Publications by authors named "Russell Hogg"

28 Publications

  • Page 1 of 1

Quantification of enamel decussation in gracile and robust capuchins (Cebus, Sapajus, Cebidae, Platyrrhini).

Am J Primatol 2021 Feb 27:e23246. Epub 2021 Feb 27.

Department of Biological Sciences, Florida Gulf Coast University, Fort Myers, Florida, USA.

Multiple behavioral and biomechanical analyses have demonstrated that capuchin monkeys (Cebus and Sapajus) are specialized for breaking down hard-object foods as compared to other cebid monkeys. In addition to a complex suite of craniodental adaptations, it has specifically been demonstrated that capuchins possess highly complex dental enamel, with extensive Hunter-Schreger banding and other decussation, that likely serve as an adaptation to resist crack propagation during hard-object feeding. Furthermore, it has been demonstrated that robust capuchins (Sapajus spp., formerly Cebus apella) demonstrate further adaptation for hard-object feeding than other capuchins, routinely breaking down extremely mechanically challenging foods. However, there has been no comparison of dental enamel complexity in robust versus gracile capuchins, to assess whether the dental enamel in Sapajus follows this same pattern of further specialization. Therefore, this study compares dental enamel complexity in images of dental thin sections from a sample of robust versus gracile capuchins using image compression ratio (ICR) analysis. ICR is a variable that correlates with enamel complexity, such that higher ICR values are indicative of increased complexity in the form of enamel decussation. We found no significant difference between robust and gracile capuchins when assessing all teeth in our sample together, however, we did find that robust capuchins have significantly higher ICR values than gracile capuchins for canine teeth, specifically. Our results support prior studies suggesting that robust capuchins are specialized to generate increased masticatory loads with their anterior dentition, specifically, as compared to gracile species.
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http://dx.doi.org/10.1002/ajp.23246DOI Listing
February 2021

A comprehensive survey of Retzius periodicities in fossil hominins and great apes.

J Hum Evol 2020 12 15;149:102896. Epub 2020 Oct 15.

Institute of Human Origins, School of Human Evolution and Social Change, Arizona State University, Tempe, AZ 85287, USA.

Recent studies have provided great insight into hominin life history evolution by utilizing incremental lines found in dental tissues to reconstruct and compare the growth records of extant and extinct humans versus other ape taxa. Among the hominins, studies that have examined Retzius periodicity (RP) variation have come to contradictory conclusions in some instances. To clarify RP variation among hominins and better place this variation in its broader evolutionary context, we conduct the most comprehensive analysis of published RP values for hominins and great apes to date. We gathered all available data from the literature on RP data from extant humans, great apes, and fossil hominins and assessed their variation using parametric and nonparametric analyses of variance. We also performed phylogenetic generalized least-squares regressions of RP data for these taxa as well as a larger set of hominoids for which RP data have been published against data for body mass, encephalization, and mean semicircular canal radius (a proxy for metabolic rate). Our results show that modern humans have a mean RP significantly differing from that of other hominins. Pongo also is significantly different from nearly all other taxa in all analyses. Our results also demonstrate that RP variation among hominins scales with respect to body mass, encephalization, and semicircular canal radius similarly to other hominids but that modern humans and Pongo stand out in this regard. Operating within the hypothesis that RP reflects autonomic biorhythms that regulate multiple life history variables, our results reinforce the idea that Homo sapiens has evolved a life history distinct from other hominins, even from other members of Homo, and suggest that many of these life history differences may be driven by hypothalamic output from the brain.
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http://dx.doi.org/10.1016/j.jhevol.2020.102896DOI Listing
December 2020

Anatomy and clinical relevance of sub occipital soft tissue connections with the dura mater in the upper cervical spine.

PeerJ 2020 10;8:e9716. Epub 2020 Aug 10.

Department of Rehabilitation Sciences, Florida Gulf Coast University, Fort Myers, FL, USA.

Background: The upper cervical region is a complex anatomical structure. Myodural bridges between posterior suboccipital muscles and the dura might be important explaining conditions associated with the upper cervical spine dysfunction such as cervicogenic headache. This cadaver study explored the upper cervical spine and evaluated the myodural bridges along with position of spinal cord in response to passive motion of upper cervical spine.

Methods: A total of seven adult cadavers were used in this exploratory study. The suboccipital muscles and nuchal ligament were exposed. Connections between the Rectus Capitis Posterior major/minor and the Obliquus Capitis minor, the nuchal ligament, posterior aspect of the cervical spine, flavum ligament and the dura were explored and confirmed with histology. The position of the spinal cord was evaluated with passive motions of the upper cervical spine.

Outcomes: In all cadavers connective tissues attaching the Rectus Capitis Posterior Major to the posterior atlanto-occipital membrane were identified. In the sagittal dissection we observed connection between the nuchal ligament and the dura. Histology revealed that the connection is collagenous in nature. The spinal cord moves within the spinal canal during passive movement.

Discussion: The presence of tissue connections between ligament, bone and muscles in the suboccipital region was confirmed. The nuchal ligament was continuous with the menigiovertebral ligament and the dura. Passive upper cervical motion results in spinal cord motion within the canal and possible tensioning of nerve and ligamentous connections.
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http://dx.doi.org/10.7717/peerj.9716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425638PMC
August 2020

Enamel multidien biological timing and body size variability among individuals of Chinese Han and Tibetan origins.

Ann Hum Biol 2020 Jul 13:1-7. Epub 2020 Jul 13.

Department of Biomaterials, New York University College of Dentistry, New York, NY, USA.

Aims: To measure the number of days of enamel formation between periodic striae of Retzius growth lines, the Retzius periodicity (RP), and to compare this multi-day, or multidien rhythm, to body height and weight among people from Beijing, China and Lhasa, Tibet/China.

Subjects And Methods: Subjects requiring dental extractions from clinics in Beijing, China ( = 338) and Lhasa, Tibet/China ( = 227) provided a tooth and body size information. Multiple observers examined histological sections of the teeth and recorded RP. RP values were statistically compared to body height and weight.

Results: In Beijing and Lhasa samples, respectively, average height was 166.38 and 165.70 cm, average weight was 59.53 and 66.53 kg, and average RP was 7.47 and 7.69 d. Statistically significant differences were found between Beijing and Lhasa weight and RP means. Correlations for height and weight against RP were significant, but only comparatively strong for height.

Conclusions: Supporting the negative correlation presented in previous studies, RP is negatively associated with height and weight among a large intraspecific sample of people from Beijing and Lhasa. RP represents a metabolic-mediated multidien biological timing mechanism responsible for the rate of cell proliferation and maintenance of the body.
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http://dx.doi.org/10.1080/03014460.2020.1785010DOI Listing
July 2020

Patterns of surgical care for women with ovarian cancer in New South Wales.

Aust N Z J Obstet Gynaecol 2020 08 26;60(4):592-597. Epub 2020 May 26.

The Cancer Institute NSW, Sydney, New South Wales, Australia.

Background: Little is known about the delivery of surgical services and outcomes for women with ovarian cancer across New South Wales (NSW).

Aim: The study objective was to provide a descriptive analysis of the proportion of women who had surgery for ovarian cancer in NSW in specialist gynaecological oncology hospitals and compare outcomes for women attending specialist and non-specialist services in NSW.

Materials And Methods: This study is a retrospective analysis of women with primary ovarian, fallopian tube or peritoneal cancer from 2009 to 2012. Data were analysed from the NSW Cancer Registry, NSW Admitted Patient Data Collection and Register of Births Deaths and Marriages. Treating hospitals were characterised as public specialist, public non-specialist and private. Morbidity and mortality outcomes are reported.

Results: The study included 1106 women. Fifty-seven hospitals performed surgery: seven public specialist, 27 private and 23 public non-specialist hospitals. The highest proportion of surgery was performed in public specialist hospitals (61%). There was considerable variation in the utilisation of public specialist hospitals between local health districts. There was no significant difference in outcomes related to the type of hospital where surgery was performed.

Conclusions: Although the majority of women are having surgery in a specialist gynaecological oncology public hospital across NSW, many are not. Women living in regional and remote NSW were less likely to have their surgery in a specialist hospital. This is the first step in understanding where women in NSW are currently receiving their surgical care, as well as the outcomes related to this.
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http://dx.doi.org/10.1111/ajo.13180DOI Listing
August 2020

Comparative dental anatomy in newborn primates: Cusp mineralization.

Anat Rec (Hoboken) 2020 09 1;303(9):2415-2475. Epub 2020 Jan 1.

School of Physical Therapy, Slippery Rock University, Slippery Rock, Pennsylvania.

Previous descriptive work on deciduous dentition of primates has focused disproportionately on great apes and humans. To address this bias in the literature, we studied 131 subadult nonhominoid specimens (including 110 newborns) describing deciduous tooth morphology and assessing maximum hydroxyapatite density (MHD). All specimens were CT scanned at 70 kVp and reconstructed at 20.5-39 μm voxels. Grayscale intensity from scans was converted to hydroxyapatite (HA) density (mg HA/cm ) using a linear conversion of grayscale values to calibration standards of known HA density (R = .99). Using Amira software, mineralized dental tissues were captured by segmenting the tooth cusps first and then capturing the remainder of the teeth at descending thresholds of gray levels. We assessed the relationship of MHD of selected teeth to cranial length using Pearson correlation coefficients. In monkeys, anterior teeth are more mineralized than postcanine teeth. In tarsiers and most lemurs and lorises, postcanine teeth are the most highly mineralized. This suggests that monkeys have a more prolonged process of dental mineralization that begins with incisors and canines, while mineralization of postcanine teeth is delayed. This may in part be a result of relatively late weaning in most anthropoid primates. Results also reveal that in lemurs and lorises, MHD of the mandibular first permanent molar (M ) negatively correlates with cranial length. In contrast, the MHD of M positively correlates with cranial length in monkeys. This supports the hypothesis that natural selection acts independently on dental growth as opposed to mineralization and indicates clear phylogenetic differences among primates.
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http://dx.doi.org/10.1002/ar.24326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269855PMC
September 2020

Application of Image Compression Ratio Analysis as a Method for Quantifying Complexity of Dental Enamel Microstructure.

Anat Rec (Hoboken) 2019 12 30;302(12):2279-2286. Epub 2019 Sep 30.

Department of Biological Sciences, Florida Gulf Coast University, Fort Myers, Florida.

It is well recognized that enamel microanatomy in mammals reflects biomechanical demands placed upon teeth, as determined by mechanical properties of species' diets, use of teeth as weapons, and so forth. However, there are limited options for researchers wishing to perform large-scale comparisons of enamel microstructure with adaptive questions in mind. This is because to date there has been no efficient method for quantification and statistical analysis of enamel complexity. Our study proposes to apply a method previously developed for quantification of 3D tooth cusp morphology to the problem of quantifying microstructural enamel complexity. Here, we use image compression ratio (ICR) as a proxy variable for enamel complexity in 2D enamel photomicrographs taken using circularly polarized transmitted light microscopy. ICR describes the relationship between a digital image captured in an uncompressed file format and the identical image that has had its file size compressed using computer algorithms; more complex images receive less compression. In our analyses, ICR analysis is able to distinguish between images of teeth with simple, radial enamel and teeth with complex decussating enamel. Moreover, our results show a significant correlation between ICR and enamel complexity ranks assigned via visual assessment. Therefore, our results demonstrate that ICR analysis provides a viable methodology for efficient comparison of overall enamel complexity among dental samples. Anat Rec, 302:2279-2286, 2019. © 2019 American Association for Anatomy.
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http://dx.doi.org/10.1002/ar.24261DOI Listing
December 2019

Histology of dental long-period biorhythms in Canis familiaris.

J Anat 2018 11 11;233(5):618-624. Epub 2018 Sep 11.

Department of Biomaterials, New York University College of Dentistry, New York, NY, USA.

Our objective is to assess variation in Havers-Halberg oscillation (HHO) periodicities among domestic dogs (Canis familiaris). The HHO is hypothesized to be a hypothalamic-generated biorhythm coordinating multiple life history variables including body mass and lifespan. Dogs have a broad mass range spanning two orders of magnitude, but this variation has been shown to result from selection on very few genetic loci, and dogs have low variation in other life history traits. Therefore, we predict that HHO variation will not be correlated to body mass among domestic dogs, as it is in anthropoid primates. To test the prediction, we examined dog HHO periodicity via manifestations in tooth enamel and dentine, quantifying HHO rhythm histologically. HHO rhythm is reflected in teeth as the number of days between secretion of successive striae of Retzius (enamel) and Andresen lines (dentine), a value referred to as Retzius periodicity (RP). We counted ca. 24-h growth lines between successive Retzius and Andresen lines to determine RP in histological thin-sections from canine teeth of 19 dogs, representing different breeds and sizes. To test our hypothesis, we regressed RP periodicity against body mass data. Dogs have low RP variation for their body mass range, with a modal periodicity of 5 days and a range of 4-6 days. RP was not significantly correlated with body mass. We conclude that mass variation in dogs does not seem driven by HHO physiology, consistent with findings that IGF1 variants produce dog mass variation. However, low RP (and by extension HHO) variation is consistent with low variation in dog lifespan and gestation, suggesting that dog life history may still be governed by HHO mechanisms even if body mass does not reflect this.
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http://dx.doi.org/10.1111/joa.12876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6183004PMC
November 2018

Inflammatory Myofibroblastic Tumors of the Female Genital Tract Are Under-recognized: A Low Threshold for ALK Immunohistochemistry Is Required.

Am J Surg Pathol 2017 Oct;41(10):1433-1442

*Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research ¶Gynaecological Oncology, Royal North Shore Hospital, St Leonards †Department of Anatomical Pathology, Royal North Shore Hospital ∥University of Sydney #Department of Obstetrics and Gynecology, St George Hospital **University of NSW ‡‡Prince of Wales Clinical School, University of New South Wales, Sydney ††Department of Medical Oncology, Prince of Wales Hospital and Royal Hospital for Women, Randwick ‡Department of Anatomical Pathology, SYDPATH, St Vincent's Hospital §The Kinghorn Cancer Centre and Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.

Inflammatory myofibroblastic tumor (IMT) of the female genital tract is under-recognized. We investigated the prevalence of ALK-positive IMT in lesions previously diagnosed as gynecologic smooth muscle tumors. Immunohistochemistry (IHC) for ALK was performed on tissue microarrays of unselected tumors resected from 2009 to 2013. Three of 1176 (0.26%) "leiomyomas" and 1 of 44 (2.3%) "leiomyosarcomas" were ALK IHC positive, confirmed translocated by fluorescence in situ hybridization (FISH) and therefore more appropriately classified as IMT. On review significant areas of all 4 tumors closely mimicked smooth muscle tumors morphologically, but all showed at least subtle/focal features suggesting IMT. Recognizing that the distinction between IMT and leiomyoma/leiomyosarcoma can be subtle, we then reviewed 1 hematoxylin and eosin slide from each patient undergoing surgery for "leiomyoma" from 2014 to 2017 and selected cases for ALK IHC with a low threshold. Of these, 30 of 571 (5.3%) underwent IHC. Two were confirmed to be IHC positive and FISH rearranged. Of the 6 IMTs, only 1 tumor with a previous diagnosis of leiomyosarcoma, an infiltrative margin and equivocal necrosis, metastasized. Of note it demonstrated a less aggressive clinical course compared with most metastatic leiomyosarcomas (alive with disease at 6 y). The patient was subsequently offered crizotinib to which she responded rapidly. In conclusion, IMTs may closely mimic gynecologic smooth muscle tumors. IMTs account for at least 5 of 1747 (0.3%) tumors previously diagnosed as leiomyoma and 1 of 44 (2.3%) as leiomyosarcoma. These tumors may be recognized prospectively with awareness of subtle/focal histologic clues, coupled with a low threshold for ALK IHC.
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http://dx.doi.org/10.1097/PAS.0000000000000909DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5598906PMC
October 2017

Lessons learnt from implementation of a Lynch syndrome screening program for patients with gynaecological malignancy.

Pathology 2017 Aug 30;49(5):457-464. Epub 2017 Jun 30.

Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, St Leonards, NSW, Australia; Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, NSW, Australia; University of Sydney, Sydney, NSW, Australia. Electronic address:

Despite a trend towards universal testing, best practice to screen patients presenting with gynaecological malignancy for Lynch syndrome (LS) is uncertain. We report our institutional experience of a co-ordinated gynaecological LS screening program. All patients with endometrial carcinoma or carcinosarcoma, or gynaecological endometrioid or clear cell carcinomas undergo reflex four panel immunohistochemistry (IHC) for MLH1, PMS2, MSH2 and MSH6 followed by cascade somatic hypermethylation analysis of the MLH1 promoter locus for dual MLH1/PMS2 negative tumours. On the basis of these results, genetic counselling and targeted germline mutation testing is then offered to patients considered at high risk of LS. From 1 August 2013 to 31 December 2015, 124 patients were screened (mean age 64.6 years). Thirty-six (29.0%) demonstrated abnormal MMR IHC: 26 (72.2%) showed dual loss of MLH1/PMS2, five (13.9%) dual loss of MSH2/MSH6, three (8.3%) isolated loss of MSH6, and two (5.6%) isolated loss of PMS2. Twenty-five of 26 (96.1%) patients with dual MLH1/PMS2 loss demonstrated MLH1 promoter methylation. Therefore, 11 (8.9%) patients screened were classified as high risk for LS, of whom nine (81.8%) accepted germline mutation testing. Three (2.4% of total screened) were confirmed to have LS, two with germline PMS2 and one with germline MSH2 mutation. Massive parallel sequencing of tumour tissue demonstrated somatic mutations which were concordant with the IHC results in the remainder. Interestingly, the one MLH1/PMS2 IHC negative but not hypermethylated tumour harboured only somatic MLH1 mutations, indicating that universal cascade methylation testing in MLH1/PMS2 IHC negative tumours is very low yield and could be reconsidered in a resource-poor setting. In conclusion, universal screening for LS in patients presenting with gynaecological malignancy using the algorithm described above identified LS in three of 124 (2.4%) of our population. Only three of nine (33.3%) patients considered at high risk for LS by combined IHC and hypermethylation analysis were proven to have LS. Only one of the LS patients was less than 50 years of age and none of these patients would have been identified had more restrictive Amsterdam or Bethesda criteria been applied.
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http://dx.doi.org/10.1016/j.pathol.2017.05.004DOI Listing
August 2017

Effect of Total Laparoscopic Hysterectomy vs Total Abdominal Hysterectomy on Disease-Free Survival Among Women With Stage I Endometrial Cancer: A Randomized Clinical Trial.

JAMA 2017 03;317(12):1224-1233

Queensland Centre for Gynaecological Cancer, University of Queensland, Herston, Australia8School of Medicine, University of Queensland, Herston, Australia.

Importance: Standard treatment for endometrial cancer involves removal of the uterus, tubes, ovaries, and lymph nodes. Few randomized trials have compared disease-free survival outcomes for surgical approaches.

Objective: To investigate whether total laparoscopic hysterectomy (TLH) is equivalent to total abdominal hysterectomy (TAH) in women with treatment-naive endometrial cancer.

Design, Setting, And Participants: The Laparoscopic Approach to Cancer of the Endometrium (LACE) trial was a multinational, randomized equivalence trial conducted between October 7, 2005, and June 30, 2010, in which 27 surgeons from 20 tertiary gynecological cancer centers in Australia, New Zealand, and Hong Kong randomized 760 women with stage I endometrioid endometrial cancer to either TLH or TAH. Follow-up ended on March 3, 2016.

Interventions: Patients were randomly assigned to undergo TAH (n = 353) or TLH (n = 407).

Main Outcomes And Measures: The primary outcome was disease-free survival, which was measured as the interval between surgery and the date of first recurrence, including disease progression or the development of a new primary cancer or death assessed at 4.5 years after randomization. The prespecified equivalence margin was 7% or less. Secondary outcomes included recurrence of endometrial cancer and overall survival.

Results: Patients were followed up for a median of 4.5 years. Of 760 patients who were randomized (mean age, 63 years), 679 (89%) completed the trial. At 4.5 years of follow-up, disease-free survival was 81.3% in the TAH group and 81.6% in the TLH group. The disease-free survival rate difference was 0.3% (favoring TLH; 95% CI, -5.5% to 6.1%; P = .007), meeting criteria for equivalence. There was no statistically significant between-group difference in recurrence of endometrial cancer (28/353 in TAH group [7.9%] vs 33/407 in TLH group [8.1%]; risk difference, 0.2% [95% CI, -3.7% to 4.0%]; P = .93) or in overall survival (24/353 in TAH group [6.8%] vs 30/407 in TLH group [7.4%]; risk difference, 0.6% [95% CI, -3.0% to 4.2%]; P = .76).

Conclusions And Relevance: Among women with stage I endometrial cancer, the use of total abdominal hysterectomy compared with total laparoscopic hysterectomy resulted in equivalent disease-free survival at 4.5 years and no difference in overall survival. These findings support the use of laparoscopic hysterectomy for women with stage I endometrial cancer.

Trial Registration: clinicaltrials.gov Identifier: NCT00096408; Australian New Zealand Clinical Trials Registry: CTRN12606000261516.
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http://dx.doi.org/10.1001/jama.2017.2068DOI Listing
March 2017

Opportunistic bilateral salpingectomy during gynaecological surgery for benign disease: A survey of current Australian practice.

Aust N Z J Obstet Gynaecol 2015 Dec 7;55(6):606-11. Epub 2015 Sep 7.

University of Sydney, Sydney, New South Wales, Australia.

Background: Recent evidence supports the fallopian tube as the site of origin for many pelvic serous cancers (PSC) including epithelial ovarian cancers (EOC). As a result, a change in practice with opportunistic bilateral salpingectomy (OBS) at the time of hysterectomy has been advocated as a preventative strategy for PSC in a low-risk population.

Aims: The aim of this study was to assess current clinical practice in Australia with respect to OBS during gynaecological surgery for benign indications.

Materials And Methods: An anonymous online survey was sent to all active Royal Australian and New Zealand College of Obstetrics and Gynaecology (RANZCOG) Fellows in Australia. Data regarding clinician demographics and the proportion of clinicians offering OBS were collected. Reasons for and against offering or discussing OBS were sought. A descriptive analysis was performed.

Results: The response rate was 26% (280/1490) with 70% of respondents offering or discussing OBS to women undergoing gynaecological surgery for benign indications, usually at the time of abdominal (96%) or laparoscopic (76%) hysterectomy. The main reason for offering or discussing OBS was current evidence to suggest the fallopian tubes as the site of origin for most EOC. Main reasons for not offering OBS were insufficient evidence to benefit the woman (36%) or being unaware of recent evidence (33%).

Conclusions: The survey responses indicate that OBS is frequently discussed or offered in Australia, usually at the time of hysterectomy. Given the lack of robust evidence to suggest a benefit at a population-based level, a national registry is recommended to monitor outcomes.
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http://dx.doi.org/10.1111/ajo.12402DOI Listing
December 2015

Lemur Biorhythms and Life History Evolution.

PLoS One 2015 12;10(8):e0134210. Epub 2015 Aug 12.

Department of Biomaterials and Biomimetics, and Department of Basic Science and Craniofacial Biology, New York University College of Dentistry, New York, New York, United States of America.

Skeletal histology supports the hypothesis that primate life histories are regulated by a neuroendocrine rhythm, the Havers-Halberg Oscillation (HHO). Interestingly, subfossil lemurs are outliers in HHO scaling relationships that have been discovered for haplorhine primates and other mammals. We present new data to determine whether these species represent the general lemur or strepsirrhine condition and to inform models about neuroendocrine-mediated life history evolution. We gathered the largest sample to date of HHO data from histological sections of primate teeth (including the subfossil lemurs) to assess the relationship of these chronobiological measures with life history-related variables including body mass, brain size, age at first female reproduction, and activity level. For anthropoids, these variables show strong correlations with HHO conforming to predictions, though body mass and endocranial volume are strongly correlated with HHO periodicity in this group. However, lemurs (possibly excepting Daubentonia) do not follow this pattern and show markedly less variability in HHO periodicity and lower correlation coefficients and slopes. Moreover, body mass is uncorrelated, and brain size and activity levels are more strongly correlated with HHO periodicity in these animals. We argue that lemurs evolved this pattern due to selection for risk-averse life histories driven by the unpredictability of the environment in Madagascar. These results reinforce the idea that HHO influences life history evolution differently in response to specific ecological selection regimes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0134210PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4534448PMC
May 2016

Lower preoperative quality of life increases postoperative risk of adverse events in women with endometrial cancer: results from the LACE trial.

Gynecol Oncol 2015 Apr 14;137(1):102-5. Epub 2015 Feb 14.

Queensland Centre for Gynaecological Cancer, QLD, Australia.

Objective: To examine the association between preoperative quality of life (QoL) and postoperative adverse events in women treated for endometrial cancer.

Methods: 760 women with apparent Stage I endometrial cancer were randomised into a clinical trial evaluating laparoscopic versus open surgery. This analysis includes women with preoperative QoL measurements, from the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire, and who were followed up for at least 6 weeks after surgery (n=684). The outcomes for this study were defined as (1) the occurrence of moderate to severe adverse events within 6 months (Common Toxicology Criteria (CTC) grade≥3); and (2) any serious adverse event (SAE). The association between preoperative QoL and the occurrence of AE was examined, after controlling for baseline comorbidity and other factors.

Results: After adjusting for other factors, odds of occurrence of AE of CTC grade≥3 were significantly increased with each unit decrease in baseline FACT-G score (OR=1.02, 95% CI 1.00-1.03, p=0.030), which was driven by physical well-being (PWB) (OR=1.09, 95% CI 1.04-1.13, p=0.0002) and functional well-being subscales (FWB) (OR=1.04, 95% CI 1.00-1.07, p=0.035). Similarly, odds of SAE occurrence were significantly increased with each unit decrease in baseline FACT-G score (OR=1.02, 95% CI 1.01-1.04, p=0.011), baseline PWB (OR=1.11, 95% CI 1.06-1.16, p<0.0001) or baseline FWB subscales (OR=1.05, 95% CI 1.01-1.10, p=0.0077).

Conclusion: Women with early endometrial cancer presenting with lower QoL prior to surgery are at higher risk of developing a serious adverse event following surgery.

Funding: Cancer Council Queensland, Cancer Council New South Wales, Cancer Council Victoria, Cancer Council, Western Australia; NHMRC project grant 456110; Cancer Australia project grant 631523; The Women and Infants Research Foundation, Western Australia; Royal Brisbane and Women's Hospital Foundation; Wesley Research Institute; Gallipoli Research Foundation; Gynetech; TYCO Healthcare, Australia; Johnson and Johnson Medical, Australia; Hunter New England Centre for Gynaecological Cancer; Genesis Oncology Trust; and Smart Health Research Grant QLD Health.
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http://dx.doi.org/10.1016/j.ygyno.2015.02.008DOI Listing
April 2015

Genomic classification of serous ovarian cancer with adjacent borderline differentiates RAS pathway and TP53-mutant tumors and identifies NRAS as an oncogenic driver.

Clin Cancer Res 2014 Dec 14;20(24):6618-30. Epub 2014 Oct 14.

Department of Gynaecological Oncology, Westmead Hospital, Sydney, New South Wales, Australia. Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, New South Wales, Australia. University of Sydney, Westmead Hospital, Sydney, New South Wales, Australia. Westmead Institute for Cancer Research, Westmead Millennium Institute, Westmead Hospital, Sydney, New South Wales, Australia.

Purpose: Low-grade serous ovarian carcinomas (LGSC) are Ras pathway-mutated, TP53 wild-type, and frequently associated with borderline tumors. Patients with LGSCs respond poorly to platinum-based chemotherapy and may benefit from pathway-targeted agents. High-grade serous carcinomas (HGSC) are TP53-mutated and are thought to be rarely associated with borderline tumors. We sought to determine whether borderline histology associated with grade 2 or 3 carcinoma was an indicator of Ras mutation, and we explored the molecular relationship between coexisting invasive and borderline histologies.

Experimental Design: We reviewed >1,200 patients and identified 102 serous carcinomas with adjacent borderline regions for analyses, including candidate mutation screening, copy number, and gene expression profiling.

Results: We found a similar frequency of low, moderate, and high-grade carcinomas with coexisting borderline histology. BRAF/KRAS alterations were common in LGSC; however, we also found recurrent NRAS mutations. Whereas borderline tumors harbored BRAF/KRAS mutations, NRAS mutations were restricted to carcinomas, representing the first example of a Ras oncogene with an obligatory association with invasive serous cancer. Coexisting borderline and invasive components showed nearly identical genomic profiles. Grade 2 cases with coexisting borderline included tumors with molecular features of LGSC, whereas others were typical of HGSC. However, all grade 3 carcinomas with coexisting borderline histology were molecularly indistinguishable from typical HGSC.

Conclusion: Our findings suggest that NRAS is an oncogenic driver in serous ovarian tumors. We demonstrate that borderline histology is an unreliable predictor of Ras pathway aberration and underscore an important role for molecular classification in identifying patients that may benefit from targeted agents.
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http://dx.doi.org/10.1158/1078-0432.CCR-14-1292DOI Listing
December 2014

Improved surgical safety after laparoscopic compared to open surgery for apparent early stage endometrial cancer: results from a randomised controlled trial.

Eur J Cancer 2012 May;48(8):1147-53

University of Queensland School of Medicine, QLD, Australia.

Aim: To compare Total Laparoscopic Hysterectomy (TLH) and Total Abdominal Hysterectomy (TAH) with regard to surgical safety.

Methods: Between October 2005 and June 2010, 760 patients with apparent early stage endometrial cancer were enroled in a multicentre, randomised clinical trial (LACE) comparing outcomes following TLH or TAH. The main study end points for this analysis were surgical adverse events (AE), hospital length of stay, conversion from laparoscopy to laparotomy, including 753 patients who completed at least 6 weeks of follow-up. Postoperative AEs were graded according to Common Toxicity Criteria (V3), and those immediately life-threatening, requiring inpatient hospitalisation or prolonged hospitalisation, or resulting in persistent or significant disability/incapacity were regarded as serious AEs.

Results: The incidence of intra-operative AEs was comparable in either group. The incidence of post-operative AE CTC grade 3+ (18.6% in TAH, 12.9% in TLH, p 0.03) and serious AE (14.3% in TAH, 8.2% in TLH, p 0.007) was significantly higher in the TAH group compared to the TLH group. Mean operating time was 132 and 107 min, and median length of hospital stay was 2 and 5 days in the TLH and TAH group, respectively (p<0.0001). The decline of haemoglobin from baseline to day 1 postoperatively was 2g/L less in the TLH group (p 0.006).

Conclusions: Compared to TAH, TLH is associated with a significantly decreased risk of major surgical AEs. A laparoscopic surgical approach to early stage endometrial cancer is safe.
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http://dx.doi.org/10.1016/j.ejca.2012.02.055DOI Listing
May 2012

Primate enamel evinces long period biological timing and regulation of life history.

J Theor Biol 2012 Jul 21;305:131-44. Epub 2012 Apr 21.

Departments of Biomaterials & Biomimetics and Basic Science & Craniofacial Biology, New York University College of Dentistry, New York, NY 10010, USA.

The factor(s) regulating the combination of traits that define the overall life history matrix of mammalian species, comprising attributes such as brain and body weight, age at sexual maturity, lifespan and others, remains a complete mystery. The principal objectives of the present research are (1) to provide evidence for a key variable effecting life history integration and (2) to provide a model for how one would go about investigating the metabolic mechanisms responsible for this rhythm. We suggest here that a biological rhythm with a period greater than the circadian rhythm is responsible for observed variation in primate life history. Evidence for this rhythm derives from studies of tooth enamel formation. Enamel contains an enigmatic periodicity in its microstructure called the striae of Retzius, which develops at species specific intervals in units of whole days. We refer to this enamel rhythm as the repeat interval (RI). For primates, we identify statistically significant relationships between RI and all common life history traits. Importantly, RI also correlates with basal and specific metabolic rates. With the exception of estrous cyclicity, all relationships share a dependence upon body mass. This dependence on body mass informs us that some aspect of metabolism is responsible for periodic energy allocations at RI timescales, regulating cell proliferation rates and growth, thus controlling the pace, patterning, and co-variation of life history traits. Estrous cyclicity relates to the long period rhythm in a body mass-independent manner. The mass-dependency and -independency of life history relationships with RI periodicity align with hypothalamic-mediated neurosecretory anterior and posterior pituitary outputs. We term this period the Havers-Halberg Oscillation (HHO), in reference to Clopton Havers, a 17th Century hard tissue anatomist, and Franz Halberg, a long-time explorer of long-period rhythms. We propose a mathematical model that may help elucidate the underlying physiological mechanism responsible for the HHO.
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http://dx.doi.org/10.1016/j.jtbi.2012.04.007DOI Listing
July 2012

Risk factors to predict the incidence of surgical adverse events following open or laparoscopic surgery for apparent early stage endometrial cancer: results from a randomised controlled trial.

Eur J Cancer 2012 Sep 12;48(14):2155-62. Epub 2012 Apr 12.

University of Queensland, School of Medicine, QLD, Australia.

Aims: To identify risk factors for major adverse events (AEs) and to develop a nomogram to predict the probability of such AEs in patients who have surgery for apparent early stage endometrial cancer.

Methods: We used data from 753 patients who were randomised to either total laparoscopic hysterectomy or total abdominal hysterectomy in the LACE trial. Serious adverse events that prolonged hospital stay or postoperative adverse events (using common terminology criteria 3+, CTCAE V3) were considered major AEs. We analysed pre-surgical characteristics that were associated with the risk of developing major AEs by multivariate logistic regression. We identified a parsimonious model by backward stepwise logistic regression. The six most significant or clinically important variables were included in the nomogram to predict the risk of major AEs within 6weeks of surgery and the nomogram was internally validated.

Results: Overall, 132 (17.5%) patients had at least one major AE. An open surgical approach (laparotomy), higher Charlson's medical co-morbidities score, moderately differentiated tumours on curettings, higher baseline Eastern Cooperative Oncology Group (ECOG) score, higher body mass index and low haemoglobin levels were associated with AE and were used in the nomogram. The bootstrap corrected concordance index of the nomogram was 0.63 and it showed good calibration.

Conclusions: Six pre-surgical factors independently predicted the risk of major AEs. This research might form the basis to develop risk reduction strategies to minimise the risk of AEs among patients undergoing surgery for apparent early stage endometrial cancer.
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http://dx.doi.org/10.1016/j.ejca.2012.03.013DOI Listing
September 2012

Life-history correlates of enamel microstructure in cebidae (Platyrrhini, Primates).

Anat Rec (Hoboken) 2011 Dec 1;294(12):2193-206. Epub 2011 Nov 1.

Department of Physical Therapy and Human Performance, Florida Gulf Coast University, Fort Myers, 33965, USA.

Previous studies have examined tooth eruption as it relates intrinsically to body mass, brain mass, and other life history variables, and extrinsically to ecological factors (e.g., age at foraging independence, environmental risk aversion, and maternal investment). Different models have been explored wherein each of these variables impacts ontogeny. However, anthropoid and strepsirhine primates exhibit interesting differences in the relationships of these ecological and life history variables with tooth eruption. Moreover, interactions between ecological variables and dental tissue growth have only been explored in the lemurs. This study examines dental microstructure of the New World monkey family, Cebidae, to provide further insight into forces influencing the evolution of primate dental ontogeny. The Cebidae were chosen because they are a diverse group which is distinct in ecology and phylogeny from the better known catarrhines of the Old World. Using phylogenetic generalized least squares analyses (PGLS), we test whether brain mass, body mass, or the three above-mentioned ecological variables have stronger correlations with enamel growth. Results show that ecological factors have stronger relationships with cebid dental growth rates than brain or body mass. Foraging independence has the most impact on overall enamel growth as it has the strongest correlation with enamel extension rates. However, another estimate of enamel growth, rate of secretion, has the highest correlation with maternal investment. Our results suggest that an overarching ecological model encompassing the three current ecological hypotheses is needed to further understand the evolution of dental ontogeny within primates.
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http://dx.doi.org/10.1002/ar.21503DOI Listing
December 2011

The functional morphology of the anterior masticatory apparatus in tree-gouging marmosets (Cebidae, Primates).

J Morphol 2011 Jul 15;272(7):833-49. Epub 2011 Apr 15.

Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, MO, USA.

Although all genera of Callitrichinae feed on tree exudates, marmosets (Callithrix and Cebuella) use specialized anterior teeth to gouge holes in trees and actively stimulate exudate flow. Behavioral studies demonstrate that marmosets use large jaw gapes but do not appear to generate large bite forces (relative to maximal ability) during gouging. Nonetheless, the anterior teeth of marmosets likely experience different loads during gouging compared to nongouging platyrrhines. We use histological data from sectioned teeth, μCTs of jaws and teeth, and in vitro tests of symphyseal strength to compare the anterior masticatory apparatus in Callithrix to nongouging tamarins (Saguinus) and other cebids. We test the hypotheses that (1) marmoset anterior teeth are adapted to accommodate relatively high stresses linked to dissipating gouging forces and (2) the mandibular symphysis does not provide increased load resistance ability compared with closely related nongouging platyrrhines. Differences in decussation between Callithrix and Saguinus are greatest in the anterior teeth, suggesting an increased load resistance ability specifically in incisor and canine enamel of Callithrix. Callithrix lower incisor crowns are labiolingually thicker suggesting increased bending resistance in this plane and improved wedging ability compared with Saguinus. Anterior tooth roots are larger relative to symphyseal bone volume in Callithrix. Anterior tooth root surface areas also are larger in marmosets for their symphyseal volume, but it remains unclear whether this relative increase is an adaptation for dissipating dental stresses versus a growth-related byproduct of relatively elongated incisors. Finally, simulated jaw loading suggests a reduced ability to withstand external forces in the Callithrix symphysis. The contrast between increased load resistance ability in the anterior dentition versus relatively reduced symphyseal strength (1) suggests a complex loading environment during gouging, (2) highlights the possibility of distinct loading patterns in the anterior teeth versus the symphysis, and (3) points to a potential mosaic pattern of dentofacial adaptations to tree gouging.
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http://dx.doi.org/10.1002/jmor.10951DOI Listing
July 2011

Comparison of expression profiles in ovarian epithelium in vivo and ovarian cancer identifies novel candidate genes involved in disease pathogenesis.

PLoS One 2011 Mar 15;6(3):e17617. Epub 2011 Mar 15.

Department of Gynaecological Oncology, Westmead Hospital, Westmead, New South Wales, Australia.

Molecular events leading to epithelial ovarian cancer are poorly understood but ovulatory hormones and a high number of life-time ovulations with concomitant proliferation, apoptosis, and inflammation, increases risk. We identified genes that are regulated during the estrous cycle in murine ovarian surface epithelium and analysed these profiles to identify genes dysregulated in human ovarian cancer, using publically available datasets. We identified 338 genes that are regulated in murine ovarian surface epithelium during the estrous cycle and dysregulated in ovarian cancer. Six of seven candidates selected for immunohistochemical validation were expressed in serous ovarian cancer, inclusion cysts, ovarian surface epithelium and in fallopian tube epithelium. Most were overexpressed in ovarian cancer compared with ovarian surface epithelium and/or inclusion cysts (EpCAM, EZH2, BIRC5) although BIRC5 and EZH2 were expressed as highly in fallopian tube epithelium as in ovarian cancer. We prioritised the 338 genes for those likely to be important for ovarian cancer development by in silico analyses of copy number aberration and mutation using publically available datasets and identified genes with established roles in ovarian cancer as well as novel genes for which we have evidence for involvement in ovarian cancer. Chromosome segregation emerged as an important process in which genes from our list of 338 were over-represented including two (BUB1, NCAPD2) for which there is evidence of amplification and mutation. NUAK2, upregulated in ovarian surface epithelium in proestrus and predicted to have a driver mutation in ovarian cancer, was examined in a larger cohort of serous ovarian cancer where patients with lower NUAK2 expression had shorter overall survival. In conclusion, defining genes that are activated in normal epithelium in the course of ovulation that are also dysregulated in cancer has identified a number of pathways and novel candidate genes that may contribute to the development of ovarian cancer.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0017617PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3057977PMC
March 2011

Uterine papillary serous carcinoma: patterns of failure and survival.

Aust N Z J Obstet Gynaecol 2009 Aug;49(4):419-25

Department of Radiation Oncology, Westmead Hospital, Sydney, New South Wales, Australia.

Objective: To evaluate the outcome in patients with uterine papillary serous carcinoma (UPSC).

Methods: A retrospective review of women treated for UPSC between 1995 and 2006 in Westmead Hospital, Sydney. The patients were treated with total abdominal hysterectomy, bilateral salpingo-oophorectomy and surgical staging. The majority of the patients had platinum-based adjuvant chemotherapy and radiotherapy. Sites of initial recurrence were documented. Overall survival (OS) and progression free survival (PFS) were estimated using Kaplan-Meier method. Univariate and multivariate analysis was performed using Cox regression analysis to test the effects of multiple prognostic factors on survival.

Results: Two-year and five-year OS was 65% and 43%. The median OS was 39 months. Two-year and five-year PFS was 60% and 35%. Macroscopic residual disease at the completion of surgery was the only significant prognostic factor associated with worse OS on both univariate and multivariate analysis (P < 0.001). The median OS was only 11 months if patients had macroscopic residual disease, and all patients died within 18 months despite adjuvant therapies. Twenty-one patients relapsed. The site(s) of initial recurrence were: vagina (five patients), pelvic lymph nodes (four patients), abdomen (11 patients), para-aortic lymph nodes (six patients), inguinal lymph nodes (two patients) and distant metastases in seven patients. Only one of 16 patients who received vaginal brachytherapy failed in the vagina, but three of seven patients who received external beam pelvic radiotherapy failed in the vagina.

Conclusion: We recommend optimal cytoreduction surgery with the aim of leaving no macroscopic disease at the end of the operation. Vaginal brachytherapy should be considered as a component of adjuvant radiotherapy. Abdominal failure was the commonest mode of failure in our cohort of patients.
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http://dx.doi.org/10.1111/j.1479-828X.2009.01016.xDOI Listing
August 2009

Lamellar bone is an incremental tissue reconciling enamel rhythms, body size, and organismal life history.

Calcif Tissue Int 2009 May 21;84(5):388-404. Epub 2009 Feb 21.

Departments of Biomaterials and Biomimetics and Basic Science and Craniofacial Biology, New York University College of Dentistry, New York, NY 10010, USA.

Mammalian enamel formation is periodic, including fluctuations attributable to the daily biological clock as well as longer-period oscillations that enigmatically correlate with body mass. Because the scaling of bone mass to body mass is an axiom of vertebrate hard tissue biology, we consider that long-period enamel formation rhythms may reflect corresponding and heretofore unrecognized rhythms in bone growth. The principal aim of this study is to seek a rhythm in bone growth demonstrably related to enamel oscillatory development. Our analytical approach is based in morphology, using a variety of hard tissue microscopy techniques. We first ascertain the relationship among long-period enamel rhythms, the striae of Retzius, and body mass using a large sample of mammalian taxa. In addition, we test whether osteocyte lacuna density (a surrogate for rates of cell proliferation) in bone is correlated with mammalian body mass. Finally, using fluorescently labeled developing bone tissues, we investigate whether the bone lamella, a fundamental microanatomical unit of bone, relates to rhythmic enamel growth increments. Our results confirm a positive correlation between long-period enamel rhythms and body mass and a negative correlation between osteocyte density and body mass. We also confirm that lamellar bone is an incremental tissue, one lamella formed in the species-specific time dependency of striae of Retzius formation. We conclude by contextualizing our morphological research with a current understanding of autonomic regulatory control of the skeleton and body mass, suggesting a central contribution to the coordination of organismal life history and body mass.
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http://dx.doi.org/10.1007/s00223-009-9221-2DOI Listing
May 2009

Craniofacial architectural constraints and their importance for reconstructing the early Homo skull KNM-ER 1470.

J Clin Pediatr Dent 2008 ;33(1):43-54

Department of Biomaterials & Biomimetics, New York University College of Dentistry, 345 East 24th Street, New York, NY 10010, USA.

Objective: Our objective is to exploit architectural constraint for the analysis and interpretation of craniofacial form, which we apply here to the reconstruction of the early Homo cranium KNM-ER 1470. We are motivated to perform this study because in the absence of biological criteria our preconceptions are likely to govern our concept of craniofacial form.

Study Design: We reassembled the fragmented parts--left and right halves of the calvaria and the face--according to mammalian craniofacial architectural constraints described by Donald H. Enlow and colleagues.

Results: When evaluated on a biological premise, KNM-ER 1470 is found to have a more prognathic midface than commonly appreciated. The relationship between facial prognathism and cranial capacity also provides an estimate downward for this specimen, from 752cc to ca. 700cc.

Conclusion: Awareness of our preconceptions is critical to the performance of relatively unbiased research in fields characterized by interpretations of morphology. When perceptual bias is relatively minimized, applied here as an architecturally constrained of KNM-ER 1470 craniofacial skeleton, we are able to provide the scientific community with a more tractable Gestalt perspective of form.
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http://dx.doi.org/10.17796/jcpd.33.1.8168115j12103nutDOI Listing
February 2009

Microinvasion links ovarian serous borderline tumor and grade 1 invasive carcinoma.

Gynecol Oncol 2007 Jul 27;106(1):44-51. Epub 2007 Apr 27.

Gynaecological Cancer Centre, Royal Hospital for Women, Sydney, Australia.

Objectives: Ovarian serous borderline tumor (SBT) and grade 1 (low grade) serous carcinoma are closely related, but, unlike SBT which has been well studied, there have been few studies looking primarily at grade 1 serous carcinoma. The objective of this study was to better understand the relationship between serous borderline tumors and grade 1 serous carcinomas.

Methods: We performed a clinicopathologic review of 46 women with SBT and 16 with grade 1 serous carcinoma.

Results: Thirteen of forty-six (28%) SBTs had a micropapillary pattern, 12/46 (26%) had evidence of microinvasion and 19/46 (41%) had extraovarian implants, of which 1/19 (5%) was invasive. Three of forty-six (7%) of SBTs recurred, all of which were originally advanced stage. No patient with a microinvasive SBT recurred. The 16 grade 1 serous carcinomas divided into those with evidence of coexisting SBTs (5 cases) and those without (11 cases). Nine of sixteen (56%) carcinomas recurred, comprising 5/5 with SBT and 4/11 without. All patients had advanced stage at diagnosis. Microinvasion, invasive implants and recurrences all showed qualitative histologic resemblance to carcinoma. There were no micropapillary areas in any of the carcinomas, although cribriform pattern was seen in these tumors.

Conclusions: Advanced stage at diagnosis was the most important prognostic marker in patients with SBT. Although a micropapillary pattern was common, it did not adversely affect prognosis per se, but was associated with a higher stage. A micropapillary pattern was not seen adjacent to microinvasion or in association with grade 1 serous carcinoma. Microinvasion was common but, in our series, did not appear to worsen the prognosis. Grade 1 serous carcinoma was less common than SBT and had a more unfavorable prognosis. The qualitative histologic similarity between microinvasion, invasive implants, recurrences and grade 1 serous carcinoma suggests that microinvasion represents early invasion and is not just another histologic pattern of SBT. We speculate that some invasive implants and recurrences may be peritoneal grade 1 serous carcinoma.
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http://dx.doi.org/10.1016/j.ygyno.2007.01.054DOI Listing
July 2007

Abdominal radical trachelectomy: a fertility-preserving option for women with early cervical cancer.

BJOG 2005 Mar;112(3):366-9

Department of Gynaecologic Oncology, St Stephen Hospital, Budapest 1096, Hungary.

Abdominal radical trachelectomy is a fertility-preserving alternative to radical hysterectomy or chemoradiation for young women with stage IA2 to IB cervical cancers. Thirty-three patients were offered this procedure. The mean age was 30.5 years (range 23-37). Three procedures were abandoned because of positive pelvic nodes (two patients) and involvement of the margin between the amputated cervix and uterine fundus (one patient). Of the remaining 30 patients, 10 had stage IA2 tumours, 15 had stage IB1 and 5 had stage IB2. During follow up of a median of 47 months (mean 32 months, range 14-75 months), no recurrences have been detected. A normal menstrual pattern resumed within eight weeks of surgery in all but two patients. Five patients attempted to conceive. Three women have fallen pregnant, resulting in one first trimester miscarriage and two caesarean section deliveries at term. Our experience suggests that abdominal radical trachelectomy provides a method of treating women with stage IA2 to IB cervical cancers with conservation of fertility without apparently compromising recurrence or survival rates. It appears to provide equivalent oncological safety to a standard Wertheim hysterectomy using a technique familiar to all practising gynaecologic oncologists.
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http://dx.doi.org/10.1111/j.1471-0528.2004.00421.xDOI Listing
March 2005

Biology of epithelial ovarian cancer: implications for screening women at high genetic risk.

J Clin Oncol 2004 Apr;22(7):1315-27

Royal Hospital for Women, Department of Medical Oncology, Sydney, Australia.

Purpose: Our aim was to analyze the clinicopathologic features of screen-detected ovarian cancers identified in women, either at general population risk or high genetic risk of ovarian cancer, who have participated in screening studies.

Methods: Studies published between 1988 and April 2003 were categorized by the population screened and the primary screening modalities used. Each report was examined with reference to the histologic type, stage, and grade of screen-detected cancers. Reports of studies of prophylactically removed ovaries from women at high risk of ovarian cancer were also reviewed.

Results: Of the stage I tumors detected by screening women at population risk, almost half were borderline ovarian tumors, granulosa-cell tumors, or germ-cell tumors, which is disproportionate to their frequency. Furthermore, of the stage I invasive epithelial cancers diagnosed in women at population risk, the majority were endometrioid, clear-cell, and mucinous histologic subtypes. Most ovarian cancers that occur in women at high genetic risk are high-grade serous cancers, and these are infrequently screen detected at an early stage.

Conclusion: The clinicopathologic features of screen-detected ovarian cancers suggest that screening may not reduce mortality in women at increased genetic risk. Prospective screening studies are required in genetically high-risk populations to answer this important question. Women electing surveillance should be aware of the lack of proven benefit and the low likelihood of detecting early stage serous cancers. Bilateral salpingo-oophorectomy appears to be the most effective approach to decrease the risk of ovarian cancer and thereby reduce mortality in high-risk women.
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http://dx.doi.org/10.1200/JCO.2004.07.179DOI Listing
April 2004

Role of systemic chemotherapy in metastatic cervical cancer.

Expert Rev Anticancer Ther 2003 Apr;3(2):234-40

Department of Medical Oncology, The Royal Hospital for Women, Randwick, NSW, Australia.

Cervical cancer is a chemoresponsive tumor. Concurrent chemotherapy with cisplatin and radiotherapy has resulted in improved survival in patients with locally advanced cervical cancer and is now standard of care. There are many active drugs in metastatic cervical cancer with cisplatin being the most active single agent. Although response rates are significantly higher with cisplatin combinations, to date, there is no evidence to suggest this is associated with an improved survival. However, this is still an area that is attracting much research interest. The role of chemotherapy in metastatic cervical cancer will be reviewed together with some of the new areas of research.
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http://dx.doi.org/10.1586/14737140.3.2.234DOI Listing
April 2003