Will the Use of Biomarkers Improve Bladder Cancer Radiotherapy Delivery?

Advances in the field of cancer biology and molecular techniques have led to a better understanding of the molecular underpinnings driving cancer development and outcomes. Simultaneously, advances in imaging have allowed for improved sensitivity in initial staging, radiotherapy planning and follow-up of numerous cancers. These two phenomena have led to the development of biomarkers that can guide therapy in multiple malignancies. In bladder cancer, there is extensive ongoing research into the identification of biomarkers that can help tailor personalised approaches for treatment based on the intrinsic tumour biology. However, the delivery of bladder cancer radiotherapy as part of trimodality therapy currently has a paucity of biomarkers to guide treatment. Here we summarise the existing literature and ongoing investigations into potential predictive and prognostic molecular and imaging biomarkers that may one day guide selection for utilisation of radiotherapy as part of trimodality therapy, guide selection of the radiosensitising agent, guide radiation dose and target, and guide surveillance for recurrence after trimodality therapy.

Penile Paget's Disease: A Case Report and Review of the Literature.

Extramammary Paget's Disease (EMPD) is a rare cutaneous, slow growing, intraepithelial adenocarcinoma that can be either primary (intraepithelial arising within the epidermis) or secondary (intraepithelial spread of a visceral carcinoma). Here we present the case of a 63-year-old male with EMPD of the glans penis stemming from underlying urothelial carcinoma. Our treatment decision elected for management with chemotherapy and local treatment with radiation therapy. Subsequent, review of the literature demonstrated a rare disease with a variety of underlying malignancies causing this secondary pathology. Caregivers should be aware of the association of Paget's disease and urothelial cancer and should have a high index of suspicion that erythematous penile lesions may represent Paget's disease and that penile biopsies should be performed early in this setting.

Multiscale analyses reveal native-like lamellar bone repair and near perfect bone-contact with porous strontium-loaded bioactive glass.

The efficient healing of critical-sized bone defects using synthetic biomaterial-based strategies is promising but remains challenging as it requires the development of biomaterials that combine a 3D porous architecture and a robust biological activity. Bioactive glasses (BGs) are attractive candidates as they stimulate a biological response that favors osteogenesis and vascularization, but amorphous 3D porous BGs are difficult to produce because conventional compositions crystallize during processing. Here, we rationally designed a porous, strontium-releasing, bioactive glass-based scaffold (pSrBG) whose composition was tailored to deliver strontium and whose properties were optimized to retain an amorphous phase, induce tissue infiltration and encourage bone formation. The hypothesis was that it would allow the repair of a critical-sized defect in an ovine model with newly-formed bone exhibiting physiological matrix composition and structural architecture. Histological and histomorphometric analyses combined with indentation testing showed pSrBG encouraged near perfect bone-to-material contact and the formation of well-organized lamellar bone. Analysis of bone quality by a combination of Raman spectral imaging, small-angle X-ray scattering, X-ray fluorescence and focused ion beam-scanning electron microscopy demonstrated that the repaired tissue was akin to that of normal, healthy bone, and incorporated small amounts of strontium in the newly formed bone mineral. These data show the potential of pSrBG to induce an efficient repair of critical-sized bone defects and establish the importance of thorough multi-scale characterization in assessing biomaterial outcomes in large animal models.

Cobalt-containing bioactive glasses reduce human mesenchymal stem cell chondrogenic differentiation despite HIF-1α stabilisation.

Bioactive glasses (BGs) are excellent delivery systems for the sustained release of therapeutic ions and have been extensively studied in the context of bone tissue engineering. More recently, due to their osteogenic properties and expanding application to soft tissue repair, BGs have been proposed as promising materials for use at the osteochondral interface. Since hypoxia plays a critical role during cartilage formation, we sought to investigate the influence of BGs releasing the hypoxia-mimicking agent cobalt (CoBGs) on human mesenchymal stem cell (hMSC) chondrogenesis, as a novel approach that may guide future osteochondral scaffold design. The CoBG dissolution products significantly increased the level of hypoxia-inducible factor-1 alpha in hMSCs in a cobalt dose-dependent manner. Continued exposure to the cobalt-containing BG extracts significantly reduced hMSC proliferation and metabolic activity, as well as chondrogenic differentiation. Overall, this study demonstrates that prolonged exposure to cobalt warrants careful consideration for cartilage repair applications.

Adjuvant Radiotherapy Use by US Radiation Oncologists After Radical Cystectomy for Muscle-invasive Bladder Cancer.

AIMS: Historic trials suggested significant toxicity with adjuvant radiotherapy (ART) after radical cystectomy for muscle-invasive bladder cancer (MIBC). However, recent trials have found improved locoregional control and the 2016 National Comprehensive Cancer Network (NCCN) guidelines recommend ART consideration for select patients at high risk of local recurrence. ART practice patterns among US radiation oncologists are unknown and we carried out a survey to explore current trends. MATERIALS AND METHODS: We conducted a survey of US radiation oncologists regarding the management of patients with cT2-3N0M0 transitional cell MIBC. Responses were reported using descriptive statistics. Chi-square and univariate logistic regression of clinical and demographic covariates were conducted, followed by multivariable logistic regression analysis to identify factors predicting for ART use. RESULTS: In total, 277 radiation oncologists completed our survey. Nearly half (46%) have used ART for MIBC at least once in the past. In ART users, indications for ART include gross residual disease (93%), positive margins (92%), pathological nodal involvement (64%), pT3 or T4 disease (46%), lymphovascular invasion (16%) and high-grade disease (13%). On univariate logistic regression, ART use was associated with the number of years in practice (P=0.04), pre-cystectomy radiation oncology consultation (P=0.004), primarily treating MIBC patients fit for cystectomy (P=0.01) and intensity-modulated radiotherapy use (P=0.01). On multivariable logistic regression analysis, routine pre-cystectomy radiation oncology consultation (odds ratio 1.91, 95% confidence interval 1.04-3.51; P=0.04) and intensity-modulated radiotherapy use (odds ratio 2.77, 95% confidence interval 1.48-5.22; P=0.002) remained associated with ART use. CONCLUSIONS: ART use is controversial in bladder cancer, yet unexpectedly has commonly been used among US radiation oncologists treating patients with MIBC after radical cystectomy. NRG-GU001 was a randomised trial in the US randomizing patients with high-risk pathological findings for observation or ART after cystectomy. However, due to poor accrual it recently closed and thus it will be up to other international trials to clarify the role of ART and identify patients benefiting form this adjuvant therapy.

Demonstration of IgG subclass (IgG1 and IgG3) in patients with positive direct antiglobulin tests.

Serologic characterization of autoantibodies helps in the management and monitoring of the course of autoimmune hemolytic anemia (AIHA). The purpose of this study was to evaluate gel centrifugation test (GCT) cards for immunoglobulin G (IgG) titer and determination of IgG subclasses IgG1 and IgG3 and their influence on hemolysis. Eighty direct antiglobulin test (DAT)-positive patients were examined with the help of GCT cards for IgG titer and IgG subclasses. The results were correlated with the presence and absence of hemolysis. A statistically significant (p < 0.005) association of hemolysis with increasing anti-IgG titer was observed. When IgG titer was 30 or less, 28 (50.91%) patients had no hemolysis, whereas 15 (93.75%) patients had features of hemolysis when titer was at least 300. Statistically significant (p < 0.005) association of subclass of IgG (IgG1, IgG3) coating the red blood cells with intravascular hemolysis was also seen. Twenty-nine (80.56%) patients had evidence of hemolysis when IgG1 or IgGl-IgG3 both were present. Gel technology is helpful to demonstrate red blood cell-bound autoantibodies and their characterization with regard to class, subclass, and titer. This information is useful to identify patients with AIHA who are at risk of severe hemolysis with adverse prognosis.

Effect of HCl on the doping and shape control of silicon nanowires.

The introduction of hydrogen chloride during the in situ doping of silicon nanowires (SiNWs) grown using the vapor-liquid-solid (VLS) mechanism was investigated. Compared with non-chlorinated atmospheres, the use of HCl with dopant gases considerably improves the surface morphology of the SiNWs, leading to extremely smooth surfaces and a greatly reduced tapering. Variations in the wire diameter are massively reduced for boron doping, and cannot be measured at 600 °C for phosphorous over several tens of micrometers. This remarkable feature is accompanied by a frozen gold migration from the catalyst, with no noticeable levels of gold clusters observed using scanning electron microscopy. A detailed study of the apparent resistivity of the NWs reveals that the dopant incorporation is effective for both types of doping. A graph linking the apparent resistivity to the dopant to silane dilution ratio is built for both types of doping and discussed in the frame of the previous results.

Cerebral venous congestion during cardio-pulmonary bypass: role of bispectral index monitoring.

A 58-year-old male patient was posted for double valve replacement under hypothermic cardiopulmonary bypass (CPB). During aortic cross-clamp (AXC), the central venous pressure (CVP) was found to have increased to 22 mmHg. After 4 minutes of sustained increase in CVP, burst suppression (SR) started increasing. After 5 min of increase in SR, bispectral index (BIS) declined rapidly to 17. Propofol infusion was stopped and re-evaluation of signs of facial congestion showed changes to that effect. The perfusionist noted steadily decreasing venous return. As soon as the superior vena cava (SVC) cannula was withdrawn by 3 cm, CVP immediately declined to 6 mmHg. The venous return in the CPB reservoir normalized and BIS returned to 42 after a transient rise to a maximum of 58 and SR decreased to 0 within 2 min of repositioning of the venous cannula. The patient was successfully extubated after 7 hours without any sequelae.

Functional organ preservation with definitive chemoradiotherapy for T4 laryngeal squamous cell carcinoma.

BACKGROUND: Randomized trials established chemoradiotherapy as standard treatment for advanced laryngeal cancer. Patients with large-volume T4 disease (LVT4) were excluded from these trials. The purpose of this study was to report T4 laryngeal cancer patient outcome, including those with LVT4 disease, treated with chemoradiotherapy. PATIENTS AND METHODS: This study is a retrospective subset analysis of 32 patients with T4 laryngeal carcinoma including LVT4 tumors treated on three consecutive protocols investigating paclitaxel (Taxol), 5-fluorouracil, hydroxyurea, and 1.5-Gy twice daily (BID) radiotherapy (TFHX). RESULTS: Median follow-up is 43 months. Four-year locoregional control (LRC), disease-free survival (DFS), overall survival (OS), and laryngectomy-free survival (LFS) was 71%, 67%, 53%, and 86%, respectively. Four patients required laryngectomy for recurrent or persistent disease. Of disease-free patients with >or=1 year follow-up, 90% demonstrated normal or understandable speech. None required laryngectomy for complications. Among LVT4 patients, 4-year LRC, DFS, OS, and LFS was 71%, 65%, 56%, and 81%, respectively. Induction chemotherapy improved 4-year LRC (90% versus 46%, P = 0.03) and DFS (84% versus 42%, P = 0.03). CONCLUSIONS: Promising control and functional outcomes are achieved with TFHX for T4 laryngeal patients. LVT4 disease had outcomes similar to patients with less advanced disease treated on Radiation Therapy Oncology Group 91-11. Induction chemotherapy improved outcomes, warranting further investigation.

Sustained release implants of chloroquine phosphate for possible use in chemoprophylaxis of malaria.

Implants of chloroquine phosphate (CQP) using biodegradable polymer, gelatin (G) and cross-linked gelatin (CLG) were prepared and evaluated to assess their physicochemical properties and in vitro release profile. The mechanism and kinetics of release were studied to correlate the release phenomenon with the formulation parameters. Out of many batches of the implants investigated, the implant prepared with 20% gelatin at 2:1 drug polymer ratio, 10% crosslinking agent and 2% plasticizer (Batch J) was found to provide optimum release behavior conforming to the requirements of a long term implant for a week. In vivo studies conducted on albino rats showed consistent therapeutic blood level over a period of 7 days. Mean residence time (MRT) of the drug released in the body, calculated as the ratio of the area under the first moment curve (AUMC) to area under concentration time curve (AUC) was 72 hr for implant against 2.42 hr for subcutaneous injection.

A simple synthetic liquid medium for development of yeast and mycelial form of pathogenic species of Candida.

Thirty two known strains of Candida species were used for evaluation of glucose, serine, ornithine, methionine, GSOM medium and its comparison with Lee's medium for the production of yeast and mycelial phase at different temperatures and on prolonged incubation. No mycelial form was observed when various Candida species in GSOM and Lee's medium were incubated at 25 degrees C up to 72 hours. Percentage of mycelial forming cells of Candida species were more in GSOM medium than Lee's medium in 48 hours at 37 degrees C. Among various species of Candida, albicans and C. parapsilosis showed maximum mycelium formation. GSOM medium can be used for growing Candida species particularly C. albicans in mycelial phase.

Clinicomycological study of tinea capitis in desert district of Rajasthan.

The clinicomycological study was conducted on 200 cases of Tinea capitis in Jodhpur. Incidence of tinea capitis among superficial mycoses was 4.43 and male to female ratio being 1.8:1. Majority of patients were from urban area (88%) and positive family history of dermatophytoses was present in 29% of cases. Majority of patients attended hospital OPD from July to October (39.%%) and January to April (49%). Persons using mustard oil as hair applicant had single or less lesions as compared to individual using other oil. Endothrix involvement of hair was seen in 78% cases and Trichophyton violaceum was predominant fungus (88.5%) recovered on culture.

Morphological identification of Candida species on glucose agar, rice extract agar and corn meal agar with and without Tween-80.

A comparative study for the identification of 32 known strains of Candida species on the basis of morphology on glucose agar, rice extract agar and corn meal agar with and without Tween 80 revealed that when Tween 80 is incorporated in the media identification is possible for 96.8% of the species within 48 hours on rice extract agar and for 96.8% of the species within 48 hours on rice extract agar and for 90.6% of the species on glucose agar. The germ tubes and chlamydospores were also produced more on rice extract agar than on 0.1% glucose agar. Rice extract agar with Tween 80 can be used as single medium for morphologic identification of Candida species. The inoculated medium is first incubated at 37 degrees C for 3 hours and examined for germ tube formation and then incubated at 25 degrees C for 24 to 72 hours and examined for appearance of chlamydospores and mycelial morphology.

Modification of immune response by glycine in animals.

Glycine (50, 100 and 300 mg/kg), administered daily for 10 days in rabbits challenged with typhoid 'H' antigen and sheep erythrocyte antigen, caused dose- dependent reduction of antibody titre. Inhibition of antibody titre observed with 300 mg/kg was comparable to immunosuppression observed with 1 mg/kg betamethasone.