Chronic myeloid leukemia in an ulcerative colitis patient receiving azathioprine: A case report.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease usually treated by azathioprine. It is a well-established risk factor for colorectal cancers and extraintestinal malignancies. Nevertheless, the risk of myeloid leukemia in patients with UC is less known. We report a case of a 51-year-old patient, with a history of extensive ulcerative colitis, who was treated with azathioprine at a dose of 2.5 mg/kg/day. Seven years later, he presented an increased count of white blood cells at 25,400/µL and of platelets at 1,382,000/µL. Peripheral blood smear showed 1% blasts and 20% myelemia. The karyotype showed the Philadelphia chromosome and the RT-PCR revealed the BCR-ABL transcript. Thus, chronic myeloid leukemia (CML) was confirmed and imatinib was prescribed. This case reported a rare and serious event in a UC patient and illustrates the importance of closely monitoring this population.

Hepatic hydrothorax: About a hospital serie of 63 cases.

BACKGROUND: Hepatic hydrothorax is a less common complication of cirrhosis with an estimated prevalence of 10- 15%. In the vast majority of cases, ascites are also present but significant pleural effusion may develop in patients without ascites. Hepatic hydrothorax is associated with cirrhosis whatever its etiology. The prognosis of hepatic hydrothorax remains unclear and is closely related to available therapeutic options. The aim of our study is to determine the prevalence of hydrothorax in cirrhotic patients, detail its clinical and therapeutic characteristics, and study the evolutive profile of cirrhotic patients with hydrothorax by comparing it to those without hydrothorax. We also search predictive factors of development of this complication in cirrhotic patients. METHODS: We conduct a retrospective and case-control study including 63 cirrhotic patients with hepatic hydrothorax hospitalized in gastroenterology department of Charles Nicolle hospital of Tunis, during a period of fiveteen years, from January 2000 to January 2015. RESULTS: The prevalence of hydrothorax was 14.5%. The mean age was 62 ± 14 years (range, 22- 86 years). The sex ratio H/F was 1.52. Hepatic hydrothorax was symptomatic in 35 patients. It was right-sided in 60%, left-sided in 24% and bilateral in 16% of cases. Hydrothorax was on average size abundance in 54% of cases. It was transsudatif in 52.5% of cases. Hepatitis C was the most frequent cause of cirrhosis (54%). Our results show that hepatic hydrothorax was present with important ascites in 35 patients. Hydrothorax was significantly related to Child-Pugh C severity of cirrhosis (p=0.0001). Hydrothorax occurence was significantly associated with a low level of albumin (p=0.001), an important hyponatremia (p=0.001) and a low prothrombin rate (p=0.02). A therapeutic thoracentesis was performed in 57% of cases. Diuretics based on spironolactone and furosemide were indicated in 30 patients. Evolution was favorable in 19 patients. Refractory hepatic hydrothorax was present in 31 patients. Death, in the days which follow the hospitalisation, was in 13 patients. The 5-years survival rate was 60%. The mean survival time of patients with hepatic hydrothorax was 8.41 years against 10.75 years at patients without hepatic hydrothorax. CONCLUSION: Hepatic hydrothorax is a common complication in our study. The improvement of the prognosis of our patients would require a better therapeutic management and especially the possibility of orthotopic liver transplantation which is the optimal therapeutic option for patients with hepatic hydrothorax.

[Immunohistochemical analysis of mismatch repair proteins in colorectal adenomas]. / Analyse immunohistochimique des protéins de réparation de I'ADN dans les adénomes colorectaux.

BACKGROUND: The deficiency of mismatch repair system is one of the main pathways in colorectal cancer. This system consists mainly of four proteins: MLH1, MSH2, MSH6 and PMS2. Colorectal cancer develops in the majority of cases from precancerous lesions called adenomas. Only few studies have reported on the deficiencies of these proteins in adenomas. AIM: In this study we used immunohistochemistry staining in colorectal adenomas to assay functional status of MLH1, MSH2, MSH6, and PMS2 proteins. METHODS: 102 adenomas from 93 patients were collected in our institution during six years (2007-2012). The immunohistochemical technique was performed with 4 antibodies: MLH1, MSH2, MSH6 and PMS2. The loss of expression was retained if adenomatous cells were not stained with positive internal control. Staining was considered as abnormal if nucleus of adenomatous cells showed low nuclear staining and / or heterogeneous one, while positive internal control had normal staining. RESULTS: Loss of expression of MSH2 and MSH6 in adenomatous cells was found in only 1 case which was a tubular adenoma 3mm high-grade dysplasia. Abnormal staining of the adenomatous cells was noted in 23 cases (22.5%) for MSH2 and in 8 cases (7.8%) for MSH6. No cases showed loss of expression of MLH1 and PMS2. Abnormal expression of MSH2 and MSH6 was not correlated with sex of patients, the location of the adenoma, its grade of dysplasia and its histological type. CONCLUSIONS: Loss of Mismatch repair proteins expression is a rare event in adenomas. However, the abnormal expression levels are higher in our study compared to those reported in the literature. This could reflect a higher rate of microsatellite instability in our patients. Multicenter and larger studies with molecular biology techniques are needed.

[Efficiency of endoscopic treatment with intra gastric balloon in severe to morbid obesity]. / Efficacité du traitement endoscopique par le ballon intragastrique au cours de l'obésité severe à morbide.

BACKGROUND: Obesity raises such a healthcare matter throughout the world. Its management is not only complex but also most often multidisciplinary. The medico-dietary treatment is of inconstant efficiency and the surgical treatment, though more efficient, presents a considerable morbidity-death rate. The endoscopic treatment through intra-gastric balloon avails a seducing alternative namely accounting for surgery preparation. AIM: To assess the efficiency of the endoscopic treatment through gastric balloon, both in the short and long term, and this is accounting for weight loss as well as tolerance. METHODS: We have carried out a retrospective study including the patients suffering from severe to morbid obesity and who had a gastric balloon implemented in our Endoscopy Unit between November 2005 and December 2007. RESULTS: Twenty one patients were included. The average age was 32,19 ± 12,65 years with extremes of 16 and 52 years. Fifteen patients suffered from morbid obesity. The patients' average weight was 134, 52 ± 26,46 kg (extremes 88 and 194 kg). Some co-morbidity was found out with 15 patients. Te balloon implementation (Héliosphère®) was carried out with no incidents in all patients. Six months after the balloon implementation, the average weight loss was 17,5% and the average loss of over weigh was 37%. In biological level, we noted a normalisation of fasting glycaemia in 28,6 % of cases, of the cholesterolemia in 100 %, of the triglyceridemia in 33,33%, of the uraemia in 42,8% and hepatic tests in 50 % of the cases. The metabolic syndrome disappeared in 28,57 % of cases. The assessment after a 5-year-period was marked by the need to surgical treatment in 4 patients and this is due to the loss of efficiency of endoscopic treatment. A bad tolerance of gastric balloon was observed in 34 % of the cases, dominated by sicknesses. Only one patient presented incoercible sicknesses with ionic troubles as well as deshydrating requiring the precocious extraction of the balloon after 48 hours of its implementation. CONCLUSION: The endoscopic treatment through intra gastric balloon is well tolerated but efficiently limited in time. It might be recommended in preparation for a surgical treatment or in case of contre- indication or surgery refusal.

Evaluation of urolithiasis in Crohn's disease in Tunisian patients.

AIM: To investigate the characteristics of urolithiasis associated with Crohn's disease (CD) in a sample of Tunisian population. METHODS: We retrospectively studied 184 patients with CD to reveal any urolithiasis during evolution. Evidence for the presence of renal calculi was obtained from plain films, ultrasonography or intravenous urography and computed tomography. RESULTS: Renal calculi were found in only three patients with CD. All patients were woman. Mean time from diagnosis of CD to diagnosis of calculi was 22 months (range 6 to 48 months). Clinical features were not specific. Calculi were bilateral in two cases. CONCLUSIONS: The rate of concurrent urolithiasis was very low in the present series of Tunisian patients. Although rare, efficient treatment and prevention of calculi formation are mandatory in CD patients'.

[Epidemiology of hepatitis C in Tunisia]. / Epidemiologie de l'hepatite C en Tunisie.

BACKGROUND: Hepatitis C virus (HCV) infection is one of the main causes of chronic liver disease worldwide. AIM: To describe epidemiological patterns of hepatitis C in Tunisia. METHODS: Literature review. RESULTS: In Tunisia, the prevalence of HCV infection is about 0, 7 % in the general population with an increased transmission in the north of the country. Genotype 1b is the most frequent (76 % - 88 %).

Pseudoachalasia as the first manifestation of signet-ring cell duodenal carcinoma.

INTRODUCTION: Pseudoachalasia is a rare clinical condition, often caused by malignancy. Rarely, this entity can reveal the underlying neoplasia. To the best of our knowledge, we report the first case of pseudoachalasia revealing a metastatic signet-ring cell carcinoma of the non-ampullary duodenum. CASE REPORT: A previously healthy 67-year-old patient presented with a 3-month history of rapidly progressive intermittent dysphagia with 20kg weight loss. An upper endoscopy showed multiple duodenal ulcerations on congestive mucosa. Duodenal biopsies revealed tumor proliferation formed by independent cells with atypical nuclei. In immunohistochemistry, tumor cells expressed pan-cytokeratin. Esophageal manometry revealed an aspect in favor of achalasia type II. The CT scan showed ascites and pleural effusion. Their punctures confirmed the presence of neoplastic cells. The diagnosis of metastatic signet-ring cell duodenal carcinoma revealed by pseudoachalasia was retained. CONCLUSION: In the presence of rapidly progressive symptoms with significant weight loss, especially in the elderly patients, malignancyassociated pseudoachalasia should be suspected.

Impaired control of effector T cells by regulatory T cells: a clue to loss of oral tolerance and autoimmunity in celiac disease?

OBJECTIVES: Regulatory T cells (Tregs) are instrumental for tolerance to self-antigens and dietary proteins. We have previously shown that interleukin (IL)-15, a cytokine overexpressed in the intestine of patients with celiac disease (CD), does not impair the generation of functional Tregs but renders human T cells resistant to Treg suppression. Treg numbers and responses of intestinal and peripheral T lymphocytes to suppression by Tregs were therefore compared in CD patients and controls. METHODS: Intraepithelial lymphocytes (IELs) and lamina propria lymphocytes (LPLs) were isolated from duodenal biopsy specimens of CD patients and controls. Concomitantly, CD4+CD25+ T lymphocytes (Tregs) were purified from blood. Responses of IELs and of LPLs, and peripheral lymphocytes (PBLs) to suppression by Tregs were tested by analyzing anti-CD3-induced proliferation and interferon (IFN)-γ production in the presence or absence of peripheral Tregs. Lamina propria and peripheral CD4+CD25+FOXP3+ T cells were assessed by flow cytometry. RESULTS: Although percentages of CD4+CD25+FOXP3+ LPLs were significantly increased in patients with active CD, proliferation and IFN-γ production of intestinal T lymphocytes were significantly less inhibited by autologous or heterologous Tregs in CD patients than in controls (P < 0.01). In all tested CD patients, IEL were unable to respond to Tregs. Resistance of LPLs and PBLs to Treg suppression was observed in patients with villous atrophy who had significantly enhanced serum levels of IL-15 compared with patients without villous atrophy and controls. CONCLUSIONS: Our results indicate that effector T lymphocytes from active CD become resistant to suppression by Tregs. This resistance might cause loss of tolerance to gluten, but also to self-antigens.

[Epidemiological, clinical and therapeutic features of hepatocellular carcinoma in cirrhotic patients]. / Aspects épidémiologiques, cliniques et thérapeutiques du carcinome hépatocellulaire chez le cirrhotique.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most frequent primitive hepatic tumor, the fifth most common cancer in the world,and the third highest cause of cancer-related mortality. The presence of cirrhosis is the main risk factor. AIM: To describe the epidemiological, clinical and therapeutic features of HCC. METHODS: Retrospective study including all the patients with HCC occurring in cirrhotic liver followed in the gastroenterological department of Charles Nicolle hospital between 1997 and 2009. RESULTS: A hundred and one patient were enrolled; 64 men and 37 women with a median age of 65.4 years (31-88 years). Cirrhosis was due to viral hepatitis B or C in 25.7% and 62.2% of cases respectively and was classified Child Pugh A, B and C in 30.7%,50.5% and 18.8% of patients respectively. HCC was inaugural in most cases (68.3 %) and it was revealed by a tumoral syndrome in 38.6% of cases, by decompensation in 22.7% and was discovered during systematic screening when cirrhosis was already known in 19.8% of cases. Diagnosis of HCC was non invasive, relying on imaging and alphafetoprotein in most cases (95%). 84 patients(83.2%) had an advanced HCC, with vascular or extra hepatic spread in 58 (57.5%) of them. Treatment was curative in 14 cases, based on surgical resection in one case and percutaneous ablation in 13 cases.Six patients received transarterial chemoembolization as a palliative treatment. In 71 patients, only symptomatic treatment was given. The median survival time was 11 months. CONCLUSION: In the majority of the cases, HCC was diagnosed at an advanced stage and treatment was only symptomatic.

[Prevalence and risk factors of thromboembolic complications in inflammatory bowel disease]. / Prévalence et facteurs de risque des complications thromboemboliques au cours des maladies inflammatoires chroniques de l'intestin.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are at increased risk of thromboembolic complications (TEC), which represent an important cause of morbidity and mortality. AIM: To assess the prevalence and risk factors of TEC in patients with IBD. METHODS: We conducted a retrospective study including all the IBD patients in the gastroenterological department of Charles Nicolle hospital between 2000 and 2010. Only thromboembolic events that had been diagnosed by an imaging procedure were counted. RESULTS: A total of 266 patients with IBD were consecutively included. TE events occurred in nine patients (3.4%); six men and three women. Their mean age was 31 years [15-64 years]. Five patients had Crohn's disease and four had ulcerative colitis. The types of TEC were deep venous thrombosis of the leg in five cases with pulmonary embolism in one of them, cerebral venous thrombosis in two cases, portal thrombosis in one case and jugular vein thrombosis in one case. Active disease was present in all cases at the time TEC occurred. CONCLUSIONS: In our study, the prevalence of TEC is 3.4% in patients with IBD. Deep venous thromboses of the leg are the most common TEC and all our cases occurs during the active phase of IBD.

Colonoscopy in elderly: feasibility, tolerance and indications: about 901 cases.

BACKGROUND: Colonoscopy is the standard investigation for colonic disease, but clinicians often are reluctant to refer elderly patients for colonoscopy because of a perception of higher risk and a high rate of incomplete examinations. AIMS: To evaluate feasibility and tolerance of this investigation in elderly and to review the most frequent indications of colonoscopy in these patients. METHODS: A pilot retrospective study including 901 patients from January 2005 to December 2009; divided into two groups. Group (I) included patients 75 years old and more, group (II) included patients 45 years old or less. All those patients underwent colonoscopy at the gastroenterology department of Charles Nicole hospital. RESULTS: The 1st group included 231 patients, and the 2nd group included 670 one. A past history of colorectal cancer was more frequent in the group I (33.3% versus 9.90%; p<0.05) however history of chronic inflammatory bowel disease was more frequent in group II (0 versus 40.6%; p<0.05). The main indication of colonoscopy was constipation in group II (6.1% versus 27%; p<0.05) and chronic diarrhoea in group I (42.9% versus 16.4%; p<0.05). Bowel preparation was poor in 30.4% cases of the group I and 12.9% of group II (p<0.05). The tolerance was similar in the two groups. The incomplete colonoscopy rate was higher in the group I (38.3% versus 23.4%; p<0.05). The most frequent cause of colonoscopy interruption was the poor preparation in group I and the bad tolerance in group II. Diverticular disease, polyps and colorectal cancers prevailed in group I, whereas inflammatory bowel disease was current in group II. CONCLUSION: In elderly patients, colonoscopy is safe, well tolerated and offers a good diagnostic yield. Its non completion was essentially due to the poor preparation. Sedation did not seem essential. The optimisation of results of colonoscopy requires an improvement of quality preparation.

Anemia-induced liver injury: A rare case revealing glucose-6-phosphate dehydrogenase deficiency.

Hypoxic hepatitis may occur due to hemodynamic mechanisms of hypoxia secondary to anemia without any context of reduced blood flow, respiratory failure, or shock state. Etiology of anemia should be investigated in order to avoid recurrence.

Pseudo-Meigs' Syndrome in Tunisian H Syndrome Female Patient: First Case Reported.

H syndrome is an extremely rare autosomal recessive affection caused by biallelic mutations in the SLC29A3 gene encoding the human equilibrative nucleoside transporter hENT3. The hallmark signs are cutaneous consisting of hyperpigmentation and hypertrichosis patches. Besides, associated systemic manifestations are highly various reflecting phenotypic pleiotropism. Herein, we report a first case of pseudo-Meigs' syndrome occurring in a young Tunisian H syndrome diagnosed patient with a novel homozygous frameshift mutation in exon 2 of the SLC29A3 gene: p.S15Pfs*86 inducing a premature stop codon. The patient developed ascites associated with left ovarian mass and she underwent surgery. After tumor resection, ascites disappeared rapidly. Histological examination showed serous cystadenoma of the ovary orienting the diagnosis towards pseudo-Meigs' syndrome.

Hepatocellular carcinoma with sarcomatous change.

BACKGROUND: Hepatocellular carcinoma (HCC) with sarcomatous change is an uncommon neoplasm with a poor prognosis. AIM: To report a new case. CASE REPORT: A 72-year-old man presented with abdominal right upper quadrant pain. The diagnosis of cirrhosis was suspected on clinical and biochemical data. On abdominal computed tomography, the mass was not enhanced in the arterial phase and exhibited peripheral enhancement during portal phase which persisted in the delayed phase. The serum alpha-fetoprotein was 500 ng/ml but since the imaging features were not typical of ordinary HCC, percutaneous liver biopsy was performed and confirmed the diagnosis of HCC with sarcomatous change. CONCLUSION: Except for liver biopsy, no diagnostic method could distinguish between sarcomatous and ordinary HCC.

[Nephrogenic ascites: an exceptional diagnosis. About one case]. / L'ascite Nephrogenique, Un Diagnostic Rare Auquel Il Faut Penser. A Propos D'une Observation.

BACKGROUND: Nephrogenic ascites is a clinical entity that manifests as refractory and exsudative ascites with unknown etiology in patients with end stage renal disease and often undergoing hemodialysis. This entity presents in practice many diagnostic and therapeutic difficulties. AIM: The aim of this study is to focus on these difficulties through a new observation. CASE REPORT: We report one case of nephrogenic ascites in chronic renal failure related to an idiopathic neurologic bladder. It's a 38 years old patient on hemodialysis for three years who consulted for exsudative ascites with a low rate of leucocytes. CONCLUSION: We conclude that nephrogenic ascites is rare. Its diagnosis is an exclusion diagnosis based on exclusion of other causes of ascites, particularly exsudative forms with low leucocytes rate. Its management is based essentially on renal transplantation and its prognosis is very poor.

Evaluation of nutritional status in patients with liver cirrhosis.

BACKGROUND: Malnutrition is a frequently reported complication in patients with liver cirrhosis. It has a high clinical and economic impact reflected by an increased morbidity and prolonged hospital stay. AIM: This preliminary prospective study aimed to determine the prevalence of malnutrition in hospitalized cirrhotic patients and to investigate whether biological and anthropometric parameters are a valuable tool for identifying malnutrition in these patients. METHODS: The nutritional status of 44 consecutive cirrhotic patients (21 men, 23 women) was assessed according to the anthropometric measurements and biochemical analysis. The diagnosis of malnutrition was based on diminished values of Mid arm muscle circumference (MAMC) and/or Triceps skinfold thikness (TST) below the 5th percentile or less than 60%. RESULTS: The aetiology of cirrhosis was viral hepatitis in 29 patients (66%). Cirrhosis was classified Child Pugh A, B or C in respectively 9, 26 and 9 patients; 37 patients (84%) have mild or tense ascite. In this study, malnutrition was found in 35 patients (79.5%), whereas 9 patients has a good nutritional status. TST and MAMC less than 60% was found in respectively 72% and 25% of patients. No significant statistical difference in epidemiological characteristics was found between malnourished and well-nourished patients. TST and MAMC decreased significantly according to the Child score (p = 0.014 and 0.032 respectively; a positive correlation was found between these two parameters and the severity of cirrhosis. CONCLUSION: In this study, the high prevalence of denutrition was associated with the severity of cirrhosis. Anthropometric parameters are valuable tools for malnutrition diagnosis.

Correlation between liver biopsy and fibrotest in the evaluation of hepatic fibrosis in patients with chronic hepatitis C.

AIM: To assess the diagnostic value of Fibrotest in comparison with liver biopsy, for the evaluation of hepatic fibrosis in patients with chronic hepatitis C. METHODS: This prospective study included in 2 years (2006-2007), consecutive patients with chronic hepatitis C naive to treatment. Fibrotest and liver biopsy were performed. Receiver operating characteristics (ROC) curves , the sensitivity, specificity, positive and negative predictive values were used to assess the diagnostic value of Fibrotest in comparison with the METAVIR classification. RESULTS: We recruited a total of 65 patients: 28 males and 37 females (mean age: 50 years); 92% of the patients had genotype 1. The histological fibrosis results were: 3.1% F0; 24.6% F1; 32.3% F2; 29.2% F3 and 10.8 % F4. The diagnostic value of Fibrotest in the detection of significant fibrosis (F2-F4) was 0. 87. A score > 0.5 has a sensitivity of 85. 1%, a specificity of 72. 2%, a positive predictive value of 88. 9%,and a negative predictive value of 65%. The diagnostic value of Fibrotest in the detection of cirrhosis (F4) was 0. 85. There were 13/65 cases of discordance (20%) for fibrosis, 4 cases were attributable to biopsy and 6 cases to Fibrotest. The discordance was unexplained in 3 cases. the size of biopsy< 15 mm [OR=2. 82, 95% CI, 1. 3-6. 07; p = 0. 008] and the stage of fibrosis F0, F1, F2 [OR =3. 35 , 95% CI, 1. 1-10. 2; p=0. 03] were considered as risk factors of discordance in multivariate analysis. CONCLUSION: This prospective study confirmed the good diagnostic value of Fibrotest as compared with the histological analysis of liver biopsy.

[Autoimmune hepatitis type 1 triggered by cytomegalovirus infection. One rare case report]. / Infection à cytomégalovirus révélatrice d'une hépatite auto immune de type 1.

BACKGROUND: Autoimmune hepatitis is chronic and uncommon disease. The pathogenesis is a complex process. Several triggers for autoimmune hepatitis particularly viral herpesviridae infection, which may induce the development of autoimmunity in predisposed individuals. AIM: Report a new case. CASE REPORT: We report a case of 17-year- woman presented with autoimmune triggered by cytomegalovirus infection. Cytomegalovirus induced autoimmune hepatitis has not been reported previously. Evolution was favourable under antiviral treatment, corticosteroid and azathioprine.