Pathological features associated with metastasis in patients with early invasive (pT1) colorectal carcinoma in colorectal polyps.

AIMS: Colorectal carcinoma (CRC) arising in a colorectal polyp with invasion limited to the submucosa is sufficiently treated by complete endoscopic resection alone in many cases. Histological features of the carcinoma including tumour size, vascular invasion and poor tumour differentiation or evidence of de-differentiation, such as tumour budding, are associated with a higher risk for metastasis such that oncological resection is recommended. However, most malignant polyps with these features do not have lymph node metastases at the time of resection, so there is a need for better refinement of the histological risk features. METHODS AND RESULTS: A total of 437 consecutive colorectal polyps with submucosal invasive carcinoma from a single centre, 57 of which had metastatic disease, were supplemented by 30 cases with known metastatic disease from two additional centres. Clinical and histological features of the polyp cancers were reviewed looking for differences between the 87 cancers with metastatic disease and the remaining cases without metastasis. A subgroup of 204 polyps removed intact was also analysed to ensure maximum histological accuracy. CONCLUSIONS: This study confirmed larger invasive tumour size, vascular invasion and poor tumour differentiation as adverse predictive features. Prominent peritumoral desmoplasia and high cytological grade were additional adverse features. A predictive logistic regression model comprised of (i) presence of any form of vascular invasion; (ii) presence of high tumour budding (BD3); (iii) width of invasive tumour component > 8 mm; (iv) depth of invasive tumour > 1.5 mm; and (v) the finding of prominent expansile desmoplasia located within and beyond the deep invasive edge of the carcinoma, showed excellent performance in predicting metastatic disease.

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

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.

Management of high and low risk malignant polyps: a population-wide analysis.

AIM: The management of malignant polyps is a treatment dilemma in selecting between polypectomy and colorectal resection. To assist clinicians, guidelines have been developed by the Association of Coloproctology of Great Britain and Ireland (ACPGBI) to provide treatment recommendations. METHODS: This study compared management strategy based on the ACPGBI risk categorization for malignant polyps. Univariable and multivariable statistical analysis was undertaken to assess the factors predicting management strategy. A population-wide analysis was performed of 1646 malignant polyps and the factors that predicted their management strategy, from Queensland, Australia, from 2011 to 2019. RESULTS: Overall, 31.55% of patients with very low or low risk disease proceeded to resection. Of those with high or very high risk disease, 36.69% did not proceed to resection. In very low and low risk polyps, age (P = 0.003) and polyp location (P < 0.001) were significantly different between the colorectal resection group and the polypectomy alone group. In those with very high or high risk polyps age (P < 0.001), type of facility (public or private) for the colonoscopy (P = 0.037), right colonic polyps compared to left colonic polyps (P = 0.015) and rectal polyps (P < 0.001) and mismatch repair mutations present (P = 0.027) were predictive of resection in high risk disease using a multivariable model. CONCLUSION: Over 30% of patients with very low and low risk malignant polyps proceeded to resection, against the advice of guidelines. Furthermore, over 35% of patients with very high or high risk malignant polyps did not proceed to resection. Education strategies may improve management decision choices. Furthermore, improvements in data collation will improve the understanding of management choices in the future.

Patient and pathological predictors of management strategy for malignant polyps following polypectomy: a systematic review and meta-analysis.

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 (I2 > 75%). 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.

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

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.

Timing of surveillance colonoscopy following malignant colorectal polypectomy in Queensland.

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.

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

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.

Malignant polyps in the COVID-19 era: a population-based analysis.

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 (r2  = 0.85, 95% prediction interval: 255.07-323.91, P < 0.001). These malignant polyps were less likely to be diagnosed in a private setting (P < 0.001), and exhibited significantly less depth of submucosal invasion (P = 0.017). There was no significant difference in the management strategy (polypectomy, resection or trans-anal resection) between 2011 and 2019 and 2020. 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.

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

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.

Examining the contribution of smoking and HPV towards the etiology of oral cavity squamous cell carcinoma using high-throughput sequencing: A prospective observational study.

Oral cavity Squamous Cell Carcinoma (OCSCC) is a common form of head and neck cancer throughout the developed and developing world. However, the etiology of OCSCC is still unclear. Here, we explored the extent to which tobacco use, Human Papillomavirus (HPV) infection and genetic and transcriptomic changes contributed to the oncogenesis of OCSCC. In a prospective observational study, we analysed fresh tissue biopsies from 45 OCSCC collected from 51 subjects presenting with OCSCC to the Brisbane Head and Neck Clinics between 2013 and 2015. Exploration of the genetic and transcriptomic landscape of the biopsies were performed using RNA sequencing (RNA-seq) and whole exome sequencing. HPV associated tumours were determined using p16 staining of histological sections and RNA sequencing. Patient demographics including tumor location within the oral cavity, and history of tobacco and alcohol use were correlated with genomic and transcriptomics analyses. About 4.5% of OCSCC were HPV associated. The most frequent mutations in the OCSCC samples were in the TP53 and CDKN2A genes, but no association of specific mutations with HPV or tobacco use was observed. Using weighted gene co-expression network analysis to explore the RNA-seq data, tumors from participants with a history of tobacco use showed a significant trend towards increased mammalian target of Rapamycin (mTOR) signaling and decreased mitochondrial respiration. In conclusion, HPV was shown to be an uncommon association with OCSCC and changes in TP53 transcriptional regulation, mTOR signaling and mitochondrial function were associated with a history of tobacco use. Larger data sets will be required to enable detection of differences which may help with development of personalized therapeutics in the future.

Sites of origin of oral cavity cancer in nonsmokers vs smokers: possible evidence of dental trauma carcinogenesis and its importance compared with human papillomavirus.

IMPORTANCE: The relatively high and possibly rising incidence of mouth squamous cell carcinoma in nonsmokers, especially women, without obvious cause has been noted by previous authors. Is chronic dental trauma and irritation a carcinogen, and what is its importance compared with human papillomavirus (HPV) oropharyngeal cancer in nonsmokers? OBJECTIVE: To determine whether oral cavity cancers occurred more commonly at sites of dental trauma and how the position of these cancers varied between nonsmokers lacking major identified carcinogens and smokers. If these cancers occurred more frequently at sites of chronic trauma, especially in nonsmokers, it would suggest chronic dental trauma as a possible carcinogen. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis of 881 patients with oral cavity or oropharyngeal cancers seen through a tertiary referral hospital between 2001 and 2011 was performed. MAIN OUTCOMES AND MEASURES: Patient medical records were analyzed to determine the location of the tumor within the oral cavity and oropharynx and how it relates to patient demographics, smoking and alcohol histories, and comorbidities. Dental histories were also sought, including use of dentures. RESULTS: Nonsmokers comprised 87 of 390 patients with mouth cancer (22%) and 48 of 334 patients with oropharyngeal cancer (14%). Female nonsmoking patients included 53 with oral cancer (61%) but only 12 with oropharyngeal squamous cell carcinoma (25%). Oral cancers occurred on the lateral tongue, a potential site of chronic dental trauma, in 57 nonsmokers (66%) compared with 107 smokers/ex-smokers (33%) (P < .001). Gingival and floor of mouth lesions occurred in older patients, possibly from chronic denture rubbing. Twenty-six patients had dental abnormalities recorded in close proximity to where their tumor developed. CONCLUSIONS AND RELEVANCE: Oral cavity cancers occur predominantly at sites of potential dental and denture trauma, especially in nonsmokers without other risk factors. Recognizing teeth irritation as a potential carcinogen would have an impact on prevention and treatment strategies.