Publications by authors named "Adam Pendlebury"

9 Publications

  • Page 1 of 1

Seborrheic Keratosis-Like Lesion of the Cervix: First Report of the Cytological Features of a Low-Risk HPV 42-Associated Lesion.

Acta Cytol 2021 22;65(5):448-452. Epub 2021 Jul 22.

Department of Pathology, Belfast Health and Social Care Trust, Belfast, United Kingdom.

Introduction: Seborrheic keratosis-like lesion of the cervix and vagina is a rare lesion and shows similar morphology to vulvar seborrheic keratosis; 3 of the 7 previously reported cases were associated with low-risk human papillomavirus (HPV) type 42. We report a case of seborrheic keratosis-like lesion of the cervix and provide the first description of the cytological features of this lesion.

Case Presentation: A woman in her late forties presented with postcoital bleeding. She had a cervical screening test following which she underwent cervical biopsy, endocervical and endometrial curettage, large loop excision of the transformation zone of the cervix, and hysterectomy.

Results: The liquid-based cytology preparation showed cohesive groups of mildly atypical squamoid cells with a spindle cell morphology, mildly increased nuclear to cytoplasmic ratio, prominent nucleoli, and occasional nuclear grooves. No koilocytes were identified. Molecular genotyping revealed positivity for HPV type 42.

Discussion/conclusion: This represents the first description of the cytological features of a seborrheic keratosis-like lesion of the cervix, which are distinctive and unusual. Whilst the mild squamous atypia raised the possibility of a low-grade squamous intraepithelial lesion, no koilocytes were identified. The association in our case with a low-risk HPV type, HPV 42, provides further evidence for a role of this HPV type in the pathogenesis of these lesions.
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September 2021

Possible high-grade squamous intraepithelial lesion (pHSIL) in the new cervical screening paradigm: The outcomes and the role of clinicopathological review.

Aust N Z J Obstet Gynaecol 2021 08 3;61(4):569-575. Epub 2021 May 3.

Department of Gynaecological Oncology, The Mercy Hospital for Women, Melbourne, Victoria, Australia.

Background: A renewed National Cervical Screening Program (NCSP) was introduced in Australia in December 2017. Under the renewed NCSP, there are limited data to guide the management of discordant colposcopy and biopsy results after a liquid-based cytology (LBC) finding of 'possible high-grade squamous intraepithelial lesion' (pHSIL).

Aims: This study aims to determine the proportion of women referred with pHSIL who are found to have HSIL, identify influencing factors of women most at risk, and examine the role that cytopathology review plays in management decisions.

Materials And Methods: Two-hundred and thirty-two women presenting to a tertiary women's hospital in Australia with pHSIL since December 2017 were identified. Women with HSIL following colposcopy directed biopsy were referred for treatment. When HSIL was not identified, these patients were referred for multidisciplinary clinicopathological review. Pathological outcomes and treatment recommendations are included.

Main Outcome Measures: The primary outcome of the study was histological confirmation of HSIL.

Results: Primary outcome data were available for 182 women (78.5%); 62 (34.1%) had HSIL on histology, three (1.7%) had adenocarcinoma in situ (AIS) and one (1%) had cervical squamous cell carcinoma (SCC). There was no association between age and the presence of HSIL. The presence of human papillomavirus 16 and/or 18 increased the likelihood of HSIL on histology (relative risk 1.9; 95% CI 1.27-2.80, P = 0.002). Fifty-nine (25.4%) women were referred for observation who had low-grade squamous intraepithelial lesion/no dysplasia.

Conclusions: Clinicopathological review optimises management and triage of patients with pHSIL on referral cytology. Understanding outcomes in these patients informs counselling and management.
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August 2021

Development of a surgical competency assessment tool for sentinel lymph node dissection by minimally invasive surgery for endometrial cancer.

Int J Gynecol Cancer 2021 05 4;31(5):647-655. Epub 2021 Mar 4.

Gynecology and Obstetrics, Charles University First Faculty of Medicine, Praha, Praha, Czech Republic.

Introduction: Sentinel lymph node dissection is widely used in the staging of endometrial cancer. Variation in surgical techniques potentially impacts diagnostic accuracy and oncologic outcomes, and poses barriers to the comparison of outcomes across institutions or clinical trial sites. Standardization of surgical technique and surgical quality assessment tools are critical to the conduct of clinical trials. By identifying mandatory and prohibited steps of sentinel lymph node (SLN) dissection in endometrial cancer, the purpose of this study was to develop and validate a competency assessment tool for use in surgical quality assurance.

Methods: A Delphi methodology was applied, included 35 expert gynecological oncology surgeons from 16 countries. Interviews identified key steps and tasks which were rated mandatory, optional, or prohibited using questionnaires. Using the surgical steps for which consensus was achieved, a competency assessment tool was developed and subjected to assessments of validity and reliability.

Results: Seventy percent consensus agreement standardized the specific mandatory, optional, and prohibited steps of SLN dissection for endometrial cancer and informed the development of a competency assessment tool. Consensus agreement identified 21 mandatory and three prohibited steps to complete a SLN dissection. The competency assessment tool was used to rate surgical quality in three preselected videos, demonstrating clear separation in the rating of the skill level displayed with mean skills summary scores differing significantly between the three videos (F score=89.4; P<0.001). Internal consistency of the items was high (Cronbach α=0.88).

Conclusion: Specific mandatory and prohibited steps of SLN dissection in endometrial cancer have been identified and validated based on consensus among a large number of international experts. A competency assessment tool is now available and can be used for surgeon selection in clinical trials and for ongoing, prospective quality assurance in routine clinical care.
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May 2021

Surgical lymph node assessment influences adjuvant therapy in clinically apparent stage I endometrioid endometrial carcinoma, meeting Mayo criteria for lymphadenectomy.

J Surg Oncol 2021 Apr 16;123(5):1292-1298. Epub 2021 Feb 16.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology and Women's Health Institute, The Cleveland Clinic Foundation, Cleveland, Ohio, USA.

Objective: To evaluate the impact of surgical lymph node assessment for clinically apparent, stage I endometrioid endometrial adenocarcinoma meeting Mayo criteria for lymphadenectomy.

Methods: Patients with endometrioid endometrial adenocarcinoma meeting Mayo criteria for lymphadenectomy who underwent hysterectomy and lymphadenectomy were identified. Algorithms for adjuvant therapy with and without lymphadenectomy were developed utilizing NCCN guidelines, PORTEC 1, and PORTEC 2. Patients served as their own control to determine the frequency of treatment modification.

Results: A total of 357 patients were analyzed. Using our algorithms treatment modification would have occurred because of lymphadenectomy in 62.8% of patients if whole pelvic external beam radiation was used for patients meeting inclusion criteria for PORTEC 1. Treatment modification would have occurred in 16.2% of patients if vaginal brachytherapy was used for patients meeting the inclusion criteria for PORTEC 2. Of the total, 53.8% of patients meeting inclusion criteria for PORTEC 1 would have had a reduction in adjuvant therapy from whole pelvic radiotherapy to vaginal brachytherapy alone. Only 9.0% of patients would have adjuvant therapy increased to include external beam radiotherapy and chemotherapy based on the presence of positive lymph nodes.

Conclusions: Applying standard adjuvant treatment algorithms to real patient data, surgical lymph node assessment appears to frequently alter treatment allocation.
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April 2021

Efficacy and toxicity of prolonged pegylated liposomal doxorubicin use in women with recurrent epithelial ovarian cancer.

Gynecol Oncol 2020 08 1;158(2):309-315. Epub 2020 Jun 1.

Division of Gynecologic Oncology, Obstetrics, Gynecology and Women's Health Institute, Cleveland Clinic, Desk A81, 9500 Euclid Avenue, Cleveland, OH 44195, United States of America.

Objective: To evaluate the efficacy and toxicity of extended duration pegylated liposomal doxorubicin (PLD) in women with recurrent epithelial ovarian carcinoma (rEOC).

Methods: Women with rEOC who received >7 cycles of PLD were retrospectively identified. Response was determined by RECIST 1.1. Progression free survival (PFS) and overall survival (OS) were calculated from PLD initiation. Toxicity was assessed by CTCAE v5.0. Kaplan Meier estimates and Cox proportional hazards were used to evaluate differences in time to recurrence or survival.

Results: 69 patients with rEOC received a median of 11.0 cycles (range, 7-115) at a median cumulative dose of 400 mg/m (range, 210-4600 mg/m); 29.0% (n = 20) had platinum sensitive and 71.0% (n = 49) had platinum resistant disease. Of the observed grade ¾ toxicities (31.9%; n = 22), dermatologic were most frequent (n = 13; 18.8%). 41 women (59.4%) experienced clinical benefit; complete response in 17.4% (n = 12), partial response in 13.0% (n = 9) and stable disease in 29.0% (n = 20). Median PFS for all patients was 13.0 months (95% CI, 10.7, 15.2); there were no significant differences between platinum sensitive versus resistant disease (15.9 months vs. 12.3 months; HR 1.15, 95% CI, 0.66, 2.00; p = .61). With extended duration PLD, median OS was 40.2 months (95% CI 30.0, 49.0); no significant differences were noted for platinum sensitive versus resistant disease (44.7 months vs. 33.3 months; HR 1.85, 95% CI, 0.91, 3.78; p = .07). Four cases (5.8%) of oral squamous cell carcinoma occurred during treatment.

Conclusions: Among women with both platinum sensitive and resistant rEOC who received >7 cycles of PLD, approximately one-half experienced sustained clinical benefit with acceptable toxicity. PLD may be considered for extended usage and maintenance in initially responding women with rEOC at least stable disease.
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August 2020

HPV swab self-collection and cervical cancer in women who have sex with women.

Med J Aust 2020 02 24;212(3):106-107.e1. Epub 2019 Dec 24.

Mercy Hospital for Women, Melbourne, VIC.

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February 2020

Long-term use of pegylated liposomal doxorubicin to a cumulative dose of 4600 mg/m2 in recurrent ovarian cancer.

Anticancer Drugs 2017 08;28(7):815-817

Cleveland Clinic Taussig Cancer Center, Cleveland, Ohio, USA.

Pegylated liposomal doxorubicin (PLD) is used widely in gynecologic oncology and other oncology disciplines. Native doxorubicin use is associated with the potential for significant toxicity. Cardiac toxicity in particular limits lifetime dose. PLD has not been shown to be associated with clinical cardiac toxicity. We report on the long-term use of PLD in a patient with recurrent high-grade serous ovarian cancer to a lifetime dose of 4600 mg/m. This therapy was associated with long-term stable disease, good performance status, and minimal adverse effects.
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August 2017

The circulating microRNA-200 family in whole blood are potential biomarkers for high-grade serous epithelial ovarian cancer.

Biomed Rep 2017 Mar 25;6(3):319-322. Epub 2017 Jan 25.

Department of Obstetrics and Gynaecology, University of Melbourne, Mercy Hospital for Women, Heidelberg, Vic 3084, Australia.

Epithelial ovarian cancer (EOC) is the leading cause of mortality with regard to gynaecological cancer. There is no effective biomarker and therefore prognosis is poor as the majority of cases are not diagnosed until advanced disease is present. MicroRNAs (miRs) are dysregulated in ovarian cancer tissue and are present in the circulation. The aim of the present study was to investigate whether circulating miRs from the miR-200 family served as potential candidate biomarkers for the early detection of EOC. Whole blood and ovarian tissue were collected from women with early (stage I/II, n=4), advanced EOC (stage III/IV, n=4), and women with benign ovarian masses (n=5). A panel of 5 miRs were studied in whole blood and ovarian tissue using Taqman RT-PCR miR assays. The expression of circulating miR-200a, miR-200b and miR-200c were upregulated (P<0.05) in ovarian cancer compared to controls, correlated with the stage of disease and reflected tissue expression. Despite a trend, there was no significant increase in the expression of miR-21 and miR-210 in the present study. In conclusion, the circulating miR-200 family may be promising candidate biomarkers for EOC that require validation in a larger study.
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March 2017

Ovarian Growing Teratoma Syndrome With Spuriously Elevated α-Fetoprotein.

J Clin Oncol 2015 Aug 7;33(24):e99-100. Epub 2014 Apr 7.

Mercy Hospital for Women; and Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia

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August 2015