Evaluation of markers out of the steroid profile for the screening of testosterone misuse. Part II: Intramuscular administration

In the fight against doping, the introduction of alternative markers to the steroid profile can be considered as an effective approach to improve the screening capabilities for the detection of testosterone (T) misuse. The aim of this study was to evaluate the potential of several T metabolites (cysteinyl conjugated and glucuronoconjugated resistant to enzymatic hydrolysis) to detect both the transdermal and the intramuscular administration of T. In Part I of the study, we studied the potential of these metabolites for the detection of T transdermal administration. Results revealed that resistant glucuronides can be a suitable complement to the current steroid profile. In this, Part II, dedicated to the intramuscular administration, we studied the potential of cysteinyl conjugated, resistant glucuronoconjugated and 1‐cyclopentenoylglycine (1‐CPG) for the detection of a single intramuscular injection of T cypionate. Possible differences in the excretion profile of all markers were explored between individuals with low basal (n=6) and medium basal (n=6) values of the testosterone/epitestosterone ratio (T/E). The results showed that all tested markers presented low intra‐individual stability in basal conditions. Despite this, all glucuronoconjugated markers and 1‐CPG, but not the cysteinyl conjugated markers, provided detection windows that were similar or longer than those obtained by markers currently included in the steroid profile. Based on the results obtained from the 2 parts of this study and from previously reported data, the potential applicability and the limitations of including these markers in the steroid profile are discussed.     

Cytoreductive Nephrectomy in Patients with Synchronous Metastases from Renal Cell Carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium

Background

The benefit of cytoreductive nephrectomy (CN) for overall survival (OS) is unclear in patients with synchronous metastatic renal cell carcinoma (mRCC) in the era of targeted therapy.

Objective

To determine OS benefit of CN compared with no CN in mRCC patients treated with targeted therapies.

Design, setting, and participants

Retrospective data from patients with synchronous mRCC (n = 1658) from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) were used to compare 982 mRCC patients who had a CN with 676 mRCC patients who did not.

Outcome measurements and statistical analysis

OS was compared and hazard ratios (HRs) adjusted for IMDC poor prognostic criteria.

Results and limitations

Patients who had CN had better IMDC prognostic profiles versus those without (favorable, intermediate, or poor in 9%, 63%, and 28% vs 1%, 45%, and 54%, respectively). The median OS of patients with CN versus without CN was 20.6 versus 9.5 mo (p < 0.0001). When adjusted for IMDC criteria to correct for imbalances, the HR of death was 0.60 (95% confidence interval, 0.52–0.69; p < 0.0001). Patients estimated to survive <12 mo may receive marginal benefit from CN. Patients who have four or more of the IMDC prognostic criteria did not benefit from CN. Data were collected retrospectively.

Conclusions

CN is beneficial in synchronous mRCC patients treated with targeted therapy, even after adjusting for prognostic factors. Patients with estimated survival times <12 mo or four or more IMDC prognostic factors may not benefit from CN. This information may aid in patient selection as we await results from randomized controlled trials.

Patient summary

We looked at the survival outcomes of metastatic renal cell carcinoma patients who did or did not have the primary tumor removed. We found that most patients benefited from tumor removal, except for those with four or more IMDC risk factors.     

Management of the Elderly Patients with High-Grade Serous Ovarian Cancer in the REAL-WORLD Setting

Treatment of elderly patients with neoplasia is challenging. Age is a known prognostic factor in ovarian cancer but the optimal treatment of elderly patients has not been determined. We undertook a retrospective analysis to determine clinical practice in advanced-stage ovarian cancer patients older than 70 years of age. Methods: Medical records of women with high-grade serous ovarian cancer, stage III and IV were retrospectively analyzed. Results: A total of 735 patients were identified with a median age of 61.5 years. 22.4% among them were older than 70 years of age at diagnosis. First-line Progression-Free Survival (PFS) and Overall Survival (OS) were significantly worse in elderly patients in comparison to the younger ones [mPFS 11.3 months vs. 14.8 months, (p < 0.001) and mOS 30.2 months vs. 45.6 months (p < 0.001)]. However, elderly patients were characterized by worse ECOG-Performance Status and they were more frequently treated with Neoadjuvant Chemotherapy followed by Interval Debulking Surgery, while often they were more frequently denied debulking surgery compared to patients under 70 years of age. Moreover, elderly patients received more frequently monotherapy with platinum as frontline treatment. In contrast, there was no significant difference in the outcome of the debulking surgery in comparison to the younger patients or the frequency that gBRCA test was performed. Age over 70 years did not retain its significance for either Progression-Free Survival or Overall Survival when adjusted for all other reported prognostic factors. Conclusions: Elderly ovarian cancer patients have a worse prognosis. Comprehensive geriatric assessment should be performed for the optimal treatment of these patients.     

Treatment of Metastatic Urothelial Carcinoma After Previous Cisplatin-based Chemotherapy for Localized Disease: A Retrospective Comparison of Different Chemotherapy Regimens

BackgroundOptimal chemotherapy for patients who received cisplatin for localized urothelial carcinoma (UC) and develop metastatic disease is unclear. We compared the efficacy of platinum-based (PBC) versus non–platinum-based (NPBC) first-line chemotherapy for metastasis.Patients and MethodsData were collected from the Retrospective International Study of Cancers of the Urothelial Tract (RISC), a database of 3024 patients from 28 international academic centers from 2005 to 2012. Patient inclusion criteria included: (1) predominant UC; (2) any primary tumor site; (3) cT2-4, cN0-N2, cM0; (4) prior receipt of perioperative/radiation cisplatin-containing chemotherapy; and (5) receipt of cytotoxic chemotherapy in the first-line metastatic setting. Multivariate Cox proportional hazards models were used to show progression-free survival (PFS) and overall survival (OS) from the first day of chemotherapy for metastatic disease to date of censor.ResultsEligibility criteria was met by 132 patients (n = 74 PBC; n = 58 NPBC). The median OS was 8.13 months (interquartile range, 4.87-16.64 months) and 8.77 months (interquartile range, 4.01-13.49 months) for PBC and NPBC, respectively. Neither OS (hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.64-1.69; P = .87) nor PFS (HR, 0.86; 95% CI, 0.56-1.31; P = .48) differed for PBC versus NPBC. However, for patients who received chemotherapy more than a year after perioperative/radiation chemotherapy, OS was superior for PBC over NPBC (HR, 0.31; 95% CI, 0.10-0.92; P = .03).ConclusionsThere is no significant outcome difference between PBC and NPBC in patients with metastatic UC who previously received cisplatin-based chemotherapy for localized disease. However, if over a year has elapsed, return to PBC is associated with superior OS.     

Nano-TiO2 particles impair adhesion of airway epithelial cells to fibronectin

Titanium dioxide engineered nanoparticles (nano-TiO₂) are widely used in the manufacturing of a number of products. Due to their size (<100 nm), when inhaled they may be deposited in the distal lung regions and damage Clara cells. We investigated the mechanisms by which short-term (1-h) incubation of human airway Clara-like (H441) cells to nano-TiO₂ (6 nm in diameter) alters the ability of H441 cells to adhere to extracellular matrix. Our results show that 1 h post-incubation, there was a 3-fold increase of extracellular H₂O₂, increased intracellular oxidative stress as demonstrated by 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) oxidation, and a 5-fold increase of phosphor-ERK1/2 as measured by Western blotting. These changes were accompanied by a 25% decrease of H441 adherence to fibronectin (p < 0.05 compared to vehicle incubated H441 cells). Pretreatment with the ERK1/2 inhibitor U0126 for 3 h, partially prevented this effect. In conclusion, short-term exposure of H441 cells to nano-TiO₂ appears to reduce adherence to fibronectin due to oxidative stress and activation of ERK1/2.     

Radical cystectomy with orthotopic neobladder for invasive bladder cancer: a critical analysis of long-term oncological, functional, and quality of life results

Purpose

The present contribution analyses long-term data regarding oncological, functional, and quality of life aspects of patients subjected to cystectomy due to malignancy with subsequent orthotopic bladder substitution.

Methods

A literature search was conducted to review literature published from 1887 until today. Oncological aspects, special considerations on female patients, quality of life, geriatric patients, and impact of minimally invasive surgery were also addressed and discussed.

Results

After more than three decades, orthotopic bladder substitution subsequent to radical cystectomy has stood the test of time by providing adequate long-term survival and low local recurrence rates. Compared to radical cystectomy, neither radiation nor chemotherapy, nor a combination of both, offer similar long-term results. Orthotopic bladder substitution does not compromise oncological outcome and can be performed with excellent results regarding functional and quality of life issues. Chronological age is generally not a contraindication for cystectomy.

Conclusion

Orthotopic bladder substitution should be the diversion of choice both in men and in women, whenever possible. For orthotopic urinary diversion, a careful patient selection considering tumor extent, patient motivation, preoperative sphincter function, other local and systemic adverse confounding factors, and overall life expectancy must be taken into account. Minimally invasive techniques are promising concepts for the future, awaiting confirmation in larger patient cohorts.     

Indications and long-term outcome after elective surgery for hepatocellular adenoma

The management of hepatocellular adenoma (HA) is dependent on several parameters, which are influencing the decision for further management. The aim of this study was to evaluate the clinical presentation, indications, and long-term outcome of surgical treatment in a single-institution analysis. Forty-nine patients underwent elective hepatectomy for HA between 1990 and 2007. Analysis parameters included demographic data, lesion number and size, diagnostic method, mode of surgery, and postoperative outcome. Mean follow-up was 108 months. Thirty-six patients underwent hormone therapy and four patients had a history of cancer before surgical treatment. The mean tumor diameter was 9.8 cm. Mild or moderate postoperative complications were recorded in 16 patients. There was no perioperative mortality. Symptoms were relieved in 95 per cent of the patients. Intratumoral hemorrhage was detected in 21 specimens (43%); malignant transformation was detected in zero specimens. Among patients with HA with clinical symptoms, tumor diameter greater than 5 cm and in male patients the indication for surgery should be given because of the high risk of tumor-related complications. Elective liver resection for HA is a safe procedure and results in a good long-term outcome.     

Relation between the presence and extent of coronary lipid core plaques detected by near-infrared spectroscopy with postpercutaneous coronary intervention myocardial infarction

We aimed to examine whether an association exists between the presence and extent of coronary lipid core plaques (LCPs) detected by near-infrared spectroscopy (NIRS) performed before percutaneous coronary intervention (PCI) with postprocedural myocardial infarction (MI). NIRS was performed in the native coronary arteries of 30 patients before PCI. Angular extent of LCP, lesion segment lipid core burden index, and block chemogram were evaluated. Cardiac biomarkers were measured before and 16 to 24 hours after PCI to determine occurrence of postprocedural MI. Mean number of 2-mm yellow blocks within the stented lesion was 1.4 ± 2.1 and mean lesion lipid core burden index was 110.3 ± 99. Using a definition of creatine kinase-MB >1 time upper limit of normal (ULN), >2 times ULN, and >3 times ULN, MI after PCI occurred in 23%, 13%, and 10% of patients, respectively. Compared to patients who did not have MI after PCI, those who did had similar clinical characteristics but received more stents and had more blocks within the stented lesion. Creatine kinase-MB increase >3 times ULN was observed in 27% of patients with ≥1 yellow block versus in none of the patients without a yellow block within the stented lesion (p = 0.02). In conclusion, PCI of LCP-positive lesions as assessed by NIRS is associated with increased risk for MI after PCI. NIRS may allow lesion-specific risk stratification before PCI and optimization of PCI strategies for myocardial injury risk minimization.     

Seroprevalence of HIV, HBV and HCV in orthopaedic patients at a tertiary hospital in Greece

Infections from hepatitis viruses and human immunodeficiency virus (HIV) as well represent a continuous risk factor to health care providers, in particular those working in surgical departments. The aim of this study was to define the prevalence of HIV, hepatitis B (HBV) and hepatitis C (HCV) viruses in patients admitted in an urban, tertiary orthopaedic department in Greece. We retrospectively studied 1,694 consecutive patients who underwent several orthopaedic procedures. All patients were tested for HIV, HBV and HCV infections. Sixty-six (3.9%) of the patients were seropositive for at least one of the studied viruses. Thirty (1.7%) were positive for HBV, 34 (2%) for HCV and 2 (0.1%) for HIV. The majority of the seropositive patients were women (53%), urban areas citizens (89.4%), and of Greek nationality (83.3%). Non-Greek nationality was the only significantly predictive factor for seropositivity (χ² = 590.2, P < 0.001). The majority of patients were not aware of their infection. A significant percentage of patients cared for at a Greek orthopaedic department were seropositive for blood-borne viruses. Non-Greek nationality is a risk factor. We believe that these data will increase awareness and will promote safer practices among health care providers in orthopaedic units.     

GoCARB in the Context of an Artificial Pancreas

Background: In an artificial pancreas (AP), the meals are either manually announced or detected and their size estimated from the blood glucose level. Both methods have limitations, which result in suboptimal postprandial glucose control. The GoCARB system is designed to provide the carbohydrate content of meals and is presented within the AP framework. Method: The combined use of GoCARB with a control algorithm is assessed in a series of 12 computer simulations. The simulations are defined according to the type of the control (open or closed loop), the use or not-use of GoCARB and the diabetics’ skills in carbohydrate estimation. Results: For bad estimators without GoCARB, the percentage of the time spent in target range (70-180 mg/dl) during the postprandial period is 22.5% and 66.2% for open and closed loop, respectively. When the GoCARB is used, the corresponding percentages are 99.7% and 99.8%. In case of open loop, the time spent in severe hypoglycemic events (<50 mg/dl) is 33.6% without the GoCARB and is reduced to 0.0% when the GoCARB is used. In case of closed loop, the corresponding percentage is 1.4% without the GoCARB and is reduced to 0.0% with the GoCARB. Conclusion: The use of GoCARB improves the control of postprandial response and glucose profiles especially in the case of open loop. However, the most efficient regulation is achieved by the combined use of the control algorithm and the GoCARB.