Gastrointestinal Dysfunction and Neuropathologic Correlations in Parkinson Disease.

INTRODUCTION: Recently, an increasing interest to nonmotor symptoms of Parkinson disease (PD) has shown. Gastrointestinal dysfunction is a prominent nonmotor manifestation of PD and precedes motor symptoms for several years. Neuropathologic studies show early accumulation of α-synuclein (α-SYN) in Lewy neurites and Lewy body in the enteric nervous system (ENS) and dorsal motor nucleus of the vagus in PD. Our study aims to investigate relationship between α-SYN deposition in ENS and gastrointestinal dysfunction in PD. MATERIALS AND METHODS: We conducted a study in Neurology Department of Charles Nicolle Hospital of Tunis during 2 years (2013 to 2014) including PD patients. Clinical data were analyzed. Digestive endoscopy with biopsies of upper digestive tract (UDT) and immunohistochemistry study were performed. RESULTS: Thirty patients (16♂/14♀) and 13 (7♂/6♀) controls were included. Average age was 65 years for patients and 63.5 years for controls. Gastrointestinal symptoms were the most frequent nonmotor symptoms occurring in 73%. Endoscopy showed motor dysfunction of upper digestive tract in 5 patients. Lesion load in α-SYN was significantly correlated with frequency and severity of gastrointestinal dysfunction and PD motor disability. CONCLUSIONS: Gastrointestinal disturbances are frequent in PD. ENS's synucleinopathy could entirely explain pathophysiology of digestive dysfunction and is correlated with severity of gastrointestinal symptoms in PD. Biopsies may show α-SYN aggregates in immunoreactive Lewy neurites in the submucosal and myenteric plexus. Thus, endoscopic and immunohistochemical exploration of ENS may be a biomarker for Parkinson enteropathy and for PD overall.

Predictive scores of early mortality from variceal gastrointestinal bleeding in cirrhotic patients.

INTRODUCTION: The variceal bleeding, main complication of portal hypertension during cirrhosis, is associated with high early mortality riskestimated between 15 and 20%. This highlights the necessity of predictive models that allow identifying high-risk patients raising the issue of amore aggressive therapeutic care. OBJECTIVE: To assess the performance of four scores for the prediction of cirrhotic patients' high early mortality risk due to digestive hemorrhageand to compare them to the Child-Pugh reference score. METHODS: We collected 87 cirrhotic patients admitted to the Gastroenterology Department of Charles Nicolle Hospital for a high digestivehemorrhage by rupture of gastric or esophageal varicose veins. RESULTS: 56 men and 31 women were included in this study. The average value of Rockall, Glasgow Blatchford, MELD and MELD-Na scores,was respectively equal to 6.19, 10.91, and 17.6 and at 20. Early mortality was 30%. The average value of all the scores was significantly higherwith the prematurely deceased patients (p<0.001). The MELD-Na score had higher sensitivity and specificity for the prediction of prematuremortality compared to the other scores but without statistical significantly difference (Area under the ROC curve: MELD-Na=0.867, p<0.001;Child-Pugh=0.809, p<0.001; Rockall=0.777, p=0.001; Glasgow-Blatchford=0.761, p<0.001; MELD=0.838, p<0.001). The predictive value of thecut-off MELD-Na score was equal to 19 with a sensitivity of 70% and a specificity of 82%. CONCLUSION: The studied four scores had a good predictive value of early mortality risk by varicose digestive hemorrhage with cirrhotic patients.

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.

[Viral B reactivation: Risk factors and prevention]. / Réactivation virable B: facteurs de risqué et prevention.

BACKGROUND: The viral B reactivation is associated to deadly serious forms. There exist populations suffering this risk yet with a possibility of prevention through a pre-emptive treatment. PURPOSES: Establishing the diagnosis of a viral B reactivation. Identifying the patients with risk of exposure to viral B reactivation and implementing the means of prevention of viral reactivation. METHODS: literature review RESULTS: the diagnosis of reactivation is not consensual. It is evoked facing a fast increase of aminotransferases with the ALAT superior to 5-10 times normal or superior to 3 times the basic value, an ascension of the HBV DNA within the serum, a reappearance of anti Hbc of IgM type with, most often, a weak title and /or a reversion Hbs. The reactivation depends on the type of treatment and of the viral B status. It was described under chemotherapy concerning the solid tumors particularly that of the breast, in haematology and increases with the resort to monoclonal antibody (anti-CD20). Under anti-TNFα a reactivation is possible within a variable deadline from the 1st to the 12th perfusion. Besides the type of treatment, the risk is more important with the patients Ag Hbs positive and correlated with the viremia. However, the patients having an occult hepatitis B or even a recovered from hepatitis are equally exposed to the risk of reactivation. CONCLUSION: viral reactivation is frequent since the larger use of immunosuppressive therapy, anti-TNFα and monoclonal antibody. The determination of the initial viral B status by a serology is indispensable. In order to indicate either surveillance or a preemptive treatment.

Association between sHLA-G and HLA-G 14-bp deletion/insertion polymorphism in Crohn's disease.

The aim of this study was to evaluate the association between the HLA-G 14-bp deletion/insertion (Del/Ins) polymorphism and soluble (s) HLA-G production in patients with Crohn's disease (CD). We analyzed also the sHLA-G molecules by ELISA and western blot in plasma samples. Among unselected patients, the 14-bp Del/Ins polymorphism was not significantly associated with increased CD risk neither for alleles (P = 0.371) nor for genotypes (P = 0.625). However, a significant association was reported between the 14-bp Del/Ins polymorphism and CD, in particular in young-onset CD patients for alleles [P = 0.020, odds ratio (OR) = 2.438, 95% confidence interval (CI): 1.13-5.25] but not with adult-onset CD patients. A significant association was reported concerning the genotype Ins/Ins for young-onset CD patients (P = 0.029, OR = 3.257, 95% CI: 1.08-9.77). We observed also a significant increase in sHLA-G measured by ELISA in CD patients compared to controls (P = 0.002). The 14-bp Del/Del and 14-bp Del/Ins genotypes are the high HLA-G producers. Among sHLA-G(positive) patients, 43% of subjects present dimers of HLA-G. The presence of dimers seems to be related to the advanced stages of the disease. The 14-bp Del/Ins polymorphism is associated with an increased risk of CD particularly in young-onset CD patients and controls sHLA-G plasma levels. Dimers of sHLA-G are frequent in advanced disease stages. The above findings indicate that the genetic 14-bp Del/Ins polymorphism in exon 8 of the HLA-G gene is associated with the risk of CD and suggest a role for sHLA-G as a prognostic marker for progressive disease.

[Inter-observes agreement of Ishak and Metavir scores in histological evaluation of chronic viral hepatitis B and C]. / Reproductibilité des scores Ishak et Métavir dans la classification histopathologique des hépatites virales chroniques B et C.

Many classification systems are currently used for histological evaluation of the severity of chronic viral hepatitis, including the Ishak and Metavir scores, but there is not a consensus classification. The objective of this work was to study the intra and inter-observers agreement of these two scores in the histopathological analysis of liver biopsies in patients with chronic viral hepatitis B or C. Fifty nine patients were included in the study, 26 had chronic hepatitis C and 33 had chronic hepatitis B. To investigate the inter-observers agreement, the liver biopsies were analyzed separately by two pathologists without prior consensus reading. The two pathologists conducted then a consensual reading before reviewing all cases independently. Cohen's kappa coefficient was calculated and in case of asymmetry Spearman's rho coefficient. Before the consensus reading, the agreement was moderate for the analysis of histological activity with both scores (Metavir: kappa=0.41, Ishak: rho=0.58). For the analysis of fibrosis, the agreement was good with both scores (Metavir: kappa=0.61, Ishak: rho=0.86). The consensus reading has improved the reproducibility of the activity that has become good with both scores (Metavir: kappa=0.77, Ishak: rho=0.76). For fibrosis improvement was observed with the Ishak score which agreement became excellent (kappa=0.81). In conclusion, we recommend in routine practice, a combined score: Metavir for activity and Ishak for fibrosis and to make a double reading for each biopsy.

[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'.

Malignant epithelioid hemangioendothelioma: a case report.

Malignant epithelioid hemangioendothelioma (EH) is a rare tumor of vascular origin. We report a case of a woman who was found to have multiple hepatic masses in the right lobe of the liver on radiologic investigations, initially misdiagnosed as a metastatic carcinoma. The diagnosis of EH was made on histopathological study and confirmed by immunohistochemistry, which showed diffuse response for CD34 marker and no response to tissue CEA, HMB-45 or S-100 protein. Partial hepatectomy was made with good results.

[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 %).

Idiopathic megacaecum: clinical features and diagnostic approach.

Congenital megacaecum is a rare entity and difficult to diagnose. The pathogenesis of this malformation is not well known since there are very few cases reported in the literature. The purpose of this observation is to describe the functional signs that may suggest this rare diagnosis and the means to confirm it. We report the case of a 22-year-old young man, who complained of constipation associated with pelvic pain in the form of gravitational pull exacerbated by standing, sitting and going down the stairs. However, symptoms seemed to be relieved by supine positions. The radiological investigations concluded that the megacaecum dipped into the pelvis, but there was no evidence of mechanical or functional obstruction distally. The treatment consisted of a laparoscopic right colectomy. The postoperative course was uneventful. The megacaecum is rare and poorly understood. The abdominal pain is directly related to fecal stasis, which increases the pressure on cecal colonic segment and this in turn causes a pull on the mesentery. The entero-MRI is valuable in the diagnosis so as to eliminate other causes of chronic abdominal pain.