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Dutasteride, an inhibitor of 5α-reductase in the prostate, was tested in a large, randomized trial to determine its ability to prevent prostate cancer. Over the 4 years of the trial, dutasteride, as compared with placebo, reduced the relative risk of biopsy-detected prostate cancer by 23%. The reduction was limited mainly to tumors with Gleason scores of 5 or 6; by year 4, there were 12 tumors with Gleason scores of 8 to 10 in the dutasteride group but only 1 in the placebo group. Dutasteride, an inhibitor of 5α-reductase in the prostate, reduced the relative risk of biopsy-detected prostate cancer by 23%; however, the reduction was limited mainly to tumors with Gleason scores of 5 or 6. The 5α-reductase inhibitors that are used to treat benign prostatic hyperplasia block the conversion of testosterone to dihydrotestosterone and may reduce the risk of prostate cancer. 1 The results of the Prostate Cancer Prevention Trial showed that finasteride, as compared with placebo, reduced the risk of prostate cancer by 25%, but among the tumors that were detected, there was a 27% increase in the number of those that had Gleason scores of 7 to 10. 2 (The Gleason score is the sum of the two most common histologic patterns or grades in a prostate tumor, each of which is graded on a . . .

Abstract Objectives Nodular regenerative hyperplasia (NRH) is a rare vascular disorder of the liver. Clinically, patients present with portal hypertension with or without a cholestatic pattern of injury. Histologically, the liver parenchyma is composed of small nodules of hypertrophic hepatocytes surrounded by atrophic hepatocytes without significant fibrosis. Nodular regenerative hyperplasia is a difficult diagnosis on biopsy specimens, but biopsy remains the gold standard for diagnosis. In this retrospective review, cytokeratin 7 (CK7) immunohistochemistry (IHC) was used to aid in the diagnosis and further characterization of NRH and NRH-like changes. Methods The H&E-stained slides, reticulin, and CK IHC were reviewed for 22 cases. The percentage of hepatocytes staining for CK7 (0%-100%), the location of staining (centrilobular hepatic progenitor cells vs periportal/bile ductular reaction), and the pattern of staining distribution (patchy or diffuse) were recorded for comparison. Results Of the 22 cases, 9 were CK7 positive. Cases of NRH, however, expressed various degrees of CK7 positivity in centrilobular hepatic progenitor cells, unlike NRH-like changes, which were either CK7 negative or CK7 positive in periportal hepatocytes or in areas of bile ductular reaction. Conclusions In cases with the appropriate clinical history and histology, CK7 immunohistochemistry can be performed to distinguish nodular regenerative hyperplasia (primary) and NRH-like changes (secondary). In difficult cases, CK7 positivity in centrilobular hepatic progenitor cells can help confirm the diagnosis of NRH. These data support NRH as a true entity with a distinct pathophysiology from NRH-like changes.

Background: Preclinical studies in endometrial cancer (EC) show that metformin reduces cellular proliferation by PI3K-AKT-mTOR inhibition. We tested the hypothesis that short-term presurgical metformin reduces cellular proliferation in atypical endometrial hyperplasia (AEH) and endometrioid EC, and assessed the feasibility of using phosphorylated PI3K-AKT-mTOR proteins as tissue end points. Methods: Women with AEH or EC received metformin 850 mg twice a day or no drug in the presurgical window between diagnosis and hysterectomy. Before and after the window, tissue samples were obtained; serum markers of insulin resistance (e.g. homeostasis model of assessment of insulin resistance index) were determined; and anthropometrics measured (e.g. BMI). Cell proliferation (Ki-67) and PI3K-AKT-mTOR phosphostatus were assessed by immunohistochemistry and scored blinded to treatment. Results: Twenty-eight metformin-treated and 12 untreated patients, well matched for age and BMI, completed the study. Metformin treatment (median 20 days, range 7–34) was associated with a 17.2% reduction in tumour Ki-67 (95% CI −27.4, −7.0, P =0.002), in a dose-dependent manner. Tumour PI3K-AKT-mTOR protein phosphostatus varied but the effects were not significant after adjusting for changes in controls. Conclusions: Short-term metformin was associated with reduced Ki-67 expression in EC. Changes in tumour PI3K-AKT-mTOR protein phosphostatus were seen in both groups. Future studies should address the variability attributed to different sampling techniques including devascularisation of the uterus at hysterectomy.

Abstract Objectives To assess congruence between World Health Organization (WHO) 1994 and endometrial intraepithelial neoplasia (EIN) classification systems of endometrial hyperplasia. Methods Systematic review and meta-analysis were performed by searching electronic databases for studies that classified endometrial hyperplasia according to both WHO 1994 and EIN systems. Congruence was based on the rate of specimens classified as EIN in WHO categories, which should be virtually 0.000 in nonatypical hyperplasia (NAH) and 1.000 in atypical hyperplasia (AH). Subgroup analyses were performed based on architecture complexity. Results Eight studies with 1,352 hyperplasias were included. Congruence with EIN criteria was fair in NAH (0.241) and moderate in AH (0.815). Subgroup analyses of NAH showed high congruence in simple NAH (0.065), null in complex NAH (0.517), null in simple AH (0.148), and high in complex AH (0.901). Conclusions WHO 1994 system is not congruent with the EIN system and cannot be directly translated into a dual classification.

The standard surgery for early-stage endometrial cancer is total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy, which is associated with substantial morbidity. Total laparoscopic hysterectomy (TLH) and bilateral salpingo-oophorectomy is less invasive and is assumed to be associated with lower morbidity, particularly in obese women. This study investigated the complication rate of TLH versus TAH in women with early-stage endometrial cancer. This randomised trial was done in 21 hospitals in the Netherlands, and 26 gynaecologists with proven sufficient skills in TLH participated. 283 patients with stage I endometrioid adenocarcinoma or complex atypical hyperplasia were randomly allocated (2:1) to the intervention group (TLH, n=187) or control group (TAH, n=96). Randomisation by sequential number generation was done centrally in alternate blocks of six and three participants, with stratification by trial centre. After assignment, the study coordinators, patients, gynaecologists, and members of the panel were not masked to intervention. The primary outcome was major complication rate, assessed by an independent panel. Data were analysed by a modified intention-to-treat analysis, since two patients in both groups were excluded from the main analysis. This trial is registered with the Dutch trial registry, number NTR821. The proportion of major complications was 14·6% (27 of 185) in the TLH group versus 14·9% (14 of 94) in the TAH group, with a difference of −0·3% (95% CI −9·1 to 8·5; p=0·95). The proportion of patients with an intraoperative major complication (nine of 279 [3·2%]) was lower than the proportion with a postoperative major complication (32 of 279 [11·5%]) and did not differ between TLH (five of 185 [2·7%]) and TAH (four of 94 [4·3%]; p=0·49). The proportion of patients with a minor complication was 13·0% (24 of 185) in the TLH group and 11·7% (11 of 94) in the TAH group (p=0·76). Conversion to laparotomy occurred in 10·8% (20 of 185) of the laparoscopic procedures. TLH was associated with significantly less blood loss (p<0·0001), less use of pain medication (p<0·0001), a shorter hospital stay (p<0·0001), and a faster recovery (p=0·002), but the procedure took longer than TAH (p<0·0001). Our results showed no evidence of a benefit for TLH over TAH in terms of major complications, but TLH (done by skilled surgeons) was beneficial in terms of a shorter hospital stay, less pain, and quicker resumption of daily activities. The Dutch Organization for Health Research and Development (ZonMw), programme efficacy.

To evaluate safety and efficacy of one- vs. two-session radiofrequency ablation (RFA) of parathyroid hyperplasia for patients with secondary hyperparathyroidism (SHPT) and to compare the outcome of both methods on hypocalcemia. Patients with secondary hyperparathyroidism underwent ultrasound guided RFA of parathyroid hyperplasia. Patients were alternately assigned to either group 1 (n = 28) with RFA of all 4 glands in one session or group 2 (n = 28) with RFA of 2 glands in a first session and other 2 glands in a second session. Serum parathyroid hormone (PTH), calcium, phosphorus and alkaline phosphatase (ALP) values were measured at a series of time points after RFA. RFA parameters, including operation duration and ablation time and hospitalization length and cost, were compared between the two groups. Mean PTH decreased in group 1 from 1865.18 ± 828.93 pg/ml to 145.72 ± 119.27 pg/ml at 1 day after RFA and in group 2 from 2256.64 ± 1021.72 pg/ml to 1388.13 ± 890.15 pg/ml at 1 day after first RFA and to 137.26 ± 107.12 pg/ml at 1 day after second RFA. Group 1’s calcium level decreased to 1.79 ± 0.31 mmol/L at day 1 after RFA and group 2 decreased to 1.89 ± 0.26 mmol/L at day 1 after second session RFA (P < 0.05). Multivariate analysis showed that hypocalcemia was related to serum ALP. Patients with ALP ≥ 566 U/L had lower calcium compared to patients with ALP < 566 U/L up to a month after RFA (P < 0.05). Group 1’s RFA time and hospitalization were shorter and had lower cost compared with Group 2. US-guided RFA of parathyroid hyperplasia is a safe and effective method for treating secondary hyperparathyroidism. Single-session RFA was more cost-effective and resulted in a shorter hospital stay compared to two sessions. However, patients with two-session RFA had less hypocalcemia, especially those with high ALP.

PurposeTo compare the perioperative and functional outcomes of holmium laser enucleation of the prostate (HoLEP) and thulium laser enucleation of the prostate (ThuLEP) for the treatment of large-volume benign prostatic hyperplasia (BPH) (> 80 ml).MethodsA total of 116 consecutive patients with BPH were randomized to be treated surgically with either HoLEP (n = 58) or ThuLEP (n = 58), following the classical three-lobe enucleation technique. Follow-up was assessed at 1, 3, 6, 12 and 18 months after surgery.ResultsAt 18 months, the lower urinary tract symptom index was improved significantly in both groups compared with the baseline values. The operative time (78.4 ± 8.0 vs. 71.4 ± 6.4 min) and enucleation time (61.2 ± 5.4 vs. 56.4 ± 8.4 min) were significantly shorter for ThuLEP compared to HoLEP (both p < 0.001). There were no significant differences between the two groups regarding morcellation time, resected weight, hemoglobin decrease, catheter time and hospital stay (p > 0.05). The HoLEP and ThuLEP groups had equivalent International Prostate Symptom Scores (3 [3–3] vs. 3 [3–3], p = 0.776), quality of life (1 [1–2] vs. 2 [1–2], p = 0.809), Qmax (25.3 ± 4.8 ml/s vs. 24.7 ± 4.4 ml/s, p = 0.470), postvoid residual urine (PVR) (6.1 [2.6–20.8] vs. 7.7 [3.1–22.8] ml, p = 0.449) and PSA (0.84 ± 0.32 vs. 0.90 ± 0.34 ml, p = 0.309) at 18 months postoperatively.ConclusionBoth HoLEP and ThuLEP relieve lower urinary tract symptoms in a comparable way with high efficacy and safety. ThuLEP was statistically superior to HoLEP in operation time and enucleation time, although the differences were clinically negligible.

Evidence indicating Prostatic Urethral Lift (PUL) delivers significant improvement in symptomatic BPH with low morbidity is based on subjects with lateral lobe (LL) enlargement only. MedLift was an FDA IDE extension of the L.I.F.T. randomized study designed to examine safety and efficacy of PUL for treatment of obstructive middle lobes (OML). Inclusion criteria for this non-randomized cohort were identical to the L.I.F.T. randomized study, except for requiring an OML: ≥ 50 years of age, IPSS ≥ 13, and Qmax ≤ 12 ml/s. Primary endpoint analysis quantified improvement in IPSS over baseline and rate of post-procedure serious complications. Quantification of symptom relief, quality of life, flow rate, and sexual function occurred through 12 months. Outcomes were compared to historical L.I.F.T LL results and were combined to demonstrate the full effectiveness of PUL. Of the 71 screened subjects, 45 were enrolled. At 1, 3, 6, and 12 months, mean IPSS improved from baseline at least 13.5 points (p < 0.0001). Quality of life and BPHII were similarly improved (>60% and >70%, respectively at 3, 6, and 12 months, p < 0.0001). Mean Qmax improvement ranged from 90 to 129% (p < 0.0001). At 1 month, 86% (CI 73–94%) reported ≥70 on the Quality of Recovery scale, 80% (CI 66–89%) reported being “much” or “very much better,” and 89% (CI 76–95%) would recommend the procedure. Compared to LL subjects, OML subjects’ symptoms improved at least as much at every time point (OML range 13.5–15.9, LL range 9.9–11.1, p ≤ 0.01). On combining OML with LL data, >70% (range CI 63–81%) of subjects demonstrated ≥ 8 point improvement in IPSS through 12 months. Analysis of the combined dataset indicates ≥ 40% (CI 30–51%) of sexually active men improved the minimal clinically important difference in erectile function through 12 months. Prostates, including those with middle lobe obstruction, can be treated with the PUL procedure safely and effectively.

Proton pump inhibitors (PPIs) are frequently prescribed in combination with clopidogrel, but conflicting data exist as to whether PPIs diminish the efficacy of clopidogrel. We assessed the association between PPI use and clinical outcomes for patients treated with percutaneous coronary intervention (PCI) and dual-antiplatelet therapy (DAPT) with clopidogrel plus aspirin. In the PRODIGY trial, 1,970 patients were randomized to 6- or 24-month DAPT at 30 days from index procedure. Among them, 738 patients (37.5%) received PPI (mainly lansoprazole; 90.1%) at the time of randomization. Proton pump inhibitor users were older, were most likely to be woman, had a lower creatinine clearance, presented more frequently with acute coronary syndrome, and had a higher CRUSADE bleeding score. After adjustment, the primary efficacy end point (composite of all-cause death, myocardial infarction, and cerebrovascular accident) was similar between no PPI and PPI users (9.2% vs 11.5%, adjusted hazard ratio [HR] 1.051, 95% CI 0.788-1.400, P = .736). Bleeding rates did not differ between the 2 groups (Bleeding Academic Research Consortium type 2, 3, or 5: adjusted HR 0.996, 95% CI 0.672-1.474, P = .980). Net clinical adverse events were also similar in no PPI and PPI patients (12.9% vs 14.9%, adjusted HR 0.99, 95% CI 0.772-1.268, P = .93). Results remained consistent at sensitivity analysis when focusing on the 548 patients who remained on PPI for the whole study duration. The current findings suggest that the concomitant use of PPIs, when clinically indicated, in patients receiving clopidogrel is not associated with adverse clinical outcome.

To evaluate the effects of electroacupuncture (EA) on the International Prostate Symptom Score (IPSS), postvoid residual urine (PVR), and maximum urinary flow rate (Qmax), and explore the difference between EA at acupoints and non-acupoints in patients with moderate to severe benign prostate hyperplasia (BPH). Men with BPH and IPSS ≥8 were enrolled. Participants were randomly allocated to receive EA at acupoint (treatment group, n = 50) and EA at non-acupoint (control group, n = 50). The primary outcome measure includes the change of IPSS at the 6th week and the secondary outcome measures include changes of PVR and Qmax at the 6th week and change of IPSS at the 18th week. 100/192 patients were included. At the 6th week, treatment group patients had a 4.51 (p<0.001) and 4.12 (p<0.001) points greater decline in IPSS than the control group in the intention to treat (ITT) and per-protocol (PP) populations. At the 18th week, a 3.2 points (p = 0.001) greater decline was found in IPSS for the treatment. No significant differences were found between the two groups in Qmax at the 6th week (p = 0.819). No significant difference was observed in PVR (P = 0.35). Acupoint EA at BL 33 had better effects on IPSS, but no difference on PVR and Qmax as compared with non-acupoint EA. The results indicate that EA is effective in improving patient's quality of life and acupoint may have better therapeutic effects than non-acupoints in acupuncture treatments of BPH. ClinicalTrials.gov NCT01218243.