinical benefit from AAP treatment.
DESIGN, SETTING, AND PARTICIPANTS: A total of 1088 mCRPC patients treated with either AAP or prednisone in the first-line setting in COU-AA-302 were included in this post hoc analysis.
INTERVENTION: Abiraterone acetate1000mg daily versus placebo, both plus prednisone 10mg daily.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Univariate and multivariable Cox regression analyses were performed, including clinical and pathological parameters for the primary end points overall survival (OS) and radiographic progression-free survival (rPFS), and secondary study end points. Tumor-associated baseline parameters independently impacting OS were applied to stratify patients according to possible treatment effects.
RESULTS AND LIMITATIONS: Baseline prostate-specific antigen (PSA), tumor-related pain as assessed by the Brief Pain Inventory-Short Form (BPI-SF), and Gleason score (GS) at primary diagnosis were identified as tumor-associated variables that independently impacted OS. AAP significantly improved outcomes versus prednisone in both group 1 (BPI-SF 0-1 and PSA <80 ng/ml and GS <8; p=0.006; hazard ratio [HR]: 0.61) and group 2 (BPI-SF 2-3 and/or PSA ≥80 ng/ml and/or GS ≥8; p=0.03; HR: 0.84). The differences observed for treatment effects between groups 1 and 2 for OS (HR: 0.61 vs 0.84), rPFS (HR: 0.41 vs 0.59), and time to chemotherapy (HR: 0.64 vs 0.71) were not statistically significant.
CONCLUSIONS: AAP significantly improved outcomes in mCRPC patients compared with prednisone alone regardless of baseline pain and PSA level, and GS at primary diagnosis with no significant differences between observed treatment effects in groups 1 and 2.
PATIENT SUMMARY: Treatment with abiraterone acetate and prednisone (compared with treatment with prednisone only) for metastatic castration-resistant prostate cancer increased survival in all patients in the study regardless of pain, prostate-specific antigen levels at the start of treatment, and Gleason score at primary diagnosis.
Oncology (3) Prostatic Neoplasms (3), Neoplasms (3), more mentions
Oral ulipristal acetate (Esmya(®); Fibristal(®)), a synthetic selective progesterone receptor modulator, is the first selective progesterone modulator to be approved for the treatment of uterine fibroids. It was initially approved for the preoperative treatment of moderate to severe uterine fibroid symptoms in women of reproductive age. Recently, the indication was extended in the EU to include the intermittent treatment of moderate to severe uterine fibroid symptoms. This narrative review summarizes pharmacological, efficacy and tolerability data relevant to the preoperative and intermittent use of ulipristal acetate in patients with symptomatic uterine fibroids. Ulipristal acetate is an effective and generally well tolerated treatment for patients with symptomatic uterine fibroids, both as preoperative, single-course treatment and as intermittent, longer-term treatment. It is noninferior in efficacy to intramuscular leuprolide acetate, as a preoperative treatment, and is associated with a lower rate of hot flashes, a common adverse event with gonadotropin-releasing hormone analogues. Thus, ulipristal acetate is an effective option for both preoperative and intermittent treatment of moderate to severe, symptomatic uterine fibroids in women of reproductive age.
In this review, we describe current therapies for mCRPC, the rationale for anti-PARP therapies, the pharmacology of olaparib for prostatecancer, clinical trials of olaparib for mCRPC, our clinical experience with olaparib for prostate cancer at a comprehensive cancer center, and future directions of olaparib for the treatment of ...
Oncology (11) Prostatic Neoplasms (11), Neoplasms (1), more mentions
Since the first coronary angioplasty on Sept 16, 1977, the field of percutaneous coronary intervention has evolved rapidly. Now marking its 40th anniversary, percutaneous coronary intervention has become one of the most common medical procedures worldwide. Much of this progress has been due to the iteration and improvement of angioplasty technologies. Balloon angioplasty was limited by unpredictable procedural outcomes due to vessel dissection and recoil, and a high rate of restenosis. The introduction of stents resulted in more stable early results and lower rates of restenosis, although early stent thrombosis and neointimal hyperplasia causing vessel renarrowing were key limitations. Drug-eluting stents delivering antiproliferative agents significantly lowered the rates of restenosis, permitting widespread use of percutaneous coronary intervention in more advanced and complex disease. Although fully bioresorbable scaffolds have the potential to further improve long-term outcomes, they have not yet achieved results equivalent to those of conventional metallic drug-eluting stents in the early years after implantation. Progress in catheter technology did not occur in isolation, and the success of percutaneous coronary intervention is also due to important advances in intracoronary imaging, and adjunct pharmacotherapy-each of which is reviewed in other papers in this Series.
BACKGROUND: Androgen deprivation therapy (ADT) plus docetaxel is the standard of care in fit men with metastatic castration-naive prostate cancer (mCNPC) following results from GETUG-AFU 15, CHAARTED, and STAMPEDE. No data are available on the efficacy of treatments used for metastatic castration-resistant prostate cancer (mCRPC) in men treated upfront with ADT plus docetaxel for mCNPC.
OBJECTIVE: To investigate the efficacy and tolerance of subsequent treatments in patients treated upfront with chemo-hormonal therapy for mCNPC.
DESIGN, SETTING, AND PARTICIPANTS: Retrospective data from the GETUG-AFU 15 phase 3 trial were collected for treatments received for mCRPC.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: For the first three lines of salvage treatment for mCRPC we investigated the biochemical progression-free survival, maximum prostate-specific antigen (PSA) decline, overall survival, and tolerance.
RESULTS AND LIMITATIONS: Overall, 245 patients received at least one treatment for mCRPC. For docetaxel used in first-line, a PSA decline ≥50% was observed in 25/66 (38%) and in 4/20 patients (20%) who had received upfront ADT alone and ADT plus docetaxel (p=0.14). The median biochemical progression-free survival was 6.0 mo (95% confidence interval: 3.6-7.7) and 4.1 mo (95% confidence interval: 1.3-4.9), respectively. For docetaxel used in first- or second-line, a PSA decline ≥50% was observed in 36/80 (45%) and in 4/29 patients (14%) who had received upfront ADT alone and ADT plus docetaxel (p=0.07). PSA declines ≥50% were observed with bicalutamide in 12/28 (43%) and 4/23 patients (17%) who had received upfront ADT alone and ADT plus docetaxel. Among men treated upfront with ADT plus docetaxel who received abiraterone or enzalutamide for mCRPC, 10/19 patients (53%) achieved a PSA decline ≥50%. Few grade 3-4 events occurred. Study limitations include the observational design and retrospective characteristics of this analysis, without standardized therapeutic salvage protocols, and the limited number of patients in some of the treatment subgroups.
CONCLUSIONS: Docetaxel rechallenge following progression to mCRPC after upfront ADT plus docetaxel for mCNPC was active only in a limited number of patients. Available data on abiraterone and enzalutamide support maintained efficacy in this setting. The lack of standardized therapeutic protocols for men developing mCRPC limits the comparability between patients.
PATIENT SUMMARY: Rechallenging docetaxel at castration-resistance was active only in a limited number of patients treated upfront with chemo-hormonal therapy for metastatic castration-naive prostate cancer. Anticancer activity was suggested with abiraterone or enzalutamide in this setting.
Abstract: Broad-spectrum antibiotics for recurrent multidrug-resistant urinary tract infections (UTIs) disrupt the gut microbiome and promote antibiotic resistance. Fecal microbiota transplantation led to resolution of recurrent Clostridium difficile, significantly decreased recurrent UTI frequency, and improved antibiotic susceptibility profile of UTI-causing organisms Keyword: C. difficile infection. Keyword: fecal transplant.