Translational gastroenterology and hepatology最新文献

Immunotherapy represents the newest pillar in cancer care. Although there are increasing data showing the efficacy of immunotherapy there is a spectrum of response across unselected populations of cancer patients. In fact, response rates can be poor even among patients with immunogenic tumors for reasons that remain poorly understood. A promising clinical strategy to improve outcomes, which is supported by an abundance of preclinical data, is combining immunotherapy with radiation therapy. Here we review the existing evidence and future directions for combining immunotherapy and radiation therapy for patients with gastrointestinal cancers.

Non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are becoming the leading causes of chronic liver disease worldwide, significantly impacting public health and healthcare cost. The development of fibrosis is the main factor leading to early mortality and morbidity in NAFLD and ALD. Thus, it is important to timely and reliably evaluate these diseases at early stages, when fibrosis is not advanced or when steatosis predominates. Liver biopsy has been the standard of reference for fibrosis and steatosis, however, its invasiveness precludes its widespread use. There is growing research on non-invasive methods for diagnosing and stratifying fibrosis and steatosis in NAFLD and ALD. This review presents clinical evidence on the use of non-invasive assessment of liver disease (blood-based and imaging-based) in patients with NALFD and ALD, and proposes algorithms incorporating these tests into their management.

Hereditary iron overload includes several disorders characterized by iron accumulation in tissues, organs, or even single cells or subcellular compartments. They are determined by mutations in genes directly involved in hepcidin regulation, cellular iron uptake, management and export, iron transport and storage. Systemic forms are characterized by increased serum ferritin with or without high transferrin saturation, and with or without functional iron deficient anemia. Hemochromatosis includes five different genetic forms all characterized by high transferrin saturation and serum ferritin, but with different penetrance and expression. Mutations in HFE, HFE2, HAMP and TFR2 lead to inadequate or severely reduced hepcidin synthesis that, in turn, induces increased intestinal iron absorption and macrophage iron release leading to tissue iron overload. The severity of hepcidin down-regulation defines the severity of iron overload and clinical complications. Hemochromatosis type 4 is caused by dominant gain-of-function mutations of ferroportin preventing hepcidin-ferroportin binding and leading to hepcidin resistance. Ferroportin disease is due to loss-of-function mutation of SLC40A1 that impairs the iron export efficiency of ferroportin, causes iron retention in reticuloendothelial cell and hyperferritinemia with normal transferrin saturation. Aceruloplasminemia is caused by defective iron release from storage and lead to mild microcytic anemia, low serum iron, and iron retention in several organs including the brain, causing severe neurological manifestations. Atransferrinemia and DMT1 deficiency are characterized by iron deficient erythropoiesis, severe microcytic anemia with high transferrin saturation and parenchymal iron overload due to secondary hepcidin suppression. Diagnosis of the different forms of hereditary iron overload disorders involves a sequential strategy that combines clinical, imaging, biochemical, and genetic data. Management of iron overload relies on two main therapies: blood removal and iron chelators. Specific therapeutic options are indicated in patients with atransferrinemia, DMT1 deficiency and aceruloplasminemia.

Lymphadenectomy is a central component of surgery for gastric cancer. However, controversies over the optimal extent of lymphadenectomy in gastric cancer surgery have persisted for several decades. In Eastern countries where the incidence of gastric cancer is high, surgeons have performed extensive lymphadenectomy (D2 lymphadenectomy) with low morbidity and mortality, while most Western surgeons have advocated for more limited lymphadenectomies according to the results of Dutch trial and MRC trial. Initially, these trials had failed to show survival benefit of D2 procedure and instead, found pancreaticosplenectomy performed as part of the D2 procedure associated with high incidence of morbidity and mortality. Subsequently, superiority of D2 lymphadenectomy on survival was demonstrated based on updated results. Moreover, spleen and pancreas preserving D2 lymphadenectomy are being performed safely in Western countries. Today, there is an international consensus on performing D2 lymphadenectomy as the standard procedure for advanced gastric cancer and is widely accepted as the standard procedure for gastric cancer surgery. The significance of the extent of lymphadenectomy is intimately associated with the prognostic importance of nodal metastases as the most powerful indicator of recurrence and survival for patients after curative gastrectomy. Maruyama computer program could be used to estimate the risk of lymph node metastasis in each nodal station. The Maruyama Index could be used to assess the adequacy of lymphadenectomy in gastric cancer. Positive lymph node ratio is calculated as the ratio of positive lymph nodes to all harvested lymph nodes, which might be a more precise predictor of prognosis than the absolute number of positive lymph nodes. While D2 lymphadenectomy enables the accurate staging of the disease, reduces the incidence of locoregional recurrences and thus contribute to an improved overall survival; performing lymphadenectomy beyond D2 is unlikely to improve survival. Therapeutic D2+ lymphadenectomy for advanced gastric cancer requires further evaluations, especially for patients receiving neo-adjuvant or conversion treatments.

Alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) are commonest causes of chronic liver disease in developing as well as developed countries. Their incidence has increased due to widespread easy availability of alcohol and sedentary life style of people. NAFLD is a spectrum which includes fatty liver (NAFL) which is considered benign disease, steatohepatitis (NASH) which indicates ongoing injury to liver and cirrhosis of liver. Similarly, ALD spectrum comprises simple steatosis, alcoholic hepatitis, and cirrhosis and its complications. Most of the time there is significant overlap between these diseases and clinical presentation depends upon the stage of liver disease. Most of the NAFLD patients are asymptomatic and diagnosed to have fatty liver while undergoing routine health check up. ALD requires significant history of alcohol intake which is supportive by radiological and biochemical tests. In both NAFLD and ALD patients, liver enzymes are seldom raised beyond five times the upper limit of normal. Liver biopsy is required for diagnosis of NASH as it is a histological diagnosis and sometimes in alcoholic hepatitis for confirmation if diagnosis is in doubt. Non-invasive markers and prognostic scores have been developed for avoiding liver biopsy in assessment and treatment response of NASH and alcoholic hepatitis patients.

Background: To demonstrate the feasibility and reliability of a novel imaging modality, contrast enhanced ultrasound (CEUS), in evaluating for distal small bowel inflammation in pediatric Crohn's disease (CD), and compare this to concurrently obtained magnetic resonance imaging (MRI) findings.

Methods: Pediatric patients diagnosed with or having suspicion of CD with small bowel involvement, whose disease merited imaging with an MRI, concurrently underwent imaging with CEUS. We assessed the ability of CEUS to demonstrate distal small bowel disease by evaluating wall thickness, enhancement pattern, mucosal disruption and pericolonic inflammation. Concordance between imaging modalities was then assessed.

Results: Twenty patients were recruited for the study, 16 with known CD, 3 with concern for CD, and one with known colitis, but unknown bowel disease status. Six patients (3 with prior diagnosis of CD, 3 without) had absence of bowel enhancement on both ultrasound and MRI. Eleven patients with findings of inflammation and enhancement on MRI also had concurrent evidence of enhancement on CEUS. Three patients who had no evidence of inflammation on MRI, with known CD, had prominent bowel enhancement on CEUS. One patient with known colitis, whom we enrolled to evaluate for small bowel disease, had no evidence on either MRI or CEUS, however CEUS showed significant fat stranding around the colon, supporting the diagnosis of CD.

Conclusions: The sensitivity of CEUS to detect bowel inflammation when seen on MRI was 100%. In addition, CEUS may also have the ability to detect bowel inflammation, even in the presence of a normal MRI.

Nonalcoholic steatohepatitis (NASH) is the fastest growing indication for liver transplant (LT)worldwide and is deemed to be the foremost indication in the near future. Recurrence of NASH can occur post LT and has been observed to be a common phenomenon. Baseline metabolic co-morbidities and worsening of metabolic profile post LT are the principal drivers of NASH recurrence. Liver biopsy remains the gold standard for establishing the diagnosis. However, noninvasive methods including transient elastography (TE) and magnetic resonance imaging (MRI) seem to be promising. The implications of recurrent NASH on post LT outcomes, graft steatosis, progression to fibrosis, overall survival, and cardiovascular associations warrant careful evaluation. Control of metabolic parameters and weight gain along with tailored immunosuppression remain the cornerstone of management. Extrapolation of the ever-increasing armamentarium of NASH pharmacotherapy specifically in this population of recurrent NAFLD remains a challenge for the future.

Over the past few years, the innovative field of magnifying endoscopy has been expanding with various cutting-edge technologies, one of which is endocytoscopy, to facilitate improvement in the detection and diagnosis of gastrointestinal lesions. Endocytoscopy is a novel ultra-high magnification endoscopic technique enabling high-quality in-vivo assessment of lesions found in the gastrointestinal tract with the use of intraprocedural stains. The main scope of this review article is to offer a closer look at the latest endocytoscopic technology and its clinical application in the upper gastrointestinal tract, especially in the esophagus and stomach, as well as to introduce readers to our simplified and up-to-date endocytoscopic classification, specifically developed for the esophagus and stomach, for the in-vivo assessment and diagnosis of esophageal and gastric lesions. Despite the good accuracy of endocytoscopy in the diagnosis of esophageal and gastric lesions in recent studies, some challenges still remain (e.g., staining method and standardized endocytoscopic classification). Through continuous evaluation and improvement of methods and skills, these challenges may be overcome thus establishing current techniques and classification, paving the way for further advances in the field of endocytoscopy and magnifying endoscopy. In all, endocytoscopy seems to aid in the in-vivo diagnosis of gastrointestinal tract lesions and may, in the future, revolutionize the field of in-vivo endoscopic diagnosis of gastrointestinal cancer, representing another step towards the so-called optical biopsy.

Background: The gallstones are common health problem across the world with huge financial burden on health authorities. Obesity and insulin resistance are associated with risk of gallstones disease (GSD). The aim of this study was to assess the prevalence of metabolic syndrome (MetS) and diabetes and associated risk factors in Sudanese patients with gallstones.

Methods: A prospective cross-sectional study, enrolled patients with gallstones attending Ibn Sina Specialized Teaching Hospital for gastrointestinal and hepatobiliary diseases. A structured questionnaire was applied, anthropometric measures were taken, and blood tested for HbA1c, fasting glucose and lipid profile. Data was analysed using SPSS version 23.

Results: A total number of 151 participants were recruited in the study, 71 of them were ultrasound confirmed GSD patients, and the other 80 were controls without GSD over a period of six months. The prevalence of the MetS and diabetes was 30% and 23.9% respectively. Borderline diabetes was 16.9% and overweight and obesity constituted more than half of the sample 59.6%. Using Chi-Square test, a statistically significant association was found between MetS and HDL, TG, LDL level, waist circumference and blood pressure (BP). Absolute predictors and the risk factors for gallstone disease were waist circumference, age, HbA1c and LDL.

Conclusions: The prevalence of MetS and diabetes among gallstone patients was 30% and 23.9% respectively. Absolute predictors and the risk factors for gallstone disease were waist circumference, age, HbA1c and LDL.