Héla Elloumi

Plummer Vinson syndrome association with coeliac disease.

The association between Plummer–Vinson syndrome (PVs) and coeliac disease (CD) is not widely reported. In both entities there is iron-deficiency anaemia. This case report emphasises that the diagnosis of CD must be borne in mind each time we face a case of iron-deficiency anaemia, especially when associated with PVs. We describe two patients with CD who presented as PVs. These case reports emphasise the need of screening for CD in patients with PVs.

Intractable gastrointestinal bleeding from angiodysplasia in a patient with Bernard–Soulier syndrome

Dear Editor, Angiodysplasia is a disorder consisting of ectasia of submucosal vessels, which causes acute and chronic bleeding. The presence of concomitant bleeding diathesis can increase the frequency and severity of gastrointestinal (GI) bleeding. Bernard–Soulier syndrome (BSS) is a rare congenital bleeding disorder characterized by a prolonged bleeding time, large platelets, and thrombocytopenia. We report a patient with BSS and GI angiodysplasia who did not respond to treatment options, illustrating the challenges in the management of such cases. A 30-year-old man complaining with melena, palpitation, and severe fatigue for 3 weeks was referred to our department. He had been diagnosed with BSS at the age of 2 years, when hemostatic studies were performed for epistaxis. He is the offspring of a consanguineous firstdegree relationship. His parents did not have any bleeding history, but his sister had been diagnosed with BBS. The dysfunctional platelets in this family resulted from a mutation (Ser23 Stop) in the GPIbβ gene, which was diagnosed by PCR amplification and sequencing. On physical examination, he looked pale and had tachycardia. Digital rectal examination revealed melena. Laboratory findings were as follows: hemoglobin, 5.4 g/dl and platelet count, 30×10/μl. A peripheral smear disclosed giant platelets and anisocytosis. Endoscopy of the upper GI tract, performed after blood transfusion, showed an angiodysplasia in the duodenum with active bleeding. Therefore, treatment with octreotide was commenced, following a course of proton pump inhibitor. Endoscopic therapy, including coagulation and sclerosing injections, was performed thereafter. However, melena continued and the platelet count decreased (7×10/μl), necessitating repeated blood and platelet transfusions. Oestroprogestative therapy, activated factor VIIa replacement (rFVIIa), and desmopressin were given without success. Since supportive management was not sufficient to control bleeding, angiography and embolization were performed. However, melena recurred shortly afterwards. Laparotomywas not carried out because of the poor general condition of the patient. The patient died 3 months after the onset of bleeding. Angiodysplasia may present in the young, highlighting the possible role of the hemostatic state in its pathogenesis. The defective platelet function in our case caused a delayed cessation of bleeding, which resulted in massive hemorrhage and increasing amounts of transfusions. Although we did not measure antiplatelet or antierythrocyte antibodies, the gradually decreasing platelet count and inadequate increases in platelet and hemoglobin counts after transfusions might be indicators of alloimmunization, which could have been another factor in the bleeding tendency. Therapeutic approaches for these entities include both general and specific treatment of bleeding. Desmopressin, rFVIIa, and octreotide administration have been shown to shorten the bleeding time [1, 2]. Oestroprogestative therapy has been tried in patients with GI bleeding from angiodysplasia; however, there have been contradictory results regarding its success [3–6]. Endoscopic therapy is used to eliminate bleeding angiodysplasia, although the success of this treatment is variable. Surgical resection may be the definitive therapy in cases where the bleeding lesion is A. Ouakaa-Kchaou (*) :D. Gargouri :H. Elloumi : J. Kharrat : A. Ghorbel Department of Gastroenterology, Habib Thameur Hospital, 8, Ali Ben Ayed Street, Montfleury, 1008, Tunis, Tunisia e-mail: asma.kchaou@voila.fr

Immunohistochemistry in the diagnosis of dysplasia in chronic inflammatory bowel disease colorectal polyps

BACKGROUND AND STUDY AIMSnDevelopment of cancer is the most significant complication in inflammatory bowel disease (IBD). Distinguishing true dysplasia from reactive atypia in polyps is difficult, leading sometimes to the unsatisfactory diagnosis of indefinite for dysplasia. Therefore, there is a need for the development of markers that can help improve diagnosis. We evaluated the diagnostic value of the expression of AMACR, Ki67 and p53 by immunohistochemistry in the diagnosis of dysplasia in polyps developed on IBD.nnnPATIENTS AND METHODSnForty colorectal polyps in IBD were studied. These had been diagnosed over a period of 11years. Dysplasia was classified according to the Vienna Classification (version 2000). Immunohistochemistry was performed using anti-AMACR, anti-Ki67 and anti-p53 antibodies.nnnRESULTSnPolyps were classified as follows: 21 negative for dysplasia (ND), 10 indefinite for dysplasia (IFD), 6 low-grade dysplasia (LGD), 1 high-grade dysplasia (HGD) and 2 adenocarcinomas (ACA). AMACR positivity was observed in all polyps with HGD and ACA, 5 of the 6 LGD polyps and 3 of the 10 IFD (p=0.007). p53 immunostaining showed nuclear staining in the basal part of the crypts in 8 of the 10 IFD lesions. In ACA and HGD polyps, p53 positivity was typically observed in all epithelial cell layers (p=0.004). ACA and HGD showed diffuse and scattered staining of Ki67 along the full length of the crypts. Five lesions with LGD had extension of Ki-67 positive cells up to and into the surface epithelium. Ki67 staining in all IFD lesions was restricted to the basal third of the crypt (p<0.001). By combining the three markers, a relationship with dysplasia was statistically significant (p<0.001). Sensitivity ranged from 66.7% to 88.9% and specificity from 71.4% to 100%. The positive predictive value (PPV) for detecting dysplasia using these different antibodies ranged from 66.7% to 100% and the negative predictive value (NPV) for excluding dysplasia ranged from 85.7% to 93.3%.nnnCONCLUSIONSnThe high degree of sensitivity and specificity of AMACR, p53 and Ki67 for dysplasia in IBD suggests that these antibodies, when combined, may be useful to detect neoplastic epithelium in this condition.

Expression of epidermal growth factor receptor (EGFR) in colorectal cancer: An immunohistochemical study

BACKGROUND AND STUDY AIMnThe epidermal growth factor receptor (EGFR) plays an important role in tumourigenesis and tumour progression of colorectal cancer (CRC) and leads to the activation of intracellular signaling pathways. The use of anti-EGFR-targeted therapy has increased for patients with metastatic CRC. Today, the clinical utility of immunohistochemistry has remained somewhat inconclusive. It is based on EGFR screening methods using paraffin-embedded tumour specimen to select patients eligible for treatment. There is still lack of agreement on reproducible scoring criteria for EGFR immunohistochemistry has in various clinical trials.nnnPATIENTS AND METHODSnWe retrospectively reviewed 36 CRC patients who underwent surgeries during 2011 in Habib Thameur hospital in Tunis. We analyzed the immunohistochemical overexpression of EGFR using a score based on immunostaining intensity. In addition, we analyzed the correlation between this overexpression and patients clinicopathologic parameters.nnnRESULTSnThe positive expression rate of EGFR was 78% (28/36). Using the immunoreactivity score, 21 cases were considered low grade expression and 15 tumours were high grade. Immunohistochemical expression of EGFR showed a significant difference with tumours location (pu202f=u202f0.034) and vascular invasion (pu202f=u202f0.03). This expression was not significantly associated with age, gender, tumour size, histological type, grade, TNM staging and perineural invasion.nnnCONCLUSIONSnEGFR expression by immunohistochemistry in CRC is variably correlated with clinicopathological parameters. Its assessment by this method has still not proved its predictive value.

Known, new and emerging risk factors of hepatocellular carcinoma (review)

Hepatocellular carcinoma (HCC) is the commonest primary cancer of the liver and is a leading cause of cancer-related death worldwide. And despite effective treatment of hepatitisxa0B and C infection which is the prominent factor associated with HCC, the prevalence of this malignancy continues to rise probably due to other factors. So that, identifying risk factor of HCC is essential and effective surveillance programs are necessary in order to maximize patient outcomes. This article summarizes the known, new and emerging risk factors of HCC.

Systematic gastric biopsy in iron deficiency anaemia

BACKGROUND AND STUDY AIMSnGastric biopsies are recommended in patients with iron deficiency anaemia to identify atrophic gastritis. However, in practice, only duodenal biopsies are routinely performed. The aim of our study was to determine the value of gastric biopsies in iron deficiency anaemia.nnnPATIENTS AND METHODSnA prospective study including all patients referred for gastrointestinal endoscopy for iron deficiency anaemia from May 2008 to September 2014 was performed. All patients having endoscopic lesions which may explain occult bleeding were excluded, as well as patients using non-steroidal anti-inflammatory drugs or anticoagulation treatment. Two fundic biopsies, two antral biopsies, and one biopsy from the lesser curve were taken in all patients. Following entities were particularly looked for: chronic gastritis, Helicobacter pylori infection, intestinal metaplasia, endocrine hyperplasia and villous atrophy. In cases where intestinal metaplasia was present in the fundus and associated with endocrine hyperplasia and glandular atrophy, immunohistochemical study was performed to confirm autoimmune gastritis.nnnRESULTSnOne hundred seventy-seven patients (mean age 50u202fyears, range: 15-90) were included. Chronic gastritis was found in 149 cases (84%). Infection by Helicobacter pylori was found in 107 cases (60%). Fundic intestinal metaplasia was observed in 25 patients (14%) and was associated with Helicobacter pylori infection in 52% of cases. Atrophic gastritis was observed in 14 cases (8%) and autoimmune gastritis was confirmed in 5 cases by immunohistochemical study. One patient had on gastric biopsy a carcinoma with signet ring cells.nnnCONCLUSIONnIntestinal metaplasia was frequently observed and was mostly related to Helicobacter pylori infection. These patients require monitoring, especially if they are young because it represents a pre neoplastic condition. However, in our study autoimmune gastritis often described in the literature in case of iron deficiency anaemia was rarely seen raising the question of relative cost-efficiency of fundic biopsies during iron deficiency anaemia.

(164) Hepatic steatosis in chronic hepatitis B: Contributing factors and effect on fibrosis

AIMnTo determinate factors that contribute to the steatosiss formation in chronic hepatitis B, to evaluate its influence on the development of hepatic fibrosis and to research an eventual relation to virologic factors in a Tunisian cohort of patients.nnnMETHODSnAll patients with chronic hepatitis B confirmed by data of liver biopsy were included in this study, which was enrolled from 1990 to 2006. The studied parameters were: age, gender, body mass index, transaminases, cholesterol, triglycerides, glycaemia and DNA rate, status HBe antigen and the degree of activity and histological fibrosis was estimated according to the score of METAVIR.nnnRESULTSnFifteen patients (34.1%) among the 44 patients includes in this study had hepatic steatosis; that was mild in 10 patients (66.6%), moderate in 3 cases (20%) and severe in 2 patients (13.4%). The antigen HBe was negative in 27 patients (62.22%). The mean age of the patients having a steatosis was of 32.33 years versus 27.75 years for those who had no it (p=0.185). The transaminases rate was superior in patients with steatosis than those without, the difference was not significant. Univariate correlation between predictor variables was studied. Significant predictors to steatosis included body mass index (p=0.011) and cholesterol (p=0.037). HBe Ag status was not associated with steatosis. Neither activity nor fibrosis was correlated with steatosis.nnnCONCLUSIONnIn Tunisian patients, factors contributing to the formation of steatosis during the chronic hepatitis B were the body mass index and the rate of cholesterol. The steatosis did not seem to have an influence on the development of the hepatic fibrosis and seems to be independent on the viral effect.