Integrating artificial intelligence techniques for advancements in colorectal cancer management: navigating past and predicting future direction.

Artificial Intelligence (AI) in the last few years has emerged as a valuable tool in managing colorectal cancer, revolutionizing its management at different stages. In early detection and diagnosis, AI leverages its prowess in imaging analysis, scrutinizing CT scans, MRI, and colonoscopy views to identify polyps and tumors. This ability enables timely and accurate diagnoses, initiating treatment at earlier stages. AI has helped in personalized treatment planning because of its ability to integrate diverse patient data, including tumor characteristics, medical history, and genetic information. Integrating AI into clinical decision support systems guarantees evidence-based treatment strategy suggestions in multidisciplinary clinical settings, thus improving patient outcomes. This narrative review explores the multifaceted role of AI, spanning early detection of colorectal cancer, personalized treatment planning, polyp detection, lymph node evaluation, cancer staging, robotic colorectal surgery, and training of colorectal surgeons.

Establishment and validation of an artificial intelligence-based model for real-time detection and classification of colorectal adenoma.

Colorectal cancer (CRC) prevention requires early detection and removal of adenomas. We aimed to develop a computational model for real-time detection and classification of colorectal adenoma. Computationally constrained background based on real-time detection, we propose an improved adaptive lightweight ensemble model for real-time detection and classification of adenomas and other polyps. Firstly, we devised an adaptive lightweight network modification and effective training strategy to diminish the computational requirements for real-time detection. Secondly, by integrating the adaptive lightweight YOLOv4 with the single shot multibox detector network, we established the adaptive small object detection ensemble (ASODE) model, which enhances the precision of detecting target polyps without significantly increasing the model's memory footprint. We conducted simulated training using clinical colonoscopy images and videos to validate the method's performance, extracting features from 1148 polyps and employing a confidence threshold of 0.5 to filter out low-confidence sample predictions. Finally, compared to state-of-the-art models, our ASODE model demonstrated superior performance. In the test set, the sensitivity of images and videos reached 87.96% and 92.31%, respectively. Additionally, the ASODE model achieved an accuracy of 92.70% for adenoma detection with a false positive rate of 8.18%. Training results indicate the effectiveness of our method in classifying small polyps. Our model exhibits remarkable performance in real-time detection of colorectal adenomas, serving as a reliable tool for assisting endoscopists.

Colonic lymphomatous polyposis mantle cell lymphoma: a case report and review of literature.

INTRODUCTION: Mantle cell lymphoma is a rare lymphoma of the gastrointestinal tract that may present as multiple lymphomatous polyposis. We report a case of lymphomatous polyposis with a review of the literature. CASE REPORT: A 56-year-old man of Black ethnicity and Ivorian nationality with no relevant past medical history, consulted for a sudden onset symptoms of gastrointestinal obstruction, which evolved over 2 days. Macroscopic examination revealed the presence of multiple polyploid formations of the colonic mucosa. Histology showed diffuse lymphomatous proliferation of submucosa consisting off small lymphoid cells with a hyperchromatic crenelated nucleus, suggesting lymphomatous polyposis. Immunohistochemical examination showed expression by the tumor cells of antibodies to CD20, CD5, Bcl2, and cyclin D1. They did not express antibodies to CD10 and CD23. The Ki67 proliferation index was 25%. We have thus retained the diagnosis of mantle cell lymphomatous polyposis. CONCLUSION: Multiple lymphomatous polyposis is a rare entity characterized by the presence of numerous gastrointestinal polyploid lesions sometimes involving several segments of the gastrointestinal tract. Typical lymphoma presenting as lymphomatous polyposis is mantle cell lymphoma; although, other tumors may have this aspect.

Risk factors for delayed colorectal postpolypectomy bleeding: a meta-analysis.

BACKGROUND: To systematically analyze risk factors for delayed postpolypectomy bleeding (DPPB) in colorectum. METHODS: We searched seven large databases from inception to July 2022 to identify studies that investigated risk factors for DPPB. The effect sizes were expressed by relative risk (RR) and 95% confidence interval (95% CI). The heterogeneity was analyzed by calculating I2 values and performing sensitivity analyses. RESULTS: A total of 15 articles involving 24,074 subjects were included in the study. The incidence of DPPB was found to be 0.02% (95% CI, 0.01-0.03), with an I2 value of 98%. Our analysis revealed that male sex (RR = 1.64), history of hypertension (RR = 1.54), anticoagulation (RR = 4.04), polyp size (RR = 1.19), polyp size ≥ 10 mm (RR = 2.43), polyp size > 10 mm (RR = 3.83), polyps located in the right semicolon (RR = 2.48) and endoscopic mucosal resection (RR = 2.99) were risk factors for DPPB. CONCLUSIONS: Male sex, hypertension, anticoagulation, polyp size, polyp size ≥ 10 mm, polyps located in the right semicolon, and endoscopic mucosal resection were the risk factors for DPPB. Based on our findings, we recommend that endoscopists should fully consider and implement effective intervention measures to minimize the risk of DPPB.

The Development of Serrated Epithelial Change in Ulcerative Colitis is not Significantly Associated With Increased Histologic Inflammation.

Serrated epithelial change (SEC) in inflammatory bowel disease is most often defined as hyperplastic polyp-like mucosal change detected on random biopsies. Although SEC has been reported to be associated with an increased risk of synchronous and/or metachronous colorectal neoplasia, it remains unknown if SEC represents a form of dysplastic lesion despite the lack of morphologic evidence of dysplasia. Since the risk of colorectal neoplasia in ulcerative colitis (UC) is positively correlated with increased histologic inflammation, this study investigated if increased colonic inflammation is an independent risk factor for SEC. A cohort of 28 UC patients with SEC was analyzed and compared with 51 control UC patients without SEC. None of these patients had a history of colorectal neoplasia. For each patient with SEC, all biopsies conducted before and at the time of SEC diagnosis (versus all biopsies for each control patient) were scored by using a 4-point scoring system: no activity (no epithelial infiltration by neutrophils=0); mild activity (cryptitis only=1); moderate activity (cryptitis plus crypt abscess formation in <50% of crypts=2); and severe activity (crypt abscess formation in ≥50% of crypts, erosion, neutrophilic exudate, and/or ulceration=3). Each biopsy was designated a score, and both mean and maximum inflammation scores were calculated from all biopsies taken during each colonoscopy. The inflammation burden score was calculated for each surveillance interval by multiplying the average maximum score between each pair of surveillance episodes by the length of the surveillance interval in years. The average scores of all colonoscopies for each patient were used to assign the patient's overall mean, maximum, and inflammation burden scores. The SEC cohort included 12 (43%) men and 16 (57%) women with a mean age of 47 years at the time of the first SEC diagnosis and a long history of UC (mean: 13 y). The majority of patients (n=21; 75%) had pancolitis, and only 1 (4%) patient had primary sclerosing cholangitis. A total of 37 SEC were identified in the 28 patients, 4 (14%) of whom had multifocal SEC. SEC was predominantly found in the left colon (n=32; 86%). In the multivariate analysis, none of the 3 summative inflammation scores, including overall mean (odds ratio [OR] 1.9, P =0.489), maximum (OR 0.4, P =0.259), and inflammation burden scores (OR 1.2, P =0.223), were significantly associated with the development of SEC. Similarly, no other potential risk factors, including age, gender, ethnicity, and duration and extent of UC, were significantly correlated with the detection of SEC ( P >0.05). In conclusion, the development of SEC in UC is not significantly associated with increased histologic inflammation. Given the reported association of SEC with an increased risk of synchronous and/or metachronous colorectal neoplasia, along with the presence of molecular alterations in some cases (such as TP53 mutations and aneuploidy), SEC may represent an early morphologic indicator of segmental or pan-colonic molecular abnormalities that have not advanced enough to result in colorectal neoplasia, as opposed to being a form of dysplasia.

Prevalence of diverse colorectal polyps and risk factors for colorectal carcinoma in situ and neoplastic polyps.

BACKGROUND: Most colorectal cancers originate from precancerous polyps. This study aimed to determine the prevalence of colorectal polyps with diverse pathological morphologies and to explore the risk factors for colorectal carcinoma in situ (CCS) and neoplastic polyps. METHODS: Inpatients admitted from January 2018 to May 2023 were screened through the hospital information system. Polyps were classified according to pathological morphology. The prevalence of polyps was described by frequency and 95% confidence interval. Univariate and multivariate logistic regression analyses were used to explore the risk factors for CCS and neoplastic polyps. RESULTS: In total, 2329 individuals with 3550 polyps were recruited. Among all patients, 76.99% had neoplastic polyps and 44.31% had advanced adenomas. Tubular adenoma had the highest prevalence at 60.15%, and the prevalence of CCS was 3.86%. Patients with a colorectal polyp diameter ≥ 1.0 cm or number ≥ 3 were 8.07 times or 1.98 times more likely to develop CCS than were those with a diameter < 1.0 cm or number < 3, respectively (OR 8.07, 95%CI 4.48-14.55, p < 0.0001; and OR 1.98, 95%CI 1.27-3.09, p = 0.002). The risk of CCS with schistosome egg deposition was also significantly increased (OR 2.70, 95%CI 1.05-6.98). The higher the levels of carbohydrate antigen (CA) 724 (OR 1.01, 95%CI 1.00-1.02) and CA211 (OR 1.16, 95%CI 1.03-1.32) in patients with colorectal polyps were, the greater the risk of CCS. When colorectal neoplastic polyps were analyzed, we discovered that for each 1-year increase in age, the risk of neoplastic polyps increased by 3% (OR 1.03, 95%CI 1.02-1.04), p < 0.0001. Patients with a polyp diameter ≥ 1.0 cm had a 2.11-fold greater risk of neoplastic polyps compared to diameter < 1.0 cm patients (OR 3.11, 95%CI 2.48-3.92), p < 0.0001. In addition, multiple polyps and CA199 levels are risk factors for neoplastic polyps. CONCLUSION: More than 3/4 of colorectal polyp patients have neoplastic polyps. Patients are more inclined to develop CCS and neoplastic polyps if they have large polyps (> 1.0 cm) or multifocal polyps. The levels of the tumor markers CA724 and CA211 show some potential usefulness for predicting CCS and may be exploited for early identification of high-risk populations.

Colonic adenomatous polyp with florid presence of monoclonal lambda Russell bodies: Case report and etiopathogenic hypothesis.

Russell bodies (RBs) are round eosinophilic intracytoplasmic inclusions formed by condensed immunoglobulins in mature plasma cells, which are called Mott cells. These cells are rarely found in the gastric tract, with even less cases reported in the colorectal region. There are still many questions about this event, as it is still unknown the relationship between the agents reported of increasing the probability of appearance of these cells and the generation of RBs. In this case report we describe the fifth patient presenting an infiltration of Mott cells in a colorectal polyp, being the second case with a monoclonal origin without a neoplastic cause, and the first one monoclonal for lambda. A comparison with previously similar reported cases is also done, and a possible etiopathogenic hypothesis proposed.

Evaluation and Management of Malignant Colorectal Polyps.

The detection rate of dysplastic colorectal polyps has significantly increased with improved screening programs. Treatment of dysplastic polyps attempt to limit morbidity of a procedure while also considering the risk of occult lymph node metastasis. Therefore, a variety of methods have been developed to predict the rate of lymph node metastasis to help identify the optimal treatment of patients. These include both the endoscopic and pathologic assessment of the lesion. In order to reduce the morbidity of surgery for patients with low-risk lesions, multiple endoscopic therapies have been developed, including endoscopic mucosal resection, endoscopic submucosal dissection, endoscopic intermuscular dissection, and transanal endoscopic surgery.

A population-based analysis on the incidence of metachronous colon cancer after endoscopic resection of advanced adenomas with high-grade dysplasia: does location matter?

BACKGROUND: Advanced adenomas (AAs) with high-grade dysplasia (HGD) represent a risk factor for metachronous neoplasia, with guidelines recommending short-interval surveillance. Although the worse prognosis of proximal (vs distal) colon cancers (CCs) is established, there is paucity of evidence on the impact of laterality on the risk of subsequent neoplasia for these AAs. METHODS: Adults with HGD adenomas undergoing polypectomy were identified in the Surveillance, Epidemiology, and End Results database (2000-2019). Cumulative incidence of malignancy was estimated using the Kaplan-Meier method. Fine-Gray models assessed the effect of patient and disease characteristics on CC incidence. RESULTS: Of 3199 patients, 26% had proximal AAs. A total of 65 cases of metachronous adenocarcinoma were identified after polypectomy of 35 proximal and 30 distal adenomas with HGD. The 10-year cumulative incidence of CC was 2.3%; when stratified by location, it was 4.8% for proximal vs 1.4% for distal adenomas. Proximal location was significantly associated with increased incidence of metachronous cancer (adjusted hazard ratio, 3.32; 95% CI, 2.05-5.38). CONCLUSION: Proximal location of AAs with HGD was associated with >3-fold increased incidence of metachronous CC and shorter time to diagnosis. These data suggest laterality should be considered in the treatment and follow-up of these patients.

HOT VERSUS COLD SNARE FOR COLORECTAL POLYPECTOMIES SIZED UP TO 10MM: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS.

BACKGROUND: Colorectal cancer is the third most common cancer, and prevention relies on screening programs with resection complete resection of neoplastic lesions. OBJECTIVE: We aimed to evaluate the best snare polypectomy technique for colorectal lesions up to 10 mm, focusing on complete resection rate, and adverse events. METHODS: A comprehensive search using electronic databases was conducted to identify randomized controlled trials comparing hot versus cold snare resection for polyps sized up to 10 mm, and following PRISMA guidelines, a meta-analysis was performed. Outcomes included complete resection rate, en bloc resection rate, polypectomy, procedure times, immediate, delayed bleeding, and perforation. RESULTS: Nineteen RCTs involving 8720 patients and 17588 polyps were included. Hot snare polypectomy showed a higher complete resection rate (RD, 0.02; 95%CI [+0.00,0.04]; P=0.03; I 2=63%), but also a higher rate of delayed bleeding (RD 0.00; 95%CI [0.00, 0.01]; P=0.01; I 2=0%), and severe delayed bleeding (RD 0.00; 95%CI [0.00, 0.00]; P=0.04; I 2=0%). Cold Snare was associated with shorter polypectomy time (MD -46.89 seconds; 95%CI [-62.99, -30.79]; P<0.00001; I 2=90%) and shorter total colonoscopy time (MD -7.17 minutes; 95%CI [-9.10, -5.25]; P<0.00001; I 2=41%). No significant differences were observed in en bloc resection rate or immediate bleeding. CONCLUSION: Hot snare polypectomy presents a slightly higher complete resection rate, but, as it is associated with a longer procedure time and a higher rate of delayed bleeding compared to Cold Snare, it cannot be recommended as the gold standard approach. Individual analysis and personal experience should be considered when selecting the best approach.

Adenoma characteristics in the English Bowel Cancer Screening Programme.

AIM: The English Bowel Cancer Screening Programme detects colorectal cancers and premalignant polyps in a faecal occult blood test-positive population. The aim of this work is to describe the detection rates and characteristics of adenomas within the programme, identify predictive factors influencing the presence or absence of carcinoma within adenomas and identify the factors predicting the presence of advanced colonic neoplasia in different colon segments. METHOD: The Bowel Cancer Screening System was retrospectively searched for polyps detected during colonoscopies between June 2006 and June 2012, at which time a guaiac test was being used. Data on size, location and histological features were collected, and described. Univariate and multivariate analyses were used to determine the significant factors influencing the development of carcinoma within an adenoma. RESULTS: A total of 229 419 polyps were identified; after exclusions 136 973 adenomas from 58 334 patients were evaluated. Over half were in the rectum or sigmoid colon. Subcentimetre adenomas accounted for 69.8% of the total. The proportion of adenomas containing advanced histological features increased with increasing adenoma size up to 35 mm, then plateaued. A focus of carcinoma was found in 2282 (1.7%) adenomas, of which 95.6% were located distally. Carcinoma was identified even in diminutive adenomas (0.1%). The proportion of adenomas containing cancer was significantly higher in women than men (2.0% vs. 1.5%, p < 0.001). CONCLUSION: This national, prospectively captured dataset adds robust information about histological features of adenomas that convey an increased risk for colorectal cancer, and identifies caecal adenomas, high-grade dysplasia, increasing adenoma size, distal location and female sex as independent risk factors associated with carcinoma.

The Prognostic Importance of Cancer Stem Cells in Colorectal Polyps.

BACKGROUND: This purpose aims to investigate the usefulness of CD133, a stem cell marker, for the prognosis of colon polyps. This study aimed to assess the adenomatous polyps that have an essential role in the development of colorectal cancer. The risk of colorectal carcinogenesis can be reduced by polypectomy and close medical supervision of the patients with adenomatous polyps. The prominence of stem cells in carcinoma development is also a recognized verdict. It must be noted that stem cell evaluation in adenomatous polyps may provide information about carcinoma development. METHOD: Previously pathologically assessed colorectal polyps in 60 males and 40 females at Azerbaijan Medical University were reevaluated at the Pathology Department under the Meram Medical Faculty. Hematoxylin-eosin stained preparations were examined, and cases with and without dysplasia were determined. The image analysis program re-examined the preparations, and the same image analysis system automatically counted CD133 positive stained cells in the unit area. At the end of the follow-up period after polypectomy, the cases of malignancy were detected. RESULTS: The relationship between CD133 expression of dysplasia and malignancy was statistically compared. During the investigation, the statistically significant relationship between CD133 expression and dysplasia, as well as malignancy development, was observed in this study. CONCLUSION: During the examination, the statistical significance of CD133 expression was detected in cases with dysplasia and malignancy. The investigation of CD133 expression in colorectal polyps is crucial in determining the presence of dysplasia and malignancy development, particularly in obtaining prognostic data in colorectal polyps.

Recurrence and Carcinogenetic Rates of Colorectal Polyps.

AIM: to determin the recurrence rate of benign recto-colonic polyps in a 5-year interval, and compare the development rate of intrapolypoid carcinomatous lesions in polypectomized versus nonpolypectomized subjects. MATERIAL AND METHOD: a group of 77 patients diagnosed with recto-colonic polypoid lesions during the period 2014-2019 underwent colonoscopy at the time of study initiation and then annually during a five-year interval. Results: The recurrence rate of polyps increased annually from 5 to 12.5%; the highest rate was noted in the last two years. The five-year cumulative risk of neoplastic lesions was 73% in patients without polypectomy and 20% among those with endoscopic resection (p 0.05). Comparing the recurrence rate of benign lesions (60%) in patients without neoplastic findings with the recurrence rate of adenomas in patients with benign lesions (40%), a higher risk of recurrence was found in the first category, and seemed to be influenced by the personal history of pre-existing adenomatous lesions. CONCLUSION: an increased risk of colorectal polyps recurrence was reported during five year follow up; moreover, during the first three years an increased risk of malignant transformation was observed among cases in which endoscopic resection was not feasible when compared to those in which complete excision was feasible.

Downregulation of SMOC1 is associated with progression of colorectal traditional serrated adenomas.

BACKGROUND: Aberrant DNA methylation is prevalent in colorectal serrated lesions. We previously reported that the CpG island of SMOC1 is frequently methylated in traditional serrated adenomas (TSAs) and colorectal cancers (CRCs) but is rarely methylated in sessile serrated lesions (SSLs). In the present study, we aimed to further characterize the expression of SMOC1 in early colorectal lesions. METHODS: SMOC1 expression was analyzed immunohistochemically in a series of colorectal tumors (n = 199) and adjacent normal colonic tissues (n = 112). RESULTS: SMOC1 was abundantly expressed in normal colon and SSLs while it was significantly downregulated in TSAs, advanced adenomas and cancers. Mean immunohistochemistry scores were as follows: normal colon, 24.2; hyperplastic polyp (HP), 18.9; SSL, 23.8; SSL with dysplasia (SSLD)/SSL with early invasive cancer (EIC), 15.8; TSA, 5.4; TSA with high grade dysplasia (HGD)/EIC, 4.7; non-advanced adenoma, 21.4; advanced adenoma, 11.9; EIC, 10.9. Higher levels SMOC1 expression correlated positively with proximal colon locations and flat tumoral morphology, reflecting its abundant expression in SSLs. Among TSAs that contained both flat and protruding components, levels of SMOC1 expression were significantly lower in the protruding components. CONCLUSION: Our results suggest that reduced expression of SMOC1 is associated with progression of TSAs and conventional adenomas and that SMOC1 expression may be a biomarker for diagnosis of serrated lesions and risk prediction in colorectal tumors.

Underwater versus conventional endoscopic mucosal resection for ≥10 mm sessile or flat colorectal polyps: A systematic review and meta-analysis.

BACKGROUND AND AIM: Underwater endoscopic mucosal resection (UEMR) has been an emerging substitute for conventional EMR (CEMR). This systematic review and meta-analysis aimed at comparing the efficiency and safety of the two techniques for removing ≥10 mm sessile or flat colorectal polyps. METHODS: PubMed, Cochrane Library and Embase databases were searched up to February 2023 to identify eligible studies that compared the outcomes of UEMR and CEMR. This meta-analysis was conducted on the en bloc resection rate, R0 resection rate, complete resection rate, procedure time, adverse events rate and recurrence rate. RESULTS: Nine studies involving 1,727 colorectal polyps were included: 881 were removed by UEMR, and 846 were removed by CEMR. UEMR was associated with a significant increase in en bloc resection rate [Odds ratio(OR) 1.69, 95% confidence interval(CI) 1.36-2.10, p<0.00001, I2 = 33%], R0 resection rate(OR 1.52, 95%CI 1.14-2.03, p = 0.004, I2 = 31%) and complete resection rate(OR 1.67, 95%CI 1.06-2.62, p = 0.03, I2 = 0%) as well as a significant reduction in procedure time(MD ‒4.27, 95%CI ‒7.41 to ‒1.13, p = 0.008, I2 = 90%) and recurrence rate(OR 0.52, 95%CI 0.33-0.83, p = 0.006, I2 = 6%). Both techniques were comparable in adverse events rate. CONCLUSION: UEMR can be a safe and efficient substitute for CEMR in removing ≥10 mm sessile or flat colorectal polyps. More studies verifying the advantages of UEMR over CEMR are needed to promote its application.

Expert endoscopist assessment of colorectal polyp size using virtual scale endoscopy, visual or snare-based estimation: a prospective video-based study.

BACKGROUND AND AIMS: Accurate polyp size estimation during colonoscopy has an impact on clinical decision-making. A laser-based virtual scale endoscope (VSE) is available to allow measuring polyp size using a virtual adaptive scale. This study evaluates video-based polyp size measurement accuracy among expert endoscopists using either VSE or visual assessment (VA) with either snare as reference size or without any reference size information. METHODS: A prospective, video-based study was conducted with 10 expert endoscopists. Video sequences from 90 polyps with known reference size (fresh specimen measured using calipers) were distributed on three different slide sets so that each slide set showed the same polyp only once with either VSE, VA or snare-based information. A slide set was randomly assigned to each endoscopist. Endoscopists were asked to provide size estimation based on video review. RESULTS: Relative accuracies for VSE, VA, and snare-based estimation were 75.1% (95% CI [71.6-78.5]), 65.0% (95% CI [59.5-70.4]) and 62.0% (95% CI [54.8-69.0]), respectively. VSE yielded significantly higher relative accuracy compared to VA (p = 0.002) and to snare (p = 0.001). A significantly lower percentage of polyps 1-5 mm were misclassified as >5 mm using VSE versus VA and snare (6.52% vs. 19.6% and 17.5%, p = 0.004) and a significantly lower percentage of polyps >5 mm were misclassified as 1-5 mm using VSE versus VA and snare (11.4% vs. 31.9% and 14.9%, p = 0.038). CONCLUSIONS: Endoscopists estimate polyp size with the highest accuracy when virtual adaptive scale information is displayed. Using a snare to assist sizing did not improve measurement accuracy compared to displaying visual information alone.

Biological background of colorectal polyps and carcinomas with heterotopic ossification: A national study and literature review.

The biological mechanisms and potential clinical impact of heterotopic ossification (HO) in colorectal neoplasms are not fully understood. This study investigates the clinicopathological characteristics of colorectal neoplasms associated with HO and examines the potential role of the bone morphogenetic protein (BMP) pathway in development of HO. An artificial intelligence (AI) based classification of colorectal cancers (CRC) exhibiting HO and their association with consensus molecular subtypes (CMS) is performed. The study included 77 cases via the Dutch nationwide Pathology databank. Immunohistochemistry for BMP2, SMAD4, and Osterix was performed. An AI algorithm assessed the tumour-stroma ratio to approximate the CMS. A literature search yielded 96 case reports, which were analysed and compared with our cases for clinicopathological parameters. HO was more frequently observed in our cohort in traditional serrated adenomas (25%), tubulovillous adenomas (25%) and juvenile polyps (25%), while in the literature it was most often seen in juvenile polyps (38.2%) and inflammatory polyps (29.4%). In both cohorts, carcinomas were mostly conventional (>60%) followed by mucinous and serrated adenocarcinomas. Higher expression of BMP2, SMAD4, and Osterix was observed in tumour and/or stromal cells directly surrounding bone, indicating activation of the BMP pathway. The tumour-stroma analysis appointed >50% of the cases to the mesenchymal subtype (CMS4) (59%). HO has a predilection for serrated and juvenile/inflammatory polyps, mucinous and serrated adenocarcinomas. BMP signalling is activated and seems to play a role in formation of HO in colorectal neoplasms. In line with TGFß/BMP pathway activation associated with CMS4 CRC, HO seems associated with CMS4.

Macrophage Inflammatory Proteins (MIPs) Contribute to Malignant Potential of Colorectal Polyps and Modulate Likelihood of Cancerization Associated with Standard Risk Factors.

Better understanding of molecular changes leading to neoplastic transformation is prerequisite to optimize risk assessment and chemopreventive and surveillance strategies. Data on macrophage inflammatory proteins (MIPs) in colorectal carcinogenesis are scanty and their clinical relevance remains unknown. Therefore, transcript and protein expression of CCL3, CCL4, CXCL2, and CCL19 were determined in 173 and 62 patients, respectively, using RT-qPCR and immunohistochemistry with reference to polyps' characteristics. The likelihood of malignancy was modeled using probit regression. With the increasing malignancy potential of hyperplastic-tubular-tubulo-villous-villous polyps, the expression of CCL3, CCL4, and CCL19 in lesions decreased. CCL19 expression decreased also in normal mucosa while that of CXCL2 increased. Likewise, lesion CCL3 and lesion and normal mucosa CCL19 decreased and normal CXCL2 increased along the hyperplasia-low-high dysplasia grade. The bigger the lesion, the lower CCL3 and higher CXCL2 in normal mucosa. Singular polyps had higher CCL3, CCL4, and CCL19 levels in normal mucosa. CCL3, CCL4 and CXCL2 modulated the likelihood of malignancy associated with traditional risk factors. There was no correlation between the protein and mRNA expression of CCL3 and CCL19. In summary, the polyp-adjacent mucosa contributes to gaining potential for malignancy by polyps. MIPs may help in specifying cancerization probability estimated based on standard risk factors.