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Article: Estimation of risk posed by malignant polyps amongst colorectal surgeons in Australia and New Zealand.

Zammit, Andrew P / Brown, Ian / Hooper, John D / Clark, David A / Riddell, Andrew D

2024 Volume 40, Issue 2, Page(s) 114–120

Abstract: Purpose: The estimation of the risk posed by malignant polyps for residual or lymphatic disease plays a central role. This study investigated colorectal surgeons' assessment of these risks associated with malignant polyps.: Methods: A cross-sectional ...

Abstract	Purpose: The estimation of the risk posed by malignant polyps for residual or lymphatic disease plays a central role. This study investigated colorectal surgeons' assessment of these risks associated with malignant polyps. Methods: A cross-sectional questionnaire was electronically administered to colorectal surgeons in Australia and New Zealand in October 2022. The questionnaire contained 17 questions on demographics, when surgeons consider colorectal resection appropriate, and the risk assessment for 5 hypothetical malignant polyps. Results: The mean risk of residual or lymphatic disease that would prompt surgeons to recommend colonic resection was 5%. However, this increased to a mean risk of 10% if the malignant polyp was located in the rectum, and the only resection option was abdominoperineal resection with end-colostomy. There was high concordance between the estimated risk of residual or lymphatic disease by colorectal surgeons and the Association of Coloproctology of Great Britain and Ireland (ACPGBI) guidelines for the 5 hypothetical malignant polyps, with the ACPGBI estimated risk lying within the 95% confidence interval for 4 of the 5 malignant polyps. Nonetheless, 96.6% of surgeons felt that an online risk calculator would improve clinical practice. Conclusion: Colorectal surgeons in Australia and New Zealand accurately estimated the risk posed by malignant polyps. An online risk calculator may assist in better conveying risk to patients.
Language	English
Publishing date	2024-03-25
Publishing country	Korea (South)
Document type	Journal Article
ZDB-ID	2711906-3
ISSN	2287-9722 ; 2287-9714
ISSN (online)	2287-9722
ISSN	2287-9714
DOI	10.3393/ac.2023.00178.0025
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Article ; Online: Malignant polyps in the COVID-19 era: a population-based analysis.

Zammit, Andrew P / Brown, Ian / Hooper, John D / Clark, David A / Riddell, Andrew D

ANZ journal of surgery

2023 Volume 93, Issue 4, Page(s) 932–938

Abstract: Background: Malignant polyps represent the early development of colorectal adenocarcinoma. During 2020, there was widescale rationing of health-care resources in response to the COVID-19 pandemic. In particular there was deferral of some colonoscopy ... ...

Abstract	Background: Malignant polyps represent the early development of colorectal adenocarcinoma. During 2020, there was widescale rationing of health-care resources in response to the COVID-19 pandemic. In particular there was deferral of some colonoscopy procedures required for timely malignant polyp detection. This study sought to assess how these deferrals affected the diagnosis of malignant polyps. Methods: A population wide analysis was performed of 2079 malignant polyps, diagnosed in Queensland, Australia from 2011 to 2020. A regression analysis, with 95% prediction intervals, was produced to determine whether there was a significant impact on the number of malignant polyps diagnosed in 2020 compared to previous years. Univariate statistical analysis of patient, procedural, and pathological variables was also performed. Results: In 2020 there were 211 malignant polyps diagnosed, which was significantly lower than was predicted by the univariate regression analysis (r Conclusion: Because of the significant decrease in the number of malignant polyps, and the natural history of the disease, it is expected that there will be an increase in more advanced colorectal adenocarcinomas presenting in 2021 and beyond. This has implications for healthcare resources, particularly in light of the ongoing strain on health departments as a result of the COVID-19 pandemic.
MeSH term(s)	Humans ; Colonic Polyps/epidemiology ; Colonic Polyps/surgery ; Colonic Polyps/pathology ; Pandemics ; COVID-19/epidemiology ; Colonoscopy ; Colorectal Neoplasms/pathology ; Adenocarcinoma/surgery
Language	English
Publishing date	2023-01-24
Publishing country	Australia
Document type	Journal Article
ZDB-ID	2050749-5
ISSN	1445-2197 ; 1445-1433 ; 0004-8682
ISSN (online)	1445-2197
ISSN	1445-1433 ; 0004-8682
DOI	10.1111/ans.18253
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Zs.A 180: Show issues

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Article ; Online: Missing parameters in malignant polyp histology reports: can appropriate decisions be made?

Zammit, Andrew P / Brown, Ian / Hooper, John D / Clark, David A / Riddell, Andrew D

Pathology

2022

Abstract: The treatment of colorectal malignant polyps is dependent upon quality reporting of the histopathological features known to predict the risk of residual disease or lymph node metastasis. The Royal College of Pathologists of Australasia (RCPA) has ... ...

Abstract	The treatment of colorectal malignant polyps is dependent upon quality reporting of the histopathological features known to predict the risk of residual disease or lymph node metastasis. The Royal College of Pathologists of Australasia (RCPA) has produced protocols covering mandatory and recommended pathological parameters to be included in the pathology reporting of malignant polyps. This paper aimed to assess the quality of the pathological reporting in a population-wide analysis from 2011-2019 in Queensland, Australia. A retrospective population-wide cohort study was performed using the Queensland Oncology Repository as a data source. The number of missing pathological parameters (assessed against the RCPA protocol standards and guidelines) for each patient was then summed. Demographic and other patient details were collated. The number of patients whose recommended treatment could theoretically be altered by the full reporting of missing parameters was calculated. A total of 1,646 histopathological reports of malignant polyps were reviewed. From this, 30.8% of all reports had a sufficient number of missing parameters that may have seen an alternate management strategy chosen. The most commonly under-reported parameter from the standards was either a Haggitt or Kikuchi level with 48.6% missing. Synoptic reporting significantly reduced the mean number of missing pathological parameters (p<0.001) There was a significant improvement in the number of missing pathological details over time (p<0.001). Accurate and complete pathology reports are essential to formulate appropriate surgical recommendations after the resection of malignant polyps. In this population-based study, pathology reports remain incomplete for the established parameters despite the introduction of an RCPA structured reporting protocol. Fortunately, the quality of pathological reporting has improved since the introduction of the first RCPA protocol covering reporting of malignant polyps.
Language	English
Publishing date	2022-08-27
Publishing country	England
Document type	Journal Article
ZDB-ID	7085-3
ISSN	1465-3931 ; 0031-3025
ISSN (online)	1465-3931
ISSN	0031-3025
DOI	10.1016/j.pathol.2022.06.007
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Zs.A 723: Show issues

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Article ; Online: In comparison with polypectomy, colorectal resection is associated with improved survival for patients diagnosed with malignant polyps.

Zammit, Andrew P / Hooper, John D / Brown, Ian / Clark, David A / Riddell, Andrew D

Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland

2022 Volume 25, Issue 2, Page(s) 261–271

Abstract: Aim: Patients diagnosed with a malignant polyp generally have favourable overall survival (OS) and cancer-specific survival (CSS). However, it is unclear how choice in management for malignant polyps may affect survival.: Methods: Data from the ... ...

Abstract	Aim: Patients diagnosed with a malignant polyp generally have favourable overall survival (OS) and cancer-specific survival (CSS). However, it is unclear how choice in management for malignant polyps may affect survival. Methods: Data from the Queensland Oncology Repository was analysed to derive a population wide assessment of the impact of management strategy on OS and CSS for patients diagnosed with malignant polyps. Log-rank testing, Kaplan-Meier and Cox-regression models were performed. Patients were matched using propensity score and Mahalanobis distance matching. Results: A total of 1,646 patients were included with 240 deaths and 52 colorectal cancer related deaths until censor date. Following propensity score and Mahalanobis distance matching of patients undergoing polypectomy alone versus colorectal resection, there was no significant difference in the age groups (<60 years of age or ≥60 years of age), American Society of Anesthesiology score, comorbidity count or Association of ColoProctology of Great Britain and Ireland risk category. However, of note Log-rank testing demonstrated a significant difference in OS (p < 0.001) and CSS (p = 0.0061) between management strategies. Multivariable Cox-regression models in matched and un-matched patient cohorts demonstrated significantly lower hazards of death for OS with resection (p < 0.001). However, CSS was no longer significantly different between management groups in multivariable Cox-regression analysis (p = 0.073). Conclusion: Patients who underwent colorectal resection had significantly improved OS and CSS compared with polypectomy alone. Improved OS was furthermore seen on multivariable analysis, and in matched cohorts. Future research should investigate why this unexpected finding may be the case and whether updates to guidelines should be considered.
MeSH term(s)	Humans ; Middle Aged ; Colonic Polyps/surgery ; Colonoscopy ; Proportional Hazards Models ; Forecasting ; Colorectal Neoplasms/surgery ; Retrospective Studies
Language	English
Publishing date	2022-11-02
Publishing country	England
Document type	Journal Article
ZDB-ID	1440017-0
ISSN	1463-1318 ; 1462-8910
ISSN (online)	1463-1318
ISSN	1462-8910
DOI	10.1111/codi.16369
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Zs.A 5799: Show issues

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Article ; Online: Timing of surveillance colonoscopy following malignant colorectal polypectomy in Queensland.

Zammit, Andrew P / Brown, Ian / Hooper, John D / Clark, David A / Riddell, Andrew D

ANZ journal of surgery

2022 Volume 93, Issue 3, Page(s) 606–611

Abstract: Introduction: The management of malignant polyps presents a treatment challenge between a colorectal resection and polypectomy alone. Patients managed with polypectomy alone typically undergo surveillance for recurrent or metastatic disease, however, ... ...

Abstract	Introduction: The management of malignant polyps presents a treatment challenge between a colorectal resection and polypectomy alone. Patients managed with polypectomy alone typically undergo surveillance for recurrent or metastatic disease, however, optimal timing of surveillance methods remains unclear. Guidelines recommend for completely resected malignant polyps, that a surveillance colonoscopy be perform 12 months from diagnosis. This study sought to clarify how patients with a malignant polyp were being colonoscopically surveilled if they did not undergo colorectal resection. Methods: A retrospective, population-wide cohort analysis of all patients from 2011 to 2019 was performed using data from the Queensland Oncology Repository. Patient, procedural and pathological data were extracted for all patients diagnosed with a malignant polyp and timing of the first surveillance endoscopy was calculated. Statistical analysis comparing the timing of surveillance colonoscopy across multiple patients, procedural and histological characteristics were assessed. Results: A total of 1646 patients were identified with a malignant polyp, with 797 patients managed with polypectomy and surveillance alone. The median time to surveillance endoscopy was 182 days with the mean 220.01 days. This was substantially sooner than the recommended clinical guidelines of 365 days. There were no patient or procedural characteristics which predicted a difference in the timing of surveillance colonoscopy. No pathological factors appeared to change the timing for surveillance endoscopy (P > 0.05). Conclusion: Overall, patients had surveillance endoscopy procedures substantially earlier than guideline recommendations. However, evidence underlying these guidelines and other surveillance methods for malignant polyps are not strong. Future technological developments, including improvements in imaging techniques, may provide additional options for surveillance of malignant polyps.
MeSH term(s)	Humans ; Colonic Polyps/diagnosis ; Colonic Polyps/surgery ; Colonic Polyps/epidemiology ; Retrospective Studies ; Queensland/epidemiology ; Colonoscopy ; Colorectal Neoplasms/diagnosis ; Colorectal Neoplasms/surgery ; Colorectal Neoplasms/pathology
Language	English
Publishing date	2022-10-03
Publishing country	Australia
Document type	Journal Article
ZDB-ID	2050749-5
ISSN	1445-2197 ; 1445-1433 ; 0004-8682
ISSN (online)	1445-2197
ISSN	1445-1433 ; 0004-8682
DOI	10.1111/ans.18069
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Zs.A 180: Show issues

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Article ; Online: A population-based study of the management of rectal malignant polyps and the use of trans-anal surgery.

Zammit, Andrew P / Brown, Ian / Hooper, John D / Clark, David A / Riddell, Andrew D

ANZ journal of surgery

2022 Volume 92, Issue 11, Page(s) 2949–2955

Abstract: Introduction: Rectal malignant polyps can be managed by use of trans-anal resections (TAR). Traditional techniques of resection have been replaced by use of platforms such as trans-anal minimally invasive surgery (TAMIS) or trans-anal endoscopic ... ...

Abstract	Introduction: Rectal malignant polyps can be managed by use of trans-anal resections (TAR). Traditional techniques of resection have been replaced by use of platforms such as trans-anal minimally invasive surgery (TAMIS) or trans-anal endoscopic microsurgery (TEM). This study reviewed the management of rectal malignant polyps, in particular focussing on when clinicians used TAR. Methods: A population wide cohort study of all malignant rectal polyps diagnosed in Queensland, Australia from 2011 to 2018 was undertaken. Patient and pathological factors were compared across the management strategies of polypectomy, TAR and rectal resection. Results: Overall 430 patients were diagnosed with a malignant rectal polyp during the study period, with 103 undergoing a TAR. There was increasing use of TAR across the study period as a management strategy (P < 0.001). Polypectomy alone was more likely to be the management strategy over TAR or rectal resection if there were clear margins (P < 0.001). The distance to the closest polypectomy margin was also significantly higher in the polypectomy group with mean clearance 2.09 mm in polypectomy group versus 0.86 mm in TAR group and 0.99 mm in resection group (P < 0.001). Rectal resection was more likely to be the management strategy over TAR if there was LVI (P < 0.001), depth of invasion was deeper (P < 0.001) and there was tumour budding (P = 0.001). Conclusion: TAR is an effective management strategy for rectal polyps and is utilized particularly in rectal malignant polyps when there are close or involved margins. Future guideline development should consider incorporation of TAR given the advances in techniques afforded by TAMIS or TEM platforms.
MeSH term(s)	Humans ; Cohort Studies ; Retrospective Studies ; Treatment Outcome ; Rectal Neoplasms/surgery ; Rectal Neoplasms/pathology ; Anal Canal/pathology ; Polyps/surgery ; Margins of Excision ; Transanal Endoscopic Surgery/methods
Language	English
Publishing date	2022-07-18
Publishing country	Australia
Document type	Journal Article
ZDB-ID	2050749-5
ISSN	1445-2197 ; 1445-1433 ; 0004-8682
ISSN (online)	1445-2197
ISSN	1445-1433 ; 0004-8682
DOI	10.1111/ans.17917
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Zs.A 180: Show issues

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Article ; Online: Reactive Oxygen Species as Mediators of Disease Progression and Therapeutic Response in Colorectal Cancer.

Lyons, Nicholas J / Giri, Rabina / Begun, Jakob / Clark, David / Proud, David / He, Yaowu / Hooper, John D / Kryza, Thomas

Antioxidants & redox signaling

2023 Volume 39, Issue 1-3, Page(s) 186–205

Abstract: Significance: ...

Abstract	Significance:
MeSH term(s)	Humans ; Reactive Oxygen Species ; Colonic Neoplasms ; Apoptosis ; Disease Progression
Chemical Substances	Reactive Oxygen Species
Language	English
Publishing date	2023-04-25
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	1483836-9
ISSN	1557-7716 ; 1523-0864
ISSN (online)	1557-7716
ISSN	1523-0864
DOI	10.1089/ars.2022.0127
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Zs.A 5488: Show issues

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Article: Histone Modifying Enzymes in Gynaecological Cancers.

Ramarao-Milne, Priya / Kondrashova, Olga / Barry, Sinead / Hooper, John D / Lee, Jason S / Waddell, Nicola

Cancers

2021 Volume 13, Issue 4

Abstract: Genetic and epigenetic factors contribute to the development of cancer. Epigenetic dysregulation is common in gynaecological cancers and includes altered methylation at CpG islands in gene promoter regions, global demethylation that leads to genome ... ...

Abstract	Genetic and epigenetic factors contribute to the development of cancer. Epigenetic dysregulation is common in gynaecological cancers and includes altered methylation at CpG islands in gene promoter regions, global demethylation that leads to genome instability and histone modifications. Histones are a major determinant of chromosomal conformation and stability, and unlike DNA methylation, which is generally associated with gene silencing, are amenable to post-translational modifications that induce facultative chromatin regions, or condensed transcriptionally silent regions that decondense resulting in global alteration of gene expression. In comparison, other components, crucial to the manipulation of chromatin dynamics, such as histone modifying enzymes, are not as well-studied. Inhibitors targeting DNA modifying enzymes, particularly histone modifying enzymes represent a potential cancer treatment. Due to the ability of epigenetic therapies to target multiple pathways simultaneously, tumours with complex mutational landscapes affected by multiple driver mutations may be most amenable to this type of inhibitor. Interrogation of the actionable landscape of different gynaecological cancer types has revealed that some patients have biomarkers which indicate potential sensitivity to epigenetic inhibitors. In this review we describe the role of epigenetics in gynaecological cancers and highlight how it may exploited for treatment.
Language	English
Publishing date	2021-02-16
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13040816
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Article ; Online: The CDCP1 Signaling Hub: A Target for Cancer Detection and Therapeutic Intervention.

Khan, Tashbib / Kryza, Thomas / Lyons, Nicholas J / He, Yaowu / Hooper, John D

Cancer research

2021 Volume 81, Issue 9, Page(s) 2259–2269

Abstract: CUB-domain containing protein 1 (CDCP1) is a type I transmembrane glycoprotein that is upregulated in malignancies of the breast, lung, colorectum, ovary, kidney, liver, pancreas, and hematopoietic system. Here, we discuss CDCP1 as an important hub for ... ...

Abstract	CUB-domain containing protein 1 (CDCP1) is a type I transmembrane glycoprotein that is upregulated in malignancies of the breast, lung, colorectum, ovary, kidney, liver, pancreas, and hematopoietic system. Here, we discuss CDCP1 as an important hub for oncogenic signaling and its key roles in malignant transformation and summarize approaches focused on exploiting it for cancer diagnosis and therapy. Elevated levels of CDCP1 are associated with progressive disease and markedly poorer survival. Predominantly located on the cell surface, CDCP1 lies at the nexus of key tumorigenic and metastatic signaling cascades, including the SRC/PKCδ, PI3K/AKT, WNT, and RAS/ERK axes, the oxidative pentose phosphate pathway, and fatty acid oxidation, making important functional contributions to cancer cell survival and growth, metastasis, and treatment resistance. These findings have stimulated the development of agents that target CDCP1 for detection and treatment of a range of cancers, and results from preclinical models suggest that these approaches could be efficacious and have manageable toxicity profiles.
MeSH term(s)	Animals ; Antigens, Neoplasm/chemistry ; Antigens, Neoplasm/genetics ; Antigens, Neoplasm/metabolism ; Biomarkers, Tumor/chemistry ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Cell Adhesion Molecules/antagonists & inhibitors ; Cell Adhesion Molecules/chemistry ; Cell Adhesion Molecules/genetics ; Cell Adhesion Molecules/metabolism ; Disease Progression ; Drug Resistance, Neoplasm/drug effects ; Gene Expression Regulation, Neoplastic ; Humans ; Molecular Targeted Therapy/methods ; Neoplasms/diagnosis ; Neoplasms/drug therapy ; Neoplasms/metabolism ; Prognosis ; Protein Domains ; Signal Transduction/drug effects
Chemical Substances	Antigens, Neoplasm ; Biomarkers, Tumor ; CDCP1 protein, human ; Cell Adhesion Molecules
Language	English
Publishing date	2021-01-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-20-2978
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Article ; Online: Patient and pathological predictors of management strategy for malignant polyps following polypectomy: a systematic review and meta-analysis.

Zammit, Andrew P / Lyons, Nicholas J / Chatfield, Mark D / Hooper, John D / Brown, Ian / Clark, David A / Riddell, Andrew D

International journal of colorectal disease

2022 Volume 37, Issue 5, Page(s) 1035–1047

Abstract: Purpose: Malignant polyps present a treatment dilemma for clinicians and patients. This meta-analysis sought to identify the factors that predicted the management strategy for patients diagnosed with a malignant polyp.: Methods: A literature search ... ...

Abstract	Purpose: Malignant polyps present a treatment dilemma for clinicians and patients. This meta-analysis sought to identify the factors that predicted the management strategy for patients diagnosed with a malignant polyp. Methods: A literature search was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Cochrane Collaboration prognostic studies guidelines. Reports from 1985 onwards were included, data on patient and pathological factors were extracted and random effects meta-analysis models were used. Results: Fifteen studies were included. Seven studies evaluated lymphovascular invasion (LVI). The odds of surgery were significantly higher in malignant polyps with LVI (OR 2.20, 95% CI 1.36-3.55). Ten studies revealed the odds of surgery were significantly higher with positive polypectomy margins (OR 8.09, 95% CI 4.88-13.40). Tumour differentiation was compared in eight studies. There were significantly lower odds of surgery in malignant polyps with well/moderate differentiation compared with poor differentiation (OR 0.31, 95% CI 0.21-0.46). There were non-significant trends favouring surgical resection in younger patients, males and Haggitt 4/Kikuchi Sm3 lesions. There was considerable heterogeneity in the meta-analyses for the variables age, gender, polyp morphology and Haggitt/Kikuchi level (I Conclusion: This meta-analysis has demonstrated that LVI, positive polypectomy resection margins, and poor tumour differentiation significantly predict malignant polypectomy patients who underwent subsequent surgery. Age and gender were important factors predicting management, but not consistently across studies, whilst polyp morphology and Haggitt/Kikuchi levels did not significantly predict the management strategy. Further research may assist in understanding the management preferences.
MeSH term(s)	Colonic Polyps/pathology ; Colonic Polyps/surgery ; Colonoscopy ; Colorectal Neoplasms/surgery ; Humans ; Intestinal Polyps/pathology ; Male ; Margins of Excision ; Prognosis
Language	English
Publishing date	2022-04-08
Publishing country	Germany
Document type	Journal Article ; Meta-Analysis ; Systematic Review
ZDB-ID	84975-3
ISSN	1432-1262 ; 0179-1958
ISSN (online)	1432-1262
ISSN	0179-1958
DOI	10.1007/s00384-022-04142-6
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