Evaluating Health and Well-Being Returns on Investment in a Cancer Biobank.

Objectives: To evaluate the population health returns from investment in the Victorian Cancer Biobank (VCB), a research consortium including five hospital-integrated sample repositories located in Melbourne, Australia. Methods: This economic evaluation assigned monetary values to the health gains attributable to VCB-supported research. These were then compared with the total investment in VCB infrastructure since inception (2006-2022) to determine the return on investment (ROI). A time lag of 40 years was incorporated, recognizing the delay from investment to impact in scientific research. Health gains were therefore measured for the years 2046-2066, with a 3% discount rate applied. Health gains were measured in terms of disability-adjusted life years (DALYs) attributable to VCB-associated research, with monetary cost assigned via the standardized value of a statistical life year (AU$227,000). The age-standardized DALY rate attributable to cancer was modeled for two standpoints (1) extrapolating the current decreasing trajectory and (2) assuming nil future improvement from current rates, with 33% of the difference attributed to scientific innovation. The proportion of the aggregate health gain attributable to VCB-supported research was estimated from the number of VCB-credited scientific publications as a proportion of total oncology publications over the same period. Results: The AU$32,628,016 of public funding invested in VCB activities over the years 2006-2022 is projected to generate AU$84,561,373 in total (discounted) savings. ROI was AU$1.59 for each AU$1 invested. Conclusions: The VCB offers a strong ROI in terms of impacts on health, justifying the expenditure of public funds and supporting the use of biobanks to advance scientific research.

Does tumoral cavernous carotid stenosis predict an increased risk of future stroke in skull base meningiomas?

OBJECTIVE: Skull base meningiomas (SBMs) involving the cavernous sinus encase the internal carotid artery (ICA) and may lead to stenosis of the vessel. Although ischemic stroke has been reported in the literature, there are to the authors' knowledge no reported studies quantifying the risk of stroke in these patients. The authors aimed to determine the frequency of arterial stenosis in patients with SBMs that encase the cavernous ICA and to estimate the risk of ischemic stroke in these patients. METHODS: Records of all patients with SBM encasing the ICA whose cases were managed by the skull base multidisciplinary team at Salford Royal Hospital between 2011 and 2017 were reviewed using a two-stage approach: 1) clinical and radiological strokes were identified from electronic patient records, and 2) cases were reviewed to examine the correlation between ICA stenosis associated with SBM encasement and anatomically related stroke. Strokes that were caused by another pathology or did not occur in the perfusion territory were excluded. RESULTS: In the review of patient records the authors identified 118 patients with SBMs encasing the ICA. Of these, 62 SBMs caused stenosis. The median age at diagnosis was 70 (IQR 24) years, and 70% of the patients were female. The median follow-up was 97 (IQR 101) months. A total of 13 strokes were identified in these patients; however, only 1 case of stroke was associated with SBM encasement, which occurred in the perfusion territory of a patient without stenosis. Risk of acute stroke during the follow-up period for the entire cohort was 0.85%. CONCLUSIONS: Acute stroke in patients with ICA encasement by SBMs is rare despite the propensity of these tumors to stenose the ICA. Patients with ICA stenosis secondary to their SBM did not have a higher incidence of stroke than those with ICA encasement without stenosis. The results of this study demonstrate that prophylactic intervention to prevent stroke is not necessary in ICA stenosis secondary to SBM.

Recurrent anaplastic transformation of a Vermian region rosette forming glioneuronal tumour - A rare entity. Case report and review of literature.

INTRODUCTION AND IMPORTANCE: Rosette forming Glioneuronal tumours (RGNT) are rare WHO grade I tumours. They have been recognised as a sole entity in the WHO classification since 2007. They are typically described as having a favourable prognosis. Since their description as a distinct entity, there have been only four reports of malignant or anaplastic transformation of RGNT. We report a case of recurrent RGNT with new anaplastic histopathological features. CASE PRESENTATION: We present the case of a 48-year-old female who presented with a vermian region RGNT. The tumour recurred six years after initial surgical resection with new anaplastic transformation. Despite further surgery, chemotherapy, and radiation, the lesion continued to recur with high grade features. CLINICAL DISCUSSION: RGNT is a rare variant of a mixed glial-neuronal tumour. It has been defined as a WHO grade I lesion with a favourable prognostic course. There is growing evidence that this neoplasm can demonstrate malignant transformation with aggressive behaviour. CONCLUSION: Recurrent RGNT is a rare entity. There is a growing bank of literature surrounding this relatively new entity to aid patients and clinicians alike in management decisions. To our knowledge, we report one of only few cases of anaplastic transformation of a RGNT. A high degree of suspicion should be maintained for patients with recurrent RGNT and in suitable cases, surgical resection with adjuvant chemo-irradiation should be pursued.

Improving Public Trust in Biobanking: Roundtable Discussions from the 2021 ISBER Annual Meeting.

Biobanking is a relatively newly recognized and innovative branch of science, which includes the collection of samples and associated data from hospitals, diagnostic centers, and voluntary donations for biomedical and environmental research. It involves diverse stakeholders at the junction of society, science, ethics, law, and politics. A key element in the success of a biobank is the trust and support of public donors, clinicians, and scientists. To achieve trust, it is important to implement strategies that can increase biobank awareness in common people, and different types of communities. Biobank laws and regulations and transparent governance by the biobanks are also crucial to achieving public trust.

Decarbonization in Biobanking: A Potential New Scientific Area.

Calls to reduce or entirely remove the carbon footprint of ongoing activities, collectively termed as decarbonization, have become increasingly more vocal in health care with a number of recent, high profile consensus statements. These calls encourage the biobanking field, as one of the foundational health care research infrastructures, to consider decarbonization as a potential novel research area both in terms of the molecules and the equipment used in research. The current article provides a summary of the roundtable discussion during the 2022 ISBER Annual Meeting and Exhibits, highlighting the current knowledge gaps, challenges, and opportunities in this field. In particular, technological innovation, a greater awareness of the current situation, and behavioral change are important pieces of the puzzle to improving the future of decarbonization in biobanking, even if the eventually implemented routes between resource-abundant and resource-restricted settings might be distinctly different. This article sets the foundation for raising awareness of the subject and of subsequent steps that need to be undertaken.

Preparation of the "Lexique" for ISBER Best Practices 4th Edition for Biobankers in Indo-Pacific Rim Region.

Statement of the Problem: Several standards and guidelines for biobanks or biorepositories have been published by various parties (e.g., the International Society for Biological and Environmental Repositore [ISBER] and the International Organization for Standardization [ISO]). These documents are invaluable for improving the routine practices of the biobanks but the implementation has proven to be challenging for those biobanks from the non-English regions because these resources are mostly written in English. Proposed Solution: The World Health Organization (WHO) has recently published the International Classification of Diseases 11th Revision (ICD-11) along with a translation tool (lexique) for potential users. This has inspired us to make a similar contribution in the biobanking field. All the regional ambassadors (RAs) and director-at-large (DAL) in the Indo-Pacific Rim (IPR) region worked together to produce a similar lexique for potential users of ISBER's Best Practices (BPs) 4th edition. A lexique with languages of Hindi, Indonesian, Vietnamese, and Japanese has been prepared. Conclusions: This lexique is a comparison table between various languages and is expandable to other languages. In addition, this lexique will be a good tool for understanding the ISBER BPs 4th edition.

What Do Biomedical Researchers Want from Biobanks? Results of an Online Survey.

Aims: The purpose of biobanking is to provide biospecimens and associated data to researchers, yet the perspectives of biobank research users have been under-investigated. This study aimed to ascertain biobank research users' needs and opinions about biobanking services. Methods: An online survey was developed, which requested information about researcher demographics, localities of biobanks accessed, methods of sourcing biospecimens, and opinions on topics including but not limited to, application processes, data availability, access fees, and return of research results. There were 27 multiple choice/check box questions, 4 questions with a 10-point Likert scale, and 8 questions with provision for further comment. A web link for the survey was distributed to researchers in late 2019/early 2020 in four Australian states: New South Wales, Victoria, Western Australia, and South Australia. Results: Respondents were generally satisfied with biobank application processes and the fit for purpose of received biospecimens/data. Nonetheless, most researchers (n = 61/99, 62%) reported creating their own collections owing to gaps in sample availability and a perceived increase in efficiency. Most accessed biobanks (n = 58/74, 78%) were in close proximity (local or intrastate) to the researcher. Most researchers had limited the scope of their research owing to difficulty of obtaining biospecimens (n = 55/86, 64%) and/or data (n = 52/85, 60%), with the top three responses for additional types of data required being "more long term follow up data," "more clinical data," and "more linked government data." The top influence to use a particular biobank was cost, and the most frequently suggested improvement was reduced direct "cost of obtaining biospecimens." Conclusion: Biobanks that do not meet the needs of their end-users are unlikely to be optimally utilized or sustainable. This survey provides valuable insights to guide biobanks and other stakeholders, such as developing marketing and client engagement plans to encourage local research users and discouraging the creation of unnecessary new collections.

In vivo survival and differentiation of Friedreich ataxia iPSC-derived sensory neurons transplanted in the adult dorsal root ganglia.

Friedreich ataxia (FRDA) is an autosomal recessive disease characterized by degeneration of dorsal root ganglia (DRG) sensory neurons, which is due to low levels of the mitochondrial protein Frataxin. To explore cell replacement therapies as a possible approach to treat FRDA, we examined transplantation of sensory neural progenitors derived from human embryonic stem cells (hESC) and FRDA induced pluripotent stem cells (iPSC) into adult rodent DRG regions. Our data showed survival and differentiation of hESC and FRDA iPSC-derived progenitors in the DRG 2 and 8 weeks post-transplantation, respectively. Donor cells expressed neuronal markers, including sensory and glial markers, demonstrating differentiation to these lineages. These results are novel and a highly significant first step in showing the possibility of using stem cells as a cell replacement therapy to treat DRG neurodegeneration in FRDA as well as other peripheral neuropathies.

Lysophospholipid Signalling and the Tumour Microenvironment.

Homeostasis is the key to survival. This is as true for the tumour cell as it is for the normal host cell. Tumour cells and normal host cells constantly interact with each other, and the balance of these interactions results in the prevailing homeostatic conditions. The interactions between the milieu of signalling molecules and their effects on the host and tumour cells are known as the tumour microenvironment. The predominant balance of effects within the tumour microenvironment will determine if the tumour cells can evade the host's responses to survive and grow or if the tumour cells will be eradicated. Lysophospholipids (LPLs) are a group of lipid signalling molecules which exert their effects via autocrinic and paracrinic mechanisms. Therefore, LPLs are being explored to determine if they are potentially key signalling molecules within the tumour microenvironment. The effects of LPLs within the tumour microenvironment include modulating cell proliferation, cell survival, cell motility, angiogenesis and the immune system. These are all important activities that affect the balance of host-tumour cell interactions. This chapter expands on these functions and also the role that LPLs could play as a potential treatment target in the future.

Diverse Responses of the Biobanks in Indo-Pacific Rim Region During the COVID-19 Pandemic: Case Scenarios from Two Low- and Middle-Income Countries and Two High-Income Countries in the Indo-Pacific Rim Region.

Background: Biobankers have been unexpectedly involved in the pandemic of COVID-19 since early 2020. Although specific guidance was not available, the International Society for Biological and Environmental Repositories (ISBER) Best Practices and the ISO 20387 document have been utilized to deal with the pandemic disaster. The ISO experts and best practice experts in ISBER teamed up to share the available information and learn the experiences of biobanks concerning COVID-19 through organizing webinars, surveys, and town hall meetings. Four ISBER regional ambassadors (RAs) from the Indo-Pacific Rim (IPR) region were also actively involved at one of the town hall meetings. These RAs, who are from Australia, India, Indonesia, and Japan, and the Director-at-Large of the region, have summarized their experiences in this article. Materials and Methods: The ISBER Standards Committee COVID-19 Task Force has kindly provided the survey results. The extracted glossary from the results was categorized into 10 factors: (1) crisis management; (2) sample-related issues; (3) logistics-related issues; (4) equipment-related issues; (5) ethical, legal, and social implication-related issues; (6) operation-related issues; (7) personnel-related issues; (8) management-related issues; (9) infection-related issues; and (10) research-related issues. Each IPR RA has provided a case considering these 10 factors. Results and Discussion: Two key points have emerged from the scenarios, which are as follows: (1) impacts of the biobanks in low- and middle-income countries (LMICs) are similar to those in high-income countries (HICs) and (2) tolerance of the biobanks in LMICs is not so robust as those in HICs. Furthermore, communication strategies with internal and external stakeholders are critical for a biobank to manage this crisis. This article summarizes the impacts, indicates the opportunities that COVID-19 has brought to the biobank community, and highlights the usefulness of the network beyond biobank services. Lastly, the biobanks need to turn the challenges into opportunities to overcome the crisis.

A single-institution prospective evaluation of a neuro-oncology multidisciplinary team meeting.

Multi-disciplinary team meetings (MDTs) are considered essential to quality cancer care. For some malignancies, MDTs have been associated with improved outcomes, but data regarding the neuro-oncology MDT is limited. We prospectively described the MDT at our institution and evaluated its impact on clinical management. Cases were discussed amongst the treating team and a pre-MDT plan and reason for discussion (RFD) was documented before the MDT. Patient specific clinical data was captured prospectively, with further pathological and radiological information captured during the MDT. Subsequently, the MDT consensus decision was recorded. High impact decisions (HID) were those in which the pre-MDT plan was substantially modified. A HID rate of >10% was considered clinically significant. Adherence to MDT recommendations was recorded. Seventy-nine cases were discussed at the MDT. Fifty-two cases (66%) were male. The median age was 53 (17-84). Thirty-three cases were new diagnoses and the remainder were relapsed/progressive disease. Thirty-nine cases were primary brain tumours, 25 were metastatic tumours and 15 were other. Twenty-eight (35%) had HID. No RFDs were statistically significantly associated with a HID (p = 0.265). Adherence data was collected for 95% (75) of cases. Treatment concordance with the MDT plan occurred in 90% (67) of cases. For cases of non-concordance, six out of eight (75%) were due to patient choice. Overall, a clinically significant proportion of treatment modifications are made at the neuro-oncology MDT. There were no case types which did not benefit from MDT discussion. MDT recommendations were largely adhered to, and in cases of non-concordance, were largely due to patient choice.

Three Year Review of Dorsal Plating for Complex Intra-Articular Fractures of the Distal Radius.

BACKGROUND: The volar approach is commonly used for plating intra-articular fractures of the distal radius. Despite this, certain fracture configurations are more suitable for dorsal plate fixation. This technique has not gained favour due to the reported high incidence of extensor tendon irritation and attrition ruptures. With the advent of lower profile plates this risk has decreased. METHODS: We report on forty-six cases performed in a tertiary hand centre between January 2011 and May 2014. Patients were identified from a database of distal radius fractures treated with open reduction and internal fixation. Pre-operative radiographs and computed tomogram (CT) scans were reviewed to classify fractures and evaluate fracture configurations. Dorsal displacement of fracture fragments was present in all cases. Records and imaging were reviewed to assess bony union and complications including tendon irritation, rupture and need for further surgery. RESULTS: Plate placement was dependent on the degree of comminution in each fracture component. The combination of a dorsal and radial styloid plate was used in 52% of cases. There were no cases of tendon rupture and one case of post-operative loss of reduction. Removal of metal was performed in ten patients, mainly to improve motion and for tendon irritation (four cases each). CONCLUSIONS: Even though technically challenging, dorsal plating is useful in cases of dorsal fragment displacement and comminution, as well as complex AO-23C3 fractures with involvement of the lunate fossa. It allows stable reduction of the dorso-ulnar fragment which is important to restore DRUJ anatomy. The rate of tendon irritation and rupture is lower when compared to earlier plate designs, and removal of metal is only necessary in a few cases.

Distal radius volar rim plate: Technical and radiographic considerations.

AIM: To determine technical considerations and radiographic outcomes of the Synthes volar rim distal radius plate to treat complex intra-articular fractures. METHODS: This review highlights technical considerations learnt using this implant since it was introduced in a major trauma unit in November 2011, including anatomical reduction and whether this was maintained radiographically. RESULTS: Twenty-six of the 382 internally fixed distal radial fractures at our unit (6.8%) were deemed to require this plate in order to achieve optimal fracture fixation between November 2011 and May 2014. A further dorsal and/or radial plate was necessary in 35% and variable angle screws were used in 54% of cases. Post-operatively, mean radial height, inclination, volar tilt and ulnar variance restored were 11.7 mm, 21º, 4.3º and -1.2 mm respectively. There were no cases of non-union or flexor/extensor tendon rupture; one case of loss of fracture reduction. Overall incidence of plate removal was 15% with one plate removed for flexor and one for extensor tendon irritation. CONCLUSION: The use of a rim plate enables control of challenging far distal fracture patterns. However, additional plates were required to improve and maintain reduction. Variable angle screws were necessary in half the cases to avoid intra-articular screw penetration. If used judiciously, this implant can achieve stable fixation despite the complexity of the fracture pattern.

Expression of CD133 and CD44 in glioblastoma stem cells correlates with cell proliferation, phenotype stability and intra-tumor heterogeneity.

Glioblastoma (GBM) is a heterogeneous tumor of the brain with a poor prognosis due to recurrence and drug resistance following therapy. Genome-wide profiling has revealed the existence of distinct GBM molecular subtypes that respond differently to aggressive therapies. Despite this, molecular subtype does not predict recurrence or drug resistance and overall survival is similar across subtypes. One of the key features contributing to tumor recurrence and resistance to therapy is proposed to be an underlying subpopulation of resistant glioma stem cells (GSC). CD133 expression has been used as a marker of GSCs, however recent evidence suggests the relationship between CD133 expression, GSCs and molecular subtype is more complex than initially proposed. The expression of CD133, Olig2 and CD44 was investigated using patient derived glioma stem-like cells (PDGCs) in vitro and in vivo. Different PDGCs exhibited a characteristic equilibrium of distinct CD133+ and CD44+ subpopulations and the influence of environmental factors on the intra-tumor equilibrium of CD133+ and CD44+ cells in PDGCs was also investigated, with hypoxia inducing a CD44+ to CD133+ shift and chemo-radiotherapy inducing a CD133+ to CD44+ shift. These data suggest that surveillance and modulation of intra-tumor heterogeneity using molecular markers at initial surgery and surgery for recurrent GBM may be important for more effective management of GBM.

Molecular interactions of polo-like kinase 1 in human cancers.

Polo-like kinase 1 (PLK1) is an essential protein in communicating cell-cycle progression and DNA damage. Overexpression of PLK1 has been validated as a marker for poor prognosis in many cancers. PLK1 knockdown decreases the survival of cancer cells. PLK1 is therefore an attractive target for anticancer treatments. Several inhibitors have been developed, and some have been clinically tested to show additive effects with conventional therapies. Upstream regulation of PLK1 involves multiple interactions of proteins such as FoxM1, E2F and p21. Other cancer-related proteins such as pRB and p53 also indirectly influence PLK1 expression. With the high mutation rates of these genes seen in cancers, they may be associated with PLK1 deregulation. This raises the question of whether PLK1 overexpression is a cause or a consequence of oncogenesis. In addition, hypomethylation of the CpG island of the PLK1 promoter region contributes to its upregulation. PLK1 expression can be affected by many factors; thus, it is possible that PLK1 deregulation in each individual patient tumours could be due to different underlying mechanisms.

Nutlin-3 sensitizes nasopharyngeal carcinoma cells to cisplatin-induced cytotoxicity.

The small-molecule inhibitor of p53-Mdm2 interaction, Nutlin-3, is known to be effective against cancers expressing wild-type (wt) p53. p53 mutations are rare in nasopharyngeal carcinoma (NPC), hence targeting disruption of p53-Mdm2 interaction to reactivate p53 may offer a promising therapeutic strategy for NPC. In the present study, the effects of Nutlin-3 alone or in combination with cisplatin, a standard chemotherapeutic agent, were tested on C666-1 cells, an Epstein-Barr virus (EBV)-positive NPC cell line bearing wt p53. Treatment with Nutlin-3 activated the p53 pathway and sensitized NPC cells to the cytotoxic effects of cisplatin. The combined treatment also markedly suppressed soft agar colony growth formation and increased apoptosis of NPC cells. The effect of Nutlin-3 on NPC cells was inhibited by knockdown of p53, suggesting that its effect was p53-dependent. Extended treatment with increasing concentrations of Nutlin-3 did not result in emergence of p53 mutations in the C666-1 cells. Collectively, the present study revealed supportive evidence of the effectiveness of combining cisplatin and Nutlin-3 as a potential therapy against NPC.

Gonadotropin­releasing hormone inhibits the proliferation and motility of nasopharyngeal carcinoma cells.

Gonadotropin­releasing hormone (GnRH), or its analogues have been demonstrated to exhibit anti­proliferative effects on tumour cells in ovarian, endometrial and breast cancer through GnRH­receptors (GnRH­R). However, the role of GnRH in nasopharyngeal carcinoma (NPC) remains to be elucidated. In order to investigate the effects of GnRH in NPC, the present study examined the expression of the GnRH­R transcript in NPC and investigated the phenotypic changes in HK1 cells, a recurrent NPC­derived cell line, upon receiving GnRH treatment. Firstly, the GnRH­R transcript was demonstrated in the NPC cell lines and four snap frozen biopsies using reverse transcription­quantitative polymerase chain reaction. In addition, immunohistochemistry revealed the expression of GnRH­R in two of the eight (25%) NPC specimens. Treatment with GnRH induced a rapid increase in intracellular ionised calcium concentration in the NPC cells. GnRH and its agonists, triptorelin and leuprolide, exerted anti­proliferative effects on the NPC cells, as determined using an MTS assay. GnRH did not induce any cell cycle arrest in the HK1 cells under the conditions assessed in the present study. Time­lapse imaging demonstrated a reduction in cell motility in the GnRH­treated cells. In conclusion, GnRH, or its analogues may have antitumour effects on NPC cells. The consequences of alterations in the levels of GnRH on the progression of NPC require further examination.

Molecular subtypes, stem cells and heterogeneity: Implications for personalised therapy in glioma.

We discuss a number of recent developments that have led to new concepts regarding the biology of gliomas. Collective tissue banking, large-scale genomic, transcriptomic and methylomic expression profiling, and discoveries such as isocitrate dehydrogenase gene mutation and the C-phosphate-G island methylation phenotype have improved glioma classification schemes. Furthermore, the discovery of glioma stem cells has both enhanced and complicated our understanding. Gene signatures describing a proneural versus mesenchymal subtype within glioblastoma multiforme is reflected in both parental tumour as well as glioma stem cells and correlates with differential prognosis and response to radiation and chemotherapy. Finally, we discuss how these factors integrate with the known heterogeneity within brain cancers and the implications of this for the development of personalised therapy.