UC-associated Neoplasia Research Articles

Usefulness of Magnifying Endoscopy With Narrow‐Band Imaging for Diagnosis of Ulcerative Colitis–Associated Neoplasia

ABSTRACTBackground and AimQualitative diagnosis of ulcerative colitis–associated neoplasia (UCAN) is crucial for surveillance colonoscopy in patients with ulcerative colitis (UC). Although the utility of magnifying endoscopy with narrow‐band imaging (ME‐NBI) in sporadic neoplasia diagnosis has been reported, its efficacy in UCAN remains unclear. This study aimed to evaluate the usefulness of ME‐NBI for qualitative diagnosis of UCAN.MethodsWe generated 60 ME‐NBI images (30 UCANs and 30 nonneoplasia lesions, including 10 polypoid and 20 nonpolypoid lesions) from patients with UC who underwent colonoscopy at our hospital between 2015 and 2023. Eleven endoscopists (seven experts and four trainees) independently assessed these images. Lesions were categorized into high‐ (≥ 80%), moderate‐ (50%–79%), and low‐ (< 50%) accuracy groups on the basis of the correct diagnostic rate.ResultsOverall sensitivity, specificity, and correct diagnostic rates were 66.5%, 79.0%, and 71.8%, respectively. Experts tended to exhibit higher specificity than trainees (83% vs. 70%). Polypoid lesions showed higher sensitivity (92% vs. 54%) and lower specificity (61% vs. 88%) than nonpolypoid lesions. Overall, the kappa value was 0.411. In UCAN, 37%, 37%, and 24% were classified into the high‐, moderate‐, and low‐accuracy groups, respectively. All endoscopists assessed one case of UCAN in the low‐accuracy group as a nonneoplastic vessel with a surface pattern. Only two nonneoplasias were identified as having nonneoplastic vessel and surface patterns by all endoscopists.ConclusionsThis study demonstrated the usefulness of ME‐NBI for qualitative diagnosis, along with its limitations. A unique endoscopic diagnostic algorithm for UCAN, incorporating ME‐NBI and other modalities, is necessary.

Ki-67 distribution, α-methylacyl-CoA racemase (AMACR) expression and mucin phenotypes are associated with non-polypoid growth in ulcerative colitis-associated neoplasia.

Ulcerative colitis-associated neoplasia (UCAN) is characterised by multifocal tumourigenesis. A wide range of metachronous lesions have been reported to occur after endoscopic treatment of UCAN, which suggests the development of sporadic tumours in lesions treated as UCAN. Therefore, we aimed to evaluate differences of immunohistochemistry (IHC) in features and clinicopathological characteristics of intramucosal lesions in patients with ulcerative colitis (UC). We examined 35 intramucosal lesions resected for carcinoma or dysplasia by total colectomy from patients with UC and 71 sporadic adenomas (SAs) endoscopically resected from patients without UC. UC lesions were divided into the conventional UCAN group, defined as p53 mutant pattern andnormal expression of β-catenin, and the non-conventional UCAN group, defined as the rest. Ki-67 distribution, α-methylacyl-CoA racemase (AMACR) expression and mucin phenotypes were compared using IHC, and clinicopathological characteristics were investigated. Conventional and non-conventional UCAN lesions were located in the left colon and rectum. Relative to the SA lesions, UCAN lesions occurred in much younger patients and exhibited more frequent basal distribution of Ki-67 in tumour crypts. Conventional UCAN lesions tended to be non-polyploid and exhibited a higher frequency of normal AMACR expression than SA lesions. UC lesions were heterogeneous-only two of the eight patients with multiple lesions had lesions (both non-conventional UCAN lesions) exhibiting concordant IHC staining features. The basal pattern of Ki-67 distribution, normal expression of AMACR and a non-intestinal mucin phenotype were determined as characteristic features suggestive of UCAN. Non-polypoid growth was another a key feature of UCAN.

A Case of polyp that needed to differentiate from ulcerative colitis-associated neoplasia and for which removal with underwater EMR was useful for diagnosis

A Case of polyp that needed to differentiate from ulcerative colitis-associated neoplasia and for which removal with underwater EMR was useful for diagnosis

Clinical usefulness of image-enhanced endoscopy for the diagnosis of ulcerative colitis-associated neoplasia.

Patients with a long history of ulcerative colitis (UC) are at risk of developing a significant complication known as UC-associated neoplasia (UCAN). To reduce the risk of UCAN and the associated mortality, the current guidelines recommend initiating surveillance colonoscopy 8-10 years after confirmation of UC diagnosis. In recent years, advancements in endoscopic diagnostic technologies, including magnifying and image-enhancing techniques, have allowed for the production of high-contrast images that emphasize mucosal structures, vascular patterns, and color tones. Recently, image-enhanced endoscopy technologies have become available and offer the potential to improve the qualitative endoscopic assessment of UCAN. The use of high-definition chromoendoscopy enables the evaluation of subtle mucosal patterns in the colon. Magnifying narrow-band imaging facilitates the visualization of mucosal vascular structures. Texture and color enhancement imaging processes structure, color tone, and brightness aspects more appropriately, whereas linked color imaging optimizes the emphasis on mucosal and vascular redness. Both techniques are expected to excel in the depiction of subtle color variations and mucosal changes characteristic of UCAN. This article provides an overview of the current status and future challenges regarding the use of various image-enhanced endoscopytechniques in the diagnosis of UCAN.

Potential carcinogenic role of Reg IV in ulcerative colitis-associated colorectal neoplasia.

Early detection of ulcerative colitis-associated neoplasia (UC-N) remains a clinical challenge. Identification of molecular biomarkers for colorectal dysplasia and cancer may be extremely beneficial in early detection and managing cancer risk in long-standing ulcerative colitis (UC) patients. The aim of this work is to investigate the role of Reg IV in comparison to P53 and KRAS in UC-associated dysplasia and colorectal cancer (CRC) in order to evaluate the potential use of Reg IV for dysplasia and cancer screening in UC patients. The study was conducted on 5 groups each 20 colonic endoscopic samples: 1) Normal colonic mucosa, 2) Active UC without dysplasia/carcinoma, 3) UC-associated dysplasia, 4) UC-associated CRC (UC-CRC), 5) Sporadic CRC. All included cases were subjected to Reg IV mRNA expression analysis by quantitative reverse transcription polymerase chain reaction, and immunostaining for Reg IV, P53 and KRAS. Reg IV mRNA expression levels were found to be significantly higher in groups 3 and 4 (mean: 3.37 and 5.70, respectively). Reg IV immunostaining was highly expressed in groups 3 and 4 (mean: 45.80 and 62.35, respectively). While P53 and KRAS immunostaining was highly expressed in group 5 (mean: 64.57 and 62.90). Furthermore, Reg IV immunoexpression had shown a negative correlation with P53 and KRAS immunoexpression in groups 4 and 5. Higher expression of Reg IV in patients with UC-dysplasia and UC-CRC versus KRAS and P53 expression in sporadic CRC, suggests a potential role of Reg IV in UC carcinogenesis pathway. This could advocate the use of Reg IV as a screening biomarker for UC-N among patients with long-standing UC as well as a promising targeted therapeutic strategy.

Interventional endoscopy in inflammatory bowel disease: a comprehensive review.

Interventional endoscopy can play a key role in the multidisciplinary management of complex inflammatory bowel disease (IBD) as an adjunct to medical and surgical therapy. The primary role of interventional IBD (IIBD) includes the treatment of Crohn's disease-related stricture, fistula, and abscess. Endoscopic balloon dilation (EBD), endoscopic stricturotomy, and placement of endoscopic stents are different forms of endoscopic stricture therapy. EBD is the most widely used therapy whereas endoscopic stricturotomy has higher long-term efficacy than EBD. Fully covered and partially covered self-expanding metal stents are useful in long and refractory strictures whereas lumen-apposing metal stents can be used in short, and anastomotic strictures. Endoscopic fistula/abscess therapy includes endoscopic fistulotomy, seton placement, endoscopic ultrasound-guided drainage of rectal/pelvic abscess, and endoscopic injection of filling agents (fistula plug/glue/stem cell). Endoscopic seton placement and fistulotomy are mainly feasible in short, superficial, single tract fistula and in those with prior surgical seton placement. Similarly, endoscopic fistulotomy is usually feasible in short, superficial, single-tract fistula. Endoscopic closure therapies like over-the-scope clips, suturing, and self-expanding metal stent should be avoided for de novo/bowel to hollow organ fistulas. Other indications include management of postoperative complications in IBD such as management of surgical leaks and complications of pouchitis in ulcerative colitis. Additional indications include endoscopic resection of ulcerative colitis-associated neoplasia (by endoscopic mucosal resection, endoscopic submucosal dissection, and endoscopic full-thickness resection), retrieval of retained capsule endoscope, and control of bleeding. IIBD therapies can potentially act as a bridge between medical and surgical therapy for properly selected IBD patients.

Role of ultra-high definition endoscopy (endomicroscopy and endocytoscopy) and real-time histologic examination in inflammatory bowel disease: Scoping review.

Confocal laser endomicroscopy (CLE) and endocytoscopy (EC) are ultra-high definition (HD) imaging modalities that enable real-time histological assessment. Although existent for nearly two decades, their role in current clinical decision making in inflammatory bowel disease management is not well defined. We searched PubMed using keywords ("confocal" OR "CLE" OR "endocytoscopy") AND ("IBD" OR "inflammatory bowel" OR "Crohn*" OR "Crohn's" OR "colitis ulcerosa" OR "ulcerative colitis") between 2005 and March 2023. We identified 52 studies for detailed review. Confocal laser endomicroscopy was useful in real-time assessment of histologic inflammation and dysplasia characterization in both ulcerative colitis (UC) and Crohn's disease. Although CLE was associated with higher per-biopsy yield for UC-associated neoplasia (UCAN), the benefit was offset by higher procedure time, frequent equipment failure, and conflicting results on incremental yield over chromoendoscopy. Assessment of barrier dysfunction by CLE did not correlate with disease/endoscopic activity but could predict major adverse outcomes. The implications of residual CLE abnormalities in endoscopic remission remain uncertain. Ex vivo binding of labeled biologics can help in predicting biologic response in UC.EC can discriminate mucosal inflammatory cells by morphology and allows assessment of histologic activity. EC combined with pit pattern was better than pit pattern alone for UCAN. Artificial intelligence-assisted EC in UCAN needs further study. Ultra-HD imaging in inflammatory bowel disease can be useful in assessment of UCAN, barrier dysfunction, predicting histologic remission, and biologic response. Future controlled studies are warranted to define the role of these novel technologies in clinical decision making.

Optimizing individualized management of patients with ulcerative colitis: Identification of risk factors predicting ulcerative colitis-associated neoplasia.

The risk of developing colorectal neoplasia in patients with ulcerative colitis (UC) is increased. The purpose of this study is to analyze the risk factors of UC-associated neoplasia (UCAN) in UC patients and establish a clinical prediction model. 828 UC patients were included in this retrospective study. 602 patients were in discovery cohort and 226 patients were in validation cohort (internal validation cohort/external validation cohort: 120/106). Clinical and endoscopic data were collected. The discovery cohort was divided into UC group and UCAN group for univariate and multivariate binary logistic analyses. The UCAN clinical prediction model was established and verified. In the univariate analysis, 7 risk factors were related to UCAN. Multivariate logistic regression analysis showed that age at diagnosis of UC (OR: 1.018, 95% CI: 1.003-1.033), Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score (OR: 1.823, 95% CI: 1.562-2.128), and size of polyps (size1: OR: 6.297, 95% CI: 3.669-10.809; size2: OR: 12.014, 95% CI: 6.327-22.814) were independent risk factors of UCAN. A mathematical equation was established. The area under the ROC curve (AUC) of this model was calculated to be 0.845 (95%CI: 0.809-0.881). The sensitivity was 0.884 and the specificity was 0.688. The AUC of internal validation cohort was 0.901 (95%CI: 0.815, 0.988), sensitivity was 75.0% and specificity was 92.6%. The AUC of external validation cohort was 0.842 (95%CI: 0.709, 0.976), sensitivity was 62.5% and specificity was 93.9%. This prediction model is simple, practical, and effective for predicting the risk of UCAN, which is beneficial to the individualized management of patients with UC.

Characteristics of flat-type ulcerative colitis-associated neoplasia on chromoendoscopic imaging with indigo carmine dye spraying.

Despite recent advances in endoscopic equipment and diagnostic techniques, early detection of ulcerative colitis-associated neoplasia (UCAN) remains difficult because of the complex background of the inflamed mucosa of ulcerative colitis and the morphologic diversity of the lesions. We aimed to describe the main diagnostic patterns for UCAN in our cohort, including lateral extension surrounding flat lesions. Sixty-three lesions in 61 patients with flat-type dysplasia that were imaged with dye chromoendoscopy (DCE) were included in this analysis. These DCE images were analyzed to clarify the dye-chromoendoscopic imaging characteristics of flat dysplasia, and the lesions were broadly classified into dysplastic and nondysplastic mucosal patterns. Dysplastic mucosal patterns were classified into two types: small round patterns with round to roundish structures, and mesh patterns with intricate mesh-like structures. Lesions with a nondysplastic mucosal pattern were divided into two major types: a ripple-like type and a gyrus-like type. Of note, 35 lesions (55.6%) had a small round pattern, and 51 lesions (80.9%) had some type of mesh pattern. About 70% of lesions with small round patterns and 49% of lesions with mesh patterns were diagnosed as high-grade dysplasia or carcinoma, while about 30% of lesions with small round patterns and 51% of lesions with mesh patterns were diagnosed as low-grade dysplasia. When a characteristic mucosal pattern, such as a small round or mesh pattern, is found by DCE, the possibility of UCAN should be considered.

Effectiveness of endoscopic resection for colorectal neoplasms in ulcerative colitis: a multicenter registration study

Patients with ulcerative colitis (UC) are at risk of developing colorectal cancer (CRC). The feasibility of endoscopic resection (ER) for UC-associated neoplasia (UCAN) has been suggested, but its efficacy and safety remain unclear. We aimed to assess the efficacy and safety of ER for colorectal neoplasms in patients with UC. This was a retrospective, multicenter cohort study of patients with UC who initially underwent ER or surgery for colorectal neoplasms between April 2015 and March 2021. Patients who had prior colorectal neoplastic lesions were excluded. Among 213 males and 123 females analyzed, the mean age at UC onset was 41.6 years, and the mean age at neoplasia diagnosis was 56.1 years for 240 cases of total colitis, 59 cases of left-sided colitis, 31 cases of proctitis, and 6 cases of segmental colitis. Endoscopic mucosal resection (EMR) was performed for 142 lesions, and endoscopic submucosal dissection (ESD) was performed for 96 lesions. The perforation rate was 2.5% for all 238 lesions removed by ER and 6.3% for the 96 lesions removed by ESD. Among 146 ER lesions followed up with endoscopy, the local recurrence rate was 2.7%. The incidence of metachronous neoplasia after ER was 6.1%. All patients were followed a median of 34.7 months after initial treatment, and 5 died (all surgical cases). Overall survival was significantly higher in the ER group than in the surgery group (P = 0.0085). ER for colorectal neoplasms in UC may be acceptable in selected cases, although follow-up for metachronous lesions is necessary.

P412 Time trend in clinicopathological features and prognosis of Ulcerative Colitis associated neoplasia: A nationwide cohort in Japan

Abstract Background With an increase in the number of Ulcerative Colitis (UC) patients in Japan, UC associated neoplasia (UCAN) cases have been accumulated. Laparoscopic surgery for sporadic advanced colorectal cancer was approved in 2002 and biologic agents have been approved for UC from 2010 in Japan. However, few reports have ever examined the time trend using a large patient cohort. We aimed to clarify time trend in clinicopathological features and prognosis of UCAN with a nationwide cohort. This study was conducted as a sub-analysis of the nationwide retrospective study across 47 institutions from the Japanese Society for Cancer of the Colon and Rectum. Methods A total of 1,139 UCAN patients were identified in the nationwide cohort from 1983 to 2020. Clinicopathological features, 5-year cancer specific survival (CSS) and overall survival (OS) were compared among the following three groups by the period of UCAN diagnosis, before 2000, 2001-2010 and 2011-2020 (the results are shown in this order). Results The number of UCAN patients registered in the database were 59, 340 and 740 in each period. Age at UCAN diagnosis (47, 51, 54, median, p<0.01) and the disease duration from UC diagnosis to UCAN diagnosis (14.3, 16.0, 17.5 years, mean, p<0.01) increased through the study periods. The rate of a surveillance colonoscopy as a diagnostic procedure (36.2%, 58.6%, 72.8%, p<0.01) increased without a change in the ratios of early (pathological stage 0-I) neoplasia (60.7%, 59.5%, 62.2%, p=0.72). Laparoscopic surgery became a dominant surgical procedure in the recent cases (1.7%, 33.2%, 47.7%, p<0.01) without an increase in postoperative complication rate (39.7%, 29.2%, 29.8%, p=0.26). Improvement in 5-year CSS (77.2%, 87.5%, 90.7%, p<0.05) and OS (77.2%, 84.3%, 88.5%, p<0.05) was observed. Among pathological stage III patients, better curative resection rate (66.7%, 92.6%, 97.1%, p<0.01) and the more use of adjuvant chemotherapy in the last decade (50.0%, 58.5%, 76.6%, p<0.05) were observed. Conclusion Longer duration of UC before the diagnosis of UCAN was observed in recent cases, which might be due to the improvement of medical therapy, including biologic agents. Minimally invasive surgery prevailed without an increase in postoperative complications. Curative resection and adjuvant chemotherapy might play a role in improvement of 5-year CSS and OS.

Role of Interventional Inflammatory Bowel Disease (IBD) in the Management of Complex IBD: Initial Prospective Experience from a Tertiary Center in India

Abstract Background/Aims With the growing multidisciplinary model of practice in the management of complex inflammatory bowel disease (IBD) and rising incidence of IBD, interventional IBD (IIBD) promises to play a key role. We aimed to evaluate current the role of IIBD in India and its short-term outcomes. Methods IBD patients undergoing IIBD procedures for stricture, bleeding, colitis-associated neoplasia, therapeutic small bowel endoscopy including retained capsule retrieval and postsurgical complications were enrolled prospectively between September 2021 and May 2022. Demographic and disease details, indications, initial and redo procedure details, technical/clinical success, and complications were recorded. Results IIBD procedures were performed in total 54 patients (61% males, median age: 37.5 years, range: 21–74 years, Crohn's disease [CD]: 42, ulcerative colitis [UC]: 12 between September 2021 and April 2022). Endoscopic balloon dilation (EBD) was performed in 44 patients (56 strictures, 9% anastomotic, 9% pouch) who underwent total 83 EBD procedures in 63 sessions. Short-term clinical efficacy after maximal dilation, technical success (i.e., scope passage after EBD), and complications (all mild) were noted in 95.4, 81.8, and 9.1%, respectively. Recurrent symptoms were seen in 27.3% on short-term follow-up (1–8 months, median: 5 months) for which redilation, surgery, and endoscopic stricturotomy were done in 22.7, 2.3, and 2.3% respectively. During small bowel EBD, motorized spiral enteroscopy-guided retained capsule endoscope retrieval was done in four patients. Ulcerative colitis-associated neoplasia (UCAN) was resected endoscopically in six patients (endoscopic submucosal dissection (ESD)—1, endoscopic mucosal resection (EMR)—5). High-grade dysplasia was resected in two patients (1 ESD for recurrent UCAN, 1 EMR had residual neoplasia on follow-up treated with underwater EMR). R0 resection was achieved in 83.3%. Endoscopic hemostasis was done with hemoclipping and sclerotherapy for UC-related bleeding in two, whereas a case of CD with proximal ileal bleeding was controlled with antegrade single-balloon enteroscopy-assisted hemoclipping. Conclusions IIBD is a promising modality in resource-limited settings like India acting as a bridge between medical therapy and surgery. Surgery can be avoided in a significant proportion with good short-term outcomes. Long-term outcomes need to be evaluated.

Gene panel testing detects important genetic alterations in ulcerative colitis-associated colorectal neoplasia.

Ulcerative colitis-associated neoplasia (UCAN) harbors unique genetic alterations and mutational tendencies. The clinical application of gene panel testing enables precision medicine by tailoring treatment to individual gene alterations. We hypothesized that gene panel testing may detect clinically important genetic alterations in UCAN, with potential usefulness for the diagnosis and treatment of UCAN. In the present study, gene panel testing was used to identify genetic alterations in UCAN, and the possibility of clinical utility of gene panel testing in UCAN was investigated. The present study included 15 patients with UCAN, and gene panel testing was performed to identify genetic alterations associated with diagnosis and treatment. Genetic alterations of UCAN were compared with those of 203 patients with sporadic colorectal cancer (CRC). APC and PTEN mutations were less frequent, while RNF43 frameshift or nonsense mutations were more frequent in UCAN compared with sporadic CRC. TP53 mutations were identified in 13/15 patients (87%) with UCAN. Notably, 4/15 patients (27%) with UCAN had no genetic alterations other than TP53 mutation, while this occurred in 1/203 patients (0.5%) with sporadic CRC (P<0.001). Microsatellite instability-high was identified in 2/15 patients (13%) with UCAN. Mutational signature 3, which is associated with homologous recombination deficiency, was detected in 14/15 patients (93%) with UCAN, and enriched in UCAN compared with sporadic CRC (P=0.030). In conclusion, gene panel testing can detect important genetic alterations that can be useful for diagnosis and treatment in UCAN, and may provide clinicians with important information for tailored treatment strategies.

S2723 Endoscopic Treatment of Pouchocele

Introduction: Ileal pouch-anal anastomosis (IPAA) is a standard treatment option for patients with medically refractory ulcerative colitis (UC), UC-associated neoplasia, or familial adenomatous polyposis (FA) who require colectomy. However, this procedure is often associated with various adverse sequelae, one such rare complication being pouchocele, a form of floppy pouch complex, which describes the bulging of the anterior pouch wall into the vagina or perineum. Little is known about the management of pouchocele due to it being a rare complication. We describe a case in which a pouchocele was successfully treated with endoscopic banding ligation. Case Description/Methods: A 53-year-old woman who underwent a staged restorative proctocolectomy and IPAA for medically-refractory UC in 2019 presented with dyschezia, incomplete evacuation, and weight loss of 40 pounds. Barium defecography performed in February 2021 showed difficult evacuation due to an anterior pouchocele and a thick fold projecting into and narrowing the lumen of the pouch posteriorly (Figure). The pouchocele was treated with banding (Boston Scientific Corporation, Marlborough, MA, USA) x 7 with submucosal injection of 50% glucose. The pouchocele was further treated in the same manner during additional procedure performed in April 2021 and June 2021. After the 3 sessions of endoscopic therapy, the patient’s symptoms resolved. Repeat defecography in July 2021 showed that the anterior pouchocele became significantly smaller, with minimal associated incomplete evacuation. Discussion: There are many structural complications following IPAA that can cause mechanical obstruction. Floppy pouch complex refers to disorders in which redundant pouch or bowel leads to luminal angulation or obstruction. Pouchocele often coexists with pouch prolapse, which may be mucosal or full-thickness, and anterior, posterior, or circumferential. Patients can present with symptoms such as dyschezia, incomplete evacuation, weight loss, and frequent passing of stools. These symptoms can affect quality of life. Here, we describe the treatment of a pouchocele using banding with good results. This is a novel treatment and has not previously been described.Figure 1.: Barium defecography before treatment.

Texture and color enhancement imaging in combination with indigo carmine dye spraying to highlight the border of flat ulcerative colitis–associated neoplasia

A 45-year-old man with long-standing ulcerative colitis (UC) for 20 years was referred to our hospital because of positive horizontal margins after treatment for dysplasia. White light imaging identified whitish mucosa with scarring in the rectum (A). Histopathologic examination of the biopsy specimen revealed p53 overexpression, suggesting UC-associated neoplasia (UCAN). It was difficult to determine the extent of the lesion by using only chromoendoscopy with indigo carmine dye spraying (B), but the combination with texture and color enhancement imaging (TXI) made the boundary clear (C).

Epithelium Replacement Contributes to Field Expansion of Squamous Epithelium and Ulcerative Colitis–Associated Neoplasia

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by repeated destruction and regeneration of the colorectal epithelium. UC-associated neoplasia (UCAN) arises from a field of colorectal epithelial cells with a mutational burden, such as TP53 mutation caused by chronic inflammation; this is known as field cancerization. UCAN usually forms a flat dysplastic lesion that is difficult to detect by endoscopic examination.1 Squamous metaplasia is another example of a rare epithelium; it is characterized by the replacement of nonsquamous epithelium by stratified squamous epithelium and has been reported in patients with long-standing UC.

Possible Earlier Diagnosis of Ulcerative Colitis-Associated Neoplasia: A Retrospective Analysis of Interval Cases during Surveillance

Background: Early detection of ulcerative colitis-associated neoplasia (UCAN) is often difficult. The aim of this study was to clarify the morphology of initial UCAN. Methods: White-light colonoscopy images obtained within the 2 years before UCAN diagnosis were retrospectively reviewed. The primary endpoint was the frequency of visible or invisible neoplasia on the endoscopic images before UCAN diagnosis. The secondary endpoints were comparisons of (1) visible or invisible neoplasia on initial endoscopic images of early-stage and advanced cancers, (2) the clinical backgrounds of patients in whom neoplasia was visible or invisible on initial endoscopic images, and (3) the clinical backgrounds of patients with distinct and indistinct UCAN borders. Results: Of the 27 UCAN lesions (11 early-stage; 16 advanced-stage), 25.9% (n = 7) were initially visible and 74.1% (n = 20) were invisible. The mean interval between the last surveillance colonoscopy and UCAN diagnosis was 14.5 ± 6.7 months. Of early-stage cancers, 18.2% (n = 2) were visible and 81.8% (n = 9) were invisible. Of advanced-stage cancers, 31.3% (n = 5) were visible and 68.8% (n = 11) were invisible. Invisible lesions were significantly more common in the rectum (p = 0.011) and tended to be more common in patients with inflammation and left-sided colitis (p = 0.084, p = 0.068, respectively). Patients with indistinct UCAN borders were significantly more likely to present with inflammation than those with distinct UCAN borders (p = 0.021). Conclusion: More careful surveillance is needed because rectum lesions and inflammation are difficult to identify as neoplasia even within the 2 years before a UCAN diagnosis.

Real-World Experience of Endoscopic Submucosal Dissection for Ulcerative Colitis-Associated Neoplasia

Introduction: Patients with ulcerative colitis (UC) have an increased risk of colorectal cancer. Some studies have recently investigated endoscopic resection of UC-associated neoplasia (UCAN), but the indications for endoscopic resection of UCAN remain controversial. This study sought to clarify the problems encountered in endoscopic submucosal dissection (ESD) for UCAN. Methods: Seventeen lesions in 12 patients with UCAN (UCAN group) and 913 epithelial lesions in 824 control patients without UC (non-UC group) were evaluated. Both groups underwent ESD between January 2010 and December 2017 at Toranomon Hospital, Tokyo, Japan. Treatment outcomes of the 2 groups were compared retrospectively. Results: Univariate analysis showed that the mean tumor size was significantly smaller in the UCAN group than in the non-UC group (25.1 ± 26.7 mm vs. 31.9 ± 19.0; p = 0.0023); however, the R0 resection rate was significantly lower in the UCAN group (70.6 vs. 92.9%; p = 0.001). Multivariate analysis showed a significantly lower negative horizontal margin rate in the UCAN group (odds ratio 11.3, 95% confidence interval 3.588–34.525; p = 0.000). Discussion/Conclusion: ESD for UCAN is associated with a low-negative horizontal margin rate. When performing ESD for UCAN, it is important to evaluate the accuracy of the UCAN demarcation line, especially for flat lesions, using white-light imaging and chromoendoscopy as well as other modalities, including biopsy of surrounding tissues.

MiR‑31 promotes tumorigenesis in ulcerative colitis‑associated neoplasia via downregulation of SATB2.

Ulcerative colitis (UC) features chronic, non-infectious inflammation of the colon. The risk of ulcerative colitis-associated neoplasia (UCAN) increases in direct association with the duration of this disease. Whether miRNAs exert a regulatory effect on the pathogenesis of UCAN has remained to be elucidated. In the present study, differentially expressed genes (DEGs) and microRNAs (miRNAs/miRs) were identified using bioinformatics analysis of Gene Expression Omnibus datasets. Enrichment analyses were performed to determine the function of the DEGs. The target genes of key miRNAs were predicted using miRWalk. Validation of DEGs and miRNAs in patients with UC, UC with low-grade dysplasia and UC with high-grade dysplasia (UC-HGD) was performed using reverse transcription-quantitative PCR analysis. A total of 38 differentially expressed miRNAs and 307 mRNAs were identified from the profiles and miR-31 was validated as being overexpressed in UCAN tissues, particularly in the UC-HGD samples. Furthermore, special AT-rich DNA-binding protein 2 (SATB2) was validated as a target gene of miR-31 and SATB2 expression was negatively correlated with miR-31 expression. Therefore, miR-31 is upregulated in UCAN and it may promote tumorigenesis through downregulation of SATB2.

Positive correlation of expression of L-type amino-acid transporter 1 with colorectal tumor progression and prognosis: Higher expression in sporadic colorectal tumors compared with ulcerative colitis-associated neoplasia

The role of L-type amino-acid transporter 1 (LAT1), an oncofetal protein, in tumor progression is not well known, although it is important for the survival and proliferation of cancer cells. LAT1 expression was immunohistochemically analyzed and compared in sporadic (conventional) colorectal tumors and ulcerative colitis (UC)-associated neoplasia development and progression. LAT1 expression showed a significant stepwise increase in the order: conventional low-grade tubular adenoma, high-grade tubular adenoma, and invasive adenocarcinoma. Similarly, the same increasing trend in LAT1 expression was found in UC-associated low-grade dysplasia, high-grade dysplasia, and adenocarcinoma, whereas expression was significantly lower compared with that in an adenoma–adenocarcinoma series. LAT1 expression was predominant in the upper half of mucosal lesions in low-grade adenoma. This localized difference in LAT1 expression between the upper and lower halves of mucosal lesions disappeared in conventional high-grade adenoma and adenocarcinoma. LAT1 expression in the colorectal mucosa was significantly increased in the order: nontumor mucosa, quiescent phase of UC, and active phase of UC. Considering the histological pattern of Ki-67 labeling, LAT1 expression appeared partly related to cell proliferation, but this was not significant. In relation to the prognosis of patients with sporadic phase IV colorectal adenocarcinoma, this was significantly poorer in the group with high LAT1 expression compared with that with low LAT1 expression. This suggests LAT1 expression may be used as a companion biomarker for anti-cancer therapy targeting the LAT1 molecule in colorectal cancers.