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Article: How 3D Printing Is Reshaping Translational Research.

Sigston, Elizabeth A W

Frontiers in bioengineering and biotechnology

2021 Volume 9, Page(s) 640611

Abstract: Translational Research" has traditionally been defined as taking basic scientific findings and developing new diagnostic tools, drugs, devices and treatment options for patients, that are translated into practice, reach the people and populations for ... ...

Abstract	"Translational Research" has traditionally been defined as taking basic scientific findings and developing new diagnostic tools, drugs, devices and treatment options for patients, that are translated into practice, reach the people and populations for whom they are intended and are implemented correctly. The implication is of a unidirectional flow from "the bench to bedside". The rapidly emergent field of additive manufacturing (3D printing) is contributing to a major shift in translational medical research. This includes the concept of bidirectional or reverse translation, early collaboration between clinicians, bio-engineers and basic scientists, and an increasingly entrepreneurial mindset. This coincides with, and is strongly complemented by, the rise of systems biology. The rapid pace at which this type of translational research can occur brings a variety of potential pitfalls and ethical concerns. Regulation surrounding implantable medical devices is struggling to keep up. 3D printing has opened the way for personalization which can make clinical outcomes hard to assess and risks putting the individual before the community. In some instances, novelty and hype has led to loss of transparency of outcomes with dire consequence. Collaboration with commercial partners has potential for conflict of interest. Nevertheless, 3D printing has dramatically changed the landscape of translational research. With early recognition and management of the potential risks, the benefits of reshaping the approach to translational research are enormous. This impact will extend into many other areas of biomedical research, re-establishing that science is more than a body of research. It is a way of thinking.
Language	English
Publishing date	2021-12-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2719493-0
ISSN	2296-4185
ISSN	2296-4185
DOI	10.3389/fbioe.2021.640611
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Article ; Online: How 3D Printing Is Reshaping Translational Research

Elizabeth A. W. Sigston

Frontiers in Bioengineering and Biotechnology, Vol

2021 Volume 9

Abstract: Translational Research” has traditionally been defined as taking basic scientific findings and developing new diagnostic tools, drugs, devices and treatment options for patients, that are translated into practice, reach the people and populations for ... ...

Abstract	“Translational Research” has traditionally been defined as taking basic scientific findings and developing new diagnostic tools, drugs, devices and treatment options for patients, that are translated into practice, reach the people and populations for whom they are intended and are implemented correctly. The implication is of a unidirectional flow from “the bench to bedside”. The rapidly emergent field of additive manufacturing (3D printing) is contributing to a major shift in translational medical research. This includes the concept of bidirectional or reverse translation, early collaboration between clinicians, bio-engineers and basic scientists, and an increasingly entrepreneurial mindset. This coincides with, and is strongly complemented by, the rise of systems biology. The rapid pace at which this type of translational research can occur brings a variety of potential pitfalls and ethical concerns. Regulation surrounding implantable medical devices is struggling to keep up. 3D printing has opened the way for personalization which can make clinical outcomes hard to assess and risks putting the individual before the community. In some instances, novelty and hype has led to loss of transparency of outcomes with dire consequence. Collaboration with commercial partners has potential for conflict of interest. Nevertheless, 3D printing has dramatically changed the landscape of translational research. With early recognition and management of the potential risks, the benefits of reshaping the approach to translational research are enormous. This impact will extend into many other areas of biomedical research, re-establishing that science is more than a body of research. It is a way of thinking.
Keywords	additive manufacturing ; 3D printing ; translational research ; bioengineering ; systems biology ; biomedical ; Biotechnology ; TP248.13-248.65
Subject code	170
Language	English
Publishing date	2021-12-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
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Article ; Online: Treatment outcomes of standard (high dose) cisplatin and non-standard chemotherapy for locally advanced head and neck cancer.

Alamgeer, Muhammad / Coleman, Andrew / McDowell, Lachlan / Giddings, Charles / Safdar, Adnan / Sigston, Elizabeth / Wang, Yang / Subramaniam, Ashwin

Cancer reports (Hoboken, N.J.)

2022 Volume 6, Issue 1, Page(s) e1674

Abstract: Introduction: Concurrent chemoradiotherapy with high-dose (HD) cisplatin is the standard treatment for locally advanced head and neck squamous cell carcinoma (LA-HNSCC). Due to the higher treatment-related adverse effects with standard therapy, ... ...

Abstract	Introduction: Concurrent chemoradiotherapy with high-dose (HD) cisplatin is the standard treatment for locally advanced head and neck squamous cell carcinoma (LA-HNSCC). Due to the higher treatment-related adverse effects with standard therapy, alternative regimens (non-standard therapy), namely, lower dose weekly cisplatin, carboplatin/paclitaxel, or cetuximab are considered. There is, however, no consensus on non-standard regimens. We aimed to investigate the efficacy and safety profile of these regimens. Methods: This single centre retrospective cohort study included all consecutive adult patients with newly diagnosed LA-HNSCC treated with either standard or non-standard regimens between January 2016 and April 2021. The primary outcome was 2-year failure-free survival (FFS). The secondary outcomes included acute toxicities, hospitalisation rates, dose modifications, treatment failure rates (TFR), and overall survival. Results: About 235 patients were included in the final analysis; median age was 61 years (IQR 55-67), and 87% were male. Most had oropharyngeal tumours (85.5%) and p16-positivity was frequent (80%). About 56% received non-standard regimens: weekly cisplatin = 79 and non-cisplatin = 48. These patients had higher Charlson Comorbidity Index (CCI; p < .001) and lower European Cooperative Oncology Group (ECOG)-0 (p = .003). There was no difference in 2-year FFS (hazard ratio [HR] = 1.16; 95% confidence interval - [CI] 0.65-2.05), hospitalisation and grade-3 toxicity rates between the two regimens. Nausea and vomiting were lower in the non-standard regimen (3.0% vs. 16%, p < .001). Dose reductions, adjusted for age, sex, and CCI, were less likely in the non-standard regimen (OR = 2.36; 95%-CI: 1.01-5.49, p = .007). Conclusions: We demonstrated similar efficacy of lower dose weekly cisplatin and carboplatin/paclitaxel regimens and better safety profile of weekly cisplatin compared to standard HD cisplatin regimens for LA-HNSCC. Multicenter randomised control trials are required in HD cisplatin-ineligible patients.
MeSH term(s)	Adult ; Humans ; Male ; Middle Aged ; Female ; Cisplatin ; Carboplatin ; Squamous Cell Carcinoma of Head and Neck/drug therapy ; Retrospective Studies ; Head and Neck Neoplasms/drug therapy ; Treatment Outcome ; Paclitaxel/adverse effects
Chemical Substances	Cisplatin (Q20Q21Q62J) ; Carboplatin (BG3F62OND5) ; Paclitaxel (P88XT4IS4D)
Language	English
Publishing date	2022-07-06
Publishing country	United States
Document type	Multicenter Study ; Journal Article
ISSN	2573-8348
ISSN (online)	2573-8348
DOI	10.1002/cnr2.1674
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Article: An Emergence Framework of Carcinogenesis.

Sigston, Elizabeth A W / Williams, Bryan R G

Frontiers in oncology

2017 Volume 7, Page(s) 198

Abstract: Experimental paradigms provide the framework for the understanding of cancer, and drive research and treatment, but are rarely considered by clinicians. The somatic mutation theory (SMT), in which cancer is considered a genetic disease, has been the ... ...

Abstract	Experimental paradigms provide the framework for the understanding of cancer, and drive research and treatment, but are rarely considered by clinicians. The somatic mutation theory (SMT), in which cancer is considered a genetic disease, has been the predominant traditional model of cancer for over 50 years. More recently, alternative theories have been proposed, such as tissue organization field theory (TOFT), evolutionary models, and inflammatory models. Key concepts within the various models have led to them being difficult to reconcile. Progressively, it has been recognized that biological systems cannot be fully explained by the physicochemical properties of their constituent parts. There is an increasing call for a 'systems' approach. Incorporating the concepts of 'emergence', 'systems', 'thermodynamics', and 'chaos', a single integrated framework for carcinogenesis has been developed, enabling existing theories to become compatible as alternative mechanisms, facilitating the integration of bioinformatics and providing a structure in which translational research can flow from both 'benchtop to bedside' and 'bedside to benchtop'. In this review, a basic understanding of the key concepts of 'emergence', 'systems', 'system levels', 'complexity', 'thermodynamics', 'entropy', 'chaos', and 'fractals' is provided. Non-linear mathematical equations are included where possible to demonstrate compatibility with bioinformatics. Twelve principles that define the 'emergence framework of carcinogenesis' are developed, with principles 1-10 encapsulating the key concepts upon which the framework is built and their application to carcinogenesis. Principle 11 relates the framework to cancer progression. Principle 12 relates to the application of the framework to translational research. The 'emergence framework of carcinogenesis' collates current paradigms, concepts, and evidence around carcinogenesis into a single framework that incorporates previously incompatible viewpoints and ideas. Any researcher, scientist, or clinician involved in research, treatment, or prevention of cancer can employ this framework.
Language	English
Publishing date	2017-09-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2017.00198
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Article ; Online: An Emergence Framework of Carcinogenesis

Elizabeth A. W. Sigston / Bryan R. G. Williams

Frontiers in Oncology, Vol

2017 Volume 7

Abstract	Experimental paradigms provide the framework for the understanding of cancer, and drive research and treatment, but are rarely considered by clinicians. The somatic mutation theory (SMT), in which cancer is considered a genetic disease, has been the predominant traditional model of cancer for over 50 years. More recently, alternative theories have been proposed, such as tissue organization field theory (TOFT), evolutionary models, and inflammatory models. Key concepts within the various models have led to them being difficult to reconcile. Progressively, it has been recognized that biological systems cannot be fully explained by the physicochemical properties of their constituent parts. There is an increasing call for a ‘systems’ approach. Incorporating the concepts of ‘emergence’, ‘systems’, ‘thermodynamics’, and ‘chaos’, a single integrated framework for carcinogenesis has been developed, enabling existing theories to become compatible as alternative mechanisms, facilitating the integration of bioinformatics and providing a structure in which translational research can flow from both ‘benchtop to bedside’ and ‘bedside to benchtop’. In this review, a basic understanding of the key concepts of ‘emergence’, ‘systems’, ‘system levels’, ‘complexity’, ‘thermodynamics’, ‘entropy’, ‘chaos’, and ‘fractals’ is provided. Non-linear mathematical equations are included where possible to demonstrate compatibility with bioinformatics. Twelve principles that define the ‘emergence framework of carcinogenesis’ are developed, with principles 1–10 encapsulating the key concepts upon which the framework is built and their application to carcinogenesis. Principle 11 relates the framework to cancer progression. Principle 12 relates to the application of the framework to translational research. The ‘emergence framework of carcinogenesis’ collates current paradigms, concepts, and evidence around carcinogenesis into a single framework that incorporates previously incompatible viewpoints and ideas. Any researcher, scientist, or ...
Keywords	emergence ; systems biology ; carcinogenesis ; thermodynamics ; chaos ; entropy ; Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282
Subject code	006
Language	English
Publishing date	2017-09-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
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Article ; Online: Re: "Routine Preoperative Laryngoscopy for Thyroid Surgery Is Not Necessary Without Risk Factors" by Maher

Walgama, Evan / Sinclair, Catherine / Chen, Amy Y / Davies, Louise / Noel, Julia E / Orloff, Lisa A / Shindo, Maisie / Sigston, Elizabeth / Stack, Brendan C / Terris, David / Randolph, Gregory W

Thyroid : official journal of the American Thyroid Association

2020 Volume 30, Issue 5, Page(s) 785–786

MeSH term(s)	Humans ; Laryngoscopy ; Risk Factors ; Thyroid Gland ; Thyroidectomy ; Vocal Cord Paralysis
Language	English
Publishing date	2020-03-30
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	1086044-7
ISSN	1557-9077 ; 1050-7256
ISSN (online)	1557-9077
ISSN	1050-7256
DOI	10.1089/thy.2020.0042
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Article ; Online: Lipoblastoma: an interesting differential of paediatric lipoma.

Lim, Rebecca Sin Mei / Flatman, Sam / Sigston, Elizabeth / Longano, Anthony

ANZ journal of surgery

2014 Volume 84, Issue 5, Page(s) 387–388

MeSH term(s)	Diagnosis, Differential ; Head and Neck Neoplasms/diagnosis ; Head and Neck Neoplasms/pathology ; Humans ; Infant ; Lipoblastoma/diagnosis ; Lipoblastoma/pathology ; Lipoma/diagnosis ; Magnetic Resonance Imaging ; Male
Language	English
Publishing date	2014-05
Publishing country	Australia
Document type	Case Reports ; Journal Article
ZDB-ID	2050749-5
ISSN	1445-2197 ; 1445-1433 ; 0004-8682
ISSN (online)	1445-2197
ISSN	1445-1433 ; 0004-8682
DOI	10.1111/ans.12238
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Article: Malignant otitis externa: an Australian case series.

Chin, Ronald / Roche, Phoebe / Sigston, Elizabeth / Valance, Neil

The surgeon : journal of the Royal Colleges of Surgeons of Edinburgh and Ireland

2012 Volume 10, Issue 5, Page(s) 273–277

Abstract: Objectives: To establish a clinicopathological profile of malignant otitis externa (MOE) in an Australian tertiary referral institution.: Study design: Retrospective cohort outcomes study.: Methods: 24 patients were identified with MOE between ... ...

Abstract	Objectives: To establish a clinicopathological profile of malignant otitis externa (MOE) in an Australian tertiary referral institution. Study design: Retrospective cohort outcomes study. Methods: 24 patients were identified with MOE between January 1998 and July 2007. Patients were classified into Radiological Grades I-IV. Laboratory investigations Including C-reactive protein (CRP), white cell count (WCC), glycosylated haemoglobin (HBA1c) and average glucose level over admission were recorded. Results: Radiological Grade was significantly associated with duration of therapy (rank correlation 0.57, p = 0.004). CRP was a useful indicator confirming disease resolution. Diabetics with MOE had elevated average blood sugar levels during their Hospital admission (p < 0.001) and had poor overall glycaemic control represented by Elevated HBA1c scores (p < 0.001). Conclusions: Malignant otitis externa is a rare disease, which is best managed in a multidisciplinary team setting. This practical grading system can be used to predict the duration of therapy at time of diagnosis, which enables the efficient utilisation of Hospital resources. Poorly controlled diabetics are more susceptible to developing. MOE than diabetics with satisfactory glycaemic control and may represent a subgroup of more brittle diabetics. CRP combined with appropriate clinical and radiological investigations is useful in assessing disease resolution.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Australia ; C-Reactive Protein/analysis ; Comorbidity ; Diabetes Mellitus/epidemiology ; Diabetes Mellitus, Type 1/epidemiology ; Disease Management ; Female ; Glycated Hemoglobin A/analysis ; Humans ; Leukocyte Count ; Male ; Mastoid/diagnostic imaging ; Middle Aged ; Otitis Externa/diagnostic imaging ; Otitis Externa/epidemiology ; Retrospective Studies ; Risk Assessment ; Temporal Bone/diagnostic imaging ; Tomography, X-Ray Computed
Chemical Substances	Glycated Hemoglobin A ; C-Reactive Protein (9007-41-4)
Language	English
Publishing date	2012-10
Publishing country	Scotland
Document type	Journal Article
ZDB-ID	2102927-1
ISSN	1479-666X
ISSN	1479-666X
DOI	10.1016/j.surge.2011.09.004
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Article ; Online: Surgical margins in head and neck squamous cell carcinoma: Effect of heat artifact on immunohistochemistry as a future tool for assessment.

Sigston, Elizabeth A W / Longano, Anthony / Strzelecki, Aneta T / Williams, Bryan R G

Head & neck

2016 Volume 38, Issue 9, Page(s) 1401–1406

Abstract: Background: Margins in head and neck squamous cell carcinoma (HNSCC) are determined by morphological changes assessed via hematoxylin-eosin staining. Physiological changes may not be detected by this technique. The purpose of this study was to determine ...

Abstract	Background: Margins in head and neck squamous cell carcinoma (HNSCC) are determined by morphological changes assessed via hematoxylin-eosin staining. Physiological changes may not be detected by this technique. The purpose of this study was to determine if a protein biomarker, laminin-332γ2, overexpressed in cancer cells at the invasive front in HNSCC, remains unaffected by heat produced during resection, supporting a role for immunohistochemistry assessment of margins. Methods: Archived tissue blocks from glottic squamous cell carcinomas (SCCs) resected by CO2 laser likely to contain both cancer cells and artifact were identified; 129-paired slides were obtained. One slide of each pair was stained with hematoxylin-eosin; the second stained for laminin-332γ2. The presence of cancer cells, artifact, and positive laminin-332γ2 staining was recorded. Twenty-seven pairs met the inclusion criteria. Results: Immunohistochemistry staining of laminin-332γ is preserved in presence of heat artifact. Conclusion: This study supports use of immunohistochemistry to assess margins. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1401-1406, 2016.
MeSH term(s)	Artifacts ; Carcinoma, Squamous Cell/pathology ; Cell Adhesion Molecules/chemistry ; Female ; Head and Neck Neoplasms/pathology ; Hot Temperature ; Humans ; Immunohistochemistry ; In Vitro Techniques ; Male ; Margins of Excision ; Retrospective Studies ; Risk Factors ; Sensitivity and Specificity ; Specimen Handling ; Squamous Cell Carcinoma of Head and Neck ; Staining and Labeling/methods ; Kalinin
Chemical Substances	Cell Adhesion Molecules
Language	English
Publishing date	2016-04-04
Publishing country	United States
Document type	Evaluation Study ; Journal Article
ZDB-ID	645165-2
ISSN	1097-0347 ; 0148-6403 ; 1043-3074
ISSN (online)	1097-0347
ISSN	0148-6403 ; 1043-3074
DOI	10.1002/hed.24450
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Article ; Online: Factors leading to the use of alternate treatment modalities following transoral laser excision of T1 and T2 glottic squamous cell carcinoma.

Pham, Truong An / De Freitas, Ryan / Sigston, Elizabeth / Vallance, Neil

ANZ journal of surgery

2012 Volume 82, Issue 10, Page(s) 720–723

Abstract: Background: CO(2) transoral laser surgery and radiotherapy are both recognized as acceptable treatments for early glottic squamous cell carcinoma (SCC) with similar rates of cure. The reasons why some of the patients in our series undergoing laser ... ...

Abstract	Background: CO(2) transoral laser surgery and radiotherapy are both recognized as acceptable treatments for early glottic squamous cell carcinoma (SCC) with similar rates of cure. The reasons why some of the patients in our series undergoing laser resection as their primary modality of treatment subsequently underwent radiotherapy or chemoradiotherapy will be discussed. Methods: Retrospective study between January 2003 and August 2010 of all T1 and T2 glottic SCCs treated with laser resection at a major tertiary centre. Tis lesions were excluded. A review of the cases in which primary control with laser resection was not achieved was undertaken. Failure was defined as patients treated initially with laser resection who subsequently received radiotherapy, combined chemoradiotherapy or open surgery for the same tumour. Factors leading to failure were analysed, including tumour location, histology, stage and patient factors. Results: Thirty-one patients were identified, with the majority (27) having T1 disease. Mean number of laser excisions per patient was 1.7. Local control rate was 71% with laser alone. One patient had nodal recurrence with no primary recurrence. Mean follow-up was 32 months. Of the nine patients in whom local control was not achieved with laser alone, all had tumour at or crossing the anterior commissure. Four patients were deemed potentially curable with further excision but chose radiotherapy. Two patients were deemed appropriate for radiotherapy and chemoradiotherapy. Three patients had loco-regional recurrence and underwent laryngectomy. All had anterior commissure involvement. Conclusion: Transoral laser excision is a safe, function-preserving treatment of early glottic SCC. Anterior commissure involvement was the major factor for potential failure with laser resection in T1 and T2 glottic tumours.
MeSH term(s)	Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell/mortality ; Carcinoma, Squamous Cell/pathology ; Carcinoma, Squamous Cell/surgery ; Carcinoma, Squamous Cell/therapy ; Chemoradiotherapy, Adjuvant ; Female ; Follow-Up Studies ; Glottis/pathology ; Glottis/surgery ; Humans ; Laryngeal Neoplasms/mortality ; Laryngeal Neoplasms/pathology ; Laryngeal Neoplasms/surgery ; Laryngeal Neoplasms/therapy ; Laryngectomy ; Lasers, Gas/therapeutic use ; Male ; Middle Aged ; Neoplasm Recurrence, Local/mortality ; Neoplasm Recurrence, Local/pathology ; Neoplasm Recurrence, Local/surgery ; Neoplasm Staging ; Radiotherapy, Adjuvant ; Retrospective Studies ; Survival Analysis ; Treatment Failure
Language	English
Publishing date	2012-10
Publishing country	Australia
Document type	Evaluation Studies ; Journal Article
ZDB-ID	2050749-5
ISSN	1445-2197 ; 1445-1433 ; 0004-8682
ISSN (online)	1445-2197
ISSN	1445-1433 ; 0004-8682
DOI	10.1111/j.1445-2197.2012.06138.x
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