From amputation to limb salvage reconstruction: evolution and role of the endoprosthesis in musculoskeletal oncology

In 1943, Austin Moore developed the first endoprosthesis fashioned from Vitallium, providing the first alternative to traditional amputation as primary treatment of bone tumors. The success of the Vitallium endoprosthesis has since then led to the development of new materials and designs further advancing limb salvage and reconstructive surgery. Combined with the advent of chemotherapy use and imaging advances, conservative treatment of musculoskeletal tumors has expanded greatly. As the implantable options increased with the development of the Lewis expandable adjustable prosthesis and the noninvasive Phenix Growing prosthesis, receiving the diagnosis of a bone tumor no longer equates to automatic limb loss. Our review details the history and development of endoprostheses throughout orthopedic oncology in the treatment of musculoskeletal tumors.     

Functional differentiation of cytotoxic cancer drugs and targeted cancer therapeutics

There is no nationally or internationally binding definition of the term “cytotoxic drug” although this term is used in a variety of regulations for pharmaceutical development and manufacturing of drugs as well as in regulations for protecting medical personnel from occupational exposure in pharmacy, hospital, and other healthcare settings. The term “cytotoxic drug” is frequently used as a synonym for any and all oncology or antineoplastic drugs. Pharmaceutical companies generate and receive requests for assessments of the potential hazards of drugs regularly – including cytotoxicity. This publication is intended to provide functional definitions that help to differentiate between generically-cytotoxic cancer drugs of significant risk to normal human tissues, and targeted cancer therapeutics that pose much lesser risks. Together with specific assessments, it provides comprehensible guidance on how to assess the relevant properties of cancer drugs, and how targeted therapeutics discriminate between cancer and normal cells. The position of several regulatory agencies in the long-term is clearly to regulate all drugs regardless of classification, according to scientific risk based data. Despite ongoing discussions on how to replace the term “cytotoxic drugs” in current regulations, it is expected that its use will continue for the near future.     

Myxoid glioneuronal tumor,PDGFRA p.K385‐mutant: clinical,radiologic, and histopathologic features

“Myxoid glioneuronal tumor, PDGFRA p.K385‐mutant” is a recently described tumor entity of the central nervous system with a predilection for origin in the septum pellucidum and a defining dinucleotide mutation at codon 385 of the PDGFRA oncogene replacing lysine with either leucine or isoleucine (p.K385L/I). Clinical outcomes and optimal treatment for this new tumor entity have yet to be defined. Here, we report a comprehensive clinical, radiologic, and histopathologic assessment of eight cases. In addition to its stereotypic location in the septum pellucidum, we identify that this tumor can also occur in the corpus callosum and periventricular white matter of the lateral ventricle. Tumors centered in the septum pellucidum uniformly were associated with obstructive hydrocephalus, whereas tumors centered in the corpus callosum and periventricular white matter did not demonstrate hydrocephalus. While multiple patients were found to have ventricular dissemination or local recurrence/progression, all patients in this series remain alive at last clinical follow‐up despite only biopsy or subtotal resection without adjuvant therapy in most cases. Our study further supports “myxoid glioneuronal tumor, PDGFRA p.K385‐mutant” as a distinct CNS tumor entity and expands the spectrum of clinicopathologic and radiologic features of this neoplasm.     

Is viral E6 oncoprotein a viable target? A critical analysis in the context of cervical cancer

An understanding of the pathology of cervical cancer (CC) mediated by E6/E7 oncoproteins of high-risk human papillomavirus (HPV) was developed by late 80's. But if we look at the present scenario, not a single drug could be developed to inhibit these oncoproteins and in turn, be used specifically for the treatment of CC. The readers are advised not to presume the “viability of E6 protein” as mentioned in the title relates to just druggability of E6. The viability aspect will cover almost everything a researcher should know to develop E6 inhibitors until the preclinical stage. Herein, we have analysed the achievements and shortcomings of the scientific community in the last four decades in targeting HPV E6 against CC. Role of all HPV proteins has been briefly described for better perspective with a little detailed discussion of the role of E6. We have reviewed the articles from 1985 onward, reporting in vitro inhibition of E6. Recently, many computational studies have reported potent E6 inhibitors and these have also been reviewed. Subsequently, a critical analysis has been reported to cover the in vitro assay protocols and in vivo models to develop E6 inhibitors. A paragraph has been devoted to the role of public policy to fight CC employing vaccines and whether the vaccine against HPV has quenched the zeal to develop drugs against it. The review concludes with the challenges and the way forward.     

Consumer Participation in Quality Improvements for Chronic Disease Care: Development and Evaluation of an Interactive Patient-Centered Survey to Identify Preferred Service Initiatives

BackgroundWith increasing attention given to the quality of chronic disease care, a measurement approach that empowers consumers to participate in improving quality of care and enables health services to systematically introduce patient-centered initiatives is needed. A Web-based survey with complex adaptive questioning and interactive survey items would allow consumers to easily identify and prioritize detailed service initiatives.ObjectiveThe aim was to develop and test a Web-based survey capable of identifying and prioritizing patient-centered initiatives in chronic disease outpatient services. Testing included (1) test-retest reliability, (2) patient-perceived acceptability of the survey content and delivery mode, and (3) average completion time, completion rates, and Flesch-Kincaid reading score.MethodsIn Phase I, the Web-based Consumer Preferences Survey was developed based on a structured literature review and iterative feedback from expert groups of service providers and consumers. The touchscreen survey contained 23 general initiatives, 110 specific initiatives available through adaptive questioning, and a relative prioritization exercise. In Phase II, a pilot study was conducted within 4 outpatient clinics to evaluate the reliability properties, patient-perceived acceptability, and feasibility of the survey. Eligible participants were approached to complete the survey while waiting for an appointment or receiving intravenous therapy. The age and gender of nonconsenters was estimated to ascertain consent bias. Participants with a subsequent appointment within 14 days were asked to complete the survey for a second time.ResultsA total of 741 of 1042 individuals consented to participate (71.11% consent), 529 of 741 completed all survey content (78.9% completion), and 39 of 68 completed the test-retest component. Substantial or moderate reliability (Cohen’s kappa>0.4) was reported for 16 of 20 general initiatives with observed percentage agreement ranging from 82.1%-100.0%. The majority of participants indicated the Web-based survey was easy to complete (97.9%, 531/543) and comprehensive (93.1%, 505/543). Participants also reported the interactive relative prioritization exercise was easy to complete (97.0%, 189/195) and helped them to decide which initiatives were of most importance (84.6%, 165/195). Average completion time was 8.54 minutes (SD 3.91) and the Flesch-Kincaid reading level was 6.8. Overall, 84.6% (447/529) of participants indicated a willingness to complete a similar survey again.ConclusionsThe Web-based Consumer Preferences Survey is sufficiently reliable and highly acceptable to patients. Based on completion times and reading level, this tool could be integrated in routine clinical practice and allows consumers to easily participate in quality evaluation. Results provide a comprehensive list of patient-prioritized initiatives for patients with major chronic conditions and delivers practice-ready evidence to guide improvements in patient-centered care.