Standardizing the definition of adverse pathology for lower risk men undergoing radical prostatectomy.

PURPOSE: Numerous definitions of adverse pathology at radical prostatectomy (RP) have been proposed and implemented for both research and clinical care, and there is tremendous variation in the specific criteria used to define adverse pathology in these settings. Given the current landscape in which magnetic resonance imaging criteria and biomarker cutoffs are validated for disparate adverse pathology definitions, we sought to identify which of these is most closely tied to biochemical recurrence (BCR) after RP. MATERIALS AND METHODS: A total of 2,837 patients who underwent RP at a single institution for localized prostate cancer (PCa) were included. We evaluated the following existing definitions of adverse pathology at RP: (1) Gleason score ≥7, (2) primary Gleason pattern ≥4, (3) Gleason score ≥7 or pathologic stage T3-4, (4) pathologic stage T3-4, (5) primary Gleason pattern ≥4 or pathologic stage T3-4. The primary outcome measure was BCR. Multiple statistical techniques were used to assess BCR prediction. RESULTS: Of the 5 definitions assessed, 1 (primary Gleason pattern ≥4 or pathologic stage T3-4, 540 patients [19% of cohort]) consistently outperformed the other definitions across all statistical measures. Additionally, a total of only 13 (6.6%) and 34 (10.3%) men with very-low-risk and low-risk cancer per National Comprehensive Cancer Network guideline, respectively, met this definition of adverse pathology at the time of RP. CONCLUSIONS: Varying definitions of adverse pathology differ in their prognostic performance. The criteria defined by either primary Gleason pattern ≥4 or pT3-4 disease appears to most accurately predict BCR in this subset of patients with lower risk PCa at the time of diagnosis. Additionally, men with very-low-risk or low-risk PCa per National Comprehensive Cancer Network guidelines are relatively unlikely to have adverse pathology at the time of surgical resection. These data may help inform the use of imaging and molecular markers as well as the intensity of surveillance in men with newly diagnosed PCa.

Baseline characteristics predict risk of progression and response to combined medical therapy for benign prostatic hyperplasia (BPH).

OBJECTIVE: To better risk stratify patients, using baseline characteristics, to help optimise decision-making for men with moderate-to-severe lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) through a secondary analysis of the Medical Therapy of Prostatic Symptoms (MTOPS) trial. PATIENTS AND METHODS: After review of the literature, we identified potential baseline risk factors for BPH progression. Using bivariate tests in a secondary analysis of MTOPS data, we determined which variables retained prognostic significance. We then used these factors in Cox proportional hazard modelling to: i) more comprehensively risk stratify the study population based on pre-treatment parameters and ii) to determine which risk strata stood to benefit most from medical intervention. RESULTS: In all, 3047 men were followed in MTOPS for a mean of 4.5 years. We found varying risks of progression across quartiles. Baseline BPH Impact Index score, post-void residual urine volume, serum prostate-specific antigen (PSA) level, age, American Urological Association Symptom Index score, and maximum urinary flow rate were found to significantly correlate with overall BPH progression in multivariable analysis. CONCLUSIONS: Using baseline factors permits estimation of individual patient risk for clinical progression and the benefits of medical therapy. A novel clinical decision tool based on these analyses will allow clinicians to weigh patient-specific benefits against possible risks of adverse effects for a given patient.

Symptomatic subcapsular and perinephric hematoma following ureteroscopic lithotripsy for renal calculi.

OBJECTIVE: Ureteroscopic lithotripsy (URSL) is believed to be associated with less risk of symptomatic renal hematoma than extracorporeal shockwave lithotripsy (SWL) and percutaneous nephrolithotomy (PCNL). We sought to document the rate of and risk factors for this rare complication following URSL for renal calculi. METHODS: With Institutional Review Board approval, we reviewed 1087 cases of URSL performed between July 2009 and October 2012 for four surgeons. We identified cases for renal calculi complicated by symptomatic "hematoma" by searching electronic medical records of patients undergoing URSL with a web-based search tool and cross-referencing with a departmental quality improvement database for postoperative complications. Chi-squared tests were used to assess risk factors. RESULTS: Among 877 renal units exposed to URSL for renal calculi, 4 were complicated by symptomatic subcapsular hematomas (SH) and 3 by symptomatic perinephric hematomas (PH), yielding a 0.5% and 0.3% rate for each complication, respectively. Pain was the primary presenting symptom. Almost all cases presented within 24 to 48 hours postop. Two PH patients required postoperative blood transfusion. Four patients (two SH, two PH) were hospitalized for observation. Ureteral sheaths were used in two cases (one PH and one SH). There was no association with age, diabetes, body mass index (BMI), or operative duration (p-values all>0.05). However, hematoma did correlate with female gender, preoperative hypertension, preoperative ureteral stenting, intraoperative ureteral sheath use, and postoperative ureteral stenting (all p-values<0.0001). CONCLUSIONS: While symptomatic hematoma is a complication of URSL, the rate of such outcome (0.8%) is far less than that reported by prior series with SWL and PCNL. This may partially be attributable to collection biases, where subclinical cases are not imaged, or anchoring biases, where clinicians attribute symptoms to another possible etiology. This outcome can be morbid, but can often be conservatively managed with observation.

Understanding the relationship between tumor size, gland size, and disease aggressiveness in men with prostate cancer.

OBJECTIVE: To determine the relationship between prostate gland and tumor volume in men undergoing radical prostatectomy (RP) for prostate cancer. We hypothesized that larger tumors within smaller prostate glands are associated with more aggressive disease characteristics. METHODS: Records of patients undergoing RP from 2000-2008 at a single institution were reviewed retrospectively. The dominant nodule was considered to be the largest focus of cancer within the prostate, and the dominant nodule-to-prostate volume ratio (DNVR) was calculated according to the ratio of the dominant nodule volume to the gland weight. Cox regression was performed to assess the relationship between DNVR and both pathologic outcomes (Cancer of the Prostate Risk Assessment post-Surgical score) and biochemical recurrence (BCR). RESULTS: At a median follow-up of 3.7 years, 174 patients (7.2%) suffered BCR. There was no linear correlation between tumor volume and gland size (R = -0.09). DNVR above the median (≥0.033 cc/gm) was closely associated with high clinicopathologic risk as measured by Cancer of the Prostate Risk Assessment post-Surgical score (hazard ratio, 35.53; 95% confidence interval, 14.42-87.55 for high- vs low-risk groups). In the univariable analysis, both tumor diameter and DNVR were associated with increased risk of BCR. However, in the multivariable model, only tumor diameter remained a significant predictor of BCR (hazard ratio, 2.02; 95% confidence interval, 1.04-3.91). CONCLUSION: Increased DNVR appears to be a characteristic of aggressive prostate tumors, although it did not predict BCR in the present study. However, these data support the association between tumor diameter and BCR after RP for prostate cancer independent of other key clinicopathologic features.

Molecular classification of the natural exudates of the rosids.

Exudates of the rosid clade of the eudicots have been surveyed and characterized by carbon-13 and proton nuclear magnetic resonance spectroscopy. Of 554 samples divided roughly equally between the subclades fabids and malvids, about two-fifths are resins, a third gums, one-ninth gum resins, one-twelfth kinos, and the remaining not affiliated with these four main molecular classes. Two small new molecular classes, respectively from the Clusiaceae (xanthics) and the Zygophyllaceae (guaiacs), are identified and described.

In a survey, marked inconsistency in how oncologists judged value of high-cost cancer drugs in relation to gains in survival.

Amid calls for physicians to become better stewards of the nation's health care resources, it is important to gain insight into how physicians think about the cost-effectiveness of new treatments. Expensive new cancer treatments that can extend life raise questions about whether physicians are prepared to make "value for money" trade-offs when treating patients. We asked oncologists in the United States and Canada how much benefit, in additional months of life expectancy, a new drug would need to provide to justify its cost and warrant its use in an individual patient. The majority of oncologists agreed that a new cancer treatment that might add a year to a patient's life would be worthwhile if the cost was less than $100,000. But when given a hypothetical case of an individual patient to review, the oncologists also endorsed a hypothetical drug whose cost might be as high as $250,000 per life-year gained. The results show that oncologists are not consistent in deciding how many months an expensive new therapy should extend a person's life before the cost of therapy is justified. Moreover, the benefit that oncologists demand from new treatments in terms of length of survival does not necessarily increase according to the price of the treatment. The findings suggest that policy makers should find ways to improve how physicians are educated on the use of cost-effectiveness information and to influence physician decision making through clinical guidelines that incorporate cost-effectiveness information.

A brief history of rejuvenation operations.

PURPOSE: We discuss the place in history of operative procedures for hormonal rejuvenation. MATERIALS AND METHODS: The scientific and historical literature was reviewed. RESULTS: In the early 20th century, building on the earlier work of Berthold and Brown-Séquard, Eugen Steinach developed a combination of vasectomy and vasoligature that became known as the Steinach operation. This procedure, along with testicular implantation popularized by Serge Voronoff, was an attempt to rejuvenate older and fatigued men around the world. The early experiments and results of Steinach, Voronoff and their followers were plagued by secrecy, subjectivity and sensationalism in an effort to produce the most scientific data. These rejuvenists used their results to outcompete one another. Ultimately the lack of verifiable outcome data and the chemical isolation of the "internal secretion" (testosterone) ended this era in surgery. CONCLUSIONS: Always a work in progress, the practice of medicine has been guided by human curiosity with trial, error and success. History records aberrant paths along the way and the rejuvenation movement was one such journey. While superseded by later knowledge, the efforts of the rejuvenists comprise an interesting chapter in the development of urology, endocrinology and transplant surgery.

How long and how well: oncologists' attitudes toward the relative value of life-prolonging v. quality of life-enhancing treatments.

OBJECTIVE: To determine how oncologists value quality-enhancing v. life-prolonging outcomes attributable to chemotherapy. METHODS: The authors surveyed a random sample of 1379 US medical oncologists (members of the American Society of Clinical Oncology), presenting them with 2 scenarios involving a hypothetical new chemotherapy drug. Given their responses, the authors derived the implicit cost-effectiveness ratios each physician attributed to quality-enhancing and life-prolonging chemotherapies. RESULTS: The authors received responses from 58% of the oncologists surveyed. On average, the responses implied that oncologists were willing to prescribe treatments that cost $245,972 per quality-adjusted life-year (QALY; SD $243,663 per QALY) in life-prolonging situations v. only $119,082 per QALY (SD $197,048 per QALY) for treatments that improve quality of life but do not prolong survival (P < 0.001). This difference did not depend on age, gender, percentage of time in clinical work, or self-reported preparedness to use and interpret cost-effectiveness information (P > 0.05 for all specifications). Differences across these situations persisted even among those who considered themselves to be "well-prepared" to make cost-effectiveness decisions. CONCLUSION: Cost-effectiveness thresholds for oncologists vary widely for life-prolonging chemotherapy compared to treatments that only enhance quality of life. This difference suggests that oncologists value length of survival more highly than quality of life when making chemotherapy decisions.

Distinctions among conifer exudates by proton magnetic resonance spectroscopy.

Proton nuclear magnetic resonance spectra have been recorded of exudates harvested from 12 species from the family Araucariaceae, 40 from the Cupressaceae, and one from the Podocarpaceae. These spectra were compared with the spectra previously recorded of 82 species from the Pinaceae. These four families together represent all major groups of extant, resin-bearing conifers. A common set of 10 COSY two-dimensional cross-peaks generally define samples from the Pinaceae, a different set of six peaks define the Araucariaceae, and yet a third set of 10 peaks define the Cupressaceae, with a few exceptions. It is important that proton spectra can distinguish the Araucariaceae and the Cupressaceae, since carbon-13 spectra do not. The one-dimensional peaks not only confirm these familial distinctions but also often characterize genus and species uniquely.

Proton nuclear magnetic resonance characterization of resins from the family pinaceae.

Proton magnetic resonance spectra were recorded for solutions of resinous materials harvested from 82 species in seven genera of the gymnospermous plant family Pinaceae. Data were recorded in both one and two (COSY) dimensions. Approximately 11 peaks in the 1D spectra and 10 cross-peaks in the 2D spectra were present in almost all pinacean spectra, providing a familial diagnostic. Some 40 1D peaks or peak clusters and 60 2D cross-peaks or clusters were considered significant and are reported, when present, for all species. Whereas previous solid-state 13C data were diagnostic primarily at the family level, the patterns of 1D and 2D peaks may provide diagnostic information at the genus and species levels. These spectra constitute the first broad use of 1H NMR to study plant exudates in general and to provide taxonomic characterization in particular.