In addition to the adenoma to carcinoma sequence, colorectal carcinogenesis can occur via the serrated pathway. Studies have focused on clarification of categories and molecular features of serrated ...polyps, as well as endoscopic detection and risk assessment. Guidelines from the World Health Organization propose assigning serrated polyps to categories of hyperplastic polyps, traditional serrated adenomas, and sessile serrated lesions (SSLs). Traditional serrated adenomas and SSLs are precursors to colorectal cancer. The serrated pathway is characterized by mutations in RAS and RAF, disruptions to the Wnt signaling pathway, and widespread methylation of CpG islands. Epidemiology studies of serrated polyps have been hampered by inconsistencies in terminology and reporting, but the prevalence of serrated class polyps is 20%–40% in average-risk individuals; most serrated polyps detected are hyperplastic. SSLs, the most common premalignant serrated subtype, and are found in up to 15% of average-risk patients by high-detecting endoscopists. Variations in rate of endoscopic detection of serrated polyps indicate the need for careful examination, with adequate bowel preparation and sufficient withdrawal times. Risk factors for SSLs include white race, family history of colorectal cancer, smoking, and alcohol intake. Patients with serrated polyps, particularly SSLs and traditional serrated adenomas, have an increased risk of synchronous and metachronous advanced neoplasia. Surveillance guidelines vary among countries, but SSLs and proximal hyperplastic polyps require special attention in assignment of surveillance interval—especially in light of concerns regarding incomplete detection and resection.
Treatment of rectal cancer has changed dramatically over the last decade. The worldwide introduction of total mesorectal excision in combination with the increasing use of radio(chemo)-therapy has ...led to an improved prognosis. One of the main prognostic factors in rectal cancer is the circumferential resection margin (CRM). Since the initial description of its clinical importance in 1986, the involvement of this margin (also called lateral or radial resection margin) has been associated with a poor prognosis.
In the current review, the evidence for the importance of the CRM in more than 17,500 patients is reviewed, and the relevance of this assessment to modern treatment is assessed.
We demonstrate that, after neoadjuvant therapy (both radiotherapy and radiochemotherapy), the predictive value of the CRM for local recurrence is significantly higher than when no preoperative therapy has been applied (hazard ratio HR = 6.3 v 2.0, respectively; P < .05). Furthermore, involvement of the CRM is a powerful predictor of both development of distant metastases (HR = 2.8; 95% CI, 1.9 to 4.3) and survival (HR = 1.7; 95% CI, 1.3 to 2.3). In addition to the prognostic data, this review describes different modes of margin involvement, exact definitions, and factors influencing its presence.
CRM involvement is one of the key factors in rectal cancer treatment.
•Use of tumour regression grading is limited by lack of standardisation.•Tumour shrinkage as a response mechanism allows local excision as definite treatment.•Tumour fragmentation is associated with ...a relatively poor outcome.
Various methods categorize tumour response after neoadjuvant therapy, including down-staging and tumour regression grading. Response categories allow comparison of different treatments within clinical trials and predict outcome. A reproducible response categorization could identify subgroups with high or low risk for the most appropriate subsequent treatments, like watch and wait. Lack of standardization and interpretation difficulties currently limit the usability of these approaches. In this review we describe these difficulties for the evaluation of chemoradiation in rectal cancer.
An alternative approach of tumour response is based on patterns of residual disease, including fragmentation. We summarise the evidence behind this alternative method of response categorisation, which explains a number of very relevant clinical discrepancies. These issues include differences between downstaging and tumour regression, high local regrowth in advanced tumours during watchful waiting procedures, the importance of resection margins, the limited value of post-treatment biopsies and the relatively poor outcome of patients with a near complete pathological response. Recognition of these patterns of response can allow meaningful development of novel biomarkers in the future.
...hospitals might have postponed diagnostic evaluation or have longer turnaround times for diagnostic evaluation because many hospital-based resources are being allocated to tackle COVID-19. ......national screening programmes for breast, colorectal, and cervical cancer are temporarily halted as of March 16, 2020, to alleviate the demand on the health-care system due to COVID-19. ...misconceptions were eliminated about a heightened risk of contracting COVID-19 in a health-care setting because of inadequate policies for infection control at the institutional level and resource constraints in the delivery of essential oncological care.
Population screening for colorectal cancer (CRC) is expected to increase the number of pT1 CRCs. Local excision is an attractive treatment option, but is only oncologically safe in the absence of ...lymph node metastasis (LNM). A systematic review of the predictive value of pathological risk factors for LNM in pT1 CRC was conducted to provide data for an evidence-based decision regarding follow-up or radical surgery after local excision.
PubMed was searched for reports on predictors of LNM in pT1 CRC. Published papers written in English and containing at least 50 patients were included. Meta-analyses were performed using Review Manager 5.1.
A total of 17 studies were included involving a total of 3621 patients with available nodal status. The strongest independent predictors of LNM were lymphatic invasion (relative risk RR 5.2, 95 % confidence interval CI 4.0 - 6.8), submucosal invasion ≥ 1 mm (RR 5.2, 95 %CI 1.8 - 15.4), budding (RR 5.1, 95 %CI 3.6 - 7.3), and poor histological differentiation (RR 4.8, 95 %CI 3.3 - 6.9). Limitations of the study were: results could not be stratified according to location in the colon or rectum; very early tumors removed by polypectomy without surgical resection were not included in the meta-analysis; and included studies were primarily from Asian countries and results therefore need to be verified in Western populations.
The absence of lymphatic invasion, budding, submucosal invasion ≥ 1 mm, and poor histological differentiation were each associated with low risk of LNM. Risk stratification models integrating these factors need to be investigated further.
Tumour budding in solid cancers Lugli, Alessandro; Zlobec, Inti; Berger, Martin D ...
Nature reviews. Clinical oncology,
02/2021, Letnik:
18, Številka:
2
Journal Article
Recenzirano
Tumour budding is an emerging prognostic biomarker in colorectal cancer (CRC) and other solid cancers. Tumour buds are usually defined as isolated single cancer cells or clusters of up to four cancer ...cells located at the invasive tumour front. The prognostic value of tumour budding is now supported by a large body of evidence, whereas the utility of this phenotype as a predictive biomarker remains under investigation. The application of tumour budding indices in clinical practice requires a standardized scoring system that can be tailored to specific tumour types and clinical scenarios. In the context of CRC, tumour budding can be assessed according to the method agreed at the International Tumour Budding Consensus Conference (ITBCC) in 2016. Using the ITBCC scoring system, tumour budding is an independent predictor of lymph node metastasis in patients with pT1 CRC and of unfavourable survival in patients with stage II colon cancer. Regardless of the clinical scenario or tumour type, the assertion that 'the more tumour buds, the worse the clinical outcome' applies. In this Review, we provide an overview of tumour budding in solid cancers, highlighting the molecular and biological aspects of this phenomenon, including its associations with epithelial-mesenchymal transition and features of the tumour microenvironment. We also describe the available evidence demonstrating the value of tumour budding as a biomarker across various solid cancers.
Purpose Colorectal cancer (CRC) treatment is largely determined by tumor stage. Despite improvements made in the treatment of various types of metastatic disease, staging has not been refined. The ...role of tumor deposits (TDs) in staging remains debated. We have assessed the relation of TDs with metastatic pattern to evaluate whether TDs might add significant new information to staging. Methods We performed a systematic literature search that was focused on the role of TDs in CRC. Studies with neoadjuvant-treated patients were excluded. Data on stage, histologic factors, and outcome were extracted. Data from four large cohorts were analyzed for the relevance of the presence of TDs, lymph node metastases (LNMs), and extramural vascular invasion (EMVI) on the pattern of metastases and outcomes. Results Of 10,106 included patients with CRC, 22% presented with TDs. TDs are invariably associated with poor outcome. Presence of TDs was associated with presence of LNMs and EMVI. In a pairwise comparison, effects of TD were stronger than those of both LNMs and EMVI. In the logistic regression model, TDs in combination with LNMs is the strongest predictor for liver (odds ratio OR, 5.5), lung (OR, 4.3) and peritoneal metastases (OR, 7.0). Presence of EMVI adds information for liver and lung metastases, but not for peritoneal metastases. Conclusion We have shown that TDs are not equal to LNMs or EMVI with respect to biology and outcome. We lose valuable prognostic information by allocating TDs into nodal category N1c and only considering TDs in the absence of LNMs. Therefore, we propose that the number of TDs should be added to the number of LNMs to derive a final N stage.
To determine the prevalence and prognostic value of mismatch repair (MMR) status and its relation to BRAF mutation (BRAF(MT)) status in metastatic colorectal cancer (mCRC).
A pooled analysis of four ...phase III studies in first-line treatment of mCRC (CAIRO, CAIRO2, COIN, and FOCUS) was performed. Primary outcome parameter was the hazard ratio (HR) for median progression-free survival (PFS) and overall survival (OS) in relation to MMR and BRAF. For the pooled analysis, Cox regression analysis was performed on individual patient data.
The primary tumors of 3,063 patients were analyzed, of which 153 (5.0%) exhibited deficient MMR (dMMR) and 250 (8.2%) a BRAF(MT). BRAF(MT) was observed in 53 (34.6%) of patients with dMMR tumors compared with 197 (6.8%) of patients with proficient MMR (pMMR) tumors (P < 0.001). In the pooled dataset, median PFS and OS were significantly worse for patients with dMMR compared with pMMR tumors HR, 1.33; 95% confidence interval (CI), 1.12-1.57 and HR, 1.35; 95% CI, 1.13-1.61, respectively), and for patients with BRAF(MT) compared with BRAF wild-type (BRAF(WT)) tumors (HR, 1.34; 95% CI, 1.17-1.54 and HR, 1.91; 95% CI, 1.66-2.19, respectively). PFS and OS were significantly decreased for patients with BRAF(MT) within the group of patients with pMMR, but not for BRAF status within dMMR, or MMR status within BRAF(WT) or BRAF(MT).
Prevalence of dMMR and BRAF(MT) in patients with mCRC is low and both biomarkers confer an inferior prognosis. Our data suggest that the poor prognosis of dMMR is driven by the BRAF(MT) status.
Perineural invasion (PNI) is a possible route for metastatic spread in various cancer types, including colorectal cancer (CRC). PNI is linked to poor prognosis, but systematic analyses are lacking. ...This study systematically reviews the frequency and impact of PNI in CRC. A literature search was performed using PubMed database from inception to January 1, 2014. Data were analyzed using Review Manager 5.3. A quality assessment was performed on the basis of modified REMARK criteria. Endpoints were local recurrence (LR), 5-year disease-free survival (5yDFS), 5-year cancer-specific survival (5yCSS), and 5-year overall survival (5yOS). Meta-analysis was performed in terms of risk ratios (RR) and hazard ratios (HR) with 95% confidence interval (95% CI). In this meta-analysis, 58 articles with 22,900 patients were included. PNI was present in 18.2% of tumors. PNI is correlated with increased LR (RR 3.22, 95% CI, 2.33-4.44) and decreased 5yDFS (RR 2.35, 95% CI, 1.66-3.31), 5yCSS (RR 3.61, 95% CI, 2.76-4.72), and 5yOS (RR 2.09, 95% CI, 1.68-2.61). In multivariate analysis PNI remains an independent prognostic factor for 5yDFS, 5yCSS, and 5yOS (HR 2.35, 95% CI, 1.97-3.08; HR 1.91, 95% CI, 1.50-2.42; and HR 1.85, 95% CI, 1.63-2.12, respectively). We confirmed the strong impact of PNI for LR and survival in CRC. The prognostic value of PNI is similar to that of well-established prognostic factors as depth of invasion, differentiation grade, lymph node metastases, and lymphatic and extramural vascular invasion. Therefore, PNI should be one of the factors in the standardized reporting of CRC and might be considered a high-risk feature.
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