Selective expression of KCNA5 and KCNB1 genes in gastric and colorectal carcinoma.

BACKGROUND: Gastric and colorectal cancers are the most common malignant tumours, leading to a significant number of cancer-related deaths worldwide. Recently, increasing evidence has demonstrated that cancer cells exhibit a differential expression of potassium channels and this can contribute to cancer progression. However, their expression and localisation at the somatic level remains uncertain. In this study, we have investigated the expression levels of KCNB1 and KCNA5 genes encoding ubiquitous Kv2.1 and Kv1.5 potassium channels in gastric and colorectal tumours. METHODS: Gastric and colorectal tumoral and peritumoral tissues were collected to evaluate the expression of KCNB1 and KCNA5 mRNA by quantitative PCR. Moreover, the immunohistochemical staining profile of Kv2.1 and Kv1.5 was assessed on 40 Formalin-Fixed and Paraffin-Embedded (FFPE) gastric carcinoma tissues. Differences in gene expression between tumoral and peritumoral tissues were compared statistically with the Mann-Whitney U test. The association between the clinicopathological features of the GC patients and the expression of both Kv proteins was investigated with χ2 and Fisher's exact tests. RESULTS: The mRNA fold expression of KCNB1 and KCNA5 genes showed a lower mean in the tumoral tissues (0.06 ± 0.17, 0.006 ± 0.009) compared to peritumoral tissues (0.08 ± 0.16, 0.16 ± 0.48, respectively) without reaching the significance rate (p = 0.861, p = 0.152, respectively). Interestingly, Kv2.1 and Kv1.5 immunostaining was detectable and characterised by a large distribution in peritumoral and tumoral epithelial cells. More interestingly, inflammatory cells were also stained. Surprisingly, Kv2.1 and Kv1.5 staining was undoubtedly and predominantly detected in the cytoplasm compartment of tumour cells. Indeed, the expression of Kv2.1 in tumour cells revealed a significant association with the early gastric cancer clinical stage (p = 0.026). CONCLUSION: The data highlight, for the first time, the potential role of Kv1.5 and Kv2.1 in gastrointestinal-related cancers and suggests they may be promising prognostic markers for these tumours.

Identification of novel pathogenic MSH2 mutation and new DNA repair genes variants: investigation of a Tunisian Lynch syndrome family with discordant twins.

BACKGROUND: Lynch syndrome (LS) is a highly penetrant inherited cancer predisposition syndrome, characterized by autosomal dominant inheritance and germline mutations in DNA mismatch repair genes. Despite several genetic variations that have been identified in various populations, the penetrance is highly variable and the reasons for this have not been fully elucidated. This study investigates whether, besides pathogenic mutations, environment and low penetrance genetic risk factors may result in phenotype modification in a Tunisian LS family. PATIENTS AND METHODS: A Tunisian family with strong colorectal cancer (CRC) history that fulfill the Amsterdam I criteria for the diagnosis of Lynch syndrome was proposed for oncogenetic counseling. The index case was a man, diagnosed at the age of 33 years with CRC. He has a monozygotic twin diagnosed at the age of 35 years with crohn disease. Forty-seven years-old was the onset age of his paternal uncle withCRC. An immunohistochemical (IHC) labeling for the four proteins (MLH1, MSH2, MSH6 and PMS2) of the MisMatchRepair (MMR) system was performed for the index case. A targeted sequencing of MSH2, MLH1 and a panel of 85 DNA repair genes was performed for the index case and for his unaffected father. RESULTS: The IHC results showed a loss of MSH2 but not MLH1, MSH6 and PMS2 proteins expression. Genomic DNA screening, by targeted DNA repair genes sequencing, revealed an MSH2 pathogenic mutation (c.1552C>T; p.Q518X), confirmed by Sanger sequencing. This mutation was suspected to be a causal mutation associated to the loss of MSH2 expression and it was found in first and second degree relatives. The index case has smoking and alcohol consumption habits. Moreover, he harbors extensive genetic variations in other DNA-repair genes not shared with his unaffected father. CONCLUSION: In our investigated Tunisian family, we confirmed the LS by IHC, molecular and in silico investigations. We identified a novel pathogenic mutation described for the first time in Tunisia. These results come enriching the previously reported pathogenic mutations in LS families. Our study brings new arguments to the interpretation of MMR expression pattern and highlights new risk modifiers genes eventually implicated in CRC. Twins discordance reported in this work underscore that disease penetrance could be influenced by both genetic background and environmental factors.

Thyroid storm-induced acute liver dysfunction and portal hypertension in a patient with Graves' disease: a case report.

Thyroid storm is a life-threatening condition associated with multiorgan dysfunction and decompensation. We report the case of a 41-year-old woman having Graves' disease presented with thyroid storm complicated with liver dysfunction and portal hypertension in the absence of congestive heart failure or known liver disease. After successful therapeutic management, all biological, clinical and morphological abnormalities regressed.

Graves' disease is an immune system disorder that results in the overproduction of thyroid hormones. We report the case of a 41-year-old woman with Graves' disease who presented with reversible liver dysfunction and high blood pressure in the portal vein (located in the abdomen) following the withdrawal of her treatment.

Impact of direct-acting antiviral on subclinical atherosclerosis in chronic hepatitis C infected patients.

INTRODUCTION: The impact of direct antiviral drugs (DAAs) on extrahepatic manifestations in chronic hepatitis C (CHC) has been poorly studied. AIM: To assess the prevalence of subclinical atherosclerosis in patients with CHC and the impact of DAAs on atherosclerotic lesions. Methods A 5-year prospective evaluative study, including patients followed for CHC at hepato-gastroenterology department. The subclinical atherosclerosis was assessed by ultrasound measurement of carotid intima-media thickness (IMTc) and the highest IMTc measurements from the left and right side defined the IMTc maximum (IMTc max). IMTc>75th percentile (IMTc75) define subclinical atherosclerosis with high cardiovascular risk. Patients were evaluated before (T0) and one year after DAAs therapy achievement (T1). RESULTS: At time T0, forty patients (median age: 55 y.; sex ratio M / F = 0.48), were included. Average value of IMTc max was 0.68 ± 0.16 mm. Subclinical atherosclerosis was noted in 82.5 %. At time T1, 28 patients were evaluated, all of whom completed sustained virological response (SVR). Compared to time T0, there was a significant increase in cholesterol (p = 0.001) and triglyceride (p = 0.009) levels. IMTc max was significantly higher at time T1 compared to T0 (0.75 Vs 0.67 mm, p = 0.04). Prevalence of IMTc75 was 82.1% at time T0 and 75% at time T1 (p=0.5). CONCLUSIONS: SVR, in CHC patients treated with DAA, was associated with worsening of carotid atherosclerotic lesions.

Air embolism complicating endoscopic retrograde cholangiopancreatography.

Aim: Venous air embolism is a rare but potentially life threatening complication of endoscopic retrograde cholangiopancreatography. Diagnosis is difficult because of the lack of specific signs or symptoms. Case: A 62-year-old man underwent endoscopic retrograde cholangiopancreatography for choledocholithiasis. A cardiovascular collapse occurred during the procedure. The echocardiography showed air within the right ventricle. Aspiration of air from the right ventricle was done and saved the patient's life. Conclusion: We highlight through this case that increased awareness is essential for prompt recognition of the air embolism to allow life-saving therapy.

Endoscopic treatment is the first-line treatment for biliary stones. It may be associated with various complications. We report the case of a 62-year-old patient who underwent endoscopic treatment for biliary stone. During the procedure, he experienced disturbed cardiac function due to the passage of air bubbles into the cardiac cavities. The bubbles were aspirated with a good outcome.

Performance of the ADRESS-HCC score in the assessment of the risk of hepatocellular carcinoma in viral cirrhosis in Tunisia.

INTRODUCTION: The ADRESS-HCC score allows predicting the risk of occurrence of Hepatocellular carcinoma in cirrhosis at one year of follow-up. AIM: Measuring the performance of ADRESS-HCC in predicting the risk of degeneration on post-viral cirrhosis, in a gastroenterology department in Tunisia. METHODS: Retrospective study, including patients followed for compensated viral cirrhosis in the gastroenterology department of the Mohamed Taher Maamouri hospital. The ADRESS-HCC score was calculated at diagnosis of cirrhosis. We divided patients into two groups depending on whether they developed Hepatocellular carcinoma or not. We evaluated the performance of the ADRESS-HCC score in predicting the risk of Hepatocellular carcinoma according to a threshold value. RESULTS: We enrolled 60 patients; the mean age was 62 years. Twenty-five patients developed hepatocellular carcinoma during follow-up. The mean value of ADRESS-HCC score was 5.08. To predict the occurrence of hepatocellular carcinoma at 1 year of follow-up, the area under the curve of the ADRESS-HCC score was 0.74 (p=0.01). For a threshold value of 5.63 its sensitivity was 91 % with a negative predictive value of 95.83%. CONCLUSION: The ADRESS-HCC score had an average performance in predicting degeneration in post-viral cirrhosis.

A rare cause of spontaneous hemoperitoneum: intra-abdominal vein rupture.

Aim: Ruptures of the intra-abdominal vein causing a spontaneous hemoperitoneum in cirrhotic patients is a rare condition. However, diagnosis must be considered early in cirrhotic patients with hematic ascites as a delayed diagnosis with hemodynamic instability is associated with a poor prognosis. Case report: We present the case of a 54-year-old cirrhotic patient who presented a spontaneous hemoperitoneum due to the rupture of the intra-abdominal vein that was diagnosed during exploratory laparoscopy. Conclusion: Early diagnosis and management of spontaneous hemoperitoneum due to the rupture of intra-abdominal vein helps improve its prognosis.

Spontaneous hemoperitoneum is a rare but catastrophic condition caused by the rupture of the liver, spleen or abdominal vessels. In patients with cirrhosis, diagnosis of spotaneous hemoperitoneum is difficult. This is a case report of a 54-year-old cirrhotic man with a spontaneous hemoperitoneum due to the rupture of a vein within the abdomen. The diagnosis was suspected as the patient had signs of blood in the abdomen. To confirm spontaneous hemoperitoneum, the doctors performed a procedure called exploratory laparoscopy, which involves inserting a small camera into the abdomen. The laparoscopy confirmed the presence of blood and thus the diagnosis of spontaneous hemoperitoneum.

Multifocal nodular lesions in fatty liver mimicking neoplastic disease: a case report.

Usually, fatty hepatic infiltration is diffuse and homogeneous. However, in some cases, it can be localized simulating benign or malignant tumors. We present a case of a 61-year-old female patient with family history of malignancy: sister with lung cancer, an other sister with colon cancer and a mother with breast cancer; who presented with multiple hepatic nodules at the ultrasonography images. CT scan and MRI were not sufficient to pose a certain diagnosis which was later confirmed by liver biopsy.

In some cases, fatty hepatic infiltration may simulate benign or malignant tumors. We present a case of a 61-year-old female patient with family history of malignancy who presented with multiple hepatic nodules at the ultrasonography images. CT scan and MRI were not sufficient to pose a certain diagnosis which was later confirmed by liver biopsy.

A rare case of gastric metastasis originating from primary lung adenocarcinoma: a case report.

Unlike liver and lung, the stomach is rarely a metastatic location for cancers. We report a case of a 62-year-old man known to have lung adenocarcinoma poorly differentiated presented with melena 1 month after diagnosis. Upper endoscopy revealed an ulcerated tumor in the prepyloric antrum. The diagnosis of gastric metastasis from pulmonary cancer was confirmed by the immunohistochemical staining for the thyroid transcriptional factor-1 and the pattern cytokeratine CK7+/CK20-. In conclusion, gastric metastasis from primary lung cancer is a rare phenomenon that every clinician must keep in mind.

A 62-year-old man known to have lung adenocarcinoma poorly differentiated presented with melena 1 month after diagnosis. Upper endoscopy revealed an ulcerated tumor in the prepyloric antrum. The diagnosis of gastric metastasis from pulmonary cancer was confirmed by histology.

Update on the Role of Rifaximin in Digestive Diseases.

Various environmental factors affecting the human microbiota may lead to gut microbial imbalance and to the development of pathologies. Alterations of gut microbiota have been firmly implicated in digestive diseases such as hepatic encephalopathy, irritable bowel syndrome and diverticular disease. However, while these three conditions may all be related to dysfunction of the gut-liver-brain axis, the precise pathophysiology appears to differ somewhat for each. Herein, current knowledge on the pathophysiology of hepatic encephalopathy, irritable bowel syndrome, and diverticular disease are reviewed, with a special focus on the gut microbiota modulation associated with these disorders during therapy with rifaximin. In general, the evidence for the efficacy of rifaximin in hepatic encephalopathy appears to be well consolidated, although it is less supported for irritable bowel syndrome and diverticular disease. We reviewed current clinical practice for the management of these clinical conditions and underlined the desirability of more real-world studies to fully understand the potential of rifaximin in these clinical situations and obtain even more precise indications for the use of the drug.