Which is the best method of sterilization of tumour bone for reimplantation? a biomechanical and histopathological study

<p>Abstract</p> <p>Introduction</p> <p>Sterilization and re-usage of tumour bone for reconstruction after tumour resection is now gaining popularity in the East. This recycle tumour bone needs to be sterilized in order to eradicate the tumour cells before re-implantation for limb salvage procedures. The effect of some of these treatments on the integrity and sterility of the bone after treatment has been published but there has yet been a direct comparison between the various methods of sterilization to determine the one method that gives the best tumour kill without compromising the bone's structural integrity.</p> <p>Method</p> <p>This study was performed to evaluate the effect of several sterilization methods on the mechanical behavior of human cortical bone graft and histopathology evaluation of tumour bone samples after being processed with 4 different methods of sterilization. Fresh human cortical tumour bone is harvested from the diaphyseal region of the tumour bone were sterilized by autoclave (n =10); boiling (n =10); pasteurization (n =10); and irradiation (n =10). There were also 10 control specimens that did not receive any form of sterilization treatment. The biomechanical test conducted were stress to failure, modulus and strain to failure, which were determined from axial compression testing. Statistical analysis (ANOVA) was performed on these results. Significance level (α) and power (β) were set to 0.05 and 0.90, respectively.</p> <p>Results</p> <p>ANOVA analysis of 'failure stress', 'modulus' and 'strain to failure' demonstrated significant differences (p < 0.05) between treated cortical bone and untreated specimens under mechanical loading.</p> <p>'Stress to failure' was significantly reduced in boiled, autoclaved and irradiated cortical bone samples (p < 0.05). 'Modulus' detected significant differences in the boiled, autoclaved and pasteurization specimens compared to controls (p < 0.05). 'Strain to failure' was reduced by irradiation (p < 0.05) but not by the other three methods of treatments.</p> <p>Histopathology study revealed no viable tumour cell in any of four types of treatment group compared to the untreated control group.</p> <p>Conclusions</p> <p>Sterilization of cortical bone sample by pasteurization and to a lesser extent, irradiation does not significantly alter the mechanical properties when compared with untreated samples. Mechanical properties degrade with the use of high temperature for sterilization (boiling). All methods of sterilization gave rise to 100 percent tumour kill.</p

Niraparib and Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer

PURPOSE: Metastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease with current standard-of-care therapies. Homologous recombination repair (HRR) gene alterations, including BRCA1/2 alterations, can sensitize cancer cells to poly (ADP-ribose) polymerase inhibition, which may improve outcomes in treatment-naïve mCRPC when combined with androgen receptor signaling inhibition. METHODS: MAGNITUDE (ClinicalTrials.gov identifier: NCT03748641) is a phase III, randomized, double-blinded study that evaluates niraparib and abiraterone acetate plus prednisone (niraparib + AAP) in patients with (HRR+, n = 423) or without (HRR-, n = 247) HRR-associated gene alterations, as prospectively determined by tissue/plasma-based assays. Patients were assigned 1:1 to receive niraparib + AAP or placebo + AAP. The primary end point, radiographic progression-free survival (rPFS) assessed by central review, was evaluated first in the BRCA1/2 subgroup and then in the full HRR+ cohort, with secondary end points analyzed for the full HRR+ cohort if rPFS was statistically significant. A futility analysis was preplanned in the HRR- cohort. RESULTS: Median rPFS in the BRCA1/2 subgroup was significantly longer in the niraparib + AAP group compared with the placebo + AAP group (16.6 v 10.9 months; hazard ratio [HR], 0.53; 95% CI, 0.36 to 0.79; P = .001). In the overall HRR+ cohort, rPFS was significantly longer in the niraparib + AAP group compared with the placebo + AAP group (16.5 v 13.7 months; HR, 0.73; 95% CI, 0.56 to 0.96; P = .022). These findings were supported by improvement in the secondary end points of time to symptomatic progression and time to initiation of cytotoxic chemotherapy. In the HRR- cohort, futility was declared per the prespecified criteria. Treatment with niraparib + AAP was tolerable, with anemia and hypertension as the most reported grade ≥ 3 adverse events. CONCLUSION: Combination treatment with niraparib + AAP significantly lengthened rPFS in patients with HRR+ mCRPC compared with standard-of-care AAP

Resistance of renal cell carcinoma to targeted therapy

Targeted therapy has replaced immunotherapy as the standard of care for metastatic renal cell carcinoma (RCC). Currently available targeted agents include multi- tyrosine kinase inhibitors (axitinib, sunitinib, sorafenib and pazopanib), mammalian target of rapamycin (mTOR) kinase inhibitors (temsirolimus and everolimus) and bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF). Despite the beneficial clinical outcomes, resistance to therapy is emerging as a new challenge. Resistance to therapy can be either intrinsic or extrinsic (acquired). About 30% of patients have intrinsic resistant and almost all patients who respond initially will develop acquired resistance within 12 months of treatment. In this chapter, we summarize the current challenges of drug resistance in the effective treatment of metastatic RCC with particular emphasis on targeted therapies

Which is the best method of sterilization for recycled bone autograft in limb salvage surgery: a radiological, biomechanical and histopathological study in rabbit

Background: Limb salvage surgery is a treatment of choice for sarcomas of the extremities. One of the options in skeletal reconstruction after tumour resection is by using a recycled bone autograft. The present accepted methods of recycling bone autografts include autoclaving, pasteurization and irradiation. At the moment there is lack of studies that compare the effectiveness of various sterilization methods used for recycling bone autografts and their effects in terms of bone incorporation. This study was performed to determine the effects of different methods of sterilization on bone autografts in rabbit by radiological, biomechanical and histopathological evaluations. Methods: Fresh rabbit cortical bone is harvested from the tibial diaphysis and sterilized extracorporeally by pasteurization (n = 6), autoclaving (n = 6), irradiation (n = 6) and normal saline as control group (n = 6). The cortical bones were immediately reimplanted after the sterilization process. The subsequent process of graft incorporation was examined over a period of 12 weeks by serial radiographs, biomechanical and histopathological evaluations. Statistical analysis (ANOVA) was performed on these results. Significance level (Α) and power (Β) were set to 0.05 and 0.90, respectively. Results: Radiographic analysis showed that irradiation group has higher score in bony union compared to other sterilization groups (p = 0.041). ANOVA analysis of 'failure stress', 'modulus' and 'strain to failure' demonstrated no significant differences (p = 0.389) between treated and untreated specimens under mechanical loading. In macroscopic histopathological analysis, the irradiated group has the highest percentage of bony union (91.7 percent). However in microscopic analysis of union, the pasteurization group has significantly higher score (p = 0.041) in callus formation, osteocytes percentage and bone marrow cellularity at the end of the study indicating good union potential. Conclusions: This experimental study shown that both irradiation and pasteurization techniques have more favourable outcome in terms of bony union based on radiographic and histopathological evaluations. Autoclaving has the worst outcome. These results indicate that extracorporeal irradiation or pasteurization of bone autografts, are viable option for recycling bone autografts. However, pasteurization has the best overall outcomes because of its osteocytes preservation and bone marrow cellularity

Efficacy, safety, and prognostic indicators of first-line sunitinib in patients with metastatic renal cell carcinoma: A single center experience

Background: We assessed the efficacy and safety of sunitinib as the first-line treatment in metastatic renal cell carcinoma (mRCC) patients. The predictors of survival and efficacy in mRCC as identified from previous studies, including the Memorial Sloan Kettering Cancer Center (MSKCC) and the International Metastatic RCC Database Consortium (IMDC) factors, were also evaluated. Patients and Methods: Data from 56 patients with mRCC, treated with sunitinib at our institute (2006-2014), were analyzed retrospectively. Prognostic factors for overall survival (OS) and progression-free survival (PFS) were evaluated using univariate and multivariate analyses performed by log-rank test and Cox regression. Results: Fifty-one (91.1%) patients received starting dose of sunitinib of 50 mg/day in 4/2 schedule. The median PFS was 12.7 months (95% confidence interval [CI], 4.5-20.9 months) and the median OS was 16.9 months (95% CI, 3.8-29.9 months). The objective response rate was 27.5%. Dose interruption and reduction due to toxicities were required in 37.5% and 60.7% of patients, respectively. The most common Grades 3-4 toxicities were hand-foot syndrome (HFS) (23.2%), thrombocytopenia (16.1%), and hypertension (14.3%). The Eastern Cooperative Oncology Group performance status ≥2, hemoglobin upper limit of normal (ULN), platelet > ULN, no prior nephrectomy, metastatic sites >1, liver metastases, lymph node metastases, and development of HFS were independent prognostic factors. Conclusions: Sunitinib treatment has acceptable efficacy and safety profile in Malaysian mRCC patients. The MSKCC and IMDC factors are relevant for predicting survival in our patient cohort while HFS is a promising prognostic predictor which warrants further investigation

Development of electronic medical records for clinical and research purposes: the breast cancer module using an implementation framework in a middle income country- Malaysia

Background: Advances in medical domain has led to an increase of clinical data production which offers enhancement opportunities for clinical research sector. In this paper, we propose to expand the scope of Electronic Medical Records in the University Malaya Medical Center (UMMC) using different techniques in establishing interoperability functions between multiple clinical departments involving diagnosis, screening and treatment of breast cancer and building automatic systems for clinical audits as well as for potential data mining to enhance clinical breast cancer research in the future. Results: Quality Implementation Framework (QIF) was adopted to develop the breast cancer module as part of the in-house EMR system used at UMMC, called i-Pesakit©. The completion of the i-Pesakit© Breast Cancer Module requires management of clinical data electronically, integration of clinical data from multiple internal clinical departments towards setting up of a research focused patient data governance model. The 14 QIF steps were performed in four main phases involved in this study which are (i) initial considerations regarding host setting, (ii) creating structure for implementation, (iii) ongoing structure once implementation begins, and (iv) improving future applications. The architectural framework of the module incorporates both clinical and research needs that comply to the Personal Data Protection Act. Conclusion: The completion of the UMMC i-Pesakit© Breast Cancer Module required populating EMR including management of clinical data access, establishing information technology and research focused governance model and integrating clinical data from multiple internal clinical departments. This multidisciplinary collaboration has enhanced the quality of data capture in clinical service, benefited hospital data monitoring, quality assurance, audit reporting and research data management, as well as a framework for implementing a responsive EMR for a clinical and research organization in a typical middle-income country setting. Future applications include establishing integration with external organization such as the National Registration Department for mortality data, reporting of institutional data for national cancer registry as well as data mining for clinical research. We believe that integration of multiple clinical visit data sources provides a more comprehensive, accurate and real-time update of clinical data to be used for epidemiological studies and audits. © 2018 The Author(s)

Practical updates in medical therapy for advanced and metastatic renal cell carcinoma

The evolution of therapy for advanced or metastatic renal cell carcinoma (RCC) progressed over the past decade from using cytokine immunotherapy to targeted therapy which predominantly inhibits angiogenesis via the vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) pathways. Currently, there are several approved agents in the first-line (e.g. sunitinib, pazopanib, ipilimumab/nivolumab, bevacizumab/IFN-α combination and temsirolimus) and second-line settings (e.g. everolimus, axitinib, sorafenib, cabozantinib, nivolumab and lenvatinib/everolimus combination). These agents are used in sequence upon progression due to drug resistance or intolerable toxicities. The European Association of Urology (EAU), European Society for Medical Oncology (ESMO) and National Comprehensive Cancer Network (NCCN) guidelines recommend the use of these agents based on evidence from clinical trials and expert committee consensus. The recent approval of immune checkpoint inhibitors due to the encouraging results from clinical trials has expanded the treatment options for patients with advanced or metastatic RCC. This will hopefully improve the treatment outcomes, reduce toxicities and ameliorate quality of life for these patients