Publications by authors named "S Rachel Skinner"

775 Publications

Predictive factors for distant recurrence of colorectal cancer in patients after curative resection for stage I-III colorectal cancer in Australia.

Langenbecks Arch Surg 2021 Aug 2. Epub 2021 Aug 2.

Department of Colorectal Surgery, Alfred Hospital, 55 Commercial Road, Melbourne, VIC, 3004, Australia.

Purpose: Distant recurrence is a devastating occurrence after colorectal cancer resection. This study aimed to identify the risk factors for distant recurrence following surgery.

Methods: All consecutive colorectal cancer resections with curative intent were included from a prospectively maintained colorectal cancer database. The primary outcome was to identify predictive factors for distant recurrence of colorectal cancer.

Results: A total of 670 eligible cases were identified with 88 (13.1%) developing distant recurrence during the follow-up period. The median time to distant recurrence was 1.2 years with the most common sites of distant recurrence being the lung (44.3%) and liver (44.3%). Predictive factors for distant recurrence in colon cancer included a high tumor, nodal, and overall stage of the primary cancer (p < 0.001 for all). Surgical complications (p = 0.007), including anastomotic leak (p = 0.023), were associated with a higher risk of developing distant recurrence in rectal cancer patients. Independent variables associated with distant recurrence included tumor stage (OR 1.61, p = 0.011), nodal stage (OR 2.18, p < 0.001), and both KRAS (OR 11.04, p < 0.001) and MLH/PMS2 (OR 0.20, p = 0.035) genetic mutations. Among patients with distant recurrence, treatment with surgery conferred the best survival, with patients < 50 years of age having the best overall 5-year survival.

Conclusion: Predictive factors for distant recurrence include advanced tumor and nodal stages, and the presence of KRAS and MLH/PSM2 mutations. Clinicians should be cognizant of these risk factors, and instate close surveillance plans for patients exhibiting these features.
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http://dx.doi.org/10.1007/s00423-021-02273-yDOI Listing
August 2021

Quantifying the Effect of Location Matching on Accuracy of Multiparametric Magnetic Resonance Imaging Prior to Prostate Biopsy-A Multicentre Study.

Eur Urol Open Sci 2020 Jul 12;20:28-36. Epub 2020 Aug 12.

Department of Urology, St Vincent's Hospital Melbourne, Victoria, Australia.

Background: Multiparametric magnetic resonance imaging (mpMRI) has shown promise to improve detection of prostate cancer over conventional methods. However, most studies do not describe whether the location of mpMRI lesions match that of cancer found at biopsy, which may lead to an overestimation of accuracy.

Objective: To quantitate the effect of mapping locations of mpMRI lesions to locations of positive biopsy cores on the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of mpMRI.

Design Setting And Participant: We retrospectively identified patients having mpMRI of the prostate preceding prostate biopsy at three centres from 2013 to 2016. Men with targetable lesions on imaging underwent directed biopsy in addition to systematic biopsy. We correlated locations of positive mpMRI lesions with those of positive biopsy cores, defining a match when both were in the same sector of the prostate. We defined positive mpMRI as Prostate Imaging Reporting and Data System (PI-RADS) score ≥4 and significant cancer at biopsy as grade group ≥2.

Outcome Measurements And Statistical Analysis: Sensitivity, specificity, PPV, and NPV were calculated with and without location matching.

Results And Limitations: Of 446 patients, 247 (55.4%) had positive mpMRI and 232 (52.0%) had significant cancer at biopsy. Sensitivity and NPV for detecting significant cancer with location matching (both 63.4%) were decreased compared with those without location matching (77.6% and 73.9%, respectively). Of the 85 significant cancers not detected by mpMRI, most were of grade group 2 (64.7%, 55/85).

Conclusions: We report a 10-15% decrease in sensitivity and NPV when location matching was used to detect significant prostate cancer by mpMRI. False negative mpMRI remains an issue, highlighting the continued need for biopsy and for improving the standards around imaging quality and reporting.

Patient Summary: The true accuracy of multiparametric magnetic resonance imaging (mpMRI) must be determined to interpret results and better counsel patients. We mapped the location of positive mpMRI lesions to where cancer was found at biopsy and found, when compared with matching to cancer anywhere in the prostate, that the accuracy of mpMRI decreased by 10-15%.
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http://dx.doi.org/10.1016/j.euros.2020.07.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317842PMC
July 2020

Human papillomavirus prevalence and risk factors among Australian women 9-12 years after vaccine program introduction.

Vaccine 2021 Aug 17;39(34):4856-4863. Epub 2021 Jul 17.

Centre for Women's Infectious Diseases, The Royal Women's Hospital, Melbourne, Australia; Melbourne School of Population and Global Health, University of Melbourne, Victoria, Australia; The Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, Australia. Electronic address:

Background: In Australia, high and widespread uptake of the quadrivalent human papillomavirus (HPV) vaccine has led to substantial population-level reductions in the prevalence of quadrivalent vaccine targeted HPV genotypes 6/11/16/18 in women aged ≤ 35 years. We assessed risk factors for HPV detection among 18-35 year old women, 9-12 years after vaccine program introduction.

Methods: Women attending health services between 2015 and 2018 provided a self-collected vaginal specimen for HPV genotyping (Roche Linear Array) and completed a questionnaire. HPV vaccination status was validated against the National Register. Adjusted odds ratios (aORs) and 95% confidence intervals (CI) were calculated for factors associated with HPV detection.

Results: Among 1564 women (median age 24 years; IQR 21-27 years), Register-confirmed ≥ 1-dose vaccine coverage was highest at 69.3% and 68.1% among women aged 18-21 and 22-24 years respectively, decreasing to 42.9% among those aged 30-35 years. Overall prevalence of quadrivalent vaccine-targeted HPV types was very low (2.0%; 95% CI: 1.4-2.8%) and influenced only by vaccination status (5.5% among unvaccinated compared with 0.7% among vaccinated women; aOR = 0.13 (95% CI: 0.05-0.30)). Prevalence of remaining HPV types, at 40.4% (95% CI: 38.0-42.9%), was influenced by established risk factors for HPV infection; younger age-group (p-trend < 0.001), more recent (p < 0.001) and lifetime sexual partners (p-trend < 0.001), but not vaccination status. Prevalence of HPV31/33/45, which shared risk factors with that of non-vaccine targeted HPV types, was also lower among vaccinated (4%) compared with unvaccinated (7%) women (aOR = 0.51; 95% CI: 0.29-0.89), indicative of cross-protection.

Conclusion: Vaccination has changed the epidemiology of HPV infection in Australian women, having markedly reduced the prevalence of vaccine-targeted types, including amongst women with known risk factors for infection. Vaccinated women appear to be benefiting from modest cross-protection against types 31/33/45 afforded by the quadrivalent HPV vaccine. These results reinforce the importance of HPV vaccination.
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http://dx.doi.org/10.1016/j.vaccine.2021.07.005DOI Listing
August 2021

Comprehensive investigation of the phenotype of MEF2C-related disorders in human patients: A systematic review.

Am J Med Genet A 2021 Jun 29. Epub 2021 Jun 29.

School of Nursing, Clemson University, Clemson, South Carolina, USA.

MEF2C-related disorders (aka MEF2C-haploinsufficiency) are caused by variations in or involving the MEF2C gene and are characterized by intellectual disability, developmental delay, lack of speech, limited walking, and seizures. Despite these findings, the disorder is not easily recognized clinically. We performed a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to assemble the most comprehensive list of patients and their phenotypes. Through searching PubMed, Web of Science, and MEDLINE, 43 articles met the inclusion criteria and were fully reviewed. One hundred and seventeen patients were identified from these publications with most having a phenotype of intellectual disability, developmental delay, seizures, hypotonia, absent speech, inability to walk, stereotypic movements, and MRI abnormalities. Nonclassical findings included one patient with a question mark ear, two patients with a jugular pit, one patient with a unique neuroendocrine finding, and nine patients that did not have MEF2C deletions or disruptions but may be affected due to a positional effect on MEF2C. This systematic review characterizes the phenotype of MEF2C-related disorders, documents the severity of this condition, and will help providers to better diagnose and care for patients and their families. Additionally, this compiled information provides a comprehensive resource for investigators interested in pursuing specific genotype-phenotype correlations.
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http://dx.doi.org/10.1002/ajmg.a.62412DOI Listing
June 2021

School-based HPV vaccination positively impacts parents' attitudes toward adolescent vaccination.

Vaccine 2021 Jul 12;39(30):4190-4198. Epub 2021 Jun 12.

Speciality of Child and Adolescent Health, Faculty of Medicine and Health, University of Sydney, NSW, Australia.

Introduction: This qualitative study aimed to explore parental attitudes, knowledge and decision-making about HPV vaccination for adolescents in the context of a gender-neutral school-based Australian National Immunisation Program (NIP).

Methods: Semi-structured interviews with parents of adolescents eligible for HPV vaccination were undertaken as part of an evaluation of a cluster-randomised controlled trial of a complex intervention in 40 schools (2013-2015). In this qualitative study, we purposively recruited a nested sample of parents from 11 schools across two Australian jurisdictions. Interviews explored parent knowledge and understanding of the HPV vaccine program; HPV vaccination decision-making; their adolescent's knowledge about HPV vaccination; and their adolescent's understanding about HPV vaccination, sexual awareness and behaviour. Transcripts were analysed using inductive and deductive thematic analysis.

Results: Parents' of 22 adolescents had positive attitudes towards the program; the school-based delivery platform was the key driver shaping acceptance of and decision-making about HPV vaccination. They had difficulty recalling, or did not read, HPV vaccination information sent home. Some adolescents were involved in discussions about vaccination, with parents' responsible for ultimate vaccine decision-making. All parents supported in-school education for adolescents about HPV and HPV vaccination. Parents' knowledge about HPV vaccination was limited to cervical cancer and was largely absent regarding vaccination in males.

Conclusions: Parents' positive attitudes towards the NIP and inclusion of the HPV vaccine is central to their vaccine decision-making and acceptance. More intensive communication strategies including school education opportunities are required to improve parents' knowledge of HPV-related disease and to promote vaccine decision-making with adolescents.
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http://dx.doi.org/10.1016/j.vaccine.2021.05.051DOI Listing
July 2021
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