Automatic Identification of Paraffin Pixels on FTIR Images Acquired on FFPE Human Samples.

The transfer of mid-infrared spectral histopathology to the clinic will be possible provided that its application in clinical practice is simple. Rapid analysis of formalin-fixed paraffin-embedded (FFPE) tissue section is thus a prerequisite. The chemical dewaxing of these samples before image acquisition used by the majority of studies is in contradiction with this principle. Fortunately, the in silico analysis of the images acquired on FFPE samples is possible using extended multiplicative signal correction (EMSC). However, the removal of pure paraffin pixels is essential to perform a relevant classification of tissue spectra. So far, this task was possible only if using manual and subjective histogram analysis. In this article, we thus propose a new automatic and multivariate methodology based on the analysis of optimized combinations of EMSC regression coefficients by validity indices and KMeans clustering to separate paraffin and tissue pixels. The validation of our method is performed using simulated infrared spectral images by measuring the Jaccard index between our partitions and the image model, with values always over 0.90 for diverse baseline complexity and signal-to-noise ratio. These encouraging results were also validated on real images by comparing our method with classical ones and by computing the Jaccard index between our partitions and the KMeans partitions obtained on the infrared image acquired on the same samples but after chemical dewaxing, with values always over 0.84.

The deficit in folate and vitamin B12 triggers liver macrovesicular steatosis and inflammation in rats with dextran sodium sulfate-induced colitis.

The risks of nonalcoholic steatohepatitis (NASH) and deficiency in vitamin B12 and folate (methyl donor deficiency, MDD) are increased in inflammatory bowel disease (IBD). We investigated the influence of MDD on NASH in rats with DSS-induced colitis. Two-month-old male Wistar rats were subjected to MDD diet and/or ingestion of DSS and compared to control animals. We studied steatosis, inflammation, fibrosis, plasma levels of metabolic markers, cytokines and lipopolysaccharide, and inflammatory pathways in liver. MDD triggered a severe macrovesicular steatosis with inflammation in DSS animals that was not observed in animals subjected to DSS or MDD only. The macrovesicular steatosis was closely correlated to folate, vitamin B12, homocysteine plasma level and liver S-adenosyl methionine/S-adenosyl homocysteine (SAM/SAH) ratio. Liver inflammation was evidenced by activation of nuclear factor kappa B (NFκB) pathway and nuclear translocation of NFκB phospho-p65. MDD worsened the increase of interleukin 1-beta (IL-1ß) and abolished the increase of IL10 produced by DSS colitis. It increased monocyte chemoattractant protein 1 (MCP-1). MDD triggers liver macrovesicular steatosis and inflammation through imbalanced expression of IL-1ß vs. IL10 and increase of MCP-1 in DSS colitis. Our results suggest evaluating whether IBD patients with MDD and increase of MCP-1 are at higher risk of NASH.

Expression of the Serrated Markers Annexin A10 or Gremlin1 in Colonic Adenocarcinomas: Morphology and Prognostic Values.

Describe clinical, histological and molecular charatcteristics and prognosis values of the serrated candidate markers AnnexinA10 and Gremlin1 in colon adenocarcinomas. Immunohistochemical expression of AnnexinA10 and Gremlin1 was evaluated on 346 colonic adenocarcinomas. Clinicopathological, molecular features and prognostic characteristics were then evaluated. A total of 40 colonic adenocarcinomas expressed AnnexinA10 (11.6%) and, 115 expressed Gremlin1 (40.4%). AnnexinA10 expression was significantly associated, on univariate analyses, with female gender (p = 0.03), right tumor location (p < 0.001), differentiation grade 3 (p < 0.001), serrated adenocarcinoma subtype (p < 0.001), serrated (p < 0.001), medullary (p = 0.005), and mucinous component (p = 0.004), cytoplasmic eosinophilia (p < 0.001), discernible nuclei (p = 0.001), preserved polarity (p < 0.001), lymphatic invasion (p = 0.01), BRAFV600E mutation (p < 0.001), MSI-H status (p < 0.001) and CIMP-H status (p = 0.019). Multivariate analyses revealed that mucinous component (p = 0.002), lymphatic invasion (p = 0.02) and BRAFV600E mutation (p < 0.001) were independently associated with AnnexinA10 expression. In addition, AnnexinA10 was an indicator of poorer overall survival (OS) in UICC stage IV adenocarcinomas (p = 0.01) only. Gremlin1 expression was neither associated with serrated adenocarcinoma subtype (p = 0.51) nor with AnnexinA10 expression (p = 0,31), but was significantly associated, in univariate analysis with male gender (p = 0.002), younger age (p = 0.002), left tumor location (p = 0.04), and MSS status (p = 0.03). Gremlin1 expression was associated with better OS only in UICC stage III colon adenocarcinomas (p = 0.006). Colon adenocarcinomas expressing AnnexinA10 have distinct clinico-pathological and molecular features. AnnexinA10 expression is an indicator of poorer OS in UICC stage IV patients. Gremlin1 expression is not associated with serrated adenocarcinomas subtype. Its expression was associated with better OS in UICC Stage III patients.

Histological Remission in Ulcerative Colitis: Under the Microscope Is the Cure.

In recent years, the therapeutic goals in ulcerative colitis (UC) have become increasingly stringent. Histological features seem to be a reliable predictor of disease outcomes after therapy, and histological remission (HR) is the new frontier in the treatment of UC. Here, we first provide a historical perspective before reviewing indexes in the era of biologics; histology as a treatment goal in UC trials; the poor correlation between symptoms, endoscopy, and histology; and the impact of histology on disease outcomes. HR seems to be a promising end point for the treatment of UC because it is typically associated with better outcomes. Two new validated indexes are available to assess histology more accurately in trials, and they may also be applicable to clinical practice. Additional interventional trials are now necessary to establish definitions of HR and its potential for disease modification.

Is the Mirror Image Method Really Useful in Tumor Tissue Bank Quality Control?

Oncology research projects are highly dependent on the quality of tumor samples stored in the biobank. Microscopic control is important to ensure the quality of the frozen sample (Does the sample correspond to tumor tissue? Does the sample contain a sufficient number of tumor cells for molecular analysis?). The aim of this study was to evaluate the value of the mirror image method in quality control of colonic adenocarcinoma samples stored in a tumor bank. Microscopic concordance for the differentiation grade, malignant and normal cell percentages, necrosis, mucinous component, and ulceration was assessed on 82 colon adenocarcinoma banked samples and their paired, formalin-fixed, paraffin-embedded mirror controls. Molecular concordance for KRAS status was evaluated in 76 of these 82 cases. Morphological correspondence between frozen and mirror samples was good for the mucinous component (intraclass correlation coefficient [ICC] = 0.81), moderate for differentiation (Cohen's kappa coefficient [k] = 0.67), fair for malignant cells (ICC = 0.44), and poor for ulceration (k = 0.08), normal tissue (ICC = 0.36), and necrosis (ICC = 0.13) percentages. Molecular correspondence for KRAS status was almost perfect (95% correspondence, k = 0.88) between frozen and mirror samples. In conclusion, the mirror sample method is not a good alternative for microscopic and molecular control of frozen colonic adenocarcinoma samples.

Responsiveness of histological disease activity indices in ulcerative colitis: a post hoc analysis using data from the TOUCHSTONE randomised controlled trial.

OBJECTIVE: We evaluated the reliability and responsiveness of available but incompletely validated UC histological disease activity indices using standardised rules for centralised assessment. DESIGN: Disease activity was assessed in biopsies collected in a phase II placebo-controlled ozanimod trial by four blinded pathologists using the Geboes (GS) and modified Riley (MRS) scores, the Robarts Histopathology (RHI) and Nancy Histological (NHI) indices and a Visual Analogue Scale. Reliability was assessed with intraclass correlation coefficients (ICCs). Index responsiveness was evaluated by assessing longitudinal validity (Pearson correlations of changes in index scores and other disease measures), and effect size estimates (standardised effect size (SES)) using two criteria for change (treatment assignment and >2 point decrease in total Mayo Clinic score). Area under the receiver operating characteristic (AUROC) curve estimates evaluated the probability of the indices to discriminate between treatment and placebo. RESULTS: Inter-rater reliability of the histological indices was substantial to almost perfect (ICC>0.61), and responsiveness was moderate to large (SES estimates>0.5); 0.81 (0.52, 1.10), 0.87 (0.58, 1.17), 0.57 (0.30, 0.84) and 0.81 (0.52, 1.09) when treatment assignment was the criterion for change and 1.05 (0.80, 1.31), 1.13 (0.87, 1.39), 0.88 (0.64, 1.12) and 1.06 (0.80, 1.31) for the change in Mayo score criterion for the GS, MRS, RHI and NHI, respectively. The indices had similar drisciminative ability based on AUROC estimates (range 0.608-0.649). CONCLUSION: All four existing histological indices were similarly reliable and responsive based on this dataset.

Which evidence for a treat to target strategy in ulcerative colitis?

The main therapeutic goal of in ulcerative colitis is to maintain disease remission. The new concept of deep remission implies also a complete mucosal healing. Histological assessment of disease in UC seems to be an important prognostic factor to predict disease outcome. In this article we review current definitions of mucosal healing, histological healing, histological remission and available histological scores assessing histological activity of disease in ulcerative colitis. Comparison between mucosal healing and histological remission shows that histological remission is a better prognostic factor than mucosal healing to predict outcome in ulcerative colitis and could be a new therapeutic goal in ulcerative colitis but actually histology is not a target due to lack of evidence of clinical utility. Some investigations are needed to clearly defined histological remission and to determine its role in therapeutic strategy. Futhermore histological assessment remains an invasive exploration and other alternative as faecal markers are discuss to predict ulcerative outcome.

LRP1 expression in colon cancer predicts clinical outcome.

LRP1 (low-density lipoprotein receptor-related protein 1), a multifunctional endocytic receptor, has recently been identified as a hub within a biomarker network for multi-cancer clinical outcome prediction. As its role in colon cancer has not yet been characterized, we here investigate the relationship between LRP1 and outcome. MATERIALS AND METHODS: LRP1 mRNA expression was determined in colon adenocarcinoma and paired colon mucosa samples, as well as in stromal and tumor cells obtained after laser capture microdissection. Clinical potential was further investigated by immunohistochemistry in a population-based colon cancer series (n = 307). LRP1 methylation, mutation and miR-205 expression were evaluated and compared with LRP1 expression levels. RESULTS: LRP1 mRNA levels were significantly lower in colon adenocarcinoma cells compared with colon mucosa and stromal cells obtained after laser capture microdissection. Low LRP1 immunohistochemical expression in adenocarcinomas was associated with higher age, right-sided tumor, loss of CDX2 expression, Annexin A10 expression, CIMP-H, MSI-H and BRAFV600E mutation. Low LRP1 expression correlated with poor clinical outcome, especially in stage IV patients. While LRP1 expression was downregulated by LRP1 mutation, LRP1 promoter was never methylated. CONCLUSIONS: Loss of LRP1 expression is associated with worse colon cancer outcomes. Mechanistically, LRP1 mutation modulates LRP1 expression.

Immunohistochemical Approach to the Differential Diagnosis of Meningiomas and Their Mimics.

The differential diagnosis between meningioma and others tumors can be challenging. This study aimed to evaluate different immunohistochemical markers for the differential diagnosis between meningioma and their morphological mimics. Immunohistochemistry was performed on tissue microarray with antiepithelial membrane antigen (EMA), progesterone receptor, somatostatin receptor 2A (SSTR2A), CD34, STAT6, S100, SOX10, HMB45, MelanA, GFAP, inhibin, and BCL2 antibodies. One hundred and twenty-seven meningiomas, 26 solitary fibrous tumor/hemangiopericytomas (SFT/HPC), 39 schwannomas, 17 hemangioblastomas, 21 melanomas, 9 gliosarcomas, 5 neurofibromas, 9 peripheral primitive neuroectodermal tumors, 7 synovial sarcomas, and 5 malignant peripheral nerve sheath tumors were included in the microarray. SSTR2A was the most sensitive (95.2%) and specific (92%) marker of meningiomas. In combination, SSTR2A and/or EMA positivity reached maximal sensitivity (100%). Coexpression of SSTR2A and EMA was the most specific (94.8%) for the diagnosis of meningioma, regardless of the grade or subtype, with the exception of the differential diagnosis with synovial sarcoma. All synovial sarcomas were EMA-positive and 6/7 SSTR2A-positive. STAT6 showed optimum sensitivity and specificity (100%) for SFT/HPC. SOX10 was the most sensitive (94.3%) and specific (100%) marker to discriminate meningiomas from schwannomas. In conclusion, SSTR2A, STAT6, and SOX10 were the most sensitive and specific markers to distinguish meningiomas from their morphological mimics.

Development and validation of the Nancy histological index for UC.

OBJECTIVE: We developed a validated index for assessing histological disease activity in UC and established its responsiveness. METHODS: Two hundred biopsies were scored. The outcome was the Global Visual Evaluation (GVE). Eight histological features were tested. The Nancy index was developed by multiple linear regression and bootstrap process to create an index that best matched the GVE. Goodness of fit was assessed by the adjusted R squared (adjusted R2). The second step was the validation of the index: 100 biopsies were scored for the Nancy index by three pathologists from different centres. Inter-reader reliability was evaluated for each reader. The relationship between the change of the Nancy index and the Geboes index was assessed to assess the responsiveness. RESULTS: After backward selection with bootstrap validation, 3/8 items were selected: ulceration (adjusted R2=0.55), acute inflammatory infiltrate (adjusted R2=0.88) and chronic inflammatory infiltrate (adjusted R2=0.79). The Nancy index is defined by a 5-level classification ranging from grade 0 (absence of significant histological disease activity) to grade 4 (severely active disease). The intraclass correlation coefficient (ICC) for the intrareader reliability was 0.88 (95% CI 0.82 to 0.92) and the index had good inter-reader reliability (ICC=0.86 (0.81 to 0.99)). The correlation between the Nancy index and the Geboes score or the GVE was very good. The index had a good responsiveness with a high correlation between changes in the Geboes score and changes in the Nancy index (0.910 (0.813 to 0.955)). CONCLUSIONS: A three descriptor histological index has been validated for use in clinical practice and clinical trials.

Foetal programming by methyl donor deficiency produces steato-hepatitis in rats exposed to high fat diet.

Non-alcoholic steatohepatitis (NASH) is a manifestation of metabolic syndrome, which emerges as a major public health problem. Deficiency in methyl donors (folate and vitamin B12) during gestation and lactation is frequent in humans and produces foetal programming effects of metabolic syndrome, with small birth weight and liver steatosis at day 21 (d21), in rat pups. We investigated the effects of fetal programming on liver of rats born from deficient mothers (iMDD) and subsequently subjected to normal diet after d21 and high fat diet (HF) after d50. We observed increased abdominal fat, ASAT/ALAT ratio and angiotensin blood level, but no histological liver abnormality in d50 iMDD rats. In contrast, d185 iMDD/HF animals had hallmarks of steato-hepatitis, with increased markers of inflammation and fibrosis (caspase1, cleaved IL-1ß, α1(I) and α2(I) collagens and α-SMA), insulin resistance (HOMA-IR and Glut 2) and expression of genes involved in stellate cell stimulation and remodelling and key genes triggering NASH pathomechanisms (transforming growth factor beta super family, angiotensin and angiotensin receptor type 1). Our data showed a foetal programming effect of MDD on liver inflammation and fibrosis, which suggests investigating whether MDD during pregnancy is a risk factor of NASH in populations subsequently exposed to HF diet.

Biobanking of Fresh-Frozen Human Adenocarcinomatous and Normal Colon Tissues: Which Parameters Influence RNA Quality?

Medical research projects become increasingly dependent on biobanked tissue of high quality because the reliability of gene expression is affected by the quality of extracted RNA. Hence, the present study aimed to determine if clinical, surgical, histological, and molecular parameters influence RNA quality of normal and tumoral frozen colonic tissues. RNA Quality Index (RQI) was evaluated on 241 adenocarcinomas and 115 matched normal frozen colon tissues collected between October 2006 and December 2012. RQI results were compared to patients' age and sex, tumor site, kind of surgery, anastomosis failure, adenocarcinoma type and grade, tumor cell percentage, necrosis extent, HIF-1α and cleaved caspase-3 immunohistochemistry, and BRAF, KRAS and microsatellites status. The RQI was significantly higher in colon cancer tissue than in matched normal tissue. RQI from left-sided colonic cancers was significantly higher than RQI from right-sided cancers. The RNA quality was not affected by ischemia and storage duration. According to histological control, 7.9% of the samples were unsatisfactory because of inadequate sampling. Biobanked tumoral tissues with RQI ≥5 had lower malignant cells to stromal cells ratio than samples with RQI <5 (p <0.05). Cellularity, necrosis extent and mucinous component did not influence RQI results. Cleaved caspase-3 and HIF-1α immunolabelling were not correlated to RQI. BRAF, KRAS and microsatellites molecular status did not influence RNA quality. Multivariate analysis revealed that the tumor location, the surgical approach (laparoscopy versus open colectomy) and the occurrence of anastomotic leakage were the only parameters influencing significantly RQI results of tumor samples. We failed to identify parameter influencing RQI of normal colon samples. These data suggest that RNA quality of colonic adenocarcinoma biospecimens is determined by clinical and surgical parameters. More attention should be paid during the biobanking procedure of right-sided colon cancer or laparoscopic colectomy specimen. Histological quality control remains essential to control sampling accuracy.

Methyl-deficient diet promotes colitis and SIRT1-mediated endoplasmic reticulum stress.

BACKGROUND: Methyl donor deficiency (MDD) aggravates experimental colitis in rats and increases endoplasmic reticulum (ER) stress through decreased sirtuin 1 (SIRT1) in neuronal cells and myocardium. ER stress plays a key role in IBD pathogenesis. AIM: We investigated whether the influence of MDD on colitis resulted from an ER stress response triggered by decreased SIRT1 expression. DESIGN: The unfolded protein response (UPR), chaperones proteins, heat shock factor protein 1 (HSF1) and SIRT1 were examined in rats with MDD and dextran sulfate sodium (DSS)-induced colitis in a Caco-2 cell model with stable expression of transcobalamin-oleosin (TO) chimera, which impairs cellular availability of vitamin B12, and in IBD. The effects of SIRT1 activation were studied both in vitro and in vivo. RESULTS: MDD aggravated DSS-induced colitis clinically, endoscopically and histologically. MDD activated ER stress pathways, with increased phosphorylate-PKR-like ER kinase, P-eiF-2α, P-IRE-1α, activating transcription factor (ATF)6, XBP1-S protein and ATF4 mRNA expression levels in rats. This was accompanied by reduced SIRT1 expression level and greater acetylation of HSF1, in relation with a dramatic decrease of chaperones (binding immunoglobulin protein (BIP), heat shock protein (HSP)27 and HSP90). Adding either vitamin B12, S-adenosylmethionine or an SIRT1 activator (SRT1720) reduced the UPR in vitro. In rats, SIRT1 activation by SRT1720 prevented colitis by reducing HSF1 acetylation and increasing expression of BIP, HSP27 and HSP90. Immunohistochemistry showed impaired expression of SIRT1 in the colonic epithelium of patients with IBD. CONCLUSIONS: SIRT1 is a master regulator of ER stress and severity of experimental colitis in case of MDD. It could deserve further interest as a therapeutic target of IBD.

Prevalence of esophageal squamous papilloma (ESP) and associated cancer in northeastern France.

BACKGROUND AND STUDY AIMS: Esophageal squamous papilloma (ESP) is a rare lesion. The aims of this study were to assess the prevalence of ESP in northeastern France and the risk of associated squamous cell carcinoma (SCC). PATIENTS AND METHODS: The charts of 78 patients who were diagnosed with ESP between January 2005 and February 2013 at three hospitals in northeastern France were reviewed. RESULTS: A total of 55 305 endoscopies were performed and 78 ESP were diagnosed (0.01 %). Patients with ESP included 44 males (56.4 %), 34 females (43.6 %); median age 50, interquartile range (IQR) 19 - 86. Median follow-up was 21 months (IQR 0 - 91 mo) and median time between first and second endoscopy was 7 months (IQR 0.5 - 74 mo). Of the total number of patients, 35 (44.9 %) had a second endoscopy. Main endoscopy indication was dyspepsia (24.4 %). Most ESP were isolated (93.6 %) and located at distal esophagus (27 cm, IQR 16 - 40 cm). Median size was 3 mm (IQR 1 - 20 mm). ESP-associated endoscopic lesions were hiatal hernia in 12 patients and esophagitis in 11 patients. Endoscopic treatment was mainly excisional biopsies (60.3 %). Human papillomavirus (HPV) was not detected in the 6 patients with available data. Low dysplasia was found in 2 ESP. During follow-up endoscopies, 2 SCC were detected in 2 different patients; the first SCC was located at the previous resection site of the ESP and the second had a different location. Prevalence of associated cancer was 1.3 %. CONCLUSION: Prevalence of ESP in northeastern France is similar to that previously reported. Endoscopic findings were also broadly the same as in previous reports. The occurrence of dysplasia and SCC should strongly encourage the endoscopist to totally remove the ESP and to start an endoscopic surveillance, given the potential risk of malignant transformation.

Detection of Dysplasia or Cancer in 3.5% of Patients With Inflammatory Bowel Disease and Colonic Strictures.

BACKGROUND & AIMS: Colonic strictures complicate inflammatory bowel disease (IBD) and often lead to surgical resection to prevent dysplasia or cancer. We assessed the frequency of dysplasia and cancer among IBD patients undergoing resection of a colorectal stricture. METHODS: We analyzed data from the Groupe d'études et thérapeutiques des affections inflammatoires du tube digestif study. This was a nationwide retrospective study of 12,013 patients with IBD in France who underwent surgery for strictures at 16 centers from August 1992 through January 2014 (293 patients for a colonic stricture, 248 patients with Crohn's disease, 51% male, median age at stricture diagnosis of 38 years). Participants had no preoperative evidence of dysplasia or cancer. We collected clinical, endoscopic, surgical, and pathology data and information on outcomes. RESULTS: When patients were diagnosed with strictures, they had IBD for a median time of 8 years (3-14). The strictures were a median length of 6 cm (4-10) and caused symptoms in 70% of patients. Of patients with Crohn's disease, 3 (1%) were found to have low-grade dysplasia, 1 (0.4%) was found to have high-grade dysplasia, and 2 (0.8%) were found to have cancer. Of patients with ulcerative colitis, 1 (2%) had low-grade dysplasia, 1 (2%) had high-grade dysplasia, and 2 (5%) had cancer. All patients with dysplasia or cancer received curative surgery, except 1 who died of colorectal cancer during the follow-up period. No active disease at time of surgery was the only factor associated with dysplasia or cancer at the stricture site (odds ratio, 4.86; 95% confidence interval, 1.11-21.27; P = .036). CONCLUSIONS: In a retrospective study of patients with IBD undergoing surgery for colonic strictures, 3.5% were found to have dysplasia or cancer. These findings can be used to guide management of patients with IBD and colonic strictures.

Photodynamic therapy relieves colitis and prevents colitis-associated carcinogenesis in mice.

BACKGROUND: Inflammatory bowel diseases are incurable illnesses of the gastrointestinal tract, which substantially enhance the risk of developing colorectal carcinogenesis. Conventional photodynamic therapy is a clinically approved therapeutic modality used in the treatment of neoplastic diseases. Recent preclinical and clinical studies have shown that photodynamic therapy with low doses of photosensitizer and/or light improves inflammatory conditions, including colitis. This study aims therefore at investigating the therapeutic potential of low-dose photodynamic therapy (LDPDT) with a liposomal formulation of meta-tetra(hydroxyphenyl)chlorin (namely Foslip) in the prevention of colitis-associated cancer in mice. METHODS: LDPDT efficacy was evaluated by endoscopic, macroscopic, and histological analysis. Myeloperoxidase levels were quantified by enzyme linked immunosorbent assay and cytokines expression by quantitative RT-PCR analysis. The integrity of the intestinal barrier was evaluated by immunostaining, and bacterial composition of the fecal microbiota was determined by 454 pyrosequencing of V3-V4 region of bacterial 16S rRNA genes. RESULTS: LDPDT reduced intestinal tumor growth by decreasing the expression of a wide range of inflammatory mediators and by lowering neutrophil influx. LDPDT treatment prevents onset of a dysbiotic microbiota in the colitis-associated cancer model. CONCLUSIONS: LDPDT with Foslip could be considered as a novel treatment modality to prevent colorectal carcinogenesis in patients with inflammatory bowel disease.

Comparing histological activity indexes in UC.

BACKGROUND: Assessment of disease activity in UC is important for designing an optimal therapeutic strategy. No single histology score is considered optimum. The aim of this study was to compare intraobserver reproducibility and the interobserver agreement of available histological UC activity indexes. METHODS: One hundred and two biopsy specimens (collected between 2003 and 2014) were scored blindly by three pathologists by determining Geboes, Riley, Gramlich and Gupta indexes and global visual evaluation (GVE). Intraobserver reproducibility and interobserver agreements for index and items of index were studied by intraclass correlation coefficient for quantitative parameter and by κ values and Krippendorff index for qualitative parameters. Relationship between indexes was studied by computation of Pearson's and Spearman's correlation coefficients. RESULTS: Geboes, Riley, Gramlich and Gupta indexes and GVE showed good intraobserver reproducibility and a good interobserver agreement. Histological items that showed the best interobserver agreement were 'erosion/ulceration or surface epithelial integrity' and 'acute inflammatory cells infiltrate/neutrophils in lamina propria'. The five scores were strongly correlated. CONCLUSIONS: Correlation between indexes is strong. Intraobserver reproducibility and interobserver agreement for all indexes is very good. Histological items that showed the best interobserver agreement are 'erosion/ulceration' and 'acute inflammatory cells infiltrate/neutrophils in lamina propria'.

Histologic features predicting postoperative Crohn's disease recurrence.

Recurrence of Crohn's disease (CD) after ileal or colonic resection is common. Many studies have tried to identify predictors of postoperative recurrence (POR) in CD. A wide range of histologic features have been identified, but for most of them, the literature provided conflicting data. In last years, several studies have suggested that histologic findings including inflammatory changes within the enteric nervous system of the resection margin may be associated with CD recurrence. Herein, after briefly summarizing pathophysiology of POR, we review all histological features that have been studied so far: granulomas, histologic appearance at the margin of resection, plexitis, lymphatic vessel density in proximal margin of resection, and morphological analysis of Paneth cells. Granulomas and chronic inflammation at the margin of resection do not seem to predict POR in CD. Active disease at the margin of resection, plexitis, lymphatic vessels density, morphological analysis of Paneth cells may predict POR. Most of these histological features await replication in independent studies. Available evidence indicates that histological findings may be taken into account when developing strategies aimed at preventing postoperative CD recurrence.

Microscopic features of colorectal neoplasia in inflammatory bowel diseases.

The risk of developing dysplasia leading to colorectal cancer (CRC) is increased in both ulcerative colitis and Crohn's disease. The prognosis of CRC may be poorer in patients with inflammatory bowel disease (IBD) than in those without IBD. Most CRCs, in general, develop from a dysplastic precursor lesion. The interpretation by the pathologist of the biopsy will guide decision making in clinical practice: colonoscopic surveillance or surgical management. This review summarizes features of dysplasia (or intraepithelial neoplasia) with macroscopic and microscopic characteristics. From an endoscopic (gross) point of view, dysplasia may be classified as flat or elevated (raised); from a histological point of view, dysplasia is separated into 3 distinct categories: negative for dysplasia, indefinite for dysplasia, and positive for dysplasia with low- or high-grade dysplasia. The morphologic criteria for dysplasia are based on a combination of cytologic (nuclear and cytoplasmic) and architectural aberrations of the crypt epithelium. Immunohistochemical and molecular markers for dysplasia are reviewed and may help with dysplasia diagnosis, although diagnosis is essentially based on morphological criteria. The clinical, epidemiologic, and pathologic characteristics of IBD-related cancers are, in many aspects, different from those that occur sporadically in the general population. Herein, we summarize macroscopic and microscopic features of IBD-related colorectal carcinoma.