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 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.

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 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.

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.

Post-chemotherapy Gastric Obstruction in Diffuse Large B-Cell Lymphoma: Endoscopic Dilation Can Fix It!

Treatment of diffuse large B-cell lymphoma (DLBCL) is based on immunochemotherapy with overall good outcomes. Complications related to the treatment or the disease itself can occur during follow-up. We herein report a case of a 37-year-old male who was diagnosed with stage IV gastric DLBCL. Subsequently, he underwent R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisone) chemotherapy. After six cycles of treatment, complete remission has been achieved. But afterwards, the patient presented with a symptomatic gastric obstruction related to a tight stenosis in the antro-fundic junction. Endoscopic dilation was performed and multiple macrobiopsies within the stenosis were taken. Pathological examination concluded to the fibrous character of the stricture. In cases of post-chemotherapy obstruction in gastric DLBCL, endoscopic treatment should be attempted carefully in patients with no evidence of active lymphoma. Diagnosis of fibrosis can avoid surgery and its morbidity.

Esophageal hirudiniasis: an unusual cause of upper gastrointestinal bleeding.

Leeches are carnivorous, hermaphroditic, segmented worms mainly found in fresh water. The majority of leech attachments are external and short-lasting. Internal surfaces can be involved. Yet, esophageal attachment is very rare. We report a case of a 59-year-old female who presented with hematemesis, melena and chest pain. Upper gastrointestinal endoscopy revealed a round black foreign body in the mid-third of the esophagus identified as a leech. We carefully extracted the worm with a forceps applied to the middle of its body. The diagnosis of leech infestation should be kept in mind when exploring gastrointestinal bleeding in patients living in rural areas and those with poor living conditions.

Spleen metastases secondary to gastric neuroendocrine carcinoma: case report.

Neuroendocrine carcinoma (NEC) in the stomach represents a rare and rapidly growing type of gastric tumors. They are considered a distinct entity of neuroendocrine tumors characterized by an aggressive behavior and high metastases rate. On the other hand, spleen metastases of neuroendocrine tumors are extremely rare. We report the first case of spleen metastases of gastric neuroendocrine carcinoma. The patient was a 54-year-old male who presented with a 10-month history of epigastralgia. Upper gastro-intestinal endoscopy revealed a 5 cm ulcerative lesion located in the greater gastric curvature. Biopsies with immunohistochemical staining revealed gastric neuroendocrine carcinoma. Abdominal computed tomography showed thickening of the stomach with two large solid spleen lesions. Abdominal Magnetic Resonance Imaging and 18-fluorodexyglucose positron-emission tomography revealed peritoneal carcinosis and splenic metastases with splenic vein invasion. Clinicians should keep in mind that splenic metastases can arise from gastric neuroendocrine tumors (NETs).

Primary small bowel volvulus: A case report and literature review.

Background: Small bowel volvulus (SBV) is an aberrant rotation of the small bowel segment along the axis of its mesentery.Secondary SBV is the most frequent situation. Postoperative adhesions represent the main cause. On the other hand, primary SBV is an extremely rare situation. There are no predisposing anatomical abnormalities.Herein, we present a case of a 73-year-old-patient, with no surgical history, presenting primary SBV. Case presentation: A 73-year-old-patient presented to the emergency department with a one-day history of acute abdominal pain and vomiting. He had no medical comorbidities and no previous abdominal surgery.On examination, he was agitated and afebrile.Urgent computed tomography (CT) scan showed dilated small bowel loops with a "whirl sign".A laparotomy was performed. It revealed a 320° SBV of the distal jejunum and the proximal ileum. The small bowel was ischemic. There were no congenital malformations, no adhesions, and no internal hernia.We performed a detorsion of the small bowel. It regained good vitality. To avoid recurrence, we performed enteropexy of the terminal ileum, and the caecum to widen the mesenteric base.We noted no recurrence of the pathology after three months of follow-up. Conclusion: Primary SBV is an extremely rare situation. Physiopathology is still misunderstood. The clinical presentation is not specific. Diagnosis can be evoked by CT scan but can only be confirmed intraoperatively. The surgical treatment should be performed timely. Different techniques have been described to avoid recurrence. None of those techniques is consensual.

[Predictors of hepatic encephalopathy in patients with severe acute liver injury]. / Facteurs prédictifs de l'encéphalopathie hépatique au cours de l'atteinte hépatique aiguë sévère.

Introduction: severe acute liver injury (SALI) formerly known as severe acute hepatitis is an acute inflammation of the liver with markers of liver injury (elevated transaminases) and signs of hepatocellular failure (jaundice and INR greater than 1.5) according to the latest definition of the European Association for the Study of the Liver (EASL). An important prognostic factor in SALI is the development of hepatic encephalopathy (HE) and thus its progression to acute liver failure (ALF), formerly known as acute severe hepatitis. The purpose of this study is to investigate factors predicting the development of hepatic encephalopathy during SALI. Methods: we conducted a retrospective study of patients treated for SALI between January 2000 and December 2019. We divided patients into two groups depending on whether hepatic encephalopathy occurred. We performed an analytical study comparing the two groups according to their epidemiological, biological and evolutionary data. Results: data from the medical records of fifty-nine patients were collected. A virus was the most frequent cause (63%). Hepatic encephalopathy occurred in 15 patients (25.4%). Factors predicting the development of HE in univariate analysis were a delay in consultation of more than 9 days, an INR level of more than 2.45, a bilirubin level of more than 230 µmol/l, creatinine greater than 60.5 µmol/l, urea greater than 5.5 mmol/l and MELD score greater than 26.5 (p=0.023, p=0.017, p=0.0001, p=0.049, p=0.0001, p=0.0001 respectively). Autoimmune hepatitis and an undetermined cause were associated with the development of HE (p=0,003 and p=0,044, respectively). In multivariate analysis, autoimmune aetiology and a urea level above 5.5 mmol/l were significantly associated with the occurrence of HE. No statistically significant differences were found between the two groups with regard to age, sex and diabetes. Conclusion: SALI is a rare disease, mainly due to a virus in our country. Predictive factors of HE are important for early identification of patients at risk of adverse outcomes.

Esophageal tuberculosis as an unusual cause of dysphagia: a case report.

Esophageal tuberculosis is a rare cause of infectious esophagitis, even in countries with endemic tuberculosis. This impairment is often secondary. We report a case of secondary esophageal tuberculosis in an immunocompetent patient, clinically revealed by dysphagia. Esophagogastroduodenoscopy showed a large ulcer in the middle third of the esophagus with a fistula opening in the center of the ulcer. Histopathological examination of multiple esophageal tissue biopsies revealed epithelioid cell granulomas without caseous necrosis. We completed with Computed Tomography (CT) scan of the chest which revealed a fistula of the middle third of the esophagus, multiple mediastinal necrotic adenopathies and diffuse pulmonary micronodules suggesting miliary tuberculosis. Sputum examination for acid-fast-bacilli was positive. Anti-tuberculosis treatment resulted in a good response with complete remission. It is therefore important to recognize and include this entity in the differential diagnosis of patients with dysphagia particularly in countries with a high incidence of tuberculosis.

Jejunal diverticulitis as a rare cause of abdominal pain: a case report.

Jejunal diverticulitis is an uncommon and underdiagnosed condition. Due to the rarity of This disease, diagnosis is often difficult and delayed. Medical treatment is usually sufficient for jejunal diverticulitis without peritonitis. Surgery is required in case of generalized peritonitis or voluminous abscess complicating diverticulitis. We report the case of a 76-year-old woman who suffered from recent abdominal pain. Diagnosis of uncomplicated jejunal diverticulitis was based on computed tomography (CT) scan. The evolution was favorable after antibiotic treatment. Jejunal diverticulitis have to be evoked among the differential diagnosis of patients with abdominal pain especially in the elderly and it is important for clinicians and radiologists to have awareness about this disease.

Solitary gastric Peutz-Jeghers polyp: a case report.

Peutz-Jeghers syndrome is an inherited condition that is characterized by mucocutaneous pigmentation and hamartomatous polyposis in the gastrointestinal tract. It increases significantly the risk for developing of several cancers such as breast, colon, rectum, pancreas and stomach. Solitary Peutz-Jeghers polyp is defined as a unique hamartomatous polyp having the same histological features as Peutz-Jeghers syndrome polyps without associated intestinal polyposis, mucocutaneous pigmentation and family history of Peutz-Jeghers syndrome. Gastric solitary Peutz-Jeghers polyp is extremely rare. We found only 13 cases in the literature. We report a new case of solitary gastric Peutz-Jeghers polyp associated with a branch duct intraductal papillary mucinous neoplasm revealed by an acute pancreatitis. Computed tomography of the abdomen found a branch duct intraductal papillary mucinous neoplasm with a pedicled polypoid formation in the greater gastric curvature. Endoscopic resection was performed without complications. Histologic examination showed Peutz-Jeghers hamartomatous polyp. The risk of cancer remains unclear in this entity. Therefore, the follow-up of these patients is necessary because of the possible risk of malignancy.

Acquired double pylorus presenting as a gastrointestinal bleeding.

We present the case of a 65-year-old man without a past medical history who was admitted for gastrointestinal bleeding. The case shows an acquired double pylorus due to probable pre pyloric ulcer.

Colonic tuberculosis: a case report.

Aim: Colonic tuberculosis is rare. It accounts for 2-3% of abdominal tuberculosis. Clinical, radiological and endoscopic features are nonspecific. The diagnosis must be considered in front of chronic abdominal pain, vesperal fever and weight loss with on colonoscopy the presence of nodules or ulcers. The diagnosis is made on pathological findings. Case report: We report a case of an 82-year-old female patient with the diagnosis of colonic tuberculosis. The diagnosis were suspected on clinical presentation: chronic abdominal pain, fever and weight loss. The colonoscopy showed a nodular aspect of the left and sigmoid colonic mucosa and the pathology examination of the multiple biopsy specimens showed an epithelioid and gigantocellular granulomas with caseous necrosis. Conclusion: In front of a nonspecific clinical and endoscopic aspects, multiples colonic biopsies are mandatory to rule out differential diagnosis and confirm colonic tuberculosis.

Clinical and radiological features of colonic tuberculosis are nonspecific. The diagnosis must be considered in case of abdominal chronic pain and general symptoms. The mainly differential diagnosis are colorectal cancer or Crohn's disease. We report a case of an 82-year-old female patient with the diagnosis of colonic tuberculosis.