Geographic disparities in thyroid cancer staging at presentation: Insights from an Australian context.

BACKGROUND: Thyroid cancer diagnoses have increased over recent decades at a rate much higher than that of any other cancer in Australia. Rural patients are known to have reduced access to healthcare and may have different thyroid cancer presentation rates. This study examined the relationship between thyroid cancer diagnosis and patient rurality. METHODS: Data from the Australia and New Zealand Thyroid Cancer Registry from 2017 to 2022 were analyzed, stratifying patient postcodes into rurality groups using the Australian Statistical Geography Standard. The American Thyroid Association (ATA) guidelines were used to stratify risk categories and management to compare treatment adequacy between the groups. Statistical analysis assessed demographic, clinical, and management differences. RESULTS: Among 1766 patients, 70.6% were metropolitan (metro) and 29.4% were non-metropolitan (non-metro). Non-metro patients were older at diagnosis (median 56 vs. 50 years, p < 0.001), presented more frequently with T stage greater than 1 (stage 2-4, 41.9% vs. 34.8%, and p = 0.005), AJCC stage greater than 1 (stage 2-4, 18.5% vs. 14.6%, and p = 0.019), and cancers larger than 4 cm (14.3% vs. 9.9%, p = 0.005). No significant differences in treatment adequacy were observed between the groups for ATA low-risk cancers. CONCLUSIONS: Non-metropolitan patients in the registry present with more advanced thyroid cancer, possibly due to differences in healthcare access. Further research should assess long-term survival outcomes and influencing factors. Understanding the impact on patient outcomes and addressing healthcare access barriers can optimize thyroid cancer care across geographic regions in Australia.

Evolving challenges of leadership in surgery to improve inclusivity, representation, and well-being.

BACKGROUND: Leadership is a complex and demanding process crucial to maintaining quality in surgical systems of care. Once an autocratic practice, modern-day surgical leaders must demonstrate inclusivity, flexibility, emotional competence, team-building, and a multidisciplinary approach. The complex healthcare environment challenges those in leadership positions. The aim of this narrative review was to consolidate the major challenges facing surgeons today and to suggest evidence-based strategies to support surgical leaders. METHODS: Google Scholar, PubMed, MEDLINE, and Ovid databases were searched to review literature on the challenges faced by surgical leaders. The commonly identified areas that compromise inclusivity and productive leadership practices were consolidated into 10 main subheadings. Further research was conducted using the aforementioned databases to outline the importance of addressing such challenges, and to consolidate evidence-based strategies to resolve them. RESULTS: The importance of increasing representation of marginalized groups in leadership positions, including women, ethnic groups, the queer community, and ageing professionals, has been identified by surgical colleges in many countries. Leaders must create a collegial environment with proactive, honest communication and robust reporting pathways for victims of workplace harassment. The retention of diverse, empowering, and educating leaders relies on equitable opportunities, salaries, recognition, and support. Thus, it is important to implement formal training and mentorship, burnout prevention, conflict management, and well-being advocacy. CONCLUSION: There are two aspects to addressing challenges facing surgical leadership; improving advocacy by and for leaders. Systems must be designed to support surgical leaders through formal education and training, meaningful mentorship programmes, and well-being advocacy, thus enabling them to proactively and productively advocate and care for their patients, colleagues, and professional communities.

Speaking Up and Speaking Out: Gender Diversity in the Scientific Programme of the Royal Australasian College of Surgeons Annual Scientific Congress.

BACKGROUND: Disparities in gender representation at medical meetings have been documented despite women representing half of medical school graduating classes. Lack of role models is touted as one of a myriad of factors that perpetuate gender imbalance, particularly in the field of surgery. We evaluated the trend in gender distribution of participants at the Royal Australasian College of Surgeons (RACS) Annual Scientific Congress (ASC) and whether there was a correlation between the gender distribution of the organising committee and speakers and chairpersons invited to attend. METHODS: RACS ASC programmes from 2013 to 2018 were retrospectively analysed, examining the gender distribution of speakers, chairpersons and conveners. Trend analysis of distribution was performed, and a generalized linear mixed model was used to investigate the effect of the gender of the conveners on gender of session chairpersons and speakers. RESULTS: Between 2013 and 2018, there were non-significant increases in female speakers invited to speak from 14.9 to 21.7% (p = 0.064) and female conveners appointed from 11 to 19% (p = 0.115), but there was a significant increase in female chairs from 9.6 to 21.6% p < 0.001). Female conveners were 3 times more likely to invite female speakers than male conveners (p < 0.001) and were 20 times more likely to invite female chairs than male conveners (p < 0.001). CONCLUSION: Visible role models are important in the pursuit of gender equity in surgery in order to break down stereotypes and the hidden curriculum. Intentional effort is required to achieve parity, and such efforts could include appointing more women to organising committees of scientific meetings.

Gender Representation by Specialty Track at Surgical Meetings: The American and Australasian Experiences.

BACKGROUND: We compared the representation of women panelists at two large, general interest surgical meetings: the American College of Surgeons (ACS) Clinical Congress and Royal Australasian College of Surgeons (RACS) Scientific Congress. MATERIALS AND METHODS: We performed comprehensive analyses of panels and panelists at ACS and RACS meetings (2013-2018). Manual review was conducted to determine counts and proportions of invited panelists by gender. We made within- and between-meeting comparisons regarding gender representation by specialty track. Tracks were characterized after our review of meeting programs. RESULTS: There were 4542 panelists and 1390 panels at RACS from 2013 to 2018. At ACS, there were 3363 panelists over 693 panels. The specialty tracks with the highest proportion of men-only panels were transplant (75%) and cardiothoracic (63%) at ACS and cardiothoracic (83%) and multidisciplinary (81%) at RACS. The lowest proportions of men-only panels were in breast and pediatric surgery at ACS (5% and 11%, respectively) and breast and rural surgery at RACS (24% and 36%, respectively). At ACS, the highest proportions of women panelists were on panels in breast (63%) and endocrine surgery (48%) and in breast (44%) and rural surgery (33%) at RACS, while the lowest proportion of women panelists were in transplant (10%) and cardiothoracic (14%) at ACS and multidisciplinary (8%) and cardiothoracic (7%) at RACS. CONCLUSIONS: There is a persistent difference in gender representation at surgical meetings, particularly within certain subspecialties. Program chairs and committees could increase the proportion of women by focusing on who serves as panelists overall and within specialty tracks.

Trends in Gender Representation at the American College of Surgeons Clinical Congress and the Academic Surgical Congress: A Mixed Picture of Progress.

BACKGROUND: There has been increasing attention to gender inequity in speakers at professional meetings. The aim of this study was to evaluate temporal trends in representation of women at the Academic Surgical Congress (ASC) and American College of Surgeons Clinical Congress (CC), 2 prominent general interest, national surgical meetings. STUDY DESIGN: We reviewed ASC (2014-2019) and CC (2013-2018) meeting programs to determine counts and proportions of invited panelists and moderators by gender, including the frequency of men-only panels. We conducted trend analyses to assess for temporal change in gender representation and univariate tests of association between different measures of gender representation. RESULTS: The overall proportions of women panelists were 35% (ASC) and 28% (CC). There was a significant increase in the proportion of women panelists over the study period at the CC (23% to 34%, p = 0.007) but not at the ASC (37% to 36%, p = 0.79). The proportion of men-only panels decreased significantly over time at the CC (38% to 23%, p = 0.04), but not at the ASC (23% to 17%, p = 0.50), while the proportion of moderators at the ASC increased significantly (31% to 43%, p = 0.01), but not at the CC (29% to 37%, p = 0.40). CONCLUSIONS: Women remain in the minority of panelists and moderators at the ASC and CC meetings, and approximately 1 in 5 panels are composed entirely of men. Although progress has been made at both meetings, ongoing and deliberate attention is needed to ensure continued progress toward the goal of equitable gender representation in academic surgery.

Genetic and molecular identification of three human TPP1 functions in telomerase action: recruitment, activation, and homeostasis set point regulation.

Telomere length homeostasis is essential for the long-term survival of stem cells, and its set point determines the proliferative capacity of differentiated cell lineages by restricting the reservoir of telomeric repeats. Knockdown and overexpression studies in human tumor cells showed that the shelterin subunit TPP1 recruits telomerase to telomeres through a region termed the TEL patch. However, these studies do not resolve whether the TPP1 TEL patch is the only mechanism for telomerase recruitment and whether telomerase regulation studied in tumor cells is representative of nontransformed cells such as stem cells. Using genome engineering of human embryonic stem cells, which have physiological telomere length homeostasis, we establish that the TPP1 TEL patch is genetically essential for telomere elongation and thus long-term cell viability. Furthermore, genetic bypass, protein fusion, and intragenic complementation assays define two distinct additional mechanisms of TPP1 involvement in telomerase action at telomeres. We demonstrate that TPP1 provides an essential step of telomerase activation as well as feedback regulation of telomerase by telomere length, which is necessary to determine the appropriate telomere length set point in human embryonic stem cells. These studies reveal and resolve multiple TPP1 roles in telomere elongation and stem cell telomere length homeostasis.

Human intestinal tissue with adult stem cell properties derived from pluripotent stem cells.

Genetically engineered human pluripotent stem cells (hPSCs) have been proposed as a source for transplantation therapies and are rapidly becoming valuable tools for human disease modeling. However, many applications are limited due to the lack of robust differentiation paradigms that allow for the isolation of defined functional tissues. Here, using an endogenous LGR5-GFP reporter, we derived adult stem cells from hPSCs that gave rise to functional human intestinal tissue comprising all major cell types of the intestine. Histological and functional analyses revealed that such human organoid cultures could be derived with high purity and with a composition and morphology similar to those of cultures obtained from human biopsies. Importantly, hPSC-derived organoids responded to the canonical signaling pathways that control self-renewal and differentiation in the adult human intestinal stem cell compartment. This adult stem cell system provides a platform for studying human intestinal disease in vitro using genetically engineered hPSCs.

Time to breast cancer relapse predicted by primary tumour characteristics, not lymph node involvement.

INTRODUCTION: The risk of breast cancer recurrence has been linked to tumour size, grade, oestrogen (ER) receptor status, and degree of lymph node (LN) involvement. However, the role of these variables in predicting time to relapse is not well defined. This study was designed to identify patient and primary tumour characteristics that predict risk periods for breast cancer recurrence within our institution, to enable more tailored surveillance strategies. METHODS: We retrospectively studied a cohort of 473 patients who presented to The Queen Elizabeth Hospital, Adelaide, Australia, with recurrent breast cancer between 1968 and 2008. Patient and primary tumour characteristics were collected, including age, menopausal status, tumour grade, size, ER and progesterone receptor (PR) status, and LN involvement and modeled against time to relapse using Kaplan-Meier survival curves. RESULTS: High tumour grade, size ≥ 20 mm, ER negativity, and PR negativity were shown on univariate analysis to correlate significantly with earlier recurrence (P < 0.0001, P = 0.0012, P = 0.0006, and P = 0.006). Multivariate analysis identified tumour grade and size as significant predictors of timing of relapse after adjustment for other variables. LN involvement, menopausal status, and age did not significantly correlate with earlier recurrence. CONCLUSIONS: High tumour grade and larger size were shown to independently predict earlier breast cancer relapse. While LN involvement increases absolute recurrence risk, our study proposes that it does not influence timing of relapse. Use of these predictors will enable key risk periods for onset of relapse to be characterised according to tumour profile with more appropriate discharge to primary care providers for ongoing surveillance.

Genetic engineering of human pluripotent cells using TALE nucleases.

Targeted genetic engineering of human pluripotent cells is a prerequisite for exploiting their full potential. Such genetic manipulations can be achieved using site-specific nucleases. Here we engineered transcription activator-like effector nucleases (TALENs) for five distinct genomic loci. At all loci tested we obtained human embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) clones carrying transgenic cassettes solely at the TALEN-specified location. Our data suggest that TALENs employing the specific architectures described here mediate site-specific genome modification in human pluripotent cells with similar efficiency and precision as do zinc-finger nucleases (ZFNs).