New entity of adult ultra-short coeliac disease: the first international cohort and case-control study.

BACKGROUND: Ultra-short coeliac disease (USCD) is defined as villous atrophy only present in the duodenal bulb (D1) with concurrent positive coeliac serology. We present the first, multicentre, international study of patients with USCD. METHODS: Patients with USCD were identified from 10 tertiary hospitals (6 from Europe, 2 from Asia, 1 from North America and 1 from Australasia) and compared with age-matched and sex-matched patients with conventional coeliac disease. FINDINGS: Patients with USCD (n=137, median age 27 years, IQR 21-43 years; 73% female) were younger than those with conventional coeliac disease (27 vs 38 years, respectively, p<0.001). Immunoglobulin A-tissue transglutaminase (IgA-tTG) titres at index gastroscopy were lower in patients with USCD versus conventional coeliac disease (1.8×upper limit of normal (ULN) (IQR 1.1-5.9) vs 12.6×ULN (IQR 3.3-18.3), p<0.001).Patients with USCD had the same number of symptoms overall (median 3 (IQR 2-4) vs 3 (IQR 1-4), p=0.875). Patients with USCD experienced less iron deficiency (41.8% vs 22.4%, p=0.006).Both USCD and conventional coeliac disease had the same intraepithelial lymphocytes immunophenotype staining pattern; positive for CD3 and CD8, but not CD4.At follow-up having commenced a gluten-free diet (GFD) (median of 1181 days IQR: 440-2160 days) both USCD and the age-matched and sex-matched controls experienced a similar reduction in IgA-tTG titres (0.5 ULN (IQR 0.2-1.4) vs 0.7 ULN (IQR 0.2-2.6), p=0.312). 95.7% of patients with USCD reported a clinical improvement in their symptoms. INTERPRETATION: Patients with USCD are younger, have a similar symptomatic burden and benefit from a GFD. This study endorses the recommendation of D1 sampling as part of the endoscopic coeliac disease diagnostic workup.

Not all enteropathies are coeliac disease! Report of an infant with microvillus inclusion disease.

Primary enteropathies of infancy comprise of epithelial defects including microvillus inclusion disease, tufting enteropathy, and enteroendocrine cell dysgenesis and autoimmune enteropathies. The diseases in this group cause severe chronic (>2-3 weeks) diarrhoea starting in the first weeks of life and resulting in failure to thrive in the infant. Duodenal biopsies show moderate villous shortening together with crypt hyperplasia which are the main features causing resemblance to coeliac disease. We, hereby, report a term-born male infant of consanguineous parents. His two siblings died during infancy. He developed watery, urine-like diarrhea on the 3rd day of his life. On the postnatal 6th day he weighed 2750 grams, became dehydrated and had metabolic acidosis. Upper GI endoscopy performed on the postnatal 20th day appeared normal. Light microscopic examination of the duodenal biopsy showed moderate villous blunting, with mildly increased inflammatory cells in the lamina propria or and intraepithelial lymphocytosis. Enterocytes at the villous tips showed an irregular vacuolated appearance in the apical cytoplasm with patchy absence of the brush border demonstared by PAS and CD10. Electron microscopy revealed intracytoplasmic inclusions that were lined by intact microvilli in the apical cytoplasm of enterocytes. As he was dependent on TPN and aggressive intravenous fluid replacement he was hospitalized throughout his life. He died when he was 3 years and 4 months old. Paediatric coeliac disease is in the differential diagnosis of primary enteropathies of childhood. The differentiation lies on duodenal biopsy interpretation together with genetic analysis to detect the underlying genetic defect in childhood enteropathies.

Patterns and Grading of Gastrointestinal Graft-Versus-Host Disease: A Clinicopathologic Correlation Study.

BACKGROUND: The present study investigated gastrointestinal involvement patterns of acute graft-versus-host disease and assessed the correlation of pathologic severity with clinical grading. METHODS: Pathology reports of gastrointestinal (GI) endoscopic biopsies taken from 164 post-hematopoietic stem cell transplant patients with at least 1 endoscopic gastrointestinal biopsy diagnosed as "consistent with acute graft-versus-host disease" between 2005 and 2019 were retrieved from the automated hospital database. Endoscopic, pathologic and clinical gradings were performed using Freiburg criteria, Lerner and modified Seattle-Glucksberg grading systems, respectively. RESULTS: The majority of the patients (n = 140, 85.4%) were investigated with more than one biopsy from various gastrointestinal sites with a total of 479 biopsies: 44 (9.2%) esophagus, 90 (18.8%) stomach, 91 (19.0%) duodenum, 20 (4.2%) terminal ileum, 32 (6.7%) right colon, 87 (18.2%) left colon and, 115 (23.9%) rectum. Overall, lower gastrointestinal (n = 118/126, 93.6%) and upper gastrointestinal (n = 91/97, 93.8%) involvements were similar (P = .3). While the most severely affected site was duodenum (P = .021) in upper gastrointestinal, pathologic grades were similar in lower gastrointestinal sites, though more severe than upper gastrointestinal (P = .003). Pathologic grading had a low positive correlation with both clinical (r = 0.308, P = .001) and endoscopic grading (coefficient: 0.261, P = .003). CONCLUSION: Considering the similar graft-versus-host disease frequency of upper and lower gastrointestinal tract, distal colon evaluation with rectosigmoidoscopy seems to be a practical approach in patients with suspected gastrointestinal graft-versus-host disease. As it was positively correlated with both endoscopic and clinical grade, pathologic grading should be performed in these patients to assess gastrointestinal involvement patterns.

Gluten Induces Subtle Histological Changes in Duodenal Mucosa of Patients with Non-Coeliac Gluten Sensitivity: A Multicentre Study.

Background: Histological changes induced by gluten in the duodenal mucosa of patients with non-coeliac gluten sensitivity (NCGS) are poorly defined. Objectives: To evaluate the structural and inflammatory features of NCGS compared to controls and coeliac disease (CeD) with milder enteropathy (Marsh I-II). Methods: Well-oriented biopsies of 262 control cases with normal gastroscopy and histologic findings, 261 CeD, and 175 NCGS biopsies from 9 contributing countries were examined. Villus height (VH, in µm), crypt depth (CrD, in µm), villus-to-crypt ratios (VCR), IELs (intraepithelial lymphocytes/100 enterocytes), and other relevant histological, serologic, and demographic parameters were quantified. Results: The median VH in NCGS was significantly shorter (600, IQR: 400−705) than controls (900, IQR: 667−1112) (p < 0.001). NCGS patients with Marsh I-II had similar VH and VCR to CeD [465 µm (IQR: 390−620) vs. 427 µm (IQR: 348−569, p = 0·176)]. The VCR in NCGS with Marsh 0 was lower than controls (p < 0.001). The median IEL in NCGS with Marsh 0 was higher than controls (23.0 vs. 13.7, p < 0.001). To distinguish Marsh 0 NCGS from controls, an IEL cut-off of 14 showed 79% sensitivity and 55% specificity. IEL densities in Marsh I-II NCGS and CeD groups were similar. Conclusion: NCGS duodenal mucosa exhibits distinctive changes consistent with an intestinal response to luminal antigens, even at the Marsh 0 stage of villus architecture.

Histopathology of non-coeliac gluten sensitivity.

Diagnosis of non-coeliac gluten sensitivity (NCGS) remains still problematic due to the subjectiveness and lack of a specific biomarker. We aimed to compare NCGS duodenal mucosae with healthy individuals and Marsh type 1 coeliac disease (CD), to determine whether NCGS has characteristic histological features. A total of 44 healthy controls, 42 NCGS, and 44 type 1 CD patients were selected according to clinical, serological, and laboratory data. Duodenal biopsies were evaluated on H&E, CD, and CD117 for villus/crypt ratio, IEL counts/100 enterocytes, uneven distribution pattern with clusters of IELs in the villous epithelium, linear distribution of T lymphocytes in the basal lamina propria, and eosinophils and mast cells in the lamina propria. IEL counts were within normal range in controls (13 ± 7.65), normal or mildly increased in NCGS (24.7 ± 10.46), and increased in CD (58.79 ± 14.97) on CD3. The presence of uneven distribution pattern of IELs in the villous epithelium was significantly higher in NCGS (90.5%), in contrast to controls (27.3%) and CD (34.1%). The presence of linear distribution of T lymphocytes in the basal lamina propria (68.2%, 76.2%, 78.1%), eosinophil counts (6.85 ± 3.42, 6.21 ± 2.8, 7.62 ± 3.89), and mast cell counts (25.1 ± 5.1, 26 ± 2.9, 30.3 ± 4.4) was similar in controls, NCGS, and CD, respectively. In conclusion, duodenal mucosae in NCGS are characterized by preserved villous architecture, normal or mildly increased IELs with clusters, and eosinophils and mast cells within normal limits. We believe uneven distribution of IELs with clusters in the villous epithelium can be used as a supportive histopathological tool for NCGS in the right clinical setting.

Membranous Nephropathy with Lambda Light Chain Restriction: A Rare Form with Serum Negative and Tissue Positive PLA2R Ab.

Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in adults. Subepithelial polyclonal immunoglobulin deposits and >70% M-type phospholipase A2 receptor antibody positivity are typical findings in idiopathic MN. A 58-year-old female patient was admitted with clinical presentation of nephrotic syndrome. Autoimmune diseases, infections, and malignancies were ruled out after clinical and laboratory evaluations. Diagnostic work-up revealed serum PLA2R antibody negativity and diffuse thickening of glomerular capillary wall on biopsy, while glomerular capillary wall IgG, C3, and Lambda monotypic light chain deposition and PLA2R1 positivity were detected by immunofluorescence and immunohistochemical examination, respectively. Following prednisolone treatment, creatinine and proteinuria were markedly regressed. The MN cases with a light chain deposits are rare and experience regarding their treatment are insufficient.

Accuracy of a no-biopsy approach for the diagnosis of coeliac disease across different adult cohorts.

OBJECTIVE: We aimed to determine the predictive capacity and diagnostic yield of a 10-fold increase in serum IgA antitissue transglutaminase (tTG) antibody levels for detecting small intestinal injury diagnostic of coeliac disease (CD) in adult patients. DESIGN: The study comprised three adult cohorts. Cohort 1: 740 patients assessed in the specialist CD clinic at a UK centre; cohort 2: 532 patients with low suspicion for CD referred for upper GI endoscopy at a UK centre; cohort 3: 145 patients with raised tTG titres from multiple international sites. Marsh 3 histology was used as a reference standard against which we determined the performance characteristics of an IgA tTG titre of ≥10×ULN for a diagnosis of CD. RESULTS: Cohort 1: the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 54.0%, 90.0%, 98.7% and 12.5%, respectively. Cohort 2: the sensitivity, specificity, PPV and NPV for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 50.0%, 100.0%, 100.0% and 98.3%, respectively. Cohort 3: the sensitivity, specificity, PPV and NPV for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 30.0%, 83.0%, 95.2% and 9.5%, respectively. CONCLUSION: Our results show that IgA tTG titres of ≥10×ULN have a strong predictive value at identifying adults with intestinal changes diagnostic of CD. This study supports the use of a no-biopsy approach for the diagnosis of adult CD.

Gastric and small intestinal traditional serrated adenomas: a detailed morphologic and immunohistochemical analysis.

BACKGROUND/AIMS: Traditional serrated adenomas (TSAs), despite their low incidence in colorectum, may originate in other parts of the gastrointestinal (GI) tract, including stomach and small intestine. Malignant transformation for upper GI TSAs has recently been reported in the literature. Here, we present a series of gastric and small intestinal TSAs with the aim to characterize their morphologic and immunophenotypic features as well as their neoplastic potential in a compartmental manner using digitalized images. MATERIALS AND METHODS: The study comprised 12 GI polyps with TSA features-5 gastric and 7 small intestinal. The extent of the characteristic features of TSA, including eosinophilic cells, ectopic crypt foci (ECF), slit-like serration, foveolar epithelium, goblet cells, together with dysplastic-carcinomatous foci were assessed on digitalized H-E images and were used as reference for immunohistochemical analysis. RESULTS: All polyps in the cohort contained eosinophilic cells as the most extensive morphologic feature followed by ECF and slit-like serration in decreasing order. Serrated dysplasia was more common in gastric polyps, which more frequently showed neoplastic progression compared with the intestinal ones. CK20 was the most widely expressed marker with a preference to eosinophilic cells while ECFs were mostly negative. Ki67 showed the opposite pattern of CK20. MUC6 and MUC2 were selectively expressed in the basal zone and goblet cells, respectively. CONCLUSION: Our results showed that the presence of eosinophilic cells with pencillate nuclei commonly accompanied by ECF and slit-like serration are the defining features of gastric and small intestinal TSAs. They frequently harbor neoplastic foci, particularly in gastric location where serrated dysplasia seems to be more common.

Duodenal bulb biopsy in the diagnostic work-up of coeliac disease.

Coeliac disease (CD) is an autoimmune enteropathy which can present with patchy mucosal lesions. The aim of the present study is to investigate the significance of duodenal bulb biopsy in the diagnostic work-up of CD in both pediatric and adult patients, and to highlight the key points for pathologists. D1 (duodenal bulb) and D2 (distal duodenum) biopsies of 153 newly diagnosed serology-positive CD patients were evaluated for villous/crypt ratio and intraepithelial lymphocyte (IEL) counts on CD3-stained slides and were classified according to Marsh. Mucosal pathology was patchy in 15% (13% only D1 and 2% only D2) of patients, and 85% of patients had diffuse mucosal pathology involving both D1 and D2 biopsies which showed concordant histology in 60% and discordant in 25% of the cases. Though majority of the patients (75%) with only D1 involvement were pediatric cases, no significant difference was found between pediatric and adult patients when all cases were considered (17 vs 14%). Our results clearly indicate that without D1 sampling, diagnosis of CD would have been missed in a significant number of cases (13%), thereby highlighting the importance of taking duodenal biopsies from multiple sites in the diagnostic work-up of CD. We, therefore, conclude that every biopsy piece from both D1 and D2 should be carefully evaluated for the whole spectrum of mucosal changes caused by gluten ingestion and classified using a scheme based on Marsh to allow recognition of mild lesions.

Novel mutations of SAR1B gene in four children with chylomicron retention disease.

BACKGROUND: Intestinal lipid malabsorption, resulting from an impaired formation or secretion of chylomicrons and associated with severe hypobetalipoproteinemia (HBL), may be due to biallelic mutations in APOB (homozygous FHBL type-1), MTTP (abetalipoproteinemia), or SAR1B (chylomicron retention disease). OBJECTIVE: We investigated four children, each born from consanguineous parents, presenting with steatorrhea, malnutrition, accumulation of lipids in enterocytes, and severe hypocholesterolemia with an apparent recessive transmission. METHODS: We sequenced a panel of genes whose variants may be associated with HBL. RESULTS: Case 1, a 9-month-old male, was found to be homozygous for a SAR1B variant (c.49 C>T), predicted to encode a truncated Sar1b protein devoid of function (p.Gln17*). Case 2, a 4-year-old male, was found to be homozygous for a SAR1B missense variant [c.409 G>C, p.(Asp137His)], which affects a highly conserved residue close to the Sar1b guanosine recognition site. Case 3, a 6-year-old male, was found to be homozygous for an ∼6 kb deletion of the SAR1B gene, which eliminates exon 2; this deletion causes the loss of the ATG translation initiation codon in the SAR1B mRNA. The same homozygous mutation was found in an 11-month-old child (case 4) who was related to case 3. CONCLUSIONS: We report 4 children with intestinal lipid malabsorption were found to have chylomicron retention disease due to 3 novel variants in the SAR1B gene.

Diagnosing celiac disease: A critical overview.

The diagnosis of celiac disease (CD) no longer rests on a malabsorptive state or severe mucosal lesions. For the present, diagnosis will always require the gold-standard of a biopsy, interpreted through its progressive phases (Marsh classification). Marsh classification articulated the immunopathological spectrum of gluten-induced mucosal changes in association with the recognition of innate (Marsh I infiltration) and T cell-based adaptive (Marsh II, and the surface re-organisation typifying Marsh III lesions) responses. Through the Marsh classification the diagnostic goalposts were considerably widened thus, over its time-course, permitting countless patients to begin a gluten-free diet but who, on previous criteria, would have been denied such vital treatment. The revisions of this classification failed to provide additional insight in the interpretation of mucosal pathology. Morever, the subclassification of Marsh 3 imposed an enormous amount of extra work on pathologists with no aid in diagnosis, treatment, or prognosis. Therefore, it should now be apparent that if gastroenterologists ignore these sub-classifications in clinical decision-making, then on that basis alone, there is no need whatsoever for pathologists to persist in reporting them. Since new treatments are under critical assessment, we might have to consider use of some other higher level histological techniques sensitive enough to detect the changes sought. A promising alternative would be to hear more voices from imaginative histopathologists or morphologists together with some more insightful approaches, involving molecular-based techniques and stem cell research may be to evaluate mucosal pathology in CD.

Tumor-associated Macrophages and Neuroendocrine Differentiation Decrease the Efficacy of Bevacizumab Plus Chemotherapy in Patients With Advanced Colorectal Cancer.

BACKGROUND: In the present study, we investigated the prognostic and predictive role of neuroendocrine differentiation (NED) and tumor-associated macrophage (TAM) infiltration in tumor tissue from patients with advanced colorectal cancer who had received bevacizumab plus chemotherapy. PATIENTS AND METHODS: A total of 123 consecutive patients with advanced colorectal cancer who had received bevacizumab plus irinotecan/oxaliplatin-based combination chemotherapy were included in the present study. In addition to the clinicopathologic parameters, the presence of NED and the level of TAM infiltration were studied as covariates for survival analysis. RESULTS: The median patient age was 57 years (range, 30-76 years). The chemotherapy backbone was FOLFIRI (folinic acid, 5-fluorouracil, irinotecan) for 75% of the patients. Univariate analysis showed that only NED and TAM infiltration were significant predictive factors for progression-free survival. Left-sided tumors and low TAM infiltration were favorable factors for overall survival on univariate analysis. However, the TAM level was the only independent prognostic factor for overall survival (hazard ratio, 0.301; 95% confidence interval, 0.102-0.892). CONCLUSION: Our results suggest that increased TAM infiltration in tumor tissue and NED could decrease the efficacy of bevacizumab plus combination chemotherapy in patients with advanced colorectal cancer. TAM infiltration in the tumor tissue could be used as a biomarker in patients with advanced colorectal cancer receiving bevacizumab plus chemotherapy.

Vascular endothelial growth factor, endostatin levels and clinical features among patients with ulcerative colitis and irritable bowel syndrome and among healthy controls: a cross-sectional analytical study

ABSTRACT BACKGROUND: Increased angiogenetic activity in inflammatory bowel disease (IBD) has been shown in previous studies. The aim of this study was to evaluate the relationship of serum vascular endothelial growth factor (VEGF) and endostatin levels with clinical features and mucosal expression in patients with ulcerative colitis (UC). DESIGN AND SETTING: Cross-sectional analytical study conducted in a tertiary-level public hospital. METHODS: Serum VEGF and endostatin levels were determined in 82 individuals: 39 with UC, 28 with irritable bowel syndrome (IBS) and 15 healthy controls (HCs), using enzyme-linked immunosorbent assays (ELISA). VEGF and endostatin expressions were studied using immunohistochemistry (IHC). RESULTS: Mean serum VEGF and endostatin levels were significantly higher in patients with UC than in patients with IBS and in HCs (511.9 ± 377.5 pg/ml, 305.0 ± 121.42 pg/ml and 36.1 ± 40.6 pg/ml; P = 0.001 for VEGF; and 155.50 ± 59.8 ng/ml, 116.9 ± 23.8 ng/ml and 102.2 ± 22.4 ng/ml; P < 0.001 for endostatin, respectively). There was a positive correlation between serum VEGF and endostatin levels (r = 0.422; P < 0.01). Mean H-scores for VEGF expression were higher in the active UC group than in the inactive UC and IBS groups, in the stroma, endothelium and epithelium. Mean H-scores for endostatin expression were higher in the active UC group than in the inactive UC and IBS groups, in the stroma and endothelium. There was no endostatin expression in the epithelium. CONCLUSION: Increased endostatin appears to be a defensive reaction to increased VEGF in patients with UC.

Discriminant value of IEL counts and distribution pattern through the spectrum of gluten sensitivity: a simple diagnostic approach.

Intraepithelial lymphocytosis (IELosis) with or without villous abnormality is a characteristic feature of gluten sensitivity (GS) including celiac disease (CD) and non-celiac-GS, although various conditions may also be associated with IELosis. In order to distinguish GS from the other causes of IELosis, a threshold for IEL counts is necessary. We aimed to determine a cut-off value for IELs and monitor its value in the spectrum of GS in a large cohort. For this purpose, the duodenal biopsies from four groups of individuals including Types 1 (n = 88) and 3 (n = 92) CD, non-CD IELosis (n = 112), and control (n = 82) cases, all strictly defined by their clinical, laboratory, and serologic features, were evaluated. The number of IELs/100 enterocytes and their distribution pattern on H&E- and CD3-immunostained sections were assessed for each group. Kruskal-Wallis test and ROC curve analysis for discriminant value were employed for statistics. The IEL counts showed an increasing trend through the spectrum of mucosal pathology including controls (12.06; 21.40), non-CD IELosis (28.62; 39.46), Type 1 CD (49.27; 60.15), and Type 3 CD (58.53; 71.74) both on H&E- and CD3-immunostained sections, respectively (p < 0.001). ROC analysis revealed 20.5 on H&E and 28.5 on CD3 as the IEL cut-off values with a sensitivity of 95.9 and 87.7% and a specificity of 98.8% and 93.9%, respectively, for controls. IELs showed a diffuse distribution pattern per biopsy piece and per villus (90.9%, 100%, respectively) in nearly all of Type 1 CD cases (p < 0.001). An IEL cut-off value of 20.5 on H&E together with a diffuse distribution pattern seem to be the most discriminant features for the diagnosis of CD, even for the milder forms of the disease.

Exploring the villus.

The small intestinal villus and its associated epithelium includes enterocytes as the main cell type and differentiated goblet and argentaffin cells, while the invaginated crypt epithelium is the site of cell division and hence the origin of all epithelial components. Enterocytes form a cohesive monolayer which acts both as a permeability barrier between lumen and the interior, and an important gateway for nutrient digestion, absorption and transport. Differentiation and polarisation of enterocytes depends on cytoskeletal proteins that control cell shape and maintain functionally specialised membrane domains; extracellular matrix (ECM) receptors; channels and transporters regulating ion/solute transfer across the cell. The mesenchymally-derived basement membrane dynamically controls morphogenesis, cell differentiation and polarity, while also providing the structural basis for villi, crypts and the microvasculature of the lamina propria so that tissue morphology, crucially, is preserved in the absence of epithelium. Mucosal re-organisation requires immense cooperation between all elements within the lamina, including marked revisions of the microvasculature and extensive alterations to all basement membranes providing support for endodermal and mesenchymal components. In this context, subepithelial myofibroblasts fulfil important regulatory activities in terms of tissue morphogenesis; remodelling; control of epithelial cell development, polarity and functional attributes; and an intimate involvement in repair, inflammation and fibrosis. This paper reviews the main structural and functional aspects of the villus, including the epithelium and its outer glycocalyx and microvillous border; and subjacent to the epithelium, the basement membrane with its attached web of myo-fibroblasts together with the lamina propria core of the villi, and its microvasculature and lacteals. Finally, some comments on the rapidity with which the overall structure of the villi changes in their response to both external, and internal, influences.

Vascular endothelial growth factor, endostatin levels and clinical features among patients with ulcerative colitis and irritable bowel syndrome and among healthy controls: a cross-sectional analytical study.

BACKGROUND: Increased angiogenetic activity in inflammatory bowel disease (IBD) has been shown in previous studies. The aim of this study was to evaluate the relationship of serum vascular endothelial growth factor (VEGF) and endostatin levels with clinical features and mucosal expression in patients with ulcerative colitis (UC). DESIGN AND SETTING: Cross-sectional analytical study conducted in a tertiary-level public hospital. METHODS: Serum VEGF and endostatin levels were determined in 82 individuals: 39 with UC, 28 with irritable bowel syndrome (IBS) and 15 healthy controls (HCs), using enzyme-linked immunosorbent assays (ELISA). VEGF and endostatin expressions were studied using immunohistochemistry (IHC). RESULTS: Mean serum VEGF and endostatin levels were significantly higher in patients with UC than in patients with IBS and in HCs (511.9 ± 377.5 pg/ml, 305.0 ± 121.42 pg/ml and 36.1 ± 40.6 pg/ml; P = 0.001 for VEGF; and 155.50 ± 59.8 ng/ml, 116.9 ± 23.8 ng/ml and 102.2 ± 22.4 ng/ml; P < 0.001 for endostatin, respectively). There was a positive correlation between serum VEGF and endostatin levels (r = 0.422; P < 0.01). Mean H-scores for VEGF expression were higher in the active UC group than in the inactive UC and IBS groups, in the stroma, endothelium and epithelium. Mean H-scores for endostatin expression were higher in the active UC group than in the inactive UC and IBS groups, in the stroma and endothelium. There was no endostatin expression in the epithelium. CONCLUSION: Increased endostatin appears to be a defensive reaction to increased VEGF in patients with UC.

Newcomers in paediatric GI pathology: childhood enteropathies including very early onset monogenic IBD.

Childhood enteropathies are a group of diseases causing severe chronic (>2-3 weeks) diarrhoea often starting in the first week of life with the potential for fatal complications for the affected infant. Early identification and accurate classification of childhood enteropathies are, therefore, crucial for making treatment decisions to prevent life-threatening complications. Childhood enteropathies are classified into four groups based on the underlying pathology: (i) conditions related to defective digestion, absorption and transport of nutrients and electrolytes; (ii) disorders related to enterocyte differentiation and polarization; (iii) defects of enteroendocrine cell differentiation; and (iv) disorders associated with defective modulation of intestinal immune response. While the intestinal mucosa is usually normal in enteropathies related to congenital transport or enzyme deficiencies, the intestinal biopsy in other disorders may reveal a wide range of abnormalities varying from normal villous architecture to villous atrophy and/or inflammation, or features specific to the underlying disorder including epithelial abnormalities, lipid vacuolization in the enterocytes, absence of plasma cells, lymphangiectasia, microorganisms, and mucosal eosinophilic or histiocytic infiltration. This review intends to provide an update on small intestinal biopsy findings in childhood enteropathies, the "newcomers", including very early onset monogenic inflammatory bowel disease (IBD), in particular, for the practicing pathologist.