Publications by authors named "Gabriel Becheanu"

69 Publications

Appendiceal Endometriosis with Intestinal Metaplasia Mimicking Appendiceal Mucinous Neoplasm - A Case Report and a Concise Review for the Practicing Pathologist.

Int J Surg Pathol 2022 Jul 14:10668969221105621. Epub 2022 Jul 14.

Department of General Surgery, 434079Coltea Clinical Hospital, Bucharest, Romania.

Appendiceal endometriosis is a rare entity and, when accompanied by intestinal metaplasia, represents a challenging differential diagnosis with low-grade appendiceal mucinous neoplasm (LAMN). We present the case of a 47 years-old woman, with multiple surgical interventions for endometriosis, with persistent symptoms despite chronic hormonal treatment, with imaging showing stage IV endometriosis. Hence, en bloc low rectum resection with total hysterectomy and bilateral adnexectomy was performed, followed by appendectomy. Unexpectedly, despite the gross normal macroscopic appearance of the appendix, microscopy showed multiple endometriosis foci, consisting of endometrial glands embedded in varying amounts of endometrial stroma. As some of these glands were bordered by mucinous-type epithelium containing intestinal cells, Goblet cells, Paneth cells in addition to the presence of mucus-filled microcysts, immunohistochemistry (IHC) was performed in order to differentiate between intestinal-metaplasia and LAMN. IHC showed positivity of the endometrial epithelium for KRT7, estrogen receptor (ER) and progesterone receptor (PR). Both the appendiceal mucosa and the intestinal-type metaplastic epithelium of the glandular structures were positive for KRT20. Additionally, the endometrial stroma enclosing endometrial glands, as well as the stroma surrounding mucinous-type metaplastic epithelium, were positive for CD10, ER and PR. This patient's case draws attention to the rare occurrence of appendiceal endometriosis and the uncommon intestinal metaplasia, which can easily mimic LAMN, emphasizing the paramount importance of the differential diagnosis with this type of neoplasia.
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http://dx.doi.org/10.1177/10668969221105621DOI Listing
July 2022

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

Nutrients 2022 Jun 15;14(12). Epub 2022 Jun 15.

Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, MN 55907, USA.

Histological changes induced by gluten in the duodenal mucosa of patients with non-coeliac gluten sensitivity (NCGS) are poorly defined. To evaluate the structural and inflammatory features of NCGS compared to controls and coeliac disease (CeD) with milder enteropathy (Marsh I-II). 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. The median VH in NCGS was significantly shorter (600, IQR: 400-705) than controls (900, IQR: 667-1112) ( < 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, = 0·176)]. The VCR in NCGS with Marsh 0 was lower than controls ( < 0.001). The median IEL in NCGS with Marsh 0 was higher than controls (23.0 vs. 13.7, < 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. : NCGS duodenal mucosa exhibits distinctive changes consistent with an intestinal response to luminal antigens, even at the Marsh 0 stage of villus architecture.
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http://dx.doi.org/10.3390/nu14122487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9230100PMC
June 2022

Atypical Immunohistochemistry Features in an AFP-producing Colon Cancer.

J Gastrointestin Liver Dis 2022 06 12;31(2):159. Epub 2022 Jun 12.

Digestive Diseases and Liver Transplantation Center, Fundeni Clinical Institute, Bucharest; Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.

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http://dx.doi.org/10.15403/jgld-4104DOI Listing
June 2022

The diagnostic challenges in a child with intestinal tuberculosis.

Rom J Morphol Embryol 2021 Oct-Dec;62(4):1057-1061

3rd Pediatrics Department, Grigore Alexandrescu Emergency Children's Hospital, Bucharest, Romania;

Introduction: Romania is one of the European countries with a significant burden of tuberculosis (TB). Although pulmonary TB is still highly prevalent, intestinal TB is very rare and remains a diagnosis of exclusion, especially in children. The authors aimed to raise the awareness on this pathology by discussing the challenges faced in the management of one difficult case.

Case Presentation: A 3-year-old boy was hospitalized in the Pediatrics Department of Grigore Alexandrescu Emergency Children's Hospital, Bucharest, Romania, for abdominal pain and melena. On clinical examination, he was malnourished, with generalized edema and marked abdominal distension. Laboratory tests revealed iron-deficiency anemia, low plasma proteins, inflammatory syndrome and high fecal calprotectin. The abdominal ultrasound showed bowel wall thickening and diffuse edematous mesentery; the colonoscopy described multiple ulcers with edematous margins. Parenteral nutrition and complex antibiotic treatment were initiated with no effect. During the hospital stay, the medical staff observed how the mother chewed the patient's food. The child's pulmonary X-ray was normal, but the mother's was suggestive for pulmonary TB. The QuantiFERON® test was positive. Biopsy of the bowel mucosa revealed numerous granulomas; the Auramine O∕Rhodamine B staining of the specimen was positive. Specific TB treatment was started with good results: the patient resumed growth, abdominal pain and distention disappeared.

Conclusions: Intestinal TB poses a diagnostic challenge, especially in the absence of pulmonary disease. It may mimic many other intestinal pathologies. Since correct treatment depends on making the correct diagnosis, a high index of suspicion must be kept when facing atypical abdominal symptoms.
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http://dx.doi.org/10.47162/RJME.62.4.19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9289714PMC
June 2022

Mucosal gene expression profile of stricturing Crohn's disease: A preliminary study.

Exp Ther Med 2022 Feb 16;23(2):149. Epub 2021 Dec 16.

Department of Gastroenterology, 'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania.

Intestinal strictures are an important complication of Crohn's disease (CD), with ~40% of patients developing symptomatic obstruction within 10 years of diagnosis. However, there is a paucity of research examining the mechanisms driving the development of fibrotic strictures in CD. The present study aimed to identify the mucosal markers associated with stricturing complications by examining the differences in the gene expression profiles of two patient cohorts: Patients diagnosed with inflammatory CD (n=12) and patients with stricturing CD (n=9). For each patient, a paired sample of inflamed and uninflamed mucosa was isolated and assessed by quantitative PCR using a large panel of genes associated with inflammatory bowel disease. The presents study revealed a significantly increased level of four genes in the mucosa of patients with strictures compared with the inflammatory pattern of the disease: Formyl-peptide receptor 1 [P=0.019; fold change (FC)=11.6], C-C chemokine receptor type 1 (P=0.035; FC=5.44), IFN-γ-inducible protein 10 (P=0.037; FC=3.8) and C-C chemokine ligand 25 (P=0.048; FC=3.56). The augmented expression of these four genes in the CD stricturing phenotype, if confirmed in larger cohorts of patients, could help elucidate the mechanisms leading to disease-associated complications.
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http://dx.doi.org/10.3892/etm.2021.11072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8756406PMC
February 2022

Pembrolizumab induced steroid resistant immune mediated colitis and concurrent Clostridioides difficile infection.

J Gastrointestin Liver Dis 2021 09 22;30(3):411-413. Epub 2021 Sep 22.

Carol Davila University of Medicine and Pharmacy, Gastroenterology and Hepatology Department, Fundeni Clinic Institute, Bucharest, Romania.

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http://dx.doi.org/10.15403/jgld-3923DOI Listing
September 2021

An Unusual Etiology of Obstructive Jaundice in a Newly Diagnosed Celiac Disease Patient.

J Gastrointestin Liver Dis 2021 Mar 12;30(1):15. Epub 2021 Mar 12.

Carol Davila University of Medicine and Pharmacy, Gastroenterology Department, Fundeni Clinical Institute, Bucharest, Romania.

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http://dx.doi.org/10.15403/jgld-3343DOI Listing
March 2021

Histopathological features of low-dose organophosphate exposure.

Rom J Morphol Embryol 2020 Apr-Jun;61(2):423-432

Department of Plastic Surgery and Reconstructive Microsurgery, Emergency Clinical Hospital of Bucharest, Romania; Clinical Department No. 3, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania;

Organophosphate (OP) use remains largely available worldwide despite more strict regulatory measures, in agriculture, parks or households, leading to a daily low-dose exposure. The systemic dysfunction appears partly due to acetylcholinesterase inhibition, exhibiting a primary toxic effect on the endocrine system but also on the liver and kidneys, which are responsible for products metabolization and elimination. Prolonged OP exposure can be responsible for histopathological (HP) changes that can either evolve or worsen pre-existing conditions. We conducted an experimental study including six male Wistar rats divided into two groups (four rats in the study group and two in the control group). The subjects in the first group were administered 100 mg∕kg Chlorpyrifos half median lethal dose (LD50) at baseline and at 48 hours, under general anesthesia. Organ harvesting was achieved after one week. HP modifications were discovered in all kidney samples, with dystrophic changes and vacuolization of mesangial cells, dilation of renal tubules and epithelial atrophy. Congestion of vascular structures also occurred. The liver samples showed severe alteration in both vessels and hepatocytes. Adrenal gland impairment was confirmed through an increase in vacuole number in all areas, while a decrease in colloid content was noted in the thyroid gland simultaneously with a modified foamy aspect. This study is the first to certify the extent of organ injury induced by OP exposure, describing both glomerular and tubular involvement in the kidneys, liver necrosis and endocrine disturbances.
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http://dx.doi.org/10.47162/RJME.61.2.11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864311PMC
September 2021

Somatostatinoma and Neurofibromatosis Type 1-A Case Report and Review of the Literature.

Diagnostics (Basel) 2020 Aug 21;10(9). Epub 2020 Aug 21.

Oncology Department, Titu Maiorescu University of Medicine, 040051 Bucharest, Romania.

Somatostatinomas are rare neuroendocrine tumors (NET) that arise in the gastrointestinal (GI) tract. Because of their insidious growth, they are usually asymptomatic until late stages, presenting as malignant disease. We report the case of a 50-year-old woman who presented with epigastric abdominal pain, diarrhea and significant weight loss in the last two years. On clinical examination the patient met the criteria for neurofibromatosis type 1 (NF1). Abdominal CT and MRI revealed an infiltrative duodenal mass, with pancreatic invasion, locoregional enlarged lymph nodes and disseminated hepatic nodules. Microscopy and immunohistochemistry uncovered a neuroendocrine tumor, staining positive for chromogranin A (CgA), synaptophysin and somatostatin, with a Ki67 = 1%. Somatostatin receptors (SSTRs) type 2 were negative and SSTRs type 5 were positive in less than 50% of tumoral cells. Our patient was classified as a T3N1M1 stage IV metastatic duodenal grade 1 somatostatinoma and treatment with somatostatin analogues and chemotherapy with capecitabine and temozolomide was started, with so far abdominal imaging follow-up showing stable disease. When a patient is diagnosed with a rare NET, such as a somatostatinoma, it is of utmost importance to determine if it is a sporadic tumor or just a feature of a genetic disorder.
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http://dx.doi.org/10.3390/diagnostics10090620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555390PMC
August 2020

miRNAs-Based Molecular Signature for Mutated and Wild Type Colorectal Cancer: An Explorative Study.

J Immunol Res 2020 23;2020:4927120. Epub 2020 Jun 23.

Victor Babes National Institute of Pathology, 050096 Bucharest, Romania.

microRNAs (miRNAs) have been proposed as promising molecular biomarkers for diagnosis, prognosis, and responsive therapeutic targets in different types of cancer, including colorectal cancer (CRC). In this study, we evaluated the expression levels of 84 cancer-associated miRNAs in a cohort of 39 human samples comprising 13 peritumoral and 26 tumoral tissues from surgical specimens of CRC patients. mutations were detected in 11 tumoral samples. In a first analysis, we found 5 miRNAs (miR-215-5p, miR-9-5p, miR-138-5p, miR378a-3p, and miR-150-5p) that were significantly downregulated and one upregulated (miR-135b-5p) in tumoral tissues compared with the peritumoral tissues. Furthermore, by comparing miRNA profile between mutated CRC tissues respect to wild type CRC tissues, we found 7 miRNA (miR-27b-3p, miR-191-5p, miR-let7d-5p, miR-15b-5p, miR-98-5p, miR-10a-5p, and miR-149-5p) downregulated in mutated condition. In conclusion, we have identified a panel of miRNAs that specifically distinguish CRC tissues from peritumoral tissue and a different set of miRNAs specific for CRC with mutations. These findings may contribute to the discovering of new molecular biomarkers with clinic relevance and might shed light on novel molecular aspects of CRC.
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http://dx.doi.org/10.1155/2020/4927120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330647PMC
May 2021

Molecular Signature of Persistent Histological Inflammation in Ulcerative Colitis with Mucosal Healing.

J Gastrointestin Liver Dis 2020 Jun 3;29(2):159-166. Epub 2020 Jun 3.

Fundeni Clinical Institute, Bucharest; Carol Davila University of Medicine and Pharmacy, Bucharest; Victor Babeş National Institute of Pathology, Bucharest,Romania.

Background And Aims: Therapeutic targets in ulcerative colitis (UC) have evolved over time from clinical remission to biological and endoscopic remission. Histologic remission remains a debatable outcome due to lack of data regarding its impact on long-term evolution. The development of histologic activity scores has brought standardization. We aimed to identify mucosal markers differentiating histological inflammation from histological remission in UC patients.

Methods: The gene expression levels of 84 genes associated with inflammatory bowel diseases have been analyzed in 43 colonic mucosa samples from 30 patients with UC. The gene expression levels have been correlated with histological inflammation score of Geboes. Patients with endoscopic remission were divided by histological activity into two groups and molecular results were compared in order to identify differences in the mucosal gene expression.

Results: We found a significant Pearson correlation (p<0.001 and r>0.5) between the Geboes score and the expression of 29 genes, whereas negative correlation (p<0.001 and r<-0.50) was observed with two genes in the entire UC cohort. In the subgroup of patients with endoscopic remission three transcripts: formyl-peptide receptor 1 (FPR1), matrix metalloproteinases 1 (MMP1) and mucine 1 (MUC1) were significantly up-regulated in patients with histological inflammation compared to patients with histologic remission.

Conclusion: Our study further emphasizes the importance of histological assessment when endoscopic mucosal healing is present, as FPR1, MMP-1 and MUC1 were all significantly upregulated in patients with histological alterations.
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http://dx.doi.org/10.15403/jgld-576DOI Listing
June 2020

An Overview on Primary Sclerosing Cholangitis.

J Clin Med 2020 Mar 11;9(3). Epub 2020 Mar 11.

Carol Davila University of Medicine and Pharmacy, 7000 Bucharest, Romania.

Primary sclerosing cholangitis is a progressive liver disease characterized by chronic inflammation leading to liver fibrosis and cirrhosis. Even though the exact pathogenesis is still unclear, a combination of autoimmune, environmental, and ischemic factors could explain certain aspects of the disease. The most important diagnostic step is cholangiography, which can be obtained either by endoscopic retrograde cholangiopancreatography (ERCP), magnetic resonance cholangiography (MRCP as the gold standard), or percutaneous transhepatic cholangiography. It shows multifocal short biliary duct strictures leading to the "beaded" aspect. Cholangiocarcinoma and colorectal adenocarcinoma are the most feared complications in patients with Primary sclerosing cholangitis (PSC). Continuous screening consists of annual clinical, biochemical, and ultrasound assessments in asymptomatic patients and annual colonoscopy in patients with PSC and inflammatory bowel disease. In newly diagnosed patients with PSC, colonoscopy is mandatory and, if negative, then, a repeat colonoscopy should be performed in 3-5 years. The lack of efficient curative medical treatment makes invasive treatments such as liver transplant and endoscopy the mainstream for managing PSC and its complications. Until now, even though only ursodeoxycholic acid has shown a moderate clinical, biochemical, and even histological improvement, it has no significant influence on the risk of cholangiocarcinoma, liver transplant need, or death risk and it is no longer recommended in treating early PSC. Further studies are in progress to establish the effect of molecular-targeted therapies in PSC.
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http://dx.doi.org/10.3390/jcm9030754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141307PMC
March 2020

Ovarian metastases reported after adjuvant laparoscopic oophorectomies in breast cancer.

Rom J Morphol Embryol 2019 ;60(3):913-920

Department of General Surgery, "Colţea" Clinical Hospital, Bucharest, Romania;

Introduction: Ovarian metastases (OM) of breast cancer (BC) can occur with different rates, ranging from 3-30%, being reported after prophylactic, therapeutic ovariectomies or discovered at necropsy. The aim of the study was to review the histopathological aspects of 59 laparoscopic oophorectomies performed in our Department as part of the oncological treatment of premenopausal women with BC. A number of eight (13.55%) patients were histologically confirmed with OM. The initial tumor, node, metastasis (TNM) stage of BC tumors was advanced with no pelvic symptoms or imaging abnormalities associated. Five (62.5%) patients had unilateral ovarian involvement and three (37.5%) bilateral, two of them being associated with primary bilateral BC. The immunohistochemical markers used to confirm the breast origin of metastasis were estrogen receptor (ER), progesterone receptor (PR), gross cystic disease fluid protein 15 (GCDFP15), Wilms' tumor 1 (WT1), cancer antigen-125 (CA-125), cytokeratin 7 (CK7), cytokeratin 20 (CK20). One case showed positive cytoplasmic reaction for thyroid transcription factor-1 (TTF-1). GCDFP15 was positive in all OM and almost all (seven of eight) were noted as non-immunoreactive for WT1. Although six cases of metastatic BC were positive for CK7 and negative for CK20, only four of them retain the same immunoprofile of their primary tumor for the metastatic ovarian lesions. Only one case out of eight showed weak and focal positivity for CA-125. Three cases were positive for mucin 1 (MUC1) and epithelial membrane antigen (EMA).

Conclusions: The differential diagnosis between OM and primary ovarian cancer can be challenging for the pathologist as well and immunostaining is of help. GCFDP15 is the most specific for breast carcinoma. In contrast with the recent papers published in the literature, we detected TTF-1 cytoplasmic expression in invasive breast carcinoma by SPT24 clone.
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June 2020

Lymphocytic Esophagitis Successfully Treated by Esophageal Balloon Dilation and Topical Budesonide.

J Gastrointestin Liver Dis 2019 Dec 9;28(4):379. Epub 2019 Dec 9.

Center for Digestive Diseases and Liver Transplantation, Fundeni Clinical Institute, Bucharest, Romania; Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.

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http://dx.doi.org/10.15403/jgld-217DOI Listing
December 2019

Mucosal gene expression changes induced by anti-TNF treatment in inflammatory bowel disease patients.

Drug Dev Res 2019 09 19;80(6):831-836. Epub 2019 Jul 19.

"Fundeni" Clinical Institute, Bucharest, Romania.

In the last two decades anti-tumor necrosis factor (anti-TNF) therapy for inflammatory bowel disease (IBD) has been widely used to induce and maintain clinical and endoscopical remission, completely changing management of the disease. In this study, we aimed to identify gene expression changes in inflamed mucosa from Crohn's disease and ulcerative colitis patients treated with 5-aminosalicylic acid (5-ASA) (N = 25) or anti-TNF agents (N = 12) compared to drug-free IBD patients (N = 12) and non-IBD control subjects (N = 18). The mucosal expression of 84 genes previously associated with IBD was evaluated by qPCR. We found that both therapeutic regimens induce a decrease in LCN2, NOS2, and TFF1, the levels of which are overexpressed in drug-free patients compared to non-IBD control subjects. Interestingly, a stronger effect of anti-TNF drugs was observed on LCN2 and TFF1 levels. However, 5-ASA seems to induce a more robust reduction of NOS2 expression. Moreover, we found that anti-TNF treatment significantly increased ABCB1, leading to levels similar to those found in non-IBD control subjects.
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http://dx.doi.org/10.1002/ddr.21566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6790597PMC
September 2019

Aspects regarding nomenclature, classification and pathology of neuroendocrine neoplasms of the digestive system - a review.

Rom J Morphol Embryol 2018 ;59(3):673-678

Department of Surgery, University of Medicine and Pharmacy of Craiova, Surgery Unit, Railway Clinical Hospital, Craiova, Romania;

Neuroendocrine neoplasms (NENs) of the digestive system are composed of cells with a neuroendocrine phenotype. These tumors produce and secrete peptide hormones and biogenic amines and they are called neuroendocrine neoplasms because of the marker proteins that they share with the neural cell system. The classification and nomenclature used to designate NENs have undergone changes over the past decades due to the accumulation of evidence related to the biological characteristics and their evolution. The European Neuroendocrine Tumor Society (ENETS) proposed a classification system based on the tumor grading and staging according to their localization. The latest internationally recognized NEN classification was published by the World Health Organization (WHO) in 2010. In accordance with the 2010 WHO criteria, the determination of the NEN malignancy potential is based on grading, depending on the mitotic activity and the Ki67 proliferation index, as well as on the tumor TNM stage. It is worth emphasizing that the terms neuroendocrine tumor (NET) and neuroendocrine carcinoma (NEC), without reference to grading or differentiation, are inadequate for prognostic assessment or the therapy determination, being inappropriate in pathology reports. The functional status of the tumor is based on the clinical findings but not on the pathological data or immunohistochemically profile. Despite the inability to establish a single system of sites, these are common features to establish the basis of most systems, documentation of these features allowing for greater reliability in the pathology reporting of these neoplasms.
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December 2018

Differential Intestinal Mucosa Transcriptomic Biomarkers for Crohn's Disease and Ulcerative Colitis.

J Immunol Res 2018 17;2018:9208274. Epub 2018 Oct 17.

Fundeni Clinical Institute, 022328 Bucharest, Romania.

Genetic research has shaped the inflammatory bowel disease (IBD) landscape identifying nearly two hundred risk loci. Nonetheless, the identified variants rendered only a partial success in providing criteria for the differential diagnosis between ulcerative colitis (UC) and Crohn's disease (CD). Transcript levels from affected intestinal mucosa may serve as tentative biomarkers for improving classification and diagnosis of IBD. The aim of our study was to identify gene expression profiles specific for UC and CD, in endoscopically affected and normal intestinal colonic mucosa from IBD patients. We evaluated a panel of 84 genes related to the IBD-inflammatory pathway on 21 UC and 22 CD paired inflamed and not inflamed mucosa and on age-matched normal mucosa from 21 non-IBD controls. Two genes in UC (CCL11 and MMP10) and two in CD (C4BPB and IL1RN) showed an upregulation trend in both noninflamed and inflamed mucosa compared to controls. Our results suggest that the transcript levels of CCL11, MMP10, C4BPB, and IL1RN are candidate biomarkers that could help in clinical practice for the differential diagnosis between UC and CD and could guide new research on future therapeutic targets.
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http://dx.doi.org/10.1155/2018/9208274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6207860PMC
January 2019

Early detection of advanced pancreatic cancer after DAA-induced virological cure in a liver transplant recipient with hepatitis C recurrence.

J Gastrointestin Liver Dis 2018 03;27(1):104-105

Gastroenterology and Liver Transplant Unit, Fundeni Clinical Institute, Bucharest, Romania.

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http://dx.doi.org/10.15403/jgld.2014.1121.271.daaDOI Listing
March 2018

Brunner's gland hyperplasia - a rare cause of gastrointestinal bleeding.

J Gastrointestin Liver Dis 2018 03;27(1)

Fundeni Clinical Institute, Gastroenterology Department, Bucharest, Romania.

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http://dx.doi.org/10.15403/jgld.2014.1121.271.brnDOI Listing
March 2018

The Orientation of Gastric Biopsy Samples Improves the Inter-observer Agreement of the OLGA Staging System.

J Gastrointestin Liver Dis 2017 Dec;26(4):351-356

Gastroenterology and Hepatology Center, Fundeni Clinical Institute, Bucharest, Romania.

Background And Aims: Evaluation of severity and extension of gastric atrophy and intestinal metaplasia is recommended to identify subjects with a high risk for gastric cancer. The inter-observer agreement for the assessment of gastric atrophy is reported to be low. The aim of the study was to evaluate the inter-observer agreement for the assessment of severity and extension of gastric atrophy using oriented and unoriented gastric biopsy samples. Furthermore, the quality of biopsy specimens in oriented and unoriented samples was analyzed.

Methods: A total of 35 subjects with dyspeptic symptoms addressed for gastrointestinal endoscopy that agreed to enter the study were prospectively enrolled. The OLGA/OLGIM gastric biopsies protocol was used. From each subject two sets of biopsies were obtained (four from the antrum, two oriented and two unoriented, two from the gastric incisure, one oriented and one unoriented, four from the gastric body, two oriented and two unoriented). The orientation of the biopsy samples was completed using nitrocellulose filters (Endokit®, BioOptica, Milan, Italy). The samples were blindly examined by two experienced pathologists. Inter-observer agreement was evaluated using kappa statistic for inter-rater agreement. The quality of histopathology specimens taking into account the identification of lamina propria was analyzed in oriented vs. unoriented samples. The samples with detectable lamina propria mucosae were defined as good quality specimens. Categorical data was analyzed using chi-square test and a two-sided p value <0.05 was considered statistically significant.

Results: A total of 350 biopsy samples were analyzed (175 oriented / 175 unoriented). The kappa index values for oriented/unoriented OLGA 0/I/II/III and IV stages have been 0.62/0.13, 0.70/0.20, 0.61/0.06, 0.62/0.46, and 0.77/0.50, respectively. For OLGIM 0/I/II/III stages the kappa index values for oriented/unoriented samples were 0.83/0.83, 0.88/0.89, 0.70/0.88 and 0.83/1, respectively. No case of OLGIM IV stage was found in the present case series. Good quality histopathology specimens were described in 95.43% of the oriented biopsy samples, and in 89.14% of the unoriented biopsy samples, respectively (p=0.0275).

Conclusion: The orientation of gastric biopsies specimens improves the inter-observer agreement for the assessment of gastric atrophy.
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http://dx.doi.org/10.15403/jgld.2014.1121.264.olgDOI Listing
December 2017

The role of confocal laser endomicroscopy in assessing mucosal healing in patients with ulcerative proctitis.

Endoscopy 2017 12 29;49(12):1285. Epub 2017 Nov 29.

Center for Digestive Diseases and Liver Transplantation, Fundeni Clinical Institute, Bucharest, Romania.

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http://dx.doi.org/10.1055/s-0043-119216DOI Listing
December 2017

Giardia duodenalis associated with intestinal metaplasia of the stomach.

J Gastrointestin Liver Dis 2017 09;26(3):221

Gastroenterology and Hepatology Department, Fundeni Clinical Institute, Bucharest, Romania.

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http://dx.doi.org/10.15403/jgld.2014.1121.263.giaDOI Listing
September 2017

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

Gut 2017 12 11;66(12):2080-2086. Epub 2017 Sep 11.

Departments of Gastroenterology and Pathology, Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania.

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.
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http://dx.doi.org/10.1136/gutjnl-2017-314297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5749338PMC
December 2017

The Romanian National Program for Liver Transplantation - 852 Procedures in 815 Patients over 17 Years (2000-2017): A Continuous Evolution to Success.

Chirurgia (Bucur) 2017 May-Jun;112(3):229-243

Liver transplantation (LT) has become an established treatment for end-stage liver disease, with more than 20.000 procedures yearly worldwide. The aim of this study was to analyze the results of Romanian National Program of LT. Between April 2000 and April 2017, 817 pts received 852 LTs in Romania. Male/female ratio was 487/330, while adult/pediatric ratio was 753/64, with a mean age of 46 years (median 50 yrs; range 7 months - 68 yrs). Main LT indications were HBV cirrhosis (230 pts; 28.2%), HCC (173 pts; 21.2%), and HCV cirrhosis (137 pts; 16.8%). Waiting time and indications for LT, patient and donor demographics, graft features, surgical procedures, and short and long-term outcomes were analyzed. DDLT was performed in 682 pts (83.9%): whole LT in 662 pts (81%), split LT in 16 pts (2.3%), reduced LT in 2 pts (0.2%), and domino LT in 1 pts (0.1%). LDLT was performed in 135 pts (16.5%): right hemiliver in 93 pts (11.4%), left lateral section in 28 pts (3.4%), left hemiliver in 8 pts (1%), left hemiliver with segment 1 in 4 pts (0.5%), and dual graft LDLT in 2 pts (0.2%). Overall major morbidity rate was 31.4% (268 pts), while perioperative mortality was 7.9% (65 pts). Retransplantation rate was 4.3% (35 pts): 27 whole LTs, 3 reduced LTs, 3 split LTs, and 2 LDLT. Long-term overall 1-, 3-, and 5-year estimated survival rates for patients were 87.9%, 81.5%, and 79.1%, respectively. One-, 3-, and 5-year overall mortality on waiting list also decreased significantly over time from 31.4%, 54.1% and 63.5%, to 4.4%, 13.9% and 23.6%, respectively. The Romanian National program for liver transplantation addresses all causes of acute and chronic liver failure or liver tumors in adults and children, using all surgical techniques, with good long-term outcome. The program constantly evolved over time, leading to decreased mortality rate on the waiting list.
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http://dx.doi.org/10.21614/chirurgia.112.3.229DOI Listing
November 2017

Pancreatic solid pseudopapillary neoplasm as an incidental discovery in a patient with rectal neoplasm.

J Gastrointestin Liver Dis 2017 03;26(1)

Center for Digestive Diseases and Liver Transplantation, Fundeni Clinical Institute, Bucharest, Romania.

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http://dx.doi.org/10.15403/jgld.2014.1121.261.psnDOI Listing
March 2017

Gene expression profile of endoscopically active and inactive ulcerative colitis: preliminary data.

Rom J Morphol Embryol 2017 ;58(4):1301-1307

Department of Gastroenterology II, "Fundeni" Clinical Institute, Bucharest, Romania;

Aim: Multiple cytokines and chemokines related to immune response, apoptosis and inflammation have been identified as molecules implicated in ulcerative colitis (UC) pathogenesis. The aim of this study was to identify the differences at gene expression level of a panel of candidate genes in mucosa from patients with active UC (UCA), patients in remission (UCR), and normal controls.

Patients, Materials And Methods: Eleven individuals were enrolled in the study: eight UC patients (four with active lesions, four with mucosal healing) and three controls without inflammatory bowel disease (IBD) seen on endoscopy. All the individuals underwent mucosal biopsy during colonoscopy. Gene expression profile was evaluated by polymerase chain reaction (PCR) array, investigating 84 genes implicated in apoptosis, inflammation, immune response, cellular adhesion, tissue remodeling and mucous secretion.

Results: Seventeen and three genes out of 84 were found significantly differentially expressed in UCA and UCR compared to controls, respectively. In particular, REG1A and CHI3L1 genes reported an up-regulation in UCA with a fold difference above 200. In UCR patients, the levels of CASP1, LYZ and ISG15 were different compared to controls. However, since a significant up-regulation of both CASP1 and LYZ was observed also in the UCA group, only ISG15 levels remained associated to the remission state.

Conclusions: ISG15, that plays a key role in the innate immune response, seemed to be specifically associated to the UC remission state. These preliminary data represent a starting point for defining the gene profile of UC in different stages in Romanian population. Identification of genes implicated in UC pathogenesis could be useful to select new therapeutic targets.
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September 2018

Mucosal CCR1 gene expression as a marker of molecular activity in Crohn's disease: preliminary data.

Rom J Morphol Embryol 2017 ;58(4):1263-1268

Department of Gastroenterology II, "Fundeni" Clinical Institute, Bucharest, Romania;

Aim: A series of mechanisms of immune response, inflammation and apoptosis have been demonstrated to contribute to the appearance and evolution of Crohn's disease (CD) through the overexpression of several cytokines and chemokines in a susceptible host. The aim of this study was to identify the differences in gene expression profiles analyzing a panel of candidate genes in the mucosa from patients with active CD (CD-A), patients in remission (CD-R), and normal controls.

Patients, Materials And Methods: Nine individuals were enrolled in the study: six CD patients (three with active lesions, three with mucosal healing) and three controls without inflammatory bowel disease (IBD) seen on endoscopy. All the individuals underwent mucosal biopsy during colonoscopy. Gene expression levels of 84 genes previously associated with CD were evaluated by polymerase chain reaction (PCR) array.

Results: Ten genes out of 84 were found significantly differentially expressed in CD-A (CCL11, CCL25, DEFA5, GCG, IL17A, LCN2, REG1A, STAT3, MUC1, CCR1) and eight genes in CD-R (CASP1, IL23A, STAT1, STAT3, TNF, CCR1, CCL5, and HSP90B1) when compared to controls. A quantitative gene expression analysis revealed that CCR1 gene was more expressed in CD-A than in CD-R.

Conclusions: Our data suggest that CCR1 gene may be a putative marker of molecular activity of Crohn's disease. Following these preliminary data, a confirmation in larger cohort studies could represent a useful method in order to identify new therapeutic targets.
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September 2018

Endoscopic aspect of a severe CMV colitis induced by azathioprine in a patient with ulcerative colitis.

J Gastrointestin Liver Dis 2016 Dec;25(4):429

Gastroenterology and Hepatology Department, Fundeni Clinical Institute, Bucharest, Romania.

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http://dx.doi.org/10.15403/jgld.2014.1121.254.edaDOI Listing
December 2016

Ménétrier's disease: a rare entity which mimicks gastric cancer.

J Gastrointestin Liver Dis 2016 Jun;25(2):137

Department of Gastroenterology and Hepatology, Fundeni Clinical Institute, Bucharest, Romania.

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http://dx.doi.org/10.15403/jgld.2014.1121.252.menDOI Listing
June 2016

The Orientation of the Gastric Biopsy Specimen for the Gastric Atrophy Assessment Is Important.

J Gastrointestin Liver Dis 2016 Mar;25(1):123-4

Center of Gastroenterology and Hepatology, Fundeni Clinical Institute, Bucharest, Romania.

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http://dx.doi.org/10.15403/jgld.2014.1121.251.bsyDOI Listing
March 2016
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