Simplified Histologic Mucosal Healing Scheme (SHMHS) for inflammatory bowel disease: a nationwide multicenter study of performance and applicability.

BACKGROUND: Assessment of mucosal healing is important for the management of patients with inflammatory bowel disease (IBD), but endoscopy can miss microscopic disease areas that may relapse. Histological assessment is informative, but no single scoring system is widely adopted. We previously proposed an eight-item histological scheme for the easy, fast reporting of disease activity in the intestine. The aim of the present study was to evaluate the performance of our Simplified Histologic Mucosal Healing Scheme (SHMHS). METHODS: Between April and May 2021 pathologists and gastroenterologists in Italy were invited to contribute to this multicenter study by providing data on single endoscopic-histological examinations for their IBD patients undergoing treatment. Disease activity was expressed using SHMHS (maximum score, 8) and either Simple Endoscopic Score for Crohn's Disease (categorized into grades 0-3) or Mayo Endoscopic Subscore (range 0-3). RESULTS: Thirty hospitals provided data on 597 patients (291 Crohn's disease; 306 ulcerative colitis). The mean SHMHS score was 2.96 (SD = 2.42) and 66.8% of cases had active disease (score ≥ 2). The mean endoscopic score was 1.23 (SD = 1.05), with 67.8% having active disease (score ≥ 1). Histologic and endoscopic scores correlated (Spearman's ρ = 0.76), and scores for individual SHMHS items associated directly with endoscopic scores (chi-square p < 0.001, all comparisons). Between IBD types, scores for SHMHS items reflected differences in presentation, with cryptitis more common and erosions/ulcerations less common in Crohn's disease, and the distal colon more affected in ulcerative colitis. CONCLUSIONS: SHMHS captures the main histological features of IBD. Routine adoption may simplify pathologist workload while ensuring accurate reporting for clinical decision making.

Diagnostic interobserver variability in Crohn's disease- and ulcerative colitis-associated dysplasia: a multicenter digital survey from the IG-IBD Pathologists Group.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis, two forms of inflammatory bowel disease (IBD), are chronic and relapsing conditions of the gastrointestinal tract both characterized by long lasting chronic inflammation and increased risk of dysplasia and colorectal cancer (CRC). The aim of our study was to evaluate the interobserver agreement about IBD-associated dysplasia among pathologists belonging to the Italian Group for Inflammatory Bowel Diseases (IG-IBD P). METHODS: The present multicenter survey was performed using telepathology, supported by an open source E-learning platform. Biopsy specimens from 30 colonoscopies and from 20 patients were included. The glass slides of any case, including clinical and endoscopic data, were digitalized and uploaded on the E-learning platform. All the digital slides were grouped in 54 diagnostic "blocks". Blinded histopathological evaluation on all the digital slides was performed by 20 gastrointestinal pathologists. Closed-ended questions about (1) the occurrence of IBD; (2) the classification of IBD (as UC or CD); (3) the presence of active versus quiescent disease; (4) the presence of dysplasia; (5) the possible association of dysplasia with the sites of disease (dysplasia-associated lesion or mass-DALM vs adenoma-like mass-ALM); (6) the grading of dysplasia according to the ECCO guidelines (negative, indefinite, low grade, high grade categories) and (7) the presence of associated serrated features, were proposed in each case. Inter-observer agreement was evaluated by mean agreement percentage and kappa statistic, when suitable. RESULTS: The diagnosis of IBD was confirmed in 19 of 20 patients, 17 of 19 being classified as UC, 2 as CD. The mean interobserver agreement percentages about (1) the evidence of IBD, (2) the presence of either UC or CD and (3) the activity grading resulted to be 80%, 69% and 86%, respectively. Dysplasia was detected in 8/20 patients, with moderate agreement between pathologists (mean 72%, k 0.48). Particularly, low grade dysplasia was found in 13 biopsies (combined k 0.38), whereas high grade dysplasia in 8 (combined k 0.47). When the endoscopic and histopathological data were combined, features consistent with DALM were found in 6 of 20 patients with low grade dysplasia and those consistent with ALM in 2 patients with low grade dysplasia in a single biopsy (mean agreement: 86%). An associated serrated pattern was discovered in 4 patients (7 biopsies). CONCLUSIONS: Our study showed moderate interobserver agreement about the histopathological detection and classification of IBD-associated dysplasia. Further efforts should be undertaken to integrate the histopathological data with both the ancillary tests and molecular investigations.

Abnormal gut motility in inflammatory bowel disease: an update.

BACKGROUND: There is substantial evidence linking disturbed gastrointestinal motility to inflammation. Thus, it is not surprising that abnormalities of gastrointestinal motility play a role in inflammatory bowel disease (IBD), affecting patient outcomes. We performed a review of the literature to investigate the relationship between abnormal gut motility and IBD. METHODS: With an extensive literature search, we retrieved the pertinent articles linking disturbed gut motility to IBD in various anatomical districts. RESULTS: The evidence in the literature suggests that abnormal gastrointestinal motility plays a role in the clinical setting of IBD and may confuse the clinical picture. CONCLUSIONS: Abnormal gut motility may be important in the clinical setting of IBD. However, additional data obtained with modern techniques (e.g., magnetic resonance imaging) are needed to individuate in a more precise manner gastrointestinal motor dysfunctions, to understand the nature of clinical manifestations and properly tailor the treatment of patients.

Correction to: Inflammatory bowel disease (IBD) position statement of the Italian Society of Colorectal Surgery (SICCR): general principles of IBD management.

The affiliation of the author Silvio Danese has been incorrectly published in the original publication. The complete correct affiliation should read as follows.

Inflammatory bowel disease (IBD) position statement of the Italian Society of Colorectal Surgery (SICCR): general principles of IBD management.

The Italian Society of Colorectal Surgery (SICCR) promoted the project reported here, which consists of a Position Statement of Italian colorectal surgeons to address the surgical aspects of inflammatory bowel disease management. Members of the society were invited to express their opinions on several items proposed by the writing committee, based on evidence available in the literature. The results are presented, focusing on relevant points. The present paper is not an alternative to available guidelines; rather, it offers a snapshot of the attitudes of SICCR surgeons about the general principles of surgical treatment of inflammatory bowel disease. The committee was able to identify some points of major disagreement and suggested strategies to improve quality of available data and acceptance of guidelines.

Optimal processing of ESD specimens to avoid pathological artifacts.

BACKGROUND: En bloc endoscopic submucosal dissection (ESD) has been recently introduced as a treatment for precancerous/neoplastic gastrointestinal conditions. The aim of the present study was histological assessment of en bloc ESD specimens. METHODS: Fifty-three ESD specimens were positioned over a cellulose acetate support (40 specimens; 12 from the upper gastrointestinal tract and 28 from the lower gastrointestinal tract) or pinned with nails on polystyrene or cork (13 specimens; 7 from the upper gastrointestinal tract and 6 from the lower gastrointestinal tract). We cut consecutive 2 mm-thick sections stained with hematoxylin and eosin. From the first and the last sections, we obtained a second slide, after a 180° rotation and re-embedding. The quality of ESD samples was scored as inadequate, suboptimal and adequate, based on the amount of crushing, shearing and stretching artifacts that were scored from 0 (absent) to 2 (diffuse or maximum). From the sum of these we obtained a global artifact score (GAS). RESULTS: Removed lesions were: adenocarcinoma (5 cases), neuroendocrine tumor (NET) G1 (1 case), premalignant conditions, including adenomatous polyps (41 cases) and hyperplastic lesions (6 cases). A positive deep surgical margin was found in 8/53 cases (15%): high- and low-grade dysplastic glands were detected in 5 cases, low-grade adenocarcinoma in 2, and NET cells in 1. Dysplastic glands were detected in the lateral surgical margins of 12 ESD specimens (23%). Among the ESD specimens positioned on the cellulose acetate support, apart from the modifications due to electrocoagulation, 2 (5%) showed shearing modifications. In the group of ESD specimens fixed with nails, 5 (38%) showed shearing, 10 (77%) crushing artifacts, 11 (85%) stretching and 11 (85%) multiple holes caused by the nails. On the basis of these data all histological specimens from ESD on cellulose acetate were adequate (GAS 0-1).However, in the group of ESD fixed with nails, 1 was adequate (GAS 0), 11 suboptimal (GAS 2-5) and 1 inadequate (GAS 6). CONCLUSIONS: Specific devices including cellulose support and adequate sampling blocks can be helpful to perform accurate histological assessment of ESD specimens after en bloc ESD for precancerous/neoplastic gastrointestinal lesions, with complete analysis of the status of the margins and the entirely en bloc evaluation of the lesion.

Symptomatic sensorineural hearing loss in patients with ulcerative colitis.

BACKGROUND: Sensorineural hearing loss has been reported as an extraintestinal manifestation of inflammatory bowel disease, especially in adult patients with ulcerative colitis. However, to date only a few series have been reported in the literature, and none from Italy. The aim of the present investigation was to assess the prevalence of symptomatic sensorineural hearing loss in Italian patients with ulcerative colitis. METHODS: We retrospectively assessed the charts of all patients with ulcerative colitis who underwent otolaryngologic investigation in a 10-year period. RESULTS: Complete charts of 57 patients were available for the observation period. Reasons for head and neck investigation were transient, mild hearing loss and sporadic vertigo. Clinical and instrumental head and neck examination was unremarkable in all but one woman who complained of mild hearing loss without vertigo or tinnitus, in whom sensorineural hearing loss was diagnosed. CONCLUSIONS: In our series, sensorineural hearing loss was found in less than 2 % of adult patients with ulcerative colitis evaluated in a department of otolaryngology. Systematic evaluation for this extraintestinal manifestation should not be carried out unless hearing loss is present.

Experience with a new device for pathological assessment of colonic endoscopic submucosal dissection.

Endoscopic submucosal dissection (ESD) is gaining popularity worldwide in the treatment of neoplastic lesions of the gastrointestinal tract. However, the experience in Western countries is quite limited and restricted to large or academic centers. Besides, this approach requires an optimal pathological assessment. The aim of this study was to report our experience with colonic ESD using a new device that allows complete handling of the resected specimens and especially of lateral margins, for pathological analysis. In a 1-year period, 14 patients (6 men, 8 women, age range 50-82 years) underwent colonic ESD in a non-academic hospital. The endoscopic procedure was carried out successfully en bloc in more than 90 % of cases. Perforation requiring surgery occurred in one patient (7 %). Pathological assessment with the new device allowed entire and complete examination of both the deep and lateral margins of the excised specimens. Colonic ESD is a viable option for non-surgical treatment of large bowel lesions even in relatively small centers and in non-academic settings. The new device allows good handling of the specimens, and it seems to be useful for the entire examination of the resection margins.

Hyperhomocysteinemia in patients with Crohn's disease.

BACKGROUND: Thromboembolic complications have been reported in patients with Crohn's disease. Among the contributing factors, hyperhomocysteinemia has been described, although controversial data exist. The aim of our study was to assess the incidence of hyperhomocysteinemia in a nonselected group of patients with Crohn's disease and to determine whether it might represent a risk marker for thrombosis in such patients. METHODS: Fifty consecutive patients were recruited, and clinical and laboratory variables were compared between those without and those with hyperhomocysteinemia. In the latter, gene mutations in N5-N10-methyltetrahydrofolate reductase were searched for, and clinical and laboratory variables were related to hyperhomocysteinemia. The presence/absence of thrombotic episodes in both groups was determined. RESULTS: Both groups had similar clinically active disease, with higher C-reactive protein values found in those with hyperhomocysteinemia. Hyperhomocysteinemia was found in 46 % of patients. Of these, 74 % had moderate, 13 % intermediate, and 13 % severe increase in serum homocysteine levels. No relationship was found between homocysteine levels, and age, vitamin B12 levels, folic acid levels, Crohn's Disease Activity Index score, and CRP values. Gene mutations were found in 5 (22 %) patients, 2 homozygotes and 3 heterozygotes. None of the patients with or without hyperhomocysteinemia had episodes of venous or arterial thrombosis, or stroke. CONCLUSIONS: Hyperhomocysteinemia is frequent in patients with Crohn's disease, and it could be a cofactor for the pathogenesis of thrombotic episodes.

A unicentric cross-sectional observational study on chronic intestinal inflammation in total colonic aganglionosis: beware of an underestimated condition.

BACKGROUND: Inflammatory Bowel Diseases (IBD) are known to occur in association with Hirschsprung disease (HSCR). Most of cases are represented by Crohn Disease (CD) occurring in patients with Total Colonic Aganglionosis (TCSA) with an estimated prevalence of around 2%. Based on these considerations and on a number of provisional data belonging to our Center for Digestive Diseases, we developed a unicentric cross-sectional observational study aimed at describing phenotype, genotype, pathology and metagenomics of all patients with TCSA and Crohn-like lesions. RESULTS: Out of a series of 62 eligible TCSA patients, 48 fulfilled inclusion criteria and were enrolled in the study. Ten patients did not complete the study due to non-compliance or withdrawal of consent and were subsequently dropped out. A total of 38 patients completed the study. All patients were tested for chronic intestinal inflammation by a combination of fecal calprotectine (FC) or occult fecal blood (OFB) and underwent fecal metagenomics. Nineteen (50%) tested positive for FC, OFB, or both and subsequently underwent retrograde ileoscopy. Fourteen patients (36.8%) presented Crohn-like lesions, occurring after a median of 11.5 years after surgery (range 8 months - 21.5 years). No statistically significant differences regarding demographic, phenotype and genotype were observed comparing patients with and without lesions, except for need for blood transfusion that was more frequent in those with lesions. Faecal microbiome of patients with lesions (not that of caregivers) was less biodiverse and characterized by a reduction of Bacteroidetes, and an overabundance of Proteobacteria. FC tested negative in 3/14 patients with lesions (21%). CONCLUSIONS: Our study demonstrated an impressive 10-folds higher incidence of chronic inflammation in TCSA. Up to 50% of patients may develop IBD-like lesions postoperatively. Nonetheless, we failed in identifying specific risk factors to be used to implement prevention strategies. Based on the results of our study, we suggest screening all TCSA patients with retrograde ileoscopy regardless of FC/OFB values. The frequency of endoscopic assessments and the role of FC/OFB screening in prompting endoscopy is yet to be determined.

Beyond hematoxylin and eosin: the importance of immunohistochemical techniques for evaluating surgically resected constipated patients.

Chronic constipation requiring surgical ablation for intractability is often a frustrating condition from the pathologist's point of view. In fact, limiting the histological examination to only hematoxylin-eosin staining usually yields only the information that there are no abnormalities. By employing some simple and widely available immunohistochemical methods, discussed in this review, it is possible to gather data that may help in explaining the pathophysiological basis of constipation in these patients.

Painful constipation: a neglected entity?

Functional chronic constipation is a common symptom in daily clinical practice. Although the definition of constipation may be variable, there is usually agreement that (at least for research purposes) the definition given by the Rome Committee are useful. However, some blind spots or hidden angles remain, even in the more thorough classifications; among these, there is painful constipation, a poorly defined yet clinically encountered entity. The present article reviews the current knowledge about painful constipation, trying to put together the scarce data available, and to frame it in the more general context of chronic constipation.

Comparison of the Marsh-Oberhuber classification with a new grading system in identifying patients with latent celiac disease.

AIM: The diagnosis of celiac disease (CD) is still mainly based on pathological description. However, these descriptions are often unable to identify latent CD. The aim of this study was to evaluate whether the Marsh-Oberhuber classification and a recently proposed classification may help to identify patients with latent CD. METHODS: Biopsy samples from twelve patients with latent CD (age range 3-32 years) defined as having normal duodenal mucosa when ingesting a free diet, and subsequently developing severe villous atrophy, were retrospectively reviewed in blind according to the Marsh-Oberhuber classification and the new grading system. RESULTS: In 67% of patients the Marsh-Oberhuber and the new classification could have yielded a diagnosis of CD soon after the first biopsy (3a-3c score when reviewed according to this classification, and B2 score when reviewed according to the new grading system), thereby avoiding further (up to two more in four cases) unnecessary endoscopic procedures. CONCLUSION: Both the Marsh-Oberhuber and the new classification allow to discriminate latent CD from patients with normal mucosa. Thus, these classifications may help in identifying and treating patients at an early stage.

Eosinophilic esophagitis: an Italian experience.

BACKGROUND: Eosinophilic esophagitis is an esophageal disorder characterized by esophageal and/or upper gastrointestinal tract symptoms, and by dense esophageal eosinophilia associated with a normal gastric and duodenal mucosa. Prevalently reported in children, eosinophilic esophagitis has recently been reported with increased frequency also in adults. AIMS: The purpose of this study was to report our experience with eosinophilic esophagitis in Italy, since there are only very few series of such patients in our country. PATIENTS AND METHODS: We retrospectively reviewed the histological data of consecutive patients with a diagnosis of esophagitis or reflux disease in the period September 2004-September 2008. Eosinophils were counted where they appeared most numerous in the biopsy, with a cutoff > 15 eosinophils in more than one high-power field as diagnostic of eosinophilic esophagitis. Patients were excluded if gastric or duodenal biopsies showed a prominent eosinophilic infiltrate. RESULTS: Twenty two patients (14 adults, 8 children, age range 2-59 years) were identified according to the above criteria. The average eosinophil count was 86/ high-power field (range 31-150), associated with other pathologic features (eosinophilic microabscesses eosinophil degranulation, basal zone hyperplasia, papillary elongation). The main clinical complaints were dysphagia, food impaction, and heartburn, and endoscopic findings consisted of mucosal thickening and inelasticity, longitudinal shearing, rings, and white specks, without difference between adults and children for both clinical and endoscopic variables. CONCLUSIONS: Eosinophilic esophagitis is not rare in Italy, and displays clinical, endoscopic, and pathologic features similar to those described in other countries.

Colonoscopic findings in coeliac disease on a gluten-free diet.

BACKGROUND: to date, there are few data on colonoscopic findings in patients with celiac disease, and most of these obtained in patients with iron deficiency anaemia. AIMS: we assessed colonoscopic findings in unselected patients with coeliac disease, since there are no studies available also considering morphological aspects, and there is literature suggestion of increased prevalence of colorectal tumours. MATERIAL AND METHODS: colonoscopies with multiple biopsies were retrospectively analyzed in 42 coeliac disease patients on gluten-free diet above age 40; 16 had clinical or laboratory features of iron deficiency anaemia. Mucosal biopsies were evaluated for the presence of intraepithelial lymphocytes and of mucosal eosinophils, in addition to conventional histologic assessment, and compared with those obtained in 15 controls. RESULTS: macroscopic abnormalities (polyps, diverticula, inflammatory changes) were found in 26% of patients. Microscopic abnormalities (lymphocytic colitis, melanosis coli, rectal histiocytosis) were found in 36% of patients. None of these findings was found in controls. Coeliac disease patients had significantly higher eosinophil score than controls in the right colon, whereas this was not significantly different between groups in the left colon. CONCLUSIONS: colonoscopic findings in coeliac disease on gluten-free diet may reveal significant findings, even in patients without iron deficiency anaemia. There is the need of further studies in larger cohorts of patients to establish whether colonoscopy in these patients may be clinically useful.

Histopathology of Celiac Disease. Position Statements of the Italian Group of Gastrointestinal Pathologists (GIPAD-SIAPEC).

Celiac Disease (CeD) is an immune-mediated inflammatory disorder of the small intestine, affecting genetically susceptible individuals when exposed to gluten. Small intestinal biopsy interpretation has been the "gold standard" for celiac disease (CeD) for over 50 years. Despite today's availability of sensitive and specific serological tests, the histopathological features from mucosal biopsy play a key role in diagnosing when CeD is suspected. Such a diagnostic approach requires a multidisciplinary team to optimize both tissue sampling and interpretation via the interaction between the pathologist and the gastroenterologist. Pathologists of the Italian Group of Gastrointestinal Pathology (GIPAD-SIAPEC), together with a member (TR) of the Italian Society of Technicians (AITIC) and an expert gastroenterologist (CC), provide position statements as a practical tool for reading and interpreting the report. Moreover, a position statement was formulated about the recently described condition known as Non-Celiac Gluten Sensitivity (NCGS). Within such a diagnostic setting, both the architectural abnormalities of the duodenal mucosa, namely glandular hyperplasia, and villous atrophy and the number of intraepithelial T-lymphocytes should be well highlighted. Ancillary tests such as anti-CD3 stain are useful for an accurate count of the intraepithelial T lymphocytes when CeD or NCGS is suspected. Moreover, anti-CD3 and anti-CD8 stains are recommended in patients not responding to the gluten-free diet (GFD) to confirm a diagnosis of Refractory Celiac Disease (RCeD). Diagnostic clues about the differential diagnosis of both CeD and RCeD have also been rendered.