Search

Hooshang Lahooti,1,2 Senarath Edirimanne,1,2 John P Walsh,3,4 Leigh Delbridge,5,6 Emily J Hibbert,1,2 Jack R Wall1,2 1Thyroid Research Laboratory, Sydney Medical School – Nepean Clinical School, The University of Sydney, Kingswood, NSW, Australia; 2Nepean Blue Mountains Local Health District, Kingswood, NSW, Australia; 3Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, Australia; 4School of Medicine and Pharmacology, The University of Western Australia, Crawley, WA, Australia; 5Department of Surgery, Royal North Shore Hospital, St Leonards, NSW, Australia; 6Sydney Medical School – Northern Clinical School, The University of Sydney, NSW, Australia Background: Our studies over recent years have focused on some new ideas concerning the pathogenesis for the orbital reaction that characterizes Graves’ ophthalmopathy namely, that there are antigens expressed by thyroid tissue and orbital tissue where they are targeted by autoantibodies and/or sensitized T cells, leading to orbital inflammation. While this has been well studied for the thyroid stimulating hormone-receptor, the possible role of another major thyroid antigen, Thyroglobulin (TG), has been largely ignored.Methods: We identified novel variant 1623 A/G single nucleotide polymorphism (SNP) (rs180195) in the promoter of TG gene associated with autoimmune thyroid disorders. We genotyped the TG SNPs rs2069566, rs2076739, rs121912646, rs121912647, rs121912648, rs121912649, rs121912650, rs137854433, rs137854434, and rs180195 by MassARRAY SNP analysis using iPLEX technology in a cohort of 529 patients with thyroid autoimmunity with and without ophthalmopathy, and controls.Results: We showed that variant 1623 A/G SNP (rs180195) in the promoter of TG gene is a marker for thyroid autoimmunity, but not for ophthalmopathy. We showed that there was a significant difference in the distribution of the major allele (G) vs minor allele (A) in patients with Hashimoto’s thyroiditis (HT). In HT the wild-type (GG) genotype was less common. We showed that the genotypes homozygous AA and heterozygous GA rs180195 SNP in the promoter of TG gene were more closely associated with thyroid autoimmunity than the wild-type (GG) polymorphism, and are thus, markers of autoimmunity.Conclusion: rs180195 SNP was previously identified by Stefan et al independently of us, who showed that this TG SNP predisposed to autoimmune thyroid diseases. However, this is the first study to explore the association between TG SNPs and HT. Our findings support the notion that the thyroid and orbital disorders are not part of the same disease, ie, “Graves’ disease” or “Hashimoto’s disease”, but separate autoimmune disorders. Keywords: hyperthyroid, Hashimoto’s, thyroid eye disease, orbital, homozygote, heterozygote, T-cells

Hooshang Lahooti,1,2 Daniele Cultrone,1,2 Senarath Edirimanne,1,2 John P Walsh,3,4 Leigh Delbridge,5,6 Patrick Cregan,1,2 Bernard Champion,1,2 Jack R Wall1,21Thyroid Research Laboratory, Sydney Medical School – Nepean Clinical School, The University of Sydney, 2Nepean Blue Mountains Local Health District, Nepean Hospital, Kingswood, NSW, 3Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, 4School of Medicine and Pharmacology, The University of Western Australia, Crawley, WA, 5Department of Surgery, Royal North Shore Hospital, 6Sydney Medical School – Northern Clinical School, The University of Sydney, St Leonards, NSW, AustraliaBackground: The eye disorder associated with Graves’ disease, called Graves’ ophthalmopathy (GO), greatly reduces the quality of life in affected patients. Expression of the calsequestrin (CASQ1) protein in thyroid tissue may be the trigger for the development of eye muscle damage in patients with GO. We determined the prevalence of rs74123279, rs3747673, and rs2275703 single-nucleotide polymorphism (SNPs) in patients with autoimmune thyroid disorders, GO, Graves’ hyperthyroidism (GH), or Hashimoto’s thyroiditis (HT) and control subjects with no personal or family history of autoimmune thyroid disorders. Furthermore, we measured the concentration of the CASQ1 protein in normal and Graves’ thyroid tissue, correlating levels with parameters of the eye signs, CASQ1 antibody levels, and the CASQ1 gene polymorphism rs74123279 and rs2275703.Methods: High-quality genomic DNA was isolated from fresh blood samples, assayed for identification of rs74123279, rs3747673, and rs2275703 SNPs in CASQ1 gene by MassARRAY SNP analysis using iPLEX technology of SEQUENOM.Results: DNA samples from 300 patients and 106 control subjects (100 males, 306 females) with GO (n=74), GH (n=130), HT (n=96) and control subjects (n=106) were genotyped for the SNPs rs74123279, rs3747673 (n=405), and rs2275703 (n=407). The SNP rs74123279, rs3747673, and rs2275703 were identified as 1) common homozygous or wild type, 2) heterozygote, and 3) rare homozygous. Minor allele frequency for rs74123279, rs3747763, and rs2275703 were 21%, 40%, and 44%, respectively. Multiple comparisons of genotype frequency for rs74123279, rs3747763, and rs2275703 in the GO, GH, HT, and control groups showed P=0.06, 0.641, and 0.189, respectively. These results were substantiated by multiple comparison of alleles frequency for rs74123279, rs3838216, rs3747763, and rs2275703 in the GO, GH, HT, and control groups showed, P=0.36, 0.008, 0.66, and 0.05, respectively. Pairwise analysis of alleles frequency distribution in patients with GO showed significant probability for rs2275703, P=0.008.Conclusion: Based on their evolutionary conservation and their significant prevalence, we suggest that CASQ1 gene SNPs rs74123279, rs3838216, and rs2275703 may be considered as genetic markers for GO.Keywords: thyroid eye disease, autoimmune thyroiditis, ophthalmology, orbitopathy, eye muscles antibodies, wild-type, homozygous, heterozygous, genotyping

Background: Lifestyle has been shown to significantly effect breast cancer incidence evident in the increased risk associated with obesity, diabetes, cigarettes and alcohol. The aim of this meta-analysis was to investigate the effect of two traditionally "beneficial" lifestyle choices: physical activity and weight loss. Specifically, we aimed to investigate the effect of the timing, intensity and duration of exercise on breast cancer incidence in women classified as either normal risk or increased risk. Finally, we aimed to investigate the effect of weight loss on breast cancer incidence. Method: Studies were obtained from a database search of MEDLINE, EMBASE, PubMed, Current Contents Connect and Google Scholar. Databases were searched using subject headings, keyword searches and text word searches wherever possible using the search terms "Exercise" OR "weight loss" AND "breast cancer" OR "breast carcinoma" OR "breast neoplasm". Inclusion criteria required a confirmed diagnosis of breast cancer, reporting of an odds ratio or data to calculate an odds ratio (and 95% confidence interval) and the use of an internal control group as the comparator. Exercise was catagorised as "high intensity" if it was vigorous exercise likely to cause sweating (ie. Running, competitive sport) while lower impact activities such as walking and golf were categorized as "low intensity". The effect of the timing on breast cancer incidence was quantified across three time periods: adolescence, adulthood and post menopause. Collated data was assessed for heterogeneity and a pooled odds ratio calculated. Results: 111 studies were identified in the literature search of which 76 were included in the meta-analysis. Overall, both exercise and weight loss were associated with a significantly reduced risk of breast cancer in women (OR 0.77, 95% CI 0.72-0.81 and OR 0.74, 95% CI 0.60-0.93 respectively). Heterogeneity was high (I²=77.12) and publication bias was significant (p < 0.001). Subgrouping by menopausal status at diagnosis of breast cancer found an increased reduction in the incidence of postmenopausal breast cancer when compared with premenopausal breast cancer and exercise (OR 0.68, 95% CI 0.60-0.78 and OR 0.81, 95% CI 0.71-0.92 respectively). The protection offered by exercise was not effected by the intensity of the exercise evident in a pooled odds ratio of 0.78 (95%CI 0.70-0.86) for low intensity exercise and 0.77 (95%CI 0.69-0.85) for high intensity. A similar consistency in the level of protection was present in regards to the timing of the physical activity with regular exercise during adolescence, adulthood and post menopause associated with odds ratios of 0.79 (95% CI 0.72-0.88), 0.84 (95% CI 0.77-0.92) and 0.82 (95% CI 0.75-0.89) respectively. In regards to the subpopulation at an increased risk of breast cancer, exercise significantly reduced the incidence of breast cancer in overweight individuals (OR 0.80, 95% CI 0.68-0.94) however the reduced risk in women with a positive family history did not reach statistical significance (OR 0.78, 95% CI 0.60-1.00). Conclusion: Breast cancer incidence is significantly reduced by both physical exercise and weight loss, especially in the postmenopausal population. Intensity, timing and nature of the exercise did not significantly alter the protective effect. [ABSTRACT FROM AUTHOR]

Background: The hyperinsulinaemia associated with type 2 diabetes and the known proliferative effects of insulin lead to the hypothesis that diabetes mellitus increases the risk of breast cancer. The aim of this meta-analysis was to collate and analyse all primary observational studies investigating the risk of breast cancer associated with diabetes. In addition, we aimed to complete sub group analyses by both type of diabetes and gender of study participants to further clarify the origin of any such association between the two. Method: Studies were obtained from a database search of MEDLINE, EMBASE, PubMed, Current Contents Connect and Google Scholar with additional cross checking of reference lists. Databases were searched using subject headings, keyword searches and text word searches wherever possible using the search terms 'diabetes' AND 'breast cancer' OR 'breast carcinoma' OR 'breast neoplasm'. Inclusion criteria required a confirmed diagnosis of both diabetes and breast cancer, reporting of an odds ratio or data to calculate an unadjusted odds ratio (and 95% confidence interval) and the use of an internal control group as the comparator. Collated data was assessed for heterogeneity and a pooled odds ratio calculated. Results: 34 studies were included in the meta-analysis with 31 studies investigating breast cancer in women and 5 studies investigating breast cancer in men. Overall, we found a significantly increased risk of breast cancer associated with diabetes in both women (OR 1.25, 95% CI 1.13-1.38) and men (OR 1.40, 95% CI 1.10-1.79). The pooled odds ratio was consistent across both case control studies (OR 1.25, 95% CI 1.06-1.46) and cohort studies (OR 1.26, 95% CI 1.09-1.45). Heterogeneity was significant (I² = 73.40, p < 0.001) and publication bias was present (p = 0.03). The 31 studies investigating breast cancer in women were sub grouped by type of diabetes with the association strengthened by a diagnosis of type 2 diabetes (OR 1.32, 95% CI 1.09-1.61) but nullified with gestational diabetes (OR 1.06, 95% CI 0.79-1.40). There were insufficient studies to calculate a pooled odds ratio of the risk of breast cancer associated with type 1 diabetes. Conclusion: Diabetes increases the risk of breast cancer in both women and men. This association is strengthened in women with type 2 diabetes and supports the hypothesis that diabetes is an independent risk factor for breast cancer. [ABSTRACT FROM AUTHOR]

Despite significant advancements in early breast cancer detection, mastectomy remains a crucial treatment option for some patients. Immediate breast reconstruction post-mastectomy has emerged as an ideal procedure to minimize physical and psychosocial patient impacts, striving for improved cosmetic results. The "enhanced "Goldilocks mastectomy technique, characterized by nipple preservation or grafting and utilizing the fifth perforator anatomy, offers a sound approach to reconstruction in comorbid and large-breasted patients. This paper discusses the advantages, disadvantages, and real-world application of Goldilocks mastectomy in enhancing breast reconstruction outcomes and meeting patients' diverse needs., Competing Interests: The authors have no conflicts of interest to declare., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2024.)

Background: Reduction mammoplasty and mastopexy are potentially complicated by prior breast irradiation as part of breast conserving therapy. Associated tissue changes with therapeutic irradiation have led to surgeons deciding the risks may outweigh potential benefit for those patients. A systematic review of the existing literature was performed to explore surgical outcomes of patients undergoing delayed bilateral reduction mammoplasty or mastopexy following unilateral breast irradiation as part of breast conserving therapy., Methods: Medline, PubMed and EMBASE were searched from 1990 to 2023 according to PRISMA guidelines. Studies were combined by the generic inverse variance method on the natural logarithms of rate ratios (RR) using a random effect model in Review manager 5.4.1., Results: Fifteen studies reported outcomes in 188 patients who underwent breast reduction (BR) following unilateral breast conserving surgery and radiotherapy. The median age at BR was 51.5 years (range 39-60), and median time since radiotherapy was 48 months (range 11.7-86). We compared outcomes for irradiated breast (IB) versus non-irradiated breast (NIB). Pooled results showed higher rate of major complications in the IB (RR 2.52, 95%CI 0.96-6.63, p=0.06), but not statistically significant. However, rate of minor complications was significantly higher in the IB (RR 3.97 95%CI 1.86-8.50, p<0.0004). Incidence of fat necrosis as a discrete complication was 2× higher in IB (RR 2.14 95%CI 0.85-5.35, p-value 0.10) compared to the NIB, but not significant., Conclusion: We found breast reduction to be safe with acceptable risk of major complications. However, the overall complication rate remains higher in IB compared to NIB., Level of Evidence Iii: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of contents or the online Instructions to Authors www.springer.com/00266 ., Competing Interests: Declarations. Conflict of interest: The authors declare that there is no conflict of interest regarding the publication of this article. Human and Animal Rights: This article does not contain any studies with human participants or animals performed by any of the authors. Informed Consent: For this type of study, informed consent is not required., (© 2024. The Author(s).)

Introduction: Changes to the tumour bed following oncoplastic breast surgery complicate the administration of adjuvant radiotherapy. Consensus guidelines have called for improved interdisciplinary communication to aid adjuvant boost radiotherapy. We propose a framework of tumour bed classification following oncoplastic surgery to enhance understanding and communication between the multidisciplinary breast cancer team and facilitate effective and more precise delivery of adjuvant boost radiotherapy., Methods: A classification system was devised by grouping oncoplastic procedures based on skin incision, tissue mobilization, tumour bed distortion, seroma formation and flap reconstruction. The system is supplemented by a colour-coded pictorial guide to tumour bed rearrangement with common oncoplastic procedures., Results: A 5-tier framework was developed. Representative images were produced to describe tumour bed alterations., Conclusion: The proposed framework (OPSURGE) improves the identification of the primary tumour bed after initial breast-conserving surgery, which is imperative to both the surgeon in planning re-excision and the radiation oncologist in planning boost radiotherapy., (© 2024 The Author(s). ANZ Journal of Surgery published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Surgeons.)

Background: The incidence of hypothyroidism following hemithyroidectomy and risk factors associated with its occurrence are not completely understood. This systematic review investigated the incidence and risk factors for hypothyroidism, thyroxine supplementation following hemithyroidectomy as well as the course of post-operative hypothyroidism, including the time to hypothyroidism and incidence of transient hypothyroidism., Methods: Searches were conducted in MEDLINE, EMBASE, Scopus, and Cochrane library for studies reporting the incidence of hypothyroidism or thyroxine supplementation following hemithyroidectomy., Results: Sixty-six studies were eligible for inclusion: 36 reported risk factors, and 27 reported post-operative course of hypothyroidism. Median follow-up was 25.2 months. The pooled incidence of hypothyroidism was 29% (95% CI, 25-34%; P<0.001). Transient hypothyroidism occurred in 34% of patients (95% CI, 21-47%; P<0.001). The pooled incidence of thyroxine supplementation was 23% (95% CI, 19-27%; P<0.001), overt hypothyroidism 4% (95% CI, 2-6%, P<0.001). Risk factors for development of hypothyroidism included pre-operative thyroid stimulating hormone (TSH) (WMD, 0.87; 95% CI, 0.75-0.98; P<0.001), TSH ≥ 2 mIU/L (RR, 2.87; 95% CI, 2.43-3.40; P<0.001), female sex (RR, 1.19; 95% CI, 1.08-1.32; P=0.007), age (WMD, 2.29; 95% CI, 1.20-3.38; P<0.001), right sided hemithyroidectomy (RR, 1.35; 95% CI, 1.10-1.65, P=0.003), the presence of autoantibodies anti-TPO (RR, 1.92; 95% CI, 1.49-2.48; P<0.001), anti-Tg (RR, 1.53; 95% CI, 1.40-1.88; P<0.001), and Hashimoto's thyroiditis (RR, 2.05; 95% CI, 1.57-2.68; P=0.001)., Conclusion: A significant number of patients will develop hypothyroidism or require thyroxine following hemithyroidectomy. An awareness of patient risk factors and postoperative thyroid function course will assist in counselling patients on their risk profile and guiding management., (© 2024. The Author(s).)

Background: The incidence of thyroid cancer has been rapidly increasing in recent years largely due to improved diagnostic methods. There is evidence to suggest that in papillary thyroid microcarcinoma (PTMC), active surveillance (AS) is comparable in effectiveness compared to immediate surgery (IM). We conducted a survey of Clinicians and Surgeons from Australia and New Zealand to assess the role of AS in the management of PTMC., Methods: A short electronic survey was created on the platform Survey Monkey, separate links containing the survey were sent to various medical societies to be distributed to its members. The list of medical societies included: General Surgeons Australia, Endocrine Society of Australia, Australian and New Zealand Endocrine Surgeons, Australian and New Zealand Head and Neck Cancer Society and New Zealand Association of General Surgery., Results: We received 110 complete responses, which demonstrated that 63% of clinicians will discuss AS with patients diagnosed with PTMC. Surgeons are more likely to discuss AS compared to endocrinologists (P=0.03). Forty-eight percent of respondents report managing patients with AS in the past year, those who are able to perform thyroid ultrasounds are more likely to utilise AS (P=0.03). Common perceived barriers to AS include patient anxiety, lack of access to regular follow-up and lack of patient compliance., Conclusions: Our survey shows that Australian and New Zealand clinicians are generally aware of AS as a treatment option for PTMC, but there remain considerable barriers for common implementation., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-24-25/coif). The authors have no conflicts of interest to declare., (2024 Gland Surgery. All rights reserved.)

Aim: There has been significant progress made in developing novel targeted therapies in the neoadjuvant setting for non-metastatic HER2-positive breast cancer, which may be used in combination with conventional chemotherapy to optimise pathological responses at surgery. However, these therapies, particularly the chemotherapeutic components, may portend significant and long-lasting toxicity. Hence, de-escalation of treatment intensity has been an area of interest and was evaluated in the phase II NeoSphere study. Herein, we report the real-world pathological and survival outcomes from neoadjuvant taxane and dual HER2 blockade recorded at our centre., Methods: This was a retrospective cohort study of patients receiving neoadjuvant pertuzumab, trastuzumab and taxane chemotherapy for non-metastatic HER2-positive breast cancer at a single centre in Sydney, Australia. We collected data pertaining to baseline demographic characteristics, pathological response rates, post-surgical prescribing patterns and also undertook survival analyses for invasive disease-free survival (iDFS) as well as exploratory analyses for correlations between pre-specified clinicopathologic factors and pathological response at surgery., Results: Our population was largely similar at baseline to the NeoSphere study. 71 patients were included in the final analysis. 61% achieved a pathological complete response (pCR). Three patients received conventional chemotherapy in the adjuvant setting. 92% of included patients were alive and disease-free at 3 years of follow-up. Only 3 events of recurrence or death were recorded at a median follow-up of 32 months. No significant difference in iDFS was noted between patients achieving pCR and those with residual disease at surgery., Conclusion: This study demonstrates that de-escalated adjuvant treatment for HER2-positive early breast cancer achieved favourable pathological and long-term outcomes comparable to large trials, some utilising more intensive chemotherapeutic components., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background: An association between breast cancer and meningioma has been suggested in cohort studies. We aimed to perform a systematic review and meta-analysis to determine whether there is an association between initial breast cancer and subsequent meningioma diagnosis and vice versa., Methods: A systematic literature search was performed on Medline, Embase, Scopus and Google scholar from inception up to April 2023. A meta-analysis of selected studies was performed using Review Manager 5.4., Results: There were eight studies included in the systematic review. Seven had reported Standardized Incidence Ratio (SIR) for female patients and were suitable for the meta-analysis. Only one study reported SIR for male patients. For the association between initial breast cancer and subsequent meningioma, in 795 000 female patients with follow-up ranging from 7 to 13 years, the SIR was 1.27 (95% CI: 1.20-1.34, P-value <0.00001). For the association between initial meningioma and subsequent breast cancer, in 28 000 female patients with follow-up ranging from 6 to 15 years, the SIR was 1.32 (95% CI: 1.21-1.45, P-value <0.00001). There were low heterogeneity and no significant publication bias., Conclusion: There was a small but significant association between initial breast cancer and subsequent meningioma as well as initial meningioma and subsequent breast cancer in female patients. The potential underlying mechanisms and risk factors were unclear from current literature and would be a potential area for future research., (© 2024 The Authors. ANZ Journal of Surgery published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Surgeons.)

Background: TSH receptor autoantibodies (TRAbs) are pathognomonic for Graves' disease and are thought to also underly the pathogenesis of Graves' ophthalmopathy (GO). A decline in TRAb levels has been documented post-total thyroidectomy (TTx) in GO, however with conflicting correlations with disease outcomes. The aim of the study was to compare the effectiveness of TTx to other treatment modalities of Graves' disease and examine whether the lowering of TRAbs is associated with GO improvements., Method: We searched electronic databases including Medline, Embase, Scopus, and Web of Science until 31 September 2022 using a broad range of keywords. Patients with GO undergoing TTx with measurements of both TRAbs and progression of the disease using a validated GO scoring system were included. Fourteen studies encompassing data from 1047 patients with GO met our eligibility criteria. The PRISMA guidelines were followed, and five studies had comparable data that were suitable for a meta-analysis., Results: The Cochrane Risk of Bias tool for RCTs showed low risk of bias across most domains. The pooled odds ratio showed that more patients significantly had normalized TRAb levels post-TTx as compared to other interventions (OR: 1.36, 95% CI: 1.02-1.81, p = 0.035). But, there was no significant difference in GO improvement post-TTx as compared with other intervention groups., Conclusions: This meta-analysis shows that TRAb levels may decline largely post-TTx, but may not predict added improvements to the progression of GO. Thus, future studies with uniform designs are required to assess the minimal significant GO improvements., (© 2023. The Author(s).)

Timely delivery of adjuvant chemotherapy is crucial. With an increasing frequency of immediate breast reconstructions (IBR) following mastectomy (MAS), concerns have arisen regarding its complication rates and effects on time to chemotherapy. The aim was to conduct a systematic review and meta-analysis to determine if there is a prolonged time to chemotherapy (TTC) after IBR and MAS. Electronic databases, reference lists and relevant articles were searched systematically. Eligibility criteria included women receiving adjuvant chemotherapy who underwent either MAS only or MAS and IBR. Random-effects models were used in the analysis. A total of 29 studies were included in qualitative analysis, comprising of 156,000 patients (IBR: 57,159; MAS: 98,841). But 23 studies had sufficient data to be included in the meta-analysis. Sixteen papers concluded there was no difference in TTC compared to MAS. There was a difference of 3.50 days between TTC in IBR versus MAS (95% CI [0.42, 6.57], P value = .0256; IBR = 43.56 days, MAS = 40.38 days). The rate of patients being delayed past 90 days was not significantly higher in IBR (OR = 1.34, 95% CI [0.76, 2.38], P = .310). IBR patients were more likely to have complications compared to the MAS group (OR = 2.04, 95% CI [1.04-4.01], P < .01). We concluded that there is a statistically significant longer time to chemotherapy following IBR of 3.50 days, yet there is no difference in delays past 90 days. Therefore, the longer TTC in IBR is unlikely to be of any clinical significance., Competing Interests: Disclosure The authors declare that they have no conflict of interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

We performed a systematic review and meta-analysis of the literature regarding cardiovascular outcomes of differentiated thyroid cancer (DTC) patients who are on long term thyroid stimulating hormone suppression. Searches were carried out using Prisma guidelines in Medline, Embase, CENTRAL, CINAHL and Scopus databases. Eligible papers were those which investigated discrete cardiovascular clinical outcomes in TSH suppressed patients and meta-analysis of selected studies was performed using Revman 5.4.1. We found a total of 195 879 DTC patients with median length to follow up of 8.6 years (range 5-18.8 years). Analysis showed DTC patients to be at higher risk of atrial fibrillation (HR 1.58, 95% CI 1.40, 1.77), stroke (HR 1.14, 95% CI 1.09, 1.20) and all-cause mortality (HR 2.04, 95% CI 1.02, 4.07). However, there was no difference in risk of heart failure, ischemic heart disease or cardiovascular mortality. These findings suggest that degree of TSH suppression must be titrated to accommodate risk of cancer recurrence and cardiovascular morbidity., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Introduction: Tumor-associated macrophages (TAMs) in breast cancer are associated with a poor prognosis. Early studies of TAMs were largely limited to the pan-macrophage marker CD68, however, more recently, an increasing number of studies have used CD163, a marker expressed by alternatively activated M2 macrophages and TAM subsets. We hypothesized that CD163-positive (CD163+) TAMs would be a better predictor of survival outcomes in breast cancer compared to CD68+  TAMs., Methods: We performed a systematic literature search of trials (from 1900 to August 2020) reporting overall survival (OS) or progression-free survival (PFS), breast cancer-specific survival (BCSS), TAM phenotype, and density. Thirty-two studies with 8446 patients were included. Meta-analyses were carried out on hazard ratios (HRs) for survival outcomes of breast cancer patients with a high density of TAMs (CD68+ and/or CD163+) compared to a low density of TAMs., Results: A high density of TAMs (CD68+ and/or CD163+) was associated with decreased OS (HR 1.69, 95% CI 1.37-2.07) and reduced PFS (HR 1.64; 95% CI 1.35-1.99). Subgrouping by CD marker type showed a lower OS for high density of CD163+ TAMs (HR 2.24; 95% CI 1.71-2.92) compared to a high density of CD68+  TAMs (HR 1.5; 95% CI 1.12-2). A high density of TAMs (CD68+  and/or CD163+) in triple-negative breast cancer (TNBC) cases was associated with lower OS (HR 2.81, 95% CI 1.35-5.84)., Conclusion: Compared to CD68+  TAMs, a high density of CD163+ TAMs that express a similar phenotype to M2 macrophages are a better predictor of poor survival outcomes in breast cancer., (© 2022. The Author(s).)

Introduction: The Oncotype DX test is a genomic assay that generates a Recurrence Score (RS) predicting the 10-year risk of recurrence and response to adjuvant chemotherapy in ER+/HER2- breast cancer patients. The aims were to determine breast cancer distant recurrence and correlate with adjuvant chemoendocrine prescribing patterns based on the Oncotype DX recurrence score., Methods: We conducted a retrospective single-institution case series of 71 patients who had Oncotype DX assay testing after definitive surgery between 2012 and 2016. Both node-positive and node-negative patients were included. Patients were divided into Oncotype DX low risk (RS < 11) (n = 10, 14%), intermediate risk (RS 11-25) (n = 45, 63%), and high risk (RS > 25) (n = 16, 23%). Median follow-up was 6.1 years (range 4-8.9 years). Adjuvant treatment regimens and oncological outcomes were determined . Results . Mean age at diagnosis was 56 years (range, 33-77). Invasive ductal carcinoma (IDC) accounted for the majority (87%), with most tumors measuring between 10-20 mm (52%). 48% of the cohort were node positive. 15 of 16 high-risk patients (94%) received chemotherapy. 96% of intermediate-risk patients received endocrine therapy alone, one patient received chemoendocrine therapy (2%), and one declined systemic therapy (2%). In the low-risk group, 100% received endocrine therapy only. The high-risk group had the lowest mean ER% ( P < 0.05), greatest mean mitotic rate ( P < 0.05), and greatest proportion of Ki67% > 14. Five patients developed distant recurrence (7%): three from the intermediate-risk group (7%), one from the low-risk group (10%), and one from the high-risk group (6%)., Conclusion: This is the first Australian study reporting the experience with medium-term recurrence outcomes of using the Oncotype DX assay in breast cancer. Chemotherapy was rarely given for patients with low-to-intermediate RS and always offered in high RS. This pattern of prescribing was associated with low rates of distant recurrence. National funding models should be considered., Competing Interests: The authors have no conflicts of interest., (Copyright © 2022 Joseph Do Woong Choi et al.)

Background: Serum thyroglobulin (Tg) is used in the follow-up of patients with differentiated thyroid cancers (DTC), but the presence of antithyroglobulin antibodies (TgAbs) makes Tg measurements unreliable. TgAb decline after total thyroidectomy and persistent/increasing levels may indicate cancer persistence/recurrence. Hence, we aimed to determine whether TgAb might be a reliable prognostic marker for DTC. Methods: We conducted a meta-analysis and systematic review. A comprehensive literature search was performed to identify studies of patients with DTC with known TgAb status and prognostic outcomes in five databases (Medline, Embase, PubMed, Google Scholar, and Scopus). We used a random-effects model to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs) for TgAb status and its association with DTC prognosis. Results: After analysis of 34 studies, we found that TgAb+ patients have a higher risk of lymph node metastasis (OR = 1.18 [CI 1.47-2.25]) and cancer persistence/recurrence (OR = 2.78 [CI 1.55-4.98]) than TgAb- patients. However, no significant differences in mean/median tumor size, risk of extrathyroidal extension, tumor multifocality, and cancer mortality were found between the two groups. In a comparison of TgAb trends, patients with persistent/increasing TgAb levels were found to have a higher risk of cancer persistence/recurrence (OR = 9.90 [CI 4.36-22.50]) and cancer mortality (OR = 15.18 [CI 2.99-77]) than patients with decreasing TgAb levels. Conclusions: TgAb positivity and persistent/increasing trends were associated with compromised DTC prognosis. These results suggest that TgAb may be used as a prognostic marker in the follow-up of patients with DTC.

Thyroid cancer, the most common endocrine malignancy, has patients who generally have excellent prognosis. It has been shown that elderly patients are more likely to undergo sub-therapeutic management, despite having more aggressive disease, resulting in increased mortality and morbidity. The present study aimed to quantitatively investigate the risks of elderly patients who underwent thyroidectomy for thyroid cancer regarding mortality/survival, recurrence of disease, and complications arising from thyroidectomy. A systematic search and meta-analysis was carried out using the electronic databases PubMed and Medline. We searched for articles containing epidemiological evidence of mortality and recurrence of disease in patients above the age of 60, who are treated for operatively thyroid cancer and data involving complications following total thyroidectomy. The meta-analysis consisted of a total of 16 studies meeting the inclusion and exclusion criteria. The current study confirmed that patients have increased risk of recurrence (HR 4.84; 95% CI = 22.2-10.52; I 2  = 0.00; P = 0.98) including increased risk of lymph node recurrence and distant metastases. Additionally these patients had an increased risk of complications (OR 1.82; 95% CI = 0.88-3.77; I 2  = 77.01; P = 0.005) following thyroidectomy compared to patients in the younger cohort. The current study also qualitatively compared survival data between the different age cohorts, and identified a reduced overall survival and disease free survival for elderly patients. The current study suggests that elderly patients should be classified as higher risk following total thyroidectomy for thyroid cancer and puts an emphasis is early detection and intervention., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Purpose/aim of the study: Graves' ophthalmopathy (GO) is closely related to the thyroid autoimmune disorder Graves' disease. Previous studies have suggested roles for thyroidal CD8 +  T cells and autoimmunity against calsequestrin-1 (CASQ)-1 in the link between thyroidal and orbital autoimmune reactions in GO. A role for autoimmunity against CollXIII has also been suggested. In this study, we aimed to investigate correlations between some thyroidal and peripheral blood T-cell subsets and thyroidal T-cell reactivity against CASQ1 and CollXIII in patients with GO., Materials and Methods: Fresh thyroid tissues were processed by enzyme digestion and density gradient to isolate mononuclear cells (MNCs). Peripheral blood MNCs were also isolated using density gradient. Flow-cytometric analysis was used to identify the various T-cell subsets. T -cell reactivity to CASQ1 and CollXIII was measured by a 5-day culture of the MNCs and BrdU uptake method., Results: We found a positive correlation between thyroidal CD8 +  T cells and CD8 +  T-regulatory (T-reg) cells in patients with GO. Thyroidal T cells from two out of the three patients with GO tested (66.7%) showed a positive response to CASQ1, while thyroidal T cells from none of the six Graves' Disease patients without ophthalmopathy (GD) tested showed a positive response to this antigen. Thyroidal T cells from these patient groups however, showed no significant differences in their response to CollXIII., Conclusions: Our observations provide further evidence for a possible role of thyroidal CD8 +  T cells, CD8 +  T-reg cells and the autoantigen CASQ1 in the link between thyroidal and orbital autoimmune reactions of GO.

Background: Physical activity and weight loss have been shown to reduce breast cancer incidence in numerous observational studies. The aim of this meta-analysis was to assess the effect of both physical activity and weight loss on breast cancer incidence. Specifically, we aimed to complete subgroup analyses by the intensity of physical activity and menopausal status at breast cancer diagnosis to further elucidate the relationship between physical activity, weight loss, and breast cancer incidence., Materials and Methods: Studies were obtained from a database search of MEDLINE, EMBASE, PubMed, Current Contents Connect, and Google Scholar through November 5, 2017. A random-effects model was used for pooled data., Results: There were 139 studies included in the meta-analysis, including 236,955 cases and 3,963,367 controls. Physical activity significantly reduced the risk of breast cancer (odds ratio [OR], 0.78; 95% confidence interval [CI], 0.76-0.81; P < .001), with high-intensity physical activity being slightly more protective (OR, 0.73; 95% CI, 0.65-0.81; P < .001) than low-intensity exercise (OR, 0.79; 95% CI, 0.72-0.86; P < .001). The effect size for general exercise was similar in both premenopausal (OR, 0.79; 95% CI, 0.73-0.87; P < .001) and postmenopausal (OR, 0.82; 95% CI, 0.78-0.86; P < .001) women. Additionally, weight loss reduced the risk of breast cancer incidence (OR, 0.82; 95% CI, 0.67-0.97)., Conclusion: Physical activity and weight loss significantly reduce the risk of breast cancer, irrespective of the timing and intensity of the exercise., (Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.)

Background: Thyroid cancer is one of the most common endocrine cancers whose incidence has been steadily increasing. Previous studies have suggested that multifocality in thyroid cancer is associated with poor prognosis. The present study aims to quantify the data on multifocality as a factor indicating poor prognosis by meta-analysis., Methods: A systematic search was carried out using the electronic databases PubMed and Medline. We searched for articles containing keywords of multifocality and thyroid cancer, as well as risk factors and prognostic factors for thyroid cancer (Lymph node metastases, extrathyroidal extension, distant metastases, disease recurrence, Age, tumour size. and gender). Data sets containing hazard ratios and odds ratios were then compared., Results: The meta-analysis was performed using a total of 21 articles, showed that multifocality is associated with an increased risk of development of LNM (12 Studies: OR = 1.87; 95% CI = 1.51-2.32; I2 = 49.11; p-value = .03), Extrathyroidal extension (15 Studies: OR = 3.18; 95% CI = 0.69-14.71; I2 = 95.62; p-value <.001), Tumour Size > 1 cm (3 Studies: OR = 2.75; 95% CI = 1.95-3.89; I2 = 0.00 and p-value = .88) and disease recurrence (5 Studies: HR = 2.81; 95% CI = 1.07-7.36; I2 = 95.85; p-value < .001). Risk factors that did not significantly contribute to a higher incidence of multifocality include Age >45, Male Gender., Conclusions: Multifocality in thyroid cancer is a significant risk factor for disease progression and increases the risk of disease recurrence. The present study suggests that patients who have multifocal disease should therefore be managed more aggressively from an operative and post-operative perspective., (Copyright © 2018 IJS Publishing Group Ltd. All rights reserved.)

The gain by performing sentinel lymph node biopsy (SLNB) during prophylactic mastectomy (PM) is debatable, and we performed a meta-analysis of existing literature to evaluate that the role of SLNB in subjects undergoing PM. A systematic search was conducted using MEDLINE, PubMed, EMBASE, Current Contents Connect, Cochrane library, Google Scholar, Science Direct, and Web of Science. The search identified 11 relevant articles reporting on patients who underwent SLNB at the time of PM. Data were abstracted from each study and used to calculate a pooled odds ratio (OR) and 95% confidence interval (95% CI). We included 14 studies comprising of 2,708 prophylactic mastectomies. Among 2,708 prophylactic mastectomies, the frequency of occult invasive cancer (51 cases) was 1.8% and the rate of positive SLNs (33 cases) was 1.2%. In 25 invasive cancers at the time of PM were found to have negative SLNs which avoided axillary lymph node dissection (ALND). In seven cases with positive SLNBs were found not to have invasive cancer at the time of PM and needed a subsequent ALND. Most of the patients with positive SLNs had locally advanced disease in the contralateral breast. SLNB may be suitable for patients with ipsilateral, locally advanced breast cancer and is not recommend for all patients undergoing PM., (© 2016 Wiley Periodicals, Inc.)

Previous studies have suggested an association between breast cancer and thyroid cancer; however, there has not been a formal meta-analysis which collates the existing evidence supporting the hypothesis that breast cancer or thyroid cancer predisposes an individual to developing the other. A systematic search was carried out using PubMed and Medline. We searched for articles containing epidemiological evidence of breast cancer following thyroid cancer and vice versa. Additionally, we searched for articles that included epidemiological data involving the incidence of all second primary malignancies (SPMs) following both breast cancer and thyroid cancer, and compared the datasets. The meta-analysis performed in a total of 18 studies showed that there is a significantly increased risk of developing thyroid cancer as a second primary malignancy of breast cancer (SIR = 1.59, 95 % confidence interval (CI) 1.28-1.99). Additionally, there was marginally increased risk of developing breast cancer as a second primary malignancy of thyroid cancer (SIR = 1.24, 95 % CI 1.16-1.33), compared to the general risk of developing a second primary malignancy following thyroid cancer. The findings suggest that the risk of developing thyroid cancer as a second primary malignancy of breast cancer and vice versa is increased compared to the background risk of developing other SPMs. The risk of developing thyroid cancer after a primary breast cancer was higher than the risk of developing breast cancer as a second primary malignancy of thyroid cancer. This suggests that the effects of treatment-related factors and specific pathological processes of each cancer may contribute to the increased risk rather than common risk factors including genetic factors. Elucidation of the common mechanisms between breast cancer and thyroid cancer will have important implications in both diagnostic and therapeutic management of these cancers. Benefit of thyroid ultrasound screening after breast cancer surgery needs to be assessed.

Background: Partial adrenalectomy is typically performed for the treatment of hereditary and sporadic bilateral tumours, to reduce the risk of adrenal failure, particularly in younger patients. Partial adrenalectomy proposes a postoperative steroid-free course nevertheless, is associated with the risk of local recurrence. In this study we evaluate the recurrence and functional outcomes of partial adrenalectomy., Methods: A systematic search was conducted using MEDLINE, PubMed, EMBASE, Current Contents Connect, Cochrane library, Google Scholar, Science Direct, and Web of Science. The search identified 60 relevant articles reporting on patients who underwent partial adrenalectomy. Data was extracted from each study and used to calculate a pooled event rate and 95% confidence interval (95% CI)., Results: The overall recurrence rate was 8% (95% CI: 0.05-0.12) and the 85% (95% CI: 0.78-0.9) of the patients were steroid free. The recurrence rates were the least in the retroperitoneoscopic group 1% (95% CI: 0-0.04) and Conn's syndrome group 2% (95% CI: 0.01-0.05) and highest in open group 15% (95% CI: 0.07-0.28) and Pheochromocytoma group 10% (95% CI: 0.07-0.16). Steroid independence rates were best in the Conn's syndrome group 97% (95% CI: 0.85-0.99) and laparoscopic group 88% (95% CI: 0.75-0.95)., Conclusions: Partial adrenalectomy can obviate the need for steroid replacement in the majority of patients and local recurrence rates appear to be infrequent. For patients with hereditary and bilateral adrenal tumours, partial adrenalectomy should be recommended as a primary surgical approach whenever possible., (Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.)

Background: Previous studies have shown that parathyroidectomy for primary hyperparathyroidism (PHPT) improve the function and quality of life of patients. The aim of this systematic review and meta-analysis is to determine the health-related quality of life outcomes among those having surgical management for PHPT., Methods: Several databases were searched (MEDLINE, EMBASE, PubMed, Current Contents) for studies in which health-related quality of life was measured by reliable and validated instruments (SF-36 and Paseika Questionnaire) before and after parathyroidectomy for patients with primary hyperparathyroidism (PHPT). For the SF-36, score differences greater than 5 points indicate clinically relevant changes., Results: There were six studies with quality of life data. The SF-36 data was derived from 238 patients, with a mean age of 59 years and 71% were females. The range of follow up after surgery was 6 months to one year. The pre- and post-parathyroidectomy SF-36 quality of life scale scores were vitality (44 vs. 60, p<0.001), physical functioning (51 vs. 69, p<0.001), bodily pain (50 vs. 65, p<0.001), general health (54 vs. 64, p<0.001), role physical (34 vs. 52, p<0.001), role emotional (43 vs. 59, p<0.001), role social (60 vs. 74, p<0.001), and mental health (55 vs. 71, p<0.001). The Paseika data was derived from 203 patients, with a mean age of 54 years and 67% were females. The pre- and post-parathyroidectomy Paseika scores were feeling tired (51 vs. 19, p<0.001), feeling thirsty (29 vs. 12, p<0.001), mood swings (33 vs. 12, p<0.001), joint pains (32 vs. 14, p<0.001), irritability (31 vs. 10, p<0.001), feeling blue (31 vs. 14, p<0.001), feeling weak (37 vs. 15, p<0.001), itchy (17 vs. 7, p<0.001), forgetful (27 vs. 16, p<0.001), headache (18 vs. 5, p<0.001), abdominal pain (19 vs. 8, p<0.001), bone pain (38 vs. 17, p<0.001), ability to move off chair (27 vs. 11, p<0.001)., Conclusion: Parathyroidectomy significantly improves the short to medium-term health-related quality of life of patients suffering from primary hyperparathyroidism., (Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.)

The aim of this meta-analysis was to collate and analyse all primary observational studies investigating the risk of breast cancer (BC) associated with diabetes. In addition, we aimed to complete subgroup analyses by both type of diabetes and gender of study participants to further clarify the origin of any such association between the two. Studies were obtained from a database search of MEDLINE, EMBASE, PubMed, Current Contents Connect and Google Scholar with additional cross-checking of reference lists. Collated data were assessed for heterogeneity and a pooled odds ratio (OR) calculated. Forty-three studies were included in the meta-analysis with 40 studies investigating BC in women and six studies investigating BC in men. Overall, we found a significantly increased risk of BC associated with diabetes in women (OR 1.20, 95% confidence interval (CI) 1.13-1.29). After subgroup analysis by type of diabetes, the association was unchanged with type 2 diabetes (OR 1.22, 95% CI 1.07-1.40) and nullified with gestational diabetes (OR 1.06, 95% CI 0.79-1.40). There were insufficient studies to calculate a pooled OR of the risk of BC associated with type 1 diabetes. There was an increased risk of BC in males with diabetes mellitus; however, the results did not reach statistical significance (OR 1.29, 95% CI 0.99-1.67). In conclusion, diabetes increases the risk of BC in women. This association is confirmed in women with type 2 diabetes and supports the hypothesis that diabetes is an independent risk factor for BC.

The controversial relationship between benign thyroid diseases and breast cancer (BC) has been investigated for over 50 years. Despite extensive population studies, the results as a whole have been inconsistent. The purpose of this study was to collate and analyse available data, calculating a pooled odds ratio (OR) of the risk of BC in patients diagnosed with benign thyroid diseases. Studies were obtained from a database search of MEDLINE, EMBASE, PubMed, Current Contents Connect and Google Scholar with additional cross checking of reference lists. Inclusion criteria required a confirmed diagnosis of a benign thyroid disease, reporting of an OR or data to calculate an OR (and 95% confidence interval, CI) and the use of an internal control group as the comparator. Collated data was assessed for heterogeneity and a pooled OR calculated. 28 studies were included in the meta-analysis. There was significant evidence of an increased risk of BC in patients with autoimmune thyroiditis, evident in a pooled OR 2.92 (95% CI 2.13-4.01). In addition, the results supported an increased risk associated with the presence of anti-thyroid antibodies (OR 2.02, 95% CI 1.63-2.50) and goitre (OR 2.26, 95% CI 1.39-3.69). Subgroup analysis of antibody presence revealed increased risk associated with both anti-TPO (OR 2.64, 95% CI 1.82-3.83) and anti-TG (2.71, 95% CI 1.58-4.69). Quantitative analysis of hypothyroidism and hyperthyroidism was not significant. While these results indicate an association between thyroid auto-immunity and BC, further prospective studies are required to definitively prove causality.

Aim: To quantify delays in discharge for vascular surgical patients and identify causes of such delays., Methods: A prospective audit of delays in discharge of vascular surgical admissions over a 6-month period was performed. Expected date and time of discharge was compared with actual date and time of discharge. Day-case patients, patients who died during admission and patients not under the direct care of the vascular team were excluded., Results: There were 99 elective and 51 acute admissions accounting for 729 hospital bed days. The median (range) age was 72 years (21-92) and 94% of patients were living independently in the community. Forty-seven percent of patients were discharged on the planned day and time, 21% on the planned day but at a later-than-predicted time and 32% were delayed by more than 1 day. Delays identified in this audit accounted for 135 bed days. Fifteen percent of delays were due to causes that can be improved by internal organization (e.g. delayed paperwork). The majority of the delays (85%) were due to external factors such as lack of rehabilitation beds or lack of placement facilities in nursing homes. Elderly patients and acute admissions were more likely to have long delays in discharge., Conclusion: Delays in discharge of vascular surgical patients use a lot of acute surgical bed days. Strategies to prevent delays in discharge should include not only improving internal organization and early identification and referral of patients who require rehabilitation/placement but also increased funding for such essential non-acute services.

Introduction: Incidental pancreatic cystic lesions (IPCL) are becoming an increasingly frequent clinical entity. Within this review, the differential diagnosis, investigation, and management are discussed., Methods: A MEDLINE search was performed for IPCL., Results: Incidence of IPCL varies from 0.2-0.7%, and 30-47% are premalignant or malignant. Pancreatic pseudocysts (PC), serous cystic neoplasms (SCN), intraductal papillary mucinous neoplasms (IPMN), and mucinous cystic neoplasms (MCN) are the most common pathological entities of IPCL. The use of combined modalities, including clinical characteristics, serum tumor markers, cross-sectional imaging, and endoscopic ultrasound (EUS) with cyst fluid analysis should all be used to establish an accurate preoperative diagnosis if possible. Modern multidetector computed tomography (MDCT) and magnetic resonance pancreatography (MRP) allow detailed characterization of IPCL, including size, septation, calcifications, mural nodules, and communication with main pancreatic duct. The best available cyst fluid markers of mucinous neoplasm are viscosity > or =1.6 and carcinoembryonic antigen >192 ng/ml. Although surgery is indicated for MCN or main or mixed duct IPMN, recent advances in the understanding of the natural history and increasingly accurate preoperative diagnosis allow a nonoperative approach to be undertaken for the majority of IPCL. For those treated nonoperatively, the ideal follow-up has yet to be determined., Conclusions: Emerging evidence supports selective nonoperative management for the majority of patients who have IPCL when investigated by a multimodal approach. For those in whom a suspicion of malignancy remains, surgery is indicated.