Usefulness of prostate-specific antigen (PSA) rise as a marker of prostate cancer in men treated with dutasteride: lessons from the REDUCE study

Study Type – Prognostic (RCT) Level of Evidence 1b What's known on the subject? and What does the study add? Previous studies used the decrease in PSA after 6 months of dutasteride treatment as a new ‘baseline’ PSA value from which subsequent rises may serve as a warning for prostate cancer; however, PSA tends to continue to decrease as dutasteride treatment continues. By comparing positive biopsy rates in the REDUCE study using any rise from nadir in the dutasteride arm and standard PSA decision criteria (NCCN) in the placebo arm, we demonstrated that the ability to detect prostate cancer and high grade prostate cancer is maintained with dutasteride treatment.

OBJECTIVES

? To determine if dutasteride‐treated men can be monitored safely and adequately for prostate cancer based on data from the Reduction by Dutasteride in Prostate Cancer Events (REDUCE) study. ? To analyse whether the use of treatment‐specific criteria for repeat biopsy maintains the usefulness of prostate‐specific antigen (PSA) level for detecting high grade cancers.

PATIENTS AND METHODS

? The REDUCE study was a randomized, double‐blind, placebo‐controlled investigation of whether dutasteride (0.5 mg/day) reduced the risk of biopsy‐detectable prostate cancer in men with a previous negative biopsy. ? The usefulness of PSA was evaluated using biopsy thresholds defined by National Comprehensive Cancer Network guidelines in the placebo group and any rise in PSA from nadir (the lowest PSA level achieved while in the study) in the dutasteride group. ? The number of cancers detected on biopsy in the absence of increased/suspicious PSA level as well as sensitivity, specificity, positive predictive value and negative predictive value for high grade prostate cancer detection were analysed by treatment group. ? Prostate cancer pathological characteristics were compared between men who did and did not meet biopsy thresholds.

RESULTS

? Of 8231 men randomized, 3305 (dutasteride) and 3424 (placebo) underwent at least one prostate biopsy during the study and were included in the analysis. ? If only men meeting biopsy thresholds underwent biopsy, 25% (47/191) of Gleason 7 and 24% (7/29) of Gleason 8–10 cancers would have been missed in the dutasteride group, and 37% (78/209) of Gleason 7 and 22% (4/18) Gleason 8–10 cancers would have been missed in the placebo group. ? In both groups, the incidence of Gleason 7 and Gleason 8–10 cancers generally increased with greater rises in PSA. ? Sensitivity of PSA kinetics was higher and specificity was lower for the detection of Gleason 7–10 cancers in men treated with dutasteride vs placebo. ? Men with Gleason 7 and Gleason 8–10 cancer meeting biopsy thresholds had greater numbers of positive cores, percent core involvement, and biopsy cancer volume vs men not meeting thresholds.

CONCLUSION

? Using treatment‐specific biopsy thresholds, the present study shows that the ability of PSA kinetics to detect high grade prostate cancer is maintained with dutasteride compared with placebo in men with a previous negative biopsy. ? The sensitivity of PSA kinetics with dutasteride was similar to (Gleason 8–10) or higher than (Gleason 7–10) the placebo group; however, biopsy decisions based on a single increased PSA measurement from nadir in the dutasteride group resulted in a lower specificity compared with using a comparable biopsy threshold in the placebo group, indicating the importance of confirmation of PSA measurements.     

The Impact of Intraoperative Cholangiography on Recurrent Pancreatitis and Biliary Complications in Patients with Gallstone Pancreatitis

Introduction

Although gallstone pancreatitis is initiated by the presence of stones in the common bile duct, the benefit associated with routine intraoperative cholangiography at the time of cholecystectomy in these patients is unclear. The purpose of this study, using population-based data, was to determine the impact of cholangiography on clinical outcomes after cholecystectomy for gallstone pancreatitis.

Methods

All patients who were admitted to hospital from January 1, 1997 to December 31, 2001 in Nova Scotia, Canada with pancreatitis who underwent cholecystectomy during the same admission were identified. The rates of recurrent pancreatitis and biliary complications after surgery were compared between patients who underwent cholecystectomy with intraoperative cholangiography ± common bile duct exploration and those who underwent cholecystectomy alone, using three linked administrative databases.

Results

Three hundred thirty-two patients were identified, 119 had cholangiography at the time of cholecystectomy and 213 did not. After a median follow-up of after 3.8?years, there was no difference in the rate of recurrent pancreatitis or biliary complications between those who had cholangiography ± common bile duct exploration at the time of surgery and those who did not; 13.4 versus 10.8?%, respectively (p?=?0.55).

Conclusions

These data suggest that intraoperative cholangiography does not improve outcomes after cholecystectomy for gallstone pancreatitis.     

The EMPOWER Study: Randomized, Prospective, Double-Blind, Multicenter Trial of Vagal Blockade to Induce Weight Loss in Morbid Obesity

Background

Intermittent, reversible intraabdominal vagal blockade (VBLOC? Therapy) demonstrated clinically important weight loss in feasibility trials. EMPOWER, a randomized, double-blind, prospective, controlled trial was conducted in USA and Australia.

Methods

Five hundred three subjects were enrolled at 15 centers. After informed consent, 294 subjects were implanted with the vagal blocking system and randomized to the treated (n?=?192) or control (n?=?102) group. Main outcome measures were percent excess weight loss (percent EWL) at 12?months and serious adverse events. Subjects controlled duration of therapy using an external power source; therapy involved a programmed algorithm of electrical energy delivered to the subdiaphragmatic vagal nerves to inhibit afferent/efferent vagal transmission. Devices in both groups performed regular, low-energy safety checks. Data are mean ± SEM.

Results

Study subjects consisted of 90?% females, body mass index of 41?±?1?kg/m², and age of 46?±?1?years. Device-related complications occurred in 3?% of subjects. There was no mortality. 12-month percent EWL was 17?±?2?% for the treated and 16?±?2?% for the control group. Weight loss was related linearly to hours of device use; treated and controls with ??12?h/day use achieved 30?±?4 and 22?±?8?% EWL, respectively.

Conclusions

VBLOC? therapy to treat morbid obesity was safe, but weight loss was not greater in treated compared to controls; clinically important weight loss, however, was related to hours of device use. Post-study analysis suggested that the system electrical safety checks (low charge delivered via the system for electrical impedance, safety, and diagnostic checks) may have contributed to weight loss in the control group.     

Neoadjuvant therapy of renal cell carcinoma: A novel treatment option in the era of targeted therapy?

The study was carried out to evaluate the effectiveness, toxicity and optimal duration of neoadjuvant therapy for patients with organ‐confined or locally advanced renal cell carcinoma in the era of targeted agents. A literature review was carried out using Medline/Pubmed articles, as well as congress reports from the last five American Society of Clinical Oncology, American Urological Association and European Association of Urology Annual Meetings. Neoadjuvant targeted therapy is feasible and shows toxicity similar to that seen in a palliative setting. Most studies recommend an application for 2–4 months. The current data situation is best for sunitinib. Surgery can apparently be carried out the day right after discontinuing the drug. However, even sunitinib leads to only a mean 10% decrease in primary tumor size, and one‐quarter to one‐fifth of all patients show local tumor progression during treatment. Few patients (approximately 12%) with a vena cava tumor thrombus achieve a significant decrease in its level under neoadjuvant therapy; here too, progression is observed in a significant number of cases. Even the new targeted agents show limited effectiveness in achieving relevant remissions of the primary tumor. Furthermore, tumor progression is seen in a significant percentage of patients during neoadjuvant therapy. Thus, even today in the era of targeted agents, a neoadjuvant approach should only be made in patients with localized or locally advanced renal cell carcinoma, which primarily seem to be absolutely inaccessible by (partial) nephrectomy.     

Active surveillance of small renal masses offers short‐term oncological efficacy equivalent to radical and partial nephrectomy

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Active surveillance of small renal masses has traditionally been reserved for elderly patients deemed unfit for surgery or ablation. There is increasing evidence showing the safety of active surveillance in the management of small renal masses. In this retrospective study we compared outcomes for patients with small renal masses managed with active surveillance, radical nephrectomy and partial nephrectomy. We showed that active surveillance was safe and appeared as effective as immediate surgery in the management of small renal tumours.

OBJECTIVE

• ? To compare the oncological outcomes of active surveillance (AS), radical nephrectomy (RN) and partial nephrectomy (PN) in the management of T1a small renal masses (SRMs).

PATIENTS AND METHODS

• ? At present AS is used in the treatment of SRMs in elderly patients with multiple co‐morbidities or in those who decline surgery.
• ? We identified all patients with T1a SRMs managed with RN, PN or AS.
• ? Retrospective data were collected from patient case records with survival data and cause of death cross‐referenced with the Oxford Cancer Intelligence Unit.

RESULTS

• ? A total of 202 patients with 234 T1a SRMs (solid or Bosniak IV) were identified; 71 patients were managed with AS, 41 with an RN and 90 by PN.
• ? Over a median follow‐up of 34 months the mean growth rate on AS was 0.21 cm/year with 53% of SRMs managed with AS showing negative or zero growth.
• ? No statistically significant difference was observed in overall (OS) and cancer‐specific (CSS) survival for AS, RN and PN (AS‐CSS 98.6%, AS‐OS 83%; RN‐CSS 92.6%, RN‐OS 80.4%; PN‐CSS 96.6%, PN‐OS 90.0%).

CONCLUSIONS

• ? Active surveillance of SRMs offers oncological efficacy equivalent to surgery in the short/intermediate term.
• ? The results of this study support a multicentre prospective randomized controlled trial designed to compare the oncological efficacy of AS and surgery.

     

Contralateral hip fractures and other osteoporosis-related fractures in hip fracture patients: incidence and risk factors. An observational cohort study of 1,229 patients

Purpose

To report risk factors, 1-year and overall risk for a contralateral hip and other osteoporosis-related fractures in a hip fracture population.

Methods

An observational study on 1,229 consecutive patients of 50?years and older, who sustained a hip fracture between January 2005 and June 2009. Fractures were scored retrospectively for 2005–2008 and prospectively for 2008–2009. Rates of a contralateral hip and other osteoporosis-related fractures were compared between patients with and without a history of a fracture. Previous fractures, gender, age and ASA classification were analysed as possible risk factors.

Results

The absolute risk for a contralateral hip fracture was 13.8?%, for one or more osteoporosis-related fracture(s) 28.6?%. First-, second- and third-year risk for a second hip fracture was 2, 1 and 0?%. Median (IQR) interval between both hip fractures was 18.5 (26.6) months. One-year incidence of other fractures was 6?%. Only age was a risk factor for a contralateral hip fracture, hazard ratio (HR) 1.02 (1.006–1.042, p?=?0.008). Patients with a history of a fracture (33.1?%) did not have a higher incidence of fractures during follow-up (16.7?%) than patients without fractures in their history (14?%). HR for a contralateral hip fracture for the fracture versus the non-fracture group was 1.29 (0.75–2.23, p?=?0.360).

Conclusion

The absolute risk of a contralateral hip fracture after a hip fracture is 13.8?%, the 1-year risk was 2?%, with a short interval between the 2 hip fractures. Age was a risk factor for sustaining a contralateral hip fracture; a fracture in history was not.     

The role of endoscopic ultrasound in assessing tumor response and staging after neoadjuvant chemotherapy for esophageal cancer

Background  

Although the role of endoscopic ultrasound (EUS) in the initial staging of esophageal cancer is well established, its role in assessing tumor response and staging esophageal cancers after neoadjuvant chemotherapy (NAC) is controversial, and this study aimed to investigate this role.     

Osteolysis following resorbable poly-<Emphasis Type="SmallCaps">l</Emphasis>-lactide-co-<Emphasis Type="SmallCaps">d</Emphasis>, <Emphasis Type="SmallCaps">l</Emphasis>-lactide PLIF cage use: a review of cases

Study design  

Report of case series     

Arthroscopic bone tunnel augmentation for rotator cuff repair

Transosseous repair of the rotator cuff has been shown to recreate the anatomic rotator cuff footprint in a secure and cost-efficient manner. However, the potential for sutures cutting through bone remains a concern with this strategy. Devices have been used successfully during open transosseous rotator cuff repair to augment the bone tunnels, potentially avoiding suture cut-out through the weak bone of the greater tuberosity. Recently, arthroscopic transosseous fixation of rotator cuff tears has become an alternative to arthroscopic suture anchor and open transosseous techniques. This method is expected to have the same potential pitfalls at the bone-suture interface as the open technique. The authors describe a technique for rotator cuff repair using a secure method of arthroscopic bone tunnel augmentation.     

Mechanical loading with or without weight-bearing activity: influence on bone strength index in elite female adolescent athletes engaged in water polo, gymnastics, and track-and-field

Bone health is considered not to benefit from water-based sports because of their weight-supported nature, but available evidence primarily relies on DXA technology. Our purpose was to investigate musculoskeletal health in the upper and lower body in well-trained adolescent female athletes using pQCT and compare these athletes with less-active, age- and sex-matched peers. Bone mineral content, volumetric cortical and trabecular BMD, total and cortical area, and bone strength index were assessed at the distal and proximal tibia and radius in four groups of adolescent females (mean age, 14.9?years) including water polo players (n?=?30), gymnasts (n?=?25), track-and-field athletes (n?=?34), and nonactive controls (n?=?28). Water polo players did not show any benefit in bone strength index or muscle size in the lower leg when compared with controls. In contrast, gymnasts showed 60.1?% and 53.4?% greater bone strength index at the distal and proximal tibia, respectively, than nonactive females (p?相似文献