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.

New Chimeric Groin Flap: Experimental Model in Rats.

AIM: Increased emphasis is on using tissue substitutes and stem cells to improve flap applicability and survival rates. To accomplish this, the first step is to have a versatile experimental flap, easy to harvest and use as a template. We sought to develop a reliable experimental chimeric groin flap with free mobility and reliable bloods supply that can be twisted, relocated, and integrated easily with other materials. MATERIALS AND METHODS: Ten male Wistar rats were included. The flap consists of a 2.5-cm skin paddle centered on the medial branch of the inferior epigastric artery and a 4.5/2-cm fat pad supplied by the lateral branch of the inferior epigastric artery. After being raised, flaps were resutured in their anatomical position. Flaps were followed up for 15 days. At the end of the study, the viability of flaps was analyzed by ultrahigh-frequency ultrasound, nontargeted contrast study, and histology assessment. RESULTS: All flaps survived without significant complications. Nontargeted microbubbles spread evenly in both the superficial and deep flap. Ultrasound assessment at day 15 showed no significant areas of necrosis or edema. Histology examination of 3 random flaps confirmed vessel patency and flap viability. CONCLUSION: We propose a simple, easy to harvest and reliable experimental flap which offers a main advantage of all-around mobility through its chimeric design. It is a suitable model for bioengineering studies as it can be used as a template for integration of tissue substitutes or stem cells, between its 2 components.

Role of Ultrahigh Frequency Ultrasound in Evaluating Experimental Flaps.

BACKGROUND: Experimental flap follow-up needs faster, safer, and less invasive techniques that can be easily correlated to clinical procedures. For this reason, we aimed to test the role of ultrahigh frequency ultrasound in follow-up of flap viability. Further on, we aimed to analyze if the chimeric groin flap can be mobilized in a sandwiched position without affecting its vascular supply by twisting its pedicle. METHODS: A total of 12 male Wistar rats, split into three groups, were used. Group A (n = 4) had the chimeric groin flap repositioned in a sandwich position on the anterior abdominal wall and underwent ultrahigh frequency ultrasound follow-up at days 10 and 14. Group B (n = 4) also had the flaps sandwiched, however, at day 14 the vascularity of flaps was proven by infusion of nontargeted ultrasound contrast agents, after which flaps were sent for histological analysis. Group C (C1 n = 2, C2 n = 2) was the control group. In C1 the chimeric groin flap was harvested and sent for histology on day 0, acting as a histological benchmark of flap viability, and in C2 the chimeric groin flap was re-sutured in its anatomical position and after 14 days, flaps were harvested and sent for histological analysis, acting as a direct control for Group B. RESULTS: Ultrasound showed constant vascular flow in both adipose and skin flaps in the sandwiched position. Microbubble study showed diffuse perfusion within flaps. Ultrasound measurements of flow velocity, flap volume, and percentage of vascularity showed a decrease in flap volume and increase in vascularity over 14 days. Histology showed similar viability in both groups. CONCLUSION: Ultrahigh frequency ultrasound may be a valuable tool for postoperative flap assessment, while the chimeric flap can be moved freely in a sandwich position making it suitable for adding tissue substitutes within its components.

Improvement in serum lipids and liver morphology after supplementation of the diet with fish oil is more evident under regular feeding conditions than under high-fat or mixed diets in rats.

BACKGROUND: Dietary n- 3 polyunsaturated fatty acids (PUFAs) have a role in preventing cardiovascular and hepatic diseases. However, their effects might differ significantly depending on individual dietary patterns. The aim of the present study was to evaluate the effects of dietary supplementation with ω-3 fatty acids (FA), administered in different schedules, on hepatic and aortic histological structure, lipid profile, and body weight (BW) in male Wistar rats under standard (SD), high-fat diet (HFD) and mixed feeding conditions. METHODS: PUFA treatment consisted of the administration of 50 mg/kg fish oil (FO) daily by oral gavage. HFD was obtained by adding a suspension of 4% cholesterol, thiouracil and cholic acid to the animals' drinking water. The rats were maintained on the diets for 6 weeks, and different schedules of PUFA administration were used. At 14, 28, and 42 days, the morphology of liver and aortic samples and the levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), and triglycerides (TG) were assessed. RESULTS: The HFD groups exhibited significant hyperlipidemia and aortic inflammation, with progression to atherogenesis after 6 weeks. Administration of PUFAs slightly attenuated the aortic changes in these groups and reduced the liver's tendency to steatosis. FO-induced metabolic improvement was more evident in SD than in HFD rats. For instance, after the first 2 weeks, SD animals that received PUFAs had significantly increased HDL levels vs. controls (62.375 ± 4.10 vs. 52.625 ± 8.38 mg/dL, P < 0.05), but HFD rats did not, and decreased TG levels were observed exclusively in the SD rats (57.6 ± 4.09 vs. 66 ± 4.69 mg/dL, P < 0.05). After 6 weeks of n- 3 PUFA administration, LDL was significantly lower in the SD rats than in controls (13.67 ± 4.13 vs. 30.83 ± 2.86 mg/dL, P < 0.001), but the decrease in the HFD rats, although significant (49.17 ± 5.85 mg/dL vs. 57.17 ± 4.96 g/dL, P < 0.05), was not as marked. In the mixed-diet groups, administration of 50 mg/kg/day FO for 14 days under SD conditions following 4 weeks of HFD slightly decreased TG (86.625 ± 11.67 vs. 73 ± 4.52 mg/dL, P < 0.05) and increased HDL (45.875 ± 5.28 vs. 56 ± 3.16 mg/dL). However, in these animals, n-3 PUFA administration had no effect on LDL or TC. Administration of half of the above dose failed to improve any biochemical parameters. FO protected against excessive weight gain mainly under SD conditions. CONCLUSIONS: The results show that FO confers more protection against cardiovascular risk factors (increased LDL and TG, decreased HDL) and liver lipid accumulation when given to rats consuming regular diets than when given to rats consuming a high-fat diet. This argues that priority should be given to consumption of a healthy diet rather than to the use of supplements. The effectiveness of n-3 PUFAs might be reduced in the case of hyperlipidic intake or after consumption of a high-fat diet.

Multicentric Reticulohistiocytosis Exhibiting Positive HLA-B*07 and HLA-B*08: A Case Report.

Multicentric reticulohistiocytosis (MRH) is a rare cause of destructive inflammatory arthritis involving both small, as well as larger joints. We report the case of a 40-year-old Caucasian female with a family history of neoplasia who was referred to our service witha two-month history of inflammatory joint pain. On examination, the patient had inflammatory arthritis, mainly involving the peripheral joints, sacroiliac joint pain, and numerous papulonodular mucocutaneous lesions, including periungual "coral beads". Imaging tests revealed erosive arthritis with synovitis and tenosynovitis, sacroiliac joint changes, as well as papulonodular mucosal lesions in the nasal vestibule, the oropharyngeal mucosa, and supraglottic larynx. She tested positive for HLA-B*07 (Human Leukocyte Antigen B*07) and HLA-B*08, ANA (antinuclear antibodies), RF (rheumatoid factor), anti-Ro52, anti-SSA/Ro, and anti-SSB/La antibodies. The skin biopsy was suggestive of MRH, showing a histiocyte infiltrate and frequent giant multinucleated cells. The patient exhibited favorable outcomes under Methotrexate, then Leflunomide. However, she displayed worsening clinical symptoms while under Azathioprine. To our knowledge, this is the first case of MRH to exhibit positive HLA-B*07 together with HLA-B*08. The rarity of MRH, its unknown etiology and polymorphic clinical presentation, as well as its potential neoplastic/paraneoplastic, and autoimmune nature demand extensive investigation.

ROC-king onwards: intraepithelial lymphocyte counts, distribution & role in coeliac disease mucosal interpretation.

OBJECTIVES: Counting intraepithelial lymphocytes (IEL) is central to the histological diagnosis of coeliac disease (CD), but no definitive 'normal' IEL range has ever been published. In this multicentre study, receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off between normal and CD (Marsh III lesion) duodenal mucosa, based on IEL counts on >400 mucosal biopsy specimens. DESIGN: The study was designed at the International Meeting on Digestive Pathology, Bucharest 2015. Investigators from 19 centres, eight countries of three continents, recruited 198 patients with Marsh III histology and 203 controls and used one agreed protocol to count IEL/100 enterocytes in well-oriented duodenal biopsies. Demographic and serological data were also collected. RESULTS: The mean ages of CD and control groups were 45.5 (neonate to 82) and 38.3 (2-88) years. Mean IEL count was 54±18/100 enterocytes in CD and 13±8 in normal controls (p=0.0001). ROC analysis indicated an optimal cut-off point of 25 IEL/100 enterocytes, with 99% sensitivity, 92% specificity and 99.5% area under the curve. Other cut-offs between 20 and 40 IEL were less discriminatory. Additionally, there was a sufficiently high number of biopsies to explore IEL counts across the subclassification of the Marsh III lesion. CONCLUSION: Our ROC curve analyses demonstrate that for Marsh III lesions, a cut-off of 25 IEL/100 enterocytes optimises discrimination between normal control and CD biopsies. No differences in IEL counts were found between Marsh III a, b and c lesions. There was an indication of a continuously graded dose-response by IEL to environmental (gluten) antigenic influence.

Ghrelin Expression in Atherosclerotic Plaques and Perivascular Adipose Tissue: Implications for Vascular Inflammation in Peripheral Artery Disease.

Atherosclerosis, a leading cause of peripheral artery disease (PAD), is driven by lipid accumulation and chronic inflammation within arterial walls. Objectives: This study investigates the expression of ghrelin, an anti-inflammatory peptide hormone, in plaque morphology and inflammation in patients with PAD, highlighting its potential role in age-related vascular diseases and metabolic syndrome. Methods: The analysis specifically focused on the immunohistochemical expression of ghrelin in atherosclerotic plaques and perivascular adipose tissue (PVAT) from 28 PAD patients. Detailed immunohistochemical staining was performed to identify ghrelin within these tissues, comparing its presence in various plaque types and assessing its association with markers of inflammation and macrophage polarization. Results: Significant results showed a higher prevalence of calcification in fibro-lipid plaques (63.1%) compared to fibrous plaques, with a notable difference in inflammatory infiltration between the two plaque types (p = 0.027). Complicated plaques exhibited increased ghrelin expression, suggesting a modulatory effect on inflammatory processes, although this did not reach statistical significance. The correlation between ghrelin levels and macrophage presence, especially the pro-inflammatory M1 phenotype, indicates ghrelin's involvement in the inflammatory dynamics of atherosclerosis. Conclusions: The findings propose that ghrelin may influence plaque stability and vascular inflammation, pointing to its therapeutic potential in managing atherosclerosis. The study underlines the necessity for further research to clarify ghrelin's impact on vascular health, particularly in the context of metabolic syndrome and age-related vascular alterations.

Experimental Study on Rats with Critical-Size Bone Defects Comparing Effects of Autologous Bone Graft, Equine Bone Substitute Bio-Gen® Alone or in Association with Platelet-Rich Fibrin (PRF).

BACKGROUND: A critical-sized bone defect (CsBD) is considered one that will not heal spontaneously and requires reconstruction. This study aims to compare the results of using different bone reconstructive techniques and to study the potential of platelet-rich fibrin (PRF) to enhance the healing properties of a bone substitute (BS). METHODS: In this experimental study on rats, the treatment of critical-sized bone defects was carried out by analysing four groups: a control group in which the bone defect was left empty; a group treated with Bio-Gen®; another group in which the defect was treated with PRF in combination with Bio-Gen®; and the last that was treated with autologous bone graft (ABG). The defects were evaluated by microcomputed tomography (µCT) and then histomorphometrically. RESULTS: From both the histological and imagistic point of view, the best results were registered in the ABG group, followed by the group treated with Bio-Gen® with PRF, Bio-Gen® group, and control group, with statistically significant differences. CONCLUSIONS: A 5 mm defect in the rat radius can be considered critical. ABG showed the best results in treating the bone defect. PRF significantly enhanced the efficacy of Bio-Gen®.

Regulatory T cells in gastric cancer: Key controllers from pathogenesis to therapy.

Gastric cancer (GC) is a highly aggressive malignancy that remains a significant contributor to cancer-related mortality worldwide, despite a decline in incidence in recent years. Early-stage GC poses a diagnostic challenge due to its asymptomatic nature, leading to poor prognoses for most patients. Conventional treatment approaches, including chemotherapy and surgery, have shown limited efficacy in improving outcomes for GC patients. The advent of immune checkpoint inhibitors (ICIs) has revolutionized cancer therapy, yielding durable responses across various malignancies. However, the clinical benefits of ICIs in GC have been modest, underscoring the need for a comprehensive understanding of immune cell functions within the GC tumor microenvironment (TME). Regulatory T cells (Tregs), a subset of T lymphocytes, play a pivotal role in GC development and progression and serve as prognostic biomarkers for GC patients. This review aims to elucidate the multifaceted roles of Tregs in the pathogenesis, progression, and prognosis of gastric cancer, and establish their actual and future potential as therapeutic targets. By providing insights into the intricate interplay between Tregs and the TME, this review strives to stimulate further investigation and facilitate the development of targeted Treg-based therapeutic strategies for GC.

Predictors of slow responsiveness and partial mucosal recovery in adult patients with celiac disease.

Aim: The present study aims to determine the rate of mucosal recovery and predictors of persistent mucosal damage after gluten free diet (GFD). Background: Celiac disease (CD) is a complex multi-systemic autoimmune disease triggered by exposure to dietary gluten in genetically predisposed individuals. There is still little evidence on the best method for assessing GFD adherence and mucosal recovery during treatment. Methods: The retrospective study included only adult patients (age≥18 years old), with biopsy-proven CD evaluated at a tertiary referral centre between 2016 and 2021. We performed a logistic regression analysis to identify factors associated with partial mucosal recovery (MR) after GFD. We included in the multivariate analysis parameters available at the time of CD diagnosis. Results: A total of 102 patients were enrolled, two thirds were females, median age of 39 years (yrs). The initial biopsy analysis showed different stages of villous atrophy (VA) in 79 (77.4%) cases, while in 23(22.5%) cases showed mild enteropathy (Marsh 1, 2). After at least 12 months of GFD, 26 (25.5%) patients had persistent VA despite good or excellent adherence to GFD. Younger patients (< 35yrs), who showed severe mucosal damage (Marsh 3c lesions) and who had increased anti-gliadin antibody (AGA) levels were at risk for failure to obtain mucosal recovery (MR). Logistic regression analysis demonstrated that complete mucosal atrophy (P=0.007) and high AGA antibody levels (cutoff 129 U/ml, P=0.001) were independent risk factors for lack of mucosal improvement after at least 12 months of GFD. Interestingly, genotype, tTG-IgA antibody levels, or duration of GFD levels did not influence the occurrence of MR. Conclusion: Although AGA seropositivity has lost much of their diagnostic significance in recent years due to the introduction of the more sensitive and specific antibody tests, our study reported that patients aged < 35 yrs, who showed severe mucosal damage (Marsh 3c lesions) and who had increased AGA antibody levels at diagnosis were at risk for failure to obtain MR. The elevated AGA levels at diagnosis could be used as a prognostic tool for assessing MR.

Thyroid Collision Tumors: The Presence of the Medullary Thyroid Carcinoma Component Negatively Influences the Prognosis.

Thyroid collision tumors (TCTs) are rare pathological findings, representing <1% of thyroid cancers. This study aimed to compare the main pathological features of TCTs containing medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma (PTC) components with MTC-only tumors and PTC-only tumors. Methods: The retrospective study included 69 cases diagnosed with TCTs (with simultaneous MTC and PTC components), MTC and PTC. All tumors were comparatively assessed for the classical histopathological prognostic features, including a new grading system for MTC. Results: The main component of TCTs had more frequent microscopic extrathyroidal extension (mETE) (p = 0.000), lymphovascular invasion (LVI) (p = 0.000), perineural invasion (PNI) (p = 0.044), and lymph node metastasis (p = 0.042). Additionally, the TCTs' MTC component presented with more frequent LVI (p = 0.010). Comparing TCTs' MTC and PTC components with MTC-only tumors and PTC-only tumors revealed that only the TCTs' MTC components had statistically significant more frequent mETE (p = 0.010) than MTC-only tumors. When applied to the MTC component of TCTs, the pathological parameters of the new grading system of MTC showed no correlations with other microscopic or clinical aspects. Conclusion: Using classical pathological prognostic features, the comparative analysis revealed that the main TCTs' component was more aggressive than the minor one. Contrary to PTCs, in TCTs, the medullary component was more aggressive than the papillary one, but also more aggressive than MTC-only tumors.

Is High Expression of Claudin-7 in Advanced Colorectal Carcinoma Associated with a Poor Survival Rate? A Comparative Statistical and Artificial Intelligence Study.

AIM: The need for predictive and prognostic biomarkers in colorectal carcinoma (CRC) brought us to an era where the use of artificial intelligence (AI) models is increasing. We investigated the expression of Claudin-7, a tight junction component, which plays a crucial role in maintaining the integrity of normal epithelial mucosa, and its potential prognostic role in advanced CRCs, by drawing a parallel between statistical and AI algorithms. METHODS: Claudin-7 immunohistochemical expression was evaluated in the tumor core and invasion front of CRCs from 84 patients and correlated with clinicopathological parameters and survival. The results were compared with those obtained by using various AI algorithms. RESULTS: the Kaplan-Meier univariate survival analysis showed a significant correlation between survival and Claudin-7 intensity in the invasive front (p = 0.00), a higher expression being associated with a worse prognosis, while Claudin-7 intensity in the tumor core had no impact on survival. In contrast, AI models could not predict the same outcome on survival. CONCLUSION: The study showed through statistical means that the immunohistochemical overexpression of Claudin-7 in the tumor invasive front may represent a poor prognostic factor in advanced stages of CRCs, contrary to AI models which could not predict the same outcome, probably because of the small number of patients included in our cohort.

Use of Personalized Biomarkers in Metastatic Colorectal Cancer and the Impact of AI.

Colorectal cancer is a major cause of cancer-related death worldwide and is correlated with genetic and epigenetic alterations in the colonic epithelium. Genetic changes play a major role in the pathophysiology of colorectal cancer through the development of gene mutations, but recent research has shown an important role for epigenetic alterations. In this review, we try to describe the current knowledge about epigenetic alterations, including DNA methylation and histone modifications, as well as the role of non-coding RNAs as epigenetic regulators and the prognostic and predictive biomarkers in metastatic colorectal disease that can allow increases in the effectiveness of treatments. Additionally, the intestinal microbiota's composition can be an important biomarker for the response to strategies based on the immunotherapy of CRC. The identification of biomarkers in mCRC can be enhanced by developing artificial intelligence programs. We present the actual models that implement AI technology as a bridge connecting ncRNAs with tumors and conducted some experiments to improve the quality of the model used as well as the speed of the model that provides answers to users. In order to carry out this task, we implemented six algorithms: the naive Bayes classifier, the random forest classifier, the decision tree classifier, gradient boosted trees, logistic regression and SVM.

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.

An algorithm for differentiating food antigen-related gastrointestinal symptoms.

AIM: The aim of this clinical audit was to assess patient-reported outcomes on the effect of dietary intervention, to enhance our understanding of possible treatment options in irritable bowel syndrome (IBS). BACKGROUND: A large number of food-related gastro-intestinal disorders have been attributed to IBS for decades. METHODS: Patient-reported outcomes from the records of 149 IBS patients treated at secondary and tertiary Gastroenterology outpatients in two UK hospitals between January 2014 and July 2016 were audited. Patients all presented with symptoms fulfilling Rome III-IV criteria for IBS had negative coeliac serology and did not have other gastrointestinal (GI) conditions. A modified version of a low FODMAP diet had been recommended (gluten and lactose free diet (G/LFD)) and was implemented for 6 weeks. Outcomes and dietary adherence were recorded during outpatient's consultations. RESULTS: A total of 134 patients complied with the diet optimally. The majority had an improvement rate >70% and continued with the diet. Fifty-three percent became completely or almost asymptomatic, while 27.6% had a poor response to the diet (scoring < 30%) to G/LFD. The improvement was excellent in patients with normal BMI and good in overweight and obese and where BMI <18. Over 50% did not require any follow-up within 12 months. CONCLUSION: Although it is unclear whether symptoms are triggered by gluten, fructans or lactose, elimination of gluten and lactose proved to be an effective treatment in patients with IBS. Multidisciplinary team management and implementation of detailed nutrition therapy using the audit algorithm might prove to be both cost effective and efficacious a treatment option in IBS.

Clinical and immunohistopathological study of conjunctival melanocytic lesions in pediatric and adolescent patients. A case series.

BACKGROUND: Conjunctival pigmented neoplasia can be benign, premalignant or malignant tumors. Our study aims to establish the epidemiological, gross morphological and immunohistopathological features of the conjunctival pigmented lesions in pediatric and adolescent patients (<18 years), to establish an accurate diagnosis. PATIENTS, MATERIAL AND METHODS: This is a retrospective case series study conducted within two Ophthalmology Clinics from Iasi, Romania, on seven pediatric and adolescent patients. Using the Clinical Observation Chart and the Pathology Registers over a six-years period (January 2015-December 2021), we noted the patients' demographic data, clinical data, and ophthalmological investigations of the lesion, as well as the type of their treatment. All histological sections stained with Hematoxylin-Eosin (HE) and with five antibodies [pan-cytokeratin (pan-CK) AE1∕AE3, S100 protein, Melan A, human melanoma black 45 (HMB45), and Ki67] were re-examined by four pathologists for each case, to identify the type of the conjunctival lesion and its histological and immunohistochemical features. RESULTS: The mean age of all patients was 10.28 years, and the female∕male ratio was 1.3. Right eye was more often affected (71.42%). 71.42% of cases presented an elevated lesion, 57.14% of cases showed a lightly pigmented lesion, but 14.28% of cases exhibited a pink lesion and this feature described the inflamed juvenile conjunctival nevus. In all cases (100%) the conjunctival pigmented tumor was removed with safety margins. The microscopic examination revealed a compound melanocytic nevus in 57.14% cases, a junctional conjunctival nevus in 14.28% cases, an inflamed juvenile nevus in 14.28% cases, and a conjunctival melanoma arising from a pre-existing nevus in 14.28% cases. In all cases of nevi, the nevoid melanocytes showed strong immunopositivity for Melan A and S100 protein, variable and weak immunopositivity for HMB45, and a mean Ki67 labeling index of 1.71%. Conjunctival melanoma revealed strong immunopositivity of tumor cells for HMB45, Melan A and S100 protein, and a Ki67 labeling index of 20%. In all cases, the conjunctival epithelium showed strong immunopositivity for pan-CK AE1∕AE3. All our cases (100%) had a favorable outcome after the surgical removal of the tumor. CONCLUSIONS: Any excision of a conjunctival pigmented lesion must be subject to a systematic immunohistopathological examination, and there is a set of antibodies (anti-HMB45 and anti-Ki67) that are useful for differential diagnosis between a conjunctival nevus and a conjunctival melanoma.

Aurora A is differentially expressed and regulated in chromosomal and microsatellite instable sporadic colorectal cancers.

The centrosome-associated kinase aurora A has been shown to be involved in genetic instability and to be (over)expressed in several human carcinomas. This study investigated aurora A gene copy numbers, mRNA and protein expression as well as tumour cell proliferation and aneuploidy in chromosomal and microsatellite instable sporadic colorectal cancers. Case-matched tissues of normal (n=71) and dysplastic (n=49) colorectal epithelium and invasive carcinomas (n=71) were included in this study. PCR-based microsatellite analysis classified 14/71 (20%) of carcinomas as microsatellite instable. A stepwise increase of aurora A mRNA expression (P<0.0001; quantitative RT-PCR) and aurora A protein expressing tumour cells (P=0.0141; immunohistochemistry) occurred in the adenoma-carcinoma sequence. Within invasive carcinomas, aurora A mRNA levels (P=0.0259) and aurora A positive tumour cells (P<0.0001) were closely associated with tumour cell proliferation (Ki-67 specific immunohistochemistry). Compared with chromosomal instable carcinomas, microsatellite instable carcinomas had significantly more aurora A positive tumour cells (P=0.0043) and a higher tumour cell proliferation (P=0.0335). In contrast, only chromosomal instable carcinomas exhibited marked tumour cell aneuploidy (P=0.0004, fluorescence in situ hybridization) and significantly higher aurora A gene copy numbers (P=0.0206) as compared with microsatellite instable carcinomas. This study further supports a role of aurora A in the carcinogenesis of sporadic colorectal cancers. Moreover, it demonstrates that in a minority of predominantly microsatellite instable carcinomas the presence of aurora A positive tumour cells is merely reflecting tumour cell proliferation. In contrast, the large majority of chromosomal instable carcinomas shows additional (de)regulation of aurora A by gene amplification and concomitant tumour cell aneuploidy. Thus, sporadic colorectal cancers exhibit different mechanisms of aurora A regulation and this may impact the efficacy of aurora-targeted therapies.

Sub-classification of non-inflammatory and inflammatory surgical aortic aneurysms and the association of histological characteristics with potential risk factors.

The present study aimed to analyze the histological characteristics of surgical thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA) specimens on the basis of the most recent consensus documents on non-inflammatory and inflammatory lesions. The current study also aimed to establish an association with various risk factors. Aortic wall specimens were collected from 52 patients (38 men and 14 women; age, 19-80 years) undergoing surgery for aortic dilatation at The Cardiovascular Disease Institute (Iasi, Romania). For histological evaluation, the aortic specimens (39 TAAs and 13 AAAs) were stained with hematoxylin-eosin, Van Giessen, alcian blue and Movat pentachrome. The specimens were evaluated and graded according to the severity of histopathological conditions: Fragmentation of elastic fibers, medial mucoid accumulation, smooth muscle cell loss and medial fibrosis. The severity of atherosclerotic lesions in surgically resected segments of the aorta were graded as follows: i) mild=1; ii) moderate=2; and iii) severe=3. The risk factors associated with TAA were the male sex (80%), smoking (56%), hypertension (33%) and bicuspid aortic valve (13%). Advanced age (70 years), male sex (69%) and smoking (54%) were determined to be the risk factors of AAA. The histopathological abnormalities included medial degeneration (MD) (82%), atherosclerosis (ATS) (42%) and aortitis (10%). MD was the leading histopathological diagnosis in TAA and the severity of lesions were graded as follows: Mild (8% of cases), moderate (44% of cases) and severe (31% of cases). Severe atherosclerotic lesions were identified in AAA (100% of cases). In the present study, medial degenerative aortic lesions (1, mild; 2, moderate; and 3, severe) significantly correlated with advanced age (>65 years; r=-0.39; P<0.01) and male sex (r=0.27; P<0.05). Significant correlations were also identified between atherosclerotic aortic lesions (1, mild; 2, moderate; and 3, severe) and advanced age (>65 years) (r=-0.40, P<0.01) or smoking (r=-0.29; P<0.05). Advanced age, male sex and smoking were determined to be the main risk factors for the development of degenerative aortic aneurysms.

Ulcerated intussuscepted jejunal lipoma-uncommon cause of obscure gastrointestinal bleeding: A case report.

BACKGROUND: Intestinal lipomas are rare benign gastrointestinal (GI) tumors, usually asymptomatic, but may become symptomatic as the result of some complications such as intussusception, intestinal obstruction, volvulus or bleeding. They can occur at any site along the entire GI tract, more frequent in colon and rarely in small intestine. The patient reported here is a very rare case of jejunal lipoma, ulcerated and intussuscepted, diagnosed in an adult investigated for a chronic iron deficiency anemia (IDA), and successfully managed by segmental jejunal resection. CASE SUMMARY: A 63-year-old male was referred to "St. Spiridon" Hospital, Institute of Gastroenterology and Hepatology, Iasi, to investigate an obscure GI bleeding with an IDA. After upper GI endoscopy and colonoscopy were performed, excluding potentially bleeding lesions, videocapsule endoscopy was then carried out, revealing fresh blood and a protruding lesion in proximal jejunum, findings confirmed by a single-balloon enteroscopy. Multiple biopsies were taken from the lesion, but histological results were inconclusive. Then, contrast - enhanced computed tomography was performed showing jejunal polypoid mass with homogenous fat density, suggestive for lipoma. A week later a laparotomy was performed revealing the intussuscepted jejunal segment which was resected en bloc, and sent for further histopathologic analysis. The patient made an uneventful recovery and was discharged seven days later, and at six months follow-up he had no complains and his hemoglobin returned to normal value. CONCLUSION: Lipomas are very rarely located in the jejunum, usually asymptomatic, but they may lead to complications such as intussusception and bleeding. Surgical resection remains the treatment of choice.

Visual criteria in small bowel tumors detected by capsule endoscopy - morphological description and correlations with histological type.

INTRODUCTION: Small bowel tumors (SBTs) are rare. The advent of small bowel capsule endoscopy (SBCE) revolutionized the diagnosis of small bowel pathology, the SBCE major breakthrough consequently doubled the diagnostic rate of SBTs. Being a visual technique, without ability to take biopsies, SBCE has limitations in the diagnostic work-up of SBTs. AIM: To assess if structured visual description of SBTs detected by SBCE correlates with the histological type. PATIENTS, MATERIALS AND METHODS: We included patients with SBTs, evaluated by SBCE and furthermore explored, for which a final histopathological diagnosis was made, either on biopsy tissue samples, or on surgical specimens, using routine techniques and immunohistochemistry. The SBCE findings and reports were reviewed in order to assess the main macroscopic features of the SBTs, which were further correlated with the histological type. RESULTS: SBTs frequency at SBCE was 5.2%. All SBTs presented as protruding lesions. Features as size, color, type, shape, discoloration, presence of mucosa ulceration, bleeding stigmata or potential, contributed outlining a prototype. SBCE was accurate in terms of localization and suspected diagnosis. CONCLUSIONS: Even if SBCE is a purely visual technique, thorough examination and rigorous analysis of macroscopic features, as well as adoption of a structured terminology, may successfully predict the final diagnosis, empowering SBCE not only as a trust comrade in the diagnostic pathways of SBTs, but also as a valuable standalone technique mandating the final therapeutic decision.