Caustic injury of the upper gastrointestinal tract: A comprehensive review

Prevention has a paramount role in reducing the incidence of corrosive ingestion especially in children, yet this goal is far from being reached in developing countries, where such injuries are largely unreported and their true prevalence simply cannot be extrapolated from random articles or personal experience. The specific pathophysiologic mechanisms are becoming better understood and may have a role in the future management and prevention of long-term consequences, such as esophageal strictures. Whereas the mainstay of diagnosis is considered upper gastrointestinal endoscopy, computed tomography and ultrasound are gaining a more significant role, especially in addressing the need for emergency surgery, whose morbidity and mortality remains high even in the best hands. The need to perform emergency surgery has a persistent long-term negative impact both on survival and functional outcome. Medical or endoscopic prevention of stricture is debatable, yet esophageal stents, absorbable or not, show promising data. Dilatation is the first therapeutic option for strictures and bougies should be considered especially for long, multiple and tortuous narrowing. It is crucial to avoid malnutrition, especially in developingcountries where management strategies are influenced by malnutrition and poor clinical conditions. Late reconstructive surgery, mainly using colon transposition, offers the best results in referral centers, either in children or adults, but such a difficult surgical procedure is often unavailable in developing countries. Possible late development of esophageal cancer, though probably overemphasized, entails careful and long-term endoscopic screening.

Laparoscopic fundoplication for gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) is a condition that develops when the reflux of gastric contents into the esophagus leads to troublesome symptoms and/or complications. Heartburn is the cardinal symptom, often associated with regurgitation. In patients with endoscopy-negative heartburn refractory to proton pump inhibitor (PPI) therapy and when the diagnosis of GERD is in question, direct reflux testing by impedance-pH monitoring is warranted. Laparoscopic fundoplication is the standard surgical treatment for GERD. It is highly effective in curing GERD with a 80% success rate at 20-year follow-up. The Nissen fundoplication, consisting of a total (360°) wrap, is the most commonly performed antireflux operation. To reduce postoperative dysphagia and gas bloating, partial fundoplications are also used, including the posterior (Toupet) fundoplication, and the anterior (Dor) fundoplication. Currently, there is consensus to advise laparoscopic fundoplication in PPI-responsive GERD only for those patients who develop untoward side-effects or complications from PPI therapy. PPI resistance is the real challenge in GERD. There is consensus that carefully selected GERD patients refractory to PPI therapy are eligible for laparoscopic fundoplication, provided that objective evidence of reflux as the cause of ongoing symptoms has been obtained. For this purpose, impedance-pH monitoring is regarded as the diagnostic gold standard.

Cholangiocarcinoma and malignant bile duct obstruction: A review of last decades advances in therapeutic endoscopy

In the last decades many advances have been achieved in endoscopy, in the diagnosis and therapy of cholangiocarcinoma, however blood test, magnetic resonance imaging, computed tomography scan may fail to detect neoplastic disease at early stage, thus the diagnosis of cholangiocarcinoma is achieved usually at unresectable stage. In the last decades the role of endoscopy has moved from a diagnostic role to an invaluable therapeutic tool for patients affected by malignant bile duct obstruction. One of the major issues for cholangiocarcinoma is bile ducts occlusion, leading to jaundice, cholangitis and hepatic failure. Currently, endoscopy has a key role in the work up of cholangiocarcinoma, both in patients amenable to surgical intervention as well as in those unfit for surgery or not amenable to immediate surgical curative resection owing to locally advanced or advanced disease, with palliative intention. Endoscopy allows successful biliary drainage and stenting in more than 90% of patients with malignant bile duct obstruction, and allows rapid reduction of jaundice decreasing the risk of biliary sepsis. When biliary drainage and stenting cannot be achieved with endoscopy alone, endoscopic ultrasound-guided biliary drainage represents an effective alternative method affording successful biliary drainage in more than 80% of cases. The purpose of this review is to focus on the currently available endoscopic management options in patients with cholangiocarcinoma.

Hyperhomocysteinemia and hypercoagulability in primary biliary cirrhosis

AIM： To assess the hypercoagulability in PBC and its relationship with homocysteine （HCY） and various components of the haemostatic system. METHODS： We investigated 51 PBC patients （43F/8M; mean age： 63±13.9 yr） and 102 healthy subjects （86 women/16 men, 63±13 yr）, and evaluated the haemostatic process in whole blood by the Sonoclot analysis and the platelet function by PFA-100 device. We then measured HCY （fasting and after methionine loading）, tissue factor （TF）, thrombin-antithrombin complexes （TAT）, D-dimer （D-D）, thrombomodulin （TH）, folic acid, vitamin B6 and B12 plasma levels. C677T 5,10-methylenetetrahydrofolate reductase （HTHFR） polymorphism was analyzed. RESULTS： Sonoclot RATE values of patients were significantly （P〈 0.001） higher than those of controls. Sonoclot time to peak values and PFA-100 closure times were comparable in patients and controls. TAT, TF and HCY levels, both in the fasting and post-methionine loading, were significantly （P〈0.001） higher in patients than in controls. Vitamin deficiencies were detected in 45/51 patients （88.2%）. The prevalence of the homozygous TT677 MTHFR genotype was significantly higher in patients （31.4%） than in controls （17.5%） （P〈 0.05）. Sonodot RATE values correlated significantly with HCY levels and TF.CONCLUSION： In PBC, hyper-HCY is related to hypovitaminosis and genetic predisposing factors. Increased TF and HCY levels and signs of endothelial activation areassociated with hypercoagulability and may have an important role in blood clotting activation.

炎症反应与药物治疗在脑动脉瘤治疗中的作用（英文）

Intracranial aneurysms remain important clinical concern. There is relatively low risk of rupture of symptomless aneurysms incidentally found in MRA or CTA performed due to other indications. Not all of the intracranial aneurysms should or can be treated with neurosurgery intervention or endovascular embolization. Clinical strategy for small, symptomless, unruptured aneurysms is still questionable. Mechanisms underlying aneurysms formation,progression and rupture are poorly understood. Inflammation is one of the factors suspected to participate in these processes. Therefore the aim of this manuscript is to present current state of knowledge about the role of inflammation in the formation and progression of intracranial aneurysms and in their rupture process. Current knowledge about possible pharmacological treatment of intracranial aneurysms will also be presented. Macrophages infiltration seems to participate in the formation of intracranial aneurysms. Inhibition of signals sent by macrophages may prevent the aneurysms formation. Inflammation present in the wall of the aneurysm seems to be also related to the aneurysm's rupture risk. However it does not seem to be the only cause of the degeneration,but it can be a possible target of drug therapy. Some preliminary studies in humans indicate the potential role of aspirin as a factor that decrease the level of inflammation and lower the risk of rupture of intracranial aneurysms. However further research including a greater number of subjects and a prospective randomized design are necessary to assess the role of aspirin in preventing strategy for small,symptomless,unruptured intracranial aneurysms.

New understandings of the genetic basis of isolated diopathic central hypogonadism

Idiopathic hypogonadotropic hypogonadism is a rare disease that is characterized by delayed/absent puberty and/or infertility due to an insufficient stimulation of an otherwise normal pituitary-gonadal axis by gonadotrophin-releasing hormone （GnRH） action. Because reduced or normal luteinizing hormone （LH）/follicle-stimulating hormone （FSH） levels may be observed in the affected patients, the term idiopathic central hypogonadism （ICH） appears to be more appropriate. This disease should be distinguished from central hypogonadism that is combined with other pituitary deficiencies. Isolated ICH has a complex pathogenesis and ~s fivefold more prevalent in males. ICH frequently appears in a sporadic form, but several familial cases have also been reported. This finding, in conjunction with the description of numerous pathogenetic gene variants and the generation of several knockout models, supports the existence of a strong genetic component. ICH may be associated with several morphogenetic abnormalities, which include osmic defects that, with ICH, constitute the cardinal manifestations of Kallmann syndrome （KS）. KS accounts for approximately 40% of the total ICH cases and has been generally considered to be a distinct subgroup. However, the description of several pedigrees, which include relatives who are affected either with isolated osmic defects, KS, or normo-osmic ICH （nlCH）, justifies the emerging idea that ICH is a complex genetic disease that is characterized by variable expressivity and penetrance. In this context, either multiple gene variants or environmental factors and epigenetic modifications may contribute to the variable disease manifestations. We review the genetic mechanisms that are presently known to be involved in ICH pathogenesis and provide a clinical overview of the 227 cases that have been collected by the collaborating centres of the Italian ICH Network.

Muscle fatigue in women with primary biliary cirrhosis:Spectral analysis of surface electromyography

AIM： To evaluate the myoelectric manifestations of peripheral fatigability in patients with primary biliary cirrhosis in comparison to healthy subjects. METHODS： Sixteen women with primary biliary cirrhosis without comorbidity and 13 healthy women matched for age and body mass index （BMI） completed the selfreported questionnaire fatigue impact scale. All subjects underwent surface electromyography assessment of peripheral fatigability. Anterior tibial muscle isometric voluntary contraction was executed for 20 s at 80% of maximal voluntary isometric contraction. During the exercise electromyographic signal series were recorded and root mean square （expression of central drive） as well as mean and median of electromyographic signal frequency spectrum （estimates of muscle fatigability） were com- puted. Each subject executed the trial two times. EMG parameters were normalized, then linear regression was applied and slopes were calculated. RESULTS： Seven patients were fatigued （median fatigue impact scale score： 38, range： 26-66） and 9 were not fatigued （median fatigue impact scale score： 7, range： 0-17）. The maximal voluntary isometric contraction was similar in patients （82, 54-115 N） and controls （87, 74-101 N）, and in patients with high （81, 54-115 N） and low fatigue impact scale scores （86, 65-106 N）. Root mean square as well as mean and median of frequency spectrum slopes were compared with the Mann-Whitney U test, and no significant difference was found between fatigued and non-fatigued patients and controls. CONCLUSION： No instrumental evidence of peripheral fatigability can be found in women with primary biliary cirrhosis but no comorbidity, suggesting that fatigue in such patients may be of central origin.

Sigma-1 receptor:a potential new target for Parkinson's disease?

Parkinson＇s disease （PD） is an age-related neurodegenerative disorder characterized by typical motor signs and symptoms that are due to dopamine （DA） depletion in the basal ganglia. The treatment of PD is symptomatic, and aims at replacing the lost DA input using either L-DOPA or DA agonists. The causes of PD are unknown in approximately 90% of the cases, whereas about 10% of the cases are familial and imputable to mutations in a handful of genes （the gene mutations with the strongest association with PD are shown in Table 1; for a detailed review see （Poulopoulos et al., 2012））. The genetic forms of PD have spurred an intense research on molecular pathways of neurodegeneration that converge on proteostatic deficits, mitochondrial dysfunction and oxidative stress.