Multifocal Low-grade Dysplasia Research Articles

A104 INVISIBLE COLONIC MALIGNANCY AND POSSIBLE IDIOSYNCRATIC DRUG-INDUCED LIVER INJURY FROM VEDOLIZUMAB IN A PATIENT WITH ULCERATIVE COLITIS, PRIMARY SCLEROSING CHOLANGITIS AND AUTOIMMUNE HEPATITIS OVERLAP SYNDROME

Abstract Background Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract. Due to an increased risk of developing colorectal cancer, regular surveillance for dysplastic lesions via colonoscopy is recommended. Invisible dysplasia is the abnormal development of cells noted on pathology with no visible lesion seen during colonoscopy. Primary sclerosing cholangitis (PSC) is an immune-mediated liver disease leading to progressive stricturing and fibrosis of the bile ducts. There is significant association between PSC and IBD, as up to 80% of patients with PSC having underlying IBD. Drug induced liver injury (DILI) is a common cause of acute liver failure in most Western countries. Most cases of DILI are self-limited, with resolution of laboratory and clinical findings after cessation of the offending agent. Purpose To describe a case of invisible colonic malignancy and possible idiosyncratic drug-induced liver injury from vedolizumab (VDZ) in a patient with ulcerative colitis (UC), PSC and autoimmune hepatitis (AIH) overlap syndrome. Method Patient consent was obtained. Information from electronic records was extracted, including admission notes and procedural reports. A literature review was performed using Pubmed. Result(s) A 32-year-old Caucasian female with UC on VDZ with PSC and AIH had multiple colonoscopies performed demonstrating multifocal low-grade dysplasia. However, she remained resistant to surgery. She presented to clinic with tea-coloured urine, fatigue, and scleral icterus. Investigations revealed conjugated hyperbilirubinemia with elevation in hepatocellular liver enzymes. Imaging was consistent with large duct PSC, and liver biopsy showed grade 2 chronic hepatitis raising the possibility of large bile duct obstruction. She underwent liver transplant assessment and VDZ was held. Her bilirubin and liver enzymes recovered. Given multiple colonoscopies showing multifocal dysplastic changes and the patient declining other biologics, she would ultimately undergo total proctocolectomy with end ileostomy. Pathology demonstrated mucinous adenocarcinoma with a signet ring component. Conclusion(s) Both mucinous adenocarcinoma and signet ring carcinoma are more aggressive malignancies associated with poor prognosis. Found more often in younger patients, they are often diagnosed in later stages with lymphovascular invasion. Here, there was no evidence of metastases in any of the 40 lymph nodes examined, which indicated more favourable prognosis. The mechanism by which VDZ potentially causes liver injury is unknown. Multiple therapies for PSC-AIH overlap and IBD were entertained as causative agents. However, significant improvement in clinical symptoms and serologic parameters following cessation of VDZ was temporally suggestive. This case simultaneously highlights the importance of both timely colectomy in IBD patients with high-risk features during surveillance and early recognition and cessation of potential causative medications which induce liver injury. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

The Fate of Unifocal Versus Multifocal Low-Grade Dysplasia at the Time of Colonoscopy in Patients With IBD: Erratum.

The Fate of Unifocal Versus Multifocal Low-Grade Dysplasia at the Time of Colonoscopy in Patients With IBD: Erratum.

Poor engagement and adherence predict neoplasia in inflammatory bowel disease: a case-control study.

Colorectal adenocarcinoma is an important and preventable complication of inflammatory bowel disease (IBD). A previous case series suggested mental health issues and poor engagement in care as novel risk factors. To confirm the role of patient engagement in care in the development of neoplasia using a case-control methodology. Patients in a single referral centre from 2007 to 2017 with colorectal adenocarcinoma, high-grade dysplasia or multifocal low-grade dysplasia were included as neoplasia cases. Each case was assigned up to three matched controls (matched for age, gender, underlying disease, IBD type and phenotype and disease duration). Novel and known risk factors were compared between groups. Thirty-two cases with 88 matched controls were included. Patients with neoplasia were more likely to have poor adherence to, or engagement with, care (odds ratio (OR) 4.79). They were also more likely to have chronic use of opioids (OR 3.86) and long-term prednisolone (OR 2.97). Of note, no difference was found in measures of socioeconomic disadvantage, reflecting equitable access to healthcare in the public institution where the care was studied. As previously shown, patients with neoplasia had multiple markers of increased cumulative burden of inflammation, including more IBD-related hospital admissions, elevated inflammatory markers and severe inflammation at colonoscopy. This study confirms poor adherence or engagement with care as a new risk factor for colorectal adenocarcinoma in patients with IBD; identifying a vulnerable group whom clinicians should endeavour to engage in order to avoid this catastrophic complication.

The Fate of Unifocal Versus Multifocal Low-Grade Dysplasia at the Time of Colonoscopy in Patients With IBD.

Recommendations regarding management of colorectal dysplasia in the setting of IBD continue to evolve. This study aimed to determine the rate of progression from dysplasia to adenocarcinoma, specifically focusing on the differences in unifocal and multifocal low-grade dysplasia and dysplasia found on random biopsy versus targeted biopsies. This is a retrospective review. This study was conducted at an IBD referral center. All adult patients (≥18 years of age) with a known diagnosis of either ulcerative colitis or Crohn's disease, who underwent a surveillance colonoscopy between January 1, 2010 and January 1, 2019, were selected. The primary outcomes measured were the progression of dysplasia and the risk factors for progression. A total of 23,751 surveillance colonoscopies were performed among 12,289 patients between January 1, 2010 and January 1, 2019. The mean age at colonoscopy was 52.1 years (SD 16.9 years), 307 patients (2.5%) had a history of primary sclerosing cholangitis, and 3887 (3.15%) had a family history of colorectal cancer. There was a total of 668 patients (5.4%) with low-grade dysplasia, 76 patients (0.62%) with high-grade dysplasia, and 68 patients (0.55%) with adenocarcinoma in the series. The 1-, 2-, and 5-year cumulative incidence rate of progressing from low-grade dysplasia to high-grade dysplasia were 1.6%, 4.8%, and 7.8%. The 1- and 2-year cumulative incidence rates of progressing from low-grade dysplasia to adenocarcinoma were 0.7% and 1.6%. There were no significant differences in unifocal and multifocal progression. Primary sclerosing cholangitis, ulcerative colitis, male sex, and advanced age were all found to be significant risk factors for neoplasia on multivariable analysis. A retrospective database was a source of information. Progression of low-grade dysplasia to adenocarcinoma, regardless of its being unifocal or multifocal, remains very low in the setting of adequate surveillance and medical management. The presence of multifocal low-grade dysplasia should not change the decision making to pursue ongoing endoscopic surveillance versus proctocolectomy. Patients who had primary sclerosing cholangitis with dysplasia found on random biopsies may be at highest risk for dysplasia progression. See Video Abstract at http://links.lww.com/DCR/A649. ANTECEDENTES:Las recomendaciones para el tratamiento de la displasia colorrectal en el contexto de la enfermedad inflamatoria intestinal siguen evolucionando.OBJETIVO:Determinar la tasa de progresión de displasia a adenocarcinoma, centrándose específicamente en las diferencias en displasia de bajo grado unifocal y multifocal, y displasia encontradas en biopsias aleatorias versus biopsias dirigidas.DISEÑO:Revisión retrospectiva.ÁMBITO:Centro de referencia de EII.PACIENTES:Todos los pacientes adultos (> 18 años) con un diagnóstico comprobado de colitis ulcerosa o enfermedad de Crohn que se sometieron a una colonoscopia de vigilancia entre el 1 de enero de 2010 y el 1 de enero de 2019.PRINCIPALES VARIABLES ANALIZADAS:Progresión de la displasia y factores de riesgo de progresión.RESULTADOS:Se realizaron un total de 23.751 colonoscopias de vigilancia en 12.289 pacientes entre el 1/1/2010 y el 1/1/2019. La edad media en el momento de la colonoscopia fue de 52,1 años (DE 16,9 años), 307 pacientes (2,5%) tenían antecedentes de colangitis esclerosante primaria y 3887 (3,15%) tenían antecedentes familiares de cáncer colorrectal. Hubo un total de 668 pacientes (5,4%) con displasia de bajo grado, 76 pacientes (0,62%) con displasia de alto grado y 68 pacientes (0,55%) con adenocarcinoma en la serie. La tasa de incidencia acumulada de 1, 2, 5 años de progresión de displasia de bajo grado a displasia de alto grado fue del 1,6%, 4,8% y 7,8%. Las tasas de incidencia acumulada de 1 y 2 años de progresión de displasia de bajo grado a adenocarcinoma fueron 0,7% y 1,6%, respectivamente. No hubo diferencias significativas en la progresión unifocal y multifocal. Se encontró que la colangitis esclerosante primaria, la colitis ulcerosa, el sexo masculino y la edad avanzada eran factores de riesgo significativos de neoplasia en el análisis multivariable.LIMITACIONES:Base de datos retrospectiva.CONCLUSIÓN:La progresión de la displasia de bajo grado a adenocarcinoma, independientemente de que sea unifocal o multifocal, sigue siendo muy baja en el contexto de una vigilancia y un tratamiento médico adecuados. La presencia de displasia multifocal de bajo grado no debería cambiar la toma de decisión para continuar con vigilancia endoscópica continua o realizar la proctocolectomía. Los pacientes con colangitis esclerosante primaria y displasia encontrada en biopsias aleatorias pueden tener una mayor progresión de la displasia. Consulte Video Resumen en http://links.lww.com/DCR/A649.

The Significance of Flat/Invisible Dysplasia and Nonconventional Dysplastic Subtypes in Inflammatory Bowel Disease: A Review of Their Morphologic, Clinicopathologic, and Molecular Characteristics.

Patients with inflammatory bowel disease are at significantly increased risk of dysplasia and colorectal cancer (CRC). The early detection, histologic grading, and removal of dysplasia plays a critical role in preventing the development of CRC. With advances in endoscopic visualization and resection techniques, colectomy is no longer recommended to manage dysplasia, unless surveillance colonoscopy detects flat/invisible dysplasia (either high-grade dysplasia or multifocal low-grade dysplasia) or an endoscopically unresectable lesion. Although there are numerous review articles and book chapters on the morphologic criteria of conventional (intestinal type) dysplasia, the most well-recognized form of dysplasia, at least 7 distinct nonconventional morphologic patterns of epithelial dysplasia have been recently described in inflammatory bowel disease. Most practicing pathologists are not familiar with these nonconventional subtypes and thus, may even overlook some of these dysplastic lesions as benign or reactive. However, the recognition of these subtypes is important, as some of them appear to have a high risk of developing advanced neoplasia (high-grade dysplasia or CRC) and often show molecular alterations characteristic of advanced neoplasia. This review briefly describes the morphologic criteria of conventional dysplasia but predominantly focuses on all 7 nonconventional subtypes as well as our understanding of their clinicopathologic and molecular features that can assist in their risk stratification.

Perception of Cancer Risk and Management Practice for Colitis-associated Dysplasia Is Influenced by Colonoscopy Experience and Workplace Affiliation: Results of an International Clinician Survey.

Background and AimsA successful colitis cancer surveillance programme requires effective action to be taken when dysplasia is detected. This is the first international cross-sectional study to evaluate clinician understanding of dysplasia-cancer risk and management practice since the most recent international guidelines were introduced in 2015.MethodsA 15-item international online survey was disseminated to gastroenterologists and colorectal surgeons.ResultsA total of 294 clinicians [93.5% gastroenterologists] from 60 countries responded; 23% did not have access to high-definition chromoendoscopy. University hospitals were more likely than non-academic workplaces to provide second expert histopathologist review [67% vs 46%; p = 0.002] and formal multidisciplinary team meeting discussion [73% vs 52%; p = 0.001] of dysplasia cases. Perceptions of 5-year cancer risk associated with endoscopically unresectable low-grade dysplasia varied between 0% and 100%. Non-academic hospital affiliation was predictive of lower perceived cancer risks. Although most [98.4%] respondents advised a colectomy for endoscopically unresectable visible high-grade dysplasia, only 34.4% advised a colectomy for unresectable visible low-grade dysplasia. Respondents from university hospitals were more likely to consider colectomy for multifocal low-grade dysplasia (odds ratio [OR] 2.17). If invisible unifocal low-grade dysplasia was detected, continued surveillance over colectomy was the preferred management among clinicians working mainly in private clinics [OR 9.4] and least preferred in those who had performed more than 50 surveillance colonoscopies [OR 0.41].ConclusionsClinicians with less surveillance colonoscopy experience and from non-academic centres appear to have lower cancer risk perceptions and are less likely to advocate colectomy for higher-risk low-grade dysplasia. Further education may align current management practice with clinical guidelines.

P348 Perception of cancer risk in inflammatory bowel disease-associated dysplasia and management practice is influenced by colonoscopy experience and workplace affiliation: results of an international clinician survey

Abstract Background A successful inflammatory bowel disease (IBD) surveillance cancer preventative programme requires effective action to be taken when dysplasia is detected. This is the first international cross-sectional study to evaluate current clinician understanding of IBD dysplasia risk, their management practice and adherence to the most recent international guidelines introduced since 2015. Methods A 15-item online survey was disseminated to IBD gastroenterologist and colorectal surgeon members of the British Society of Gastroenterology in June 2019 and the European Crohn’s and Colitis Organisation in February 2020. Results 294 clinicians (93.5% gastroenterologists) from 60 countries responded. A significant proportion indicated not having access to high definition chromoendoscopy IBD surveillance (23%) in their endoscopy units. University hospitals were more likely than non-academic workplaces to provide second expert histopathologist review (67% vs. 46%; p=0.002) and formal multidisciplinary team meeting discussion (73% vs. 52%; p=0.001) of dysplasia cases. Most respondents would advocate endoscopic resection of all visible dysplasia and would refer to a regional specialist therapeutic endoscopist if needed (70%). However, perceptions of 5-year cancer risk associated with endoscopically unresectable low-grade dysplasia (LGD) varied between 0 – 100% (median 20% for visible LGD and median 25% for invisible LGD). Although most (98.4%) would advise a colectomy for endoscopically unresectable visible high-grade dysplasia (HGD), only 34.4% would also advise a colectomy for unresectable visible LGD. Working at a non-academic hospital was predictive of a lower perceived cancer risk with HGD [OR 0.4 (95% CI 0.23-0.95)] and unresectable LGD. Working in a private clinic predicted surveillance preference over colectomy to manage invisible LGD [OR 9.4 (95% CI 1.19-74.1)] and multifocal LGD. Greater surveillance colonoscopy experience predicted a lower preference for continued surveillance over colectomy for invisible LGD [OR 0.41 (95% CI 0.20-0.84)]. Conclusion This study of mainly European gastroenterologists with a sub-specialist interest in IBD has revealed wide variations in colorectal cancer risk perceptions and dysplasia management practices. Clinicians with less IBD surveillance colonoscopy experience and from non-academic centres appeared to have lower cancer risk perceptions and were less likely to advocate colectomy over continued surveillance for high-risk LGD. This study suggests that further education is required to align current management practice with clinical guidelines.

Multicentre derivation and validation of a colitis-associated colorectal cancer risk prediction web tool

ObjectivePatients with ulcerative colitis (UC) diagnosed with low-grade dysplasia (LGD) have increased risk of developing advanced neoplasia (AN: high-grade dysplasia or colorectal cancer). We aimed to develop and validate a...

Non-conventional dysplastic subtypes in inflammatory bowel disease: a review of their diagnostic characteristics and potential clinical implications.

The early detection and grading of dysplasia is the current standard of care to minimize mortality from colorectal cancer (CRC) in patients with inflammatory bowel disease. With the development of advanced endoscopic resection techniques, colectomy is now reserved for patients with invisible/flat dysplasia (either high-grade [HGD] or multifocal low-grade dysplasia) or endoscopically unresectable lesions. Although most pathologists are familiar with the morphologic criteria of conventional (intestinal type) dysplasia, the most well-recognized form of dysplasia, an increasing number of diagnostic material has led to the recognition of several different morphologic patterns of epithelial dysplasia. The term “non-conventional” dysplasia has been coined to describe these changes, but to date, the recognition and full appreciation of these novel forms of dysplasia by practicing pathologists is uneven. The recognition of these non-conventional subtypes is becoming increasingly important, as some of them appear to have a higher risk of developing HGD or CRC than conventional dysplasia or sporadic adenomas. This review describes the morphologic characteristics of all seven non-conventional subtypes that have been reported to date as well as our current understanding of their clinicopathologic and molecular features that distinguish them from conventional dysplasia or sporadic adenomas.

Does Multifocal Dysplasia in Barrett’s Esophagus Increase the Risk of Progression to Esophageal Adenocarcinoma?: Presidential Poster Award

Introduction: Barrett’s Esophagus (BE), is thought to be secondary to gastroesophageal reflux disease and progresses to esophageal adenocarcinoma (EAC) in a stepwise manner. Current guidelines utilize dysplasia to guide management, but there is conflicting evidence on the extent of dysplasia for risk stratification. Here, we evaluated the effect of multifocal dysplasia on the risk for EAC and hypothesized that multifocality in low-grade dysplasia (LGD) and high-grade dysplasia (HGD) are risk factors for progression to EAC. Methods: This was a retrospective study of BE patients with, or with suspected, dysplasia presenting to an academic medical center for evaluation from 2006 to 2016. Information collected include: patient demographics; BE length; histology, including grade and presence of multifocal dysplasia; disease progression; PPI use; need for esophagectomy; and length of follow-up. All pathology specimens were read by expert GI pathologists as: no dysplasia (ND), indefinite for dysplasia (IND), LGD, or HGD. LGD or HGD was further categorized as unifocal or multifocal. Results: Of 305 BE patients with, or with suspected, dysplasia, 51 were excluded (33 ND, 18 IND). 254 BE patients were included in the final analysis: 112 LGD (unifocal=90, multifocal=22) and 142 HGD (unifocal=108, multifocal=34). In total, twenty-five patients with dysplastic BE (13 unifocal, 12 multifocal) developed EAC; all were diagnosed with intramucosal adenocarcinoma with either T1a or T1b lesions. Multifocality significantly increased the risk for progression to EAC (Table 2: RR 3.26, p=0.004), with the effect most pronounced in the subgroup with multifocal LGD as compared to those with unifocal LGD (RR 8.18, p=0.013). In patients with HGD, multifocality did not increase the risk for subsequent EAC (RR 2.31, p=0.079). Lastly, multifocal dysplasia associated with long segment BE (LSBE) significantly increased the risk for EAC (Table 3: RR 3.09, p=0.011), and HGD patients with LSBE were more at-risk for progression to EAC than that of LGD patients (RR 4.33, p=0.007). Conclusion: Multifocal dysplasia significantly increases the risk of progressing from BE to EAC and is especially important in BE patients with LGD. Identification of the extent of dysplasia is also essential in patients with LSBE, particularly those diagnosed with HGD. If confirmed, incorporating dysplasia multifocality into the BE management algorithm should be considered.335_A Figure 1 No Caption available.335_B Figure 2 No Caption available.335_C Figure 3. Short Segment (SS) BE is defined as <3 cm in length, while Long Segment (LS) BE is defined as > or = to 3 cm in length

Sustained Resolution of Multifocal Low Grade Dysplasia in Ulcerative Colitis: A Rare Progression

Sustained Resolution of Multifocal Low Grade Dysplasia in Ulcerative Colitis: A Rare Progression

Judging the J pouch: a pictorial review

Restorative total proctocolectomy with ileal pouch-anal anastomosis is the surgery of choice for patients with medically refractory ulcerative colitis, ulcerative colitis with high-grade dysplasia or multi-focal low-grade dysplasia, and for patients with familial adenomatous polyposis. The natural history of the surgery is favorable, and patients generally experience improved quality of life and acceptable long-term functional outcome. However, some patients experience significant long-term morbidity from early and/or late pouch-related complications. When complications arise, radiologists must understand the advantages and disadvantages of the various imaging modalities that can be used to assess the pouch. Radiologist familiarity with the surgical technique, pouch anatomy, and imaging appearance of the various potential early and late complications will help facilitate appropriate clinical and surgical decision-making. This review provides an anatomic-based imaging review of the pouch and pouch-related complications, including numerous illustrative fluoroscopic and cross-sectional imaging examples.

Risk for Cancer Progression in Ulcerative Colitis with Low-Grade Dysplasia

In the past, multifocal low-grade dysplasia (LGD) verified by an expert pathologist was considered an indication for colectomy in ulcerative colitis,

Patients With Barrett’s Esophagus and Confirmed Persistent Low-Grade Dysplasia Are at Increased Risk for Progression to Neoplasia

For patients with Barrett's esophagus, the diagnosis of low-grade dysplasia (LGD) is subjective, and reported outcomes vary. We analyzed data from a multicenter study of endoscopic therapy to identify factors associated with progression to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) in patients with LGD of the esophagus. We performed a retrospective analysis of data from 255 patients with a primary diagnosis of LGD (78% men; mean age, 63 years) who participated in a randomized controlled trial of surveillance vs radiofrequency ablation in Europe. Three expert pathologists independently reviewed baseline and subsequent LGD specimens. The presence and degree of dysplasia was separately recorded for each biopsy and classified according to the Vienna Classification system. The primary end point was development of HGD or EAC. We performed univariate logistic regression analyses to assess the association between outcomes and factors such as number of pathologists confirming LGD, multifocality of LGD, and persistence of LGD over time. Of the 255 patients, 45 (18%) developed HGD or EAC during a median 42-month follow-up period (interquartile range, 25-61 months); patients were examined by a median 4 endoscopies (interquartile range, 3-6 endoscopies). The number of pathologists confirming LGD was strongly associated with progression to neoplasia; risk for progression increased greatly when all 3 pathologists agreed onLGD (odds ratio, 47.14; 95% confidence interval, 13.10-169.70). When LGD was detected at baseline and confirmed by a subsequent endoscopy, the odds for progression to neoplasia also increased greatly (odds ratio, 9.28; 95% confidence interval, 4.39-19.64). Multifocal LGD was not significantly associated with progression to neoplasia. The number of pathologists confirming LGD and persistence of LGD over time increase risk for development of HGD or EAC in patients with Barrett's esophagus and LGD. These simple, readily available variables can help stratify risk and select patients for prophylactic ablation therapy.

Colonic Neuroendocrine Carcinoma in the Setting of Ulcerative Colitis and PSC: Coincidence or Colitis-Associated?

Introduction: Ulcerative colitis (UC) patients are at increased risk of developing colorectal cancer. The risk is increased significantly in patients with concomitant primary sclerosing cholangitis (PSC). Adenocarcinoma is the most common GI cancer among IBD patients, and other types of malignancies are rarely reported. We describe a patient with IBD and PSC who was found to have an invasive adenocarcinoma with neuroendocrine features. Case Description: A 68 year-old woman with prior appendectomy and a 40-year history of UC and PSC was in long-standing stable clinical remission on sulfasalazine and undergoing annual surveillance colonoscopies by her local physician. Both parents had advanced age colorectal cancer and her older sister had recently died of gastric adenocarcinoma. During her recent surveillance colonoscopy, biopsy of an abnormal mucosal area in the cecum was interpreted as a neuroendocrine tumor. In order to define the tumor and identify synchronous lesions, a pre-operative chromoendoscopy was performed. The previously seen lesion was identified, and there was no additional dysplasia found. At the time of surgery, thickening of the ascending colon wall was noted (Image 1); histologic review of the colectomy specimen confirmed an invasive poorly differentiated adenocarcinoma with signet ring cells and neuroendocrine features (image 2), as well as other areas of multifocal low-grade dysplasia. 14/31 lymph nodes were involved with tumor. CT scan did not identify additional metastatic disease. She is currently receiving chemotherapy. Discussion: Neuroendocrine cancers are rare, often well-differentiated and clinically indolent, with the most common locations being appendiceal and rectal. These tumors are not commonly described in the setting of colitis, but neuroendocrine differentiation has been described as a possible early event in the UC neoplasia pathway, or a feature or poorly differentiated and more aggressive tumors. This patient's tumor was in an atypical location and accompanied by multi-focal low-grade dysplasia, suggesting that this was likely a colitis-associated tumor which was poorly differentiated and not the more indolent type of primary neuroendocrine tumor, like a carcinoid. The invasive nature of this tumor and advanced staging at the time of diagnosis despite her annual surveillance is a cautionary note for both clinicians and pathologists, who might otherwise be reassured by the neuroendocrine features.Figure 1Figure 2

Tu1146 Persistent and Multifocal Low Grade Dysplasia (LGD) and Topographic Location of LGD Are Not Associated With Progression to High Grade Dysplasia (HGD) or Esophageal Adenocarcinoma (EAC) in Patients With Long Segment Barrett's (Lsb)

Tu1146 Persistent and Multifocal Low Grade Dysplasia (LGD) and Topographic Location of LGD Are Not Associated With Progression to High Grade Dysplasia (HGD) or Esophageal Adenocarcinoma (EAC) in Patients With Long Segment Barrett's (Lsb)

Histological evaluation in ulcerative colitis.

This review summarizes diagnostic problems, challenges and advances in ulcerative colitis (UC). It emphasizes that, although histopathological examination plays a major role in the diagnosis and management of UC, it should always be interpreted in the context of clinical, endoscopic, and radiological findings. Accurate diagnosis requires knowledge of the classic morphological features of UC, as well as a number of atypical pathological presentations that may cause mis-classification of the disease process, either in resection or biopsy specimens. These atypical pathological presentations include rectal sparing and patchiness of disease at initial presentation of UC in pediatric patients or in the setting of medically treated UC, cecal or ascending colon inflammation in left-sided UC, and backwash ileitis in patients with severe ulcerative pancolitis. Loosely formed microgranulomas, with pale foamy histiocytes adjacent to a damaged crypt or eroded surface, should not be interpreted as evidence of Crohn’s disease. Indeterminate colitis should only be used in colectomy specimens as a provisional pathological diagnosis. Patients with UC are at risk for the development of dysplasia and carcinoma; optimal outcomes in UC surveillance programs require familiarity with the diagnostic criteria and challenges relating to UC-associated dysplasia and malignancy. Colon biopsy from UC patients should always be evaluated for dysplasia based on cytological and architectural abnormalities. Accurate interpretation and classification of dysplasia in colon biopsy from UC patients as sporadic adenoma or UC-related dysplasia [flat, adenoma-like, or dysplasia-associated lesion or mass (DALM)] requires clinical and endoscopic correlation. Isolated polypoid dysplastic lesions are considered to be sporadic adenoma if occurring outside areas of histologically proven colitis, or adenoma-like dysplasia if occurring in the diseased segment. Recent data suggest that such lesions may be treated adequately by polypectomy in the absence of flat dysplasia in the patient. UC patients with DALM or flat high-grade dysplasia should be treated by colectomy because of the high probability of adenocarcinoma. The natural history of low-grade dysplasia (LGD) is more controversial: while multifocal LGD, particularly if detected at the time of initial endoscopic examination, is treated with colectomy, unifocal flat LGD detected during surveillance may be managed by close follow-up with increased surveillance. The surveillance interval and treatment options for UC patients with dysplasia are reviewed in detail.

Colon cancer screening and surveillance in inflammatory bowel disease.

Patients with inflammatory bowel disease (IBD) have an increased risk of developing colorectal cancer (CRC). Accordingly, the duration and anatomic extent of the disease have been known to affect the development of IBD-related CRC. When CRC occurs in patients with IBD, unlike in sporadic CRC, it is difficult to detect the lesions because of mucosal changes caused by inflammation. In addition, the tumor types vary with ill-circumscribed lesions, and the cancer is difficult to diagnose and remedy at an early stage. For the diagnosis of CRC in patients with IBD, screening endoscopy is recommended 8 to 10 years after the IBD diagnosis, and surveillance colonoscopy is recommended every 1 to 2 years thereafter. The recent development of targeted biopsies using chromoendoscopy and relatively newer endoscopic techniques helps in the early diagnosis of CRC in patients with IBD. A total proctocolectomy is advisable when high-grade dysplasia or multifocal low-grade dysplasia is confirmed by screening endoscopy or surveillance colonoscopy or if a nonadenoma-like dysplasia-associated lesion or mass is detected. Currently, pharmacotherapies are being extensively studied as a way to prevent IBD-related CRC.

Inflammatory bowel disease cancer surveillance in a tertiary referral hospital: attitudes and practice

Physician adherence to guidelines for colorectal cancer (CRC) surveillance in inflammatory bowel disease (IBD) is often poor. This may lead to adverse patient outcomes and excess endoscopic workload. To assess the attitudes and practice of IBD specialists in a tertiary centre towards colonoscopic surveillance. First, a questionnaire evaluating attitudes and approach to CRC surveillance was issued to 36 clinicians at one tertiary referral hospital. Second, a retrospective audit of IBD surveillance colonoscopy practice over a 2-year period was performed. Questionnaire response rate was 97%. Sixty-nine per cent of respondents were aware of, and used, Australian guidelines. Surveillance was undertaken by all clinicians in patients with extensive colitis, 83% in patients with left-sided colitis and 51% in patients with proctitis. Seventy-six per cent used chromoendoscopy, and 47% took 10 to 20 random biopsies. Colectomy was considered appropriate in 0% for unifocal low-grade dysplasia, 35% for multifocal low-grade dysplasia and 83% for high-grade dysplasia. Sixty-six per cent would remove elevated dysplastic lesions endoscopically. The audit identified 103 surveillance colonoscopies in 81 patients. Chromoendoscopy was used in 21% of cases, and the median number of random biopsies was 13. Sixty-two per cent of colonoscopies were performed outside the guidelines in relation to colonoscopic frequency. Following colonoscopy, an appropriate recommendation for subsequent surveillance was documented in 40% of cases. Knowledge and practice of CRC surveillance in IBD vary among specialist clinicians and often deviate from guidelines. Many clinicians perform surveillance earlier and more frequently than recommended. These findings have implications for patient outcomes and workload.

Predictors of Colorectal Neoplasia Outcomes in Indefinite and Low-Grade Dysplasia in Patients with Primary Sclerosing Cholangitis and Ulcerative Colitis: ACG IBD Research Award

Purpose: Patients (pts) with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC) are at an increased risk for colorectal neoplasia. We sought to examine the natural history of low-grade dysplasia (LGD) and indefinite dysplasia (IND) in order to identify factors associated with neoplasia progression or persistence in pts with PSC-UC. Methods: We performed a retrospective review of pts with PSC and UC who were diagnosed with LGD or IND (index lesion confirmed after review by a pathologist). LGD was classified as unifocal or multifocal and flat or raised. Raised lesions in an area of colitis were considered adenoma-like dysplasia (ALD). Sporadic adenomas were excluded. Pts were excluded if they had a prior colectomy, colorectal neoplasia, or liver transplant (LT) or did not follow up beyond 60 days of their index lesion. Pts were censored at the time of colectomy, last colonoscopy or LT, whichever was earliest. The primary end-point was neoplasia progression, or persistent LGD. Covariates were included into the multivariate model if they had a p-value of ≤0.05 in the univariate analysis. Results: Sixty-three pts (IND n=47, LGD n=16) were followed for 176 pt-years. The primary endpoint was reached in 56% of pts with LGD [cancer n=1; persistent LGD (multifocal n=2; ALD n=6)] and in 28% with IND (cancer n=3; HGD n=3; multifocal LGD n=2; ALD LGD n=1; flat LGD n=4). Compared to those with IND, pts with LGD were older (57 years versus 42 years, p<0.01), and had a longer duration of UC (28 years versus 10 years, p=0.03) and PSC (9 years versus 6 years, p=0.05). Compared to LGD, IND lesions were more likely to be flat (98% versus 50%, p<0.01) and found in an area of colitis (100% versus 81% p<0.01). Univariate analysis revealed that LGD (compared to IND) was associated with the primary endpoint, HR 4.02 (1.61-9.71) p<0.01. Of those with multifocal LGD at baseline, univariate analysis showed an association with the primary endpoint, HR 5.08 (0.97-23.79) p=0.05. PSC duration was associated with the endpoint, HR 0.87 (0.74-0.99) p=0.05, in pts with LGD. However, neither was associated with the primary outcome in the multivariate analysis. Among pts with IND, 5-ASA use was associated with a reduced risk of neoplasia progression, HR 0.18 (0.04-0.70) p=0.01 on univariate analysis. A multivariate analysis for the IND group was not performed since 5-ASA use was the only significant association detected. Conclusion: Pts with PSC and UC who developed LGD were more likely to have progressive or persistent neoplasia than those who had IND. However, more than one-quarter of IND pts also developed more advanced lesions. 5-ASA use appeared to protect against neoplasia progression in pts with IND.