Techniques and efficacy of flexible endoscopic therapy of Zenker’s diverticulum

Zenker’s diverticulum(ZD) is an abnormal hypopharyngeal pouch often presenting with dysphagia. Treatment is often sought with invasive surgical management of the diverticulum being the only mode of definitive therapy.Primarily done by an open transcervical approach in the past, nowadays treatment is usually provided by otolaryngologists using a less invasive trans-oral technique with a rigid endoscope. When first described, this method grew into acceptance quickly due to its similar efficacy and vastly improved safety profile compared to the open transcervical approach. However, the main limitation with this approach is that it may not be suitable for all patients. Nonetheless, progress in the field of natural orifice endoscopic surgery over the last 10-20 years has led to the increase in utilization of the flexible endoscope in the treatment of ZD. Primarily performed by interventional gastroenterologists, this approach overcomes the prior limitation of its surgical counterpart and allows adequate visualization of the diverticulum independent of the patient’s body habitus. Additionally, it may be performed without the use of general anesthesia and in an outpatient setting, thus further increasing the utility of this modality, especially in elderly patients with other comorbidities. Today, results in more than 600 patients have been described in various published case series using different techniques and devices demonstrating a high percentage of clinical symptom resolution with low rates of adverse events. In this article, we present our experience with flexible endoscopic therapy of Zenker’s diverticulum and highlight the endoscopic technique, outcomes and adverse events related to this minimally invasive modality.     

Gilbert’s syndrome and antiviral therapy of hepatitis C

Treatment of chronic hepatitis C with type I interferons and ribavirin can be associated with exacerbation of hepatitis and sometimes liver decompensation. We report two patients with chronic hepatitis C virus infection who experienced a severe increase of bilirubin levels of up to 17 times upper the limit of normal value in the absence of deterioration of hepatic function during therapy with pegylated-interferon and ribavirin. A genetic disposition for Gilbert’s syndrome explained the adverse events and permitted a continuation of therapy leading to a sustained clearance of chronic hepatitis C infection. Since one patient jaundiced already during a lead-in treatment period with ribavirin monotherapy we suggest that hyperbilirubinaemia during combination therapy is primarily caused by ribavirin rather than by effects of interferon alpha on UDP-glucuronosyltransferase activities. Of note, both patients recovered from their initial unconjugated hyperbilirubinemia despite continuation of ribavirin therapy, which indicates that compensatory mechanisms leading to a normalization of UGT1A1 activity are likely.     

Asthma and gastroesophageal reflux disease： Effect of long-term pantoprazole therapy

AIM: To define the prevalence of gastroesophageal reflux disease (GERD) in mild persistent asthma and to value the effect of pantoprazole therapy on asthmatic symptoms. METHODS: Seven of thirty-four asthmatic patients without GERD served as the non-GERD control group. Twenty-seven of thirty-four asthmatic patients had GERD (7/27 also had erosive esophagitis, sixteen of them presented GERD symptoms. An upper gastrointestinal endoscopy was performed in all the subjects to obtain five biopsy specimens from the lower 5 cm of the esophagus. Patients were considered to have GERD when they had a dilation of intercellular space (DIS)>0.74 urn at transmission electron microscopy. Patients with GERD were treated with pantoprazole, 80 mg/day. Forced expiratory volume in one second (FEV1) was performed at entry and after 6 mo of treatment. Asthmatic symptoms were recorded. The required frequency of inhaling rapid acting β2-agonists was self-recorded in the patients' diaries. RESULTS: Seven symptomatic patients presented erosive esophagitis. Among the 18 asymptomatic patients, 11 presented DIS, while all symptomatic patients showed ultrastructural esophageal damage. Seven asymptomatic patients did not present DIS. At entry the mean of FEV1 was 1.91 L in symptomatic GERD patients and 1.88 L in asymptomatic GERD patients. After the treatment, 25 patients had a complete recovery of DIS and reflux symptoms. Twenty-three patients presented a regression of asthmatic symptoms with normalization of FEV1. Four patients reported a significant improvement of symptoms and their FEV1 was over 80%. CONCLUSION: GERD is a highly prevalent condition in asthma patients. Treatment with pantoprazole (80 mg/day) determines their improvement and complete regression.     

Management of pancreatic trauma and its consequences--guidelines or individual therapy?

BACKGROUND/AIMS: Diagnosis of pancreatic trauma and its complications may be difficult due to non-specific signs and symptoms and treatment recommendations are not unequivocal. METHODOLOGY: Clinical data of a series of 47 patients with pancreatic trauma were analyzed; most of them were polytraumatized and treated by an interdisciplinary team. RESULTS: The most common causes were traffic accidents and sport injuries with 66% and 15%, respectively. Concomitant injuries were seen in 96% (nonpancreatic intra-abdominal injuries 85% including spleen 38% and liver 34%, extra-abdominal injuries 70%). Concomitant liver injuries were treated conservatively in 31% and operatively in 69% (including hepatic packing in 38%). Concomitant splenic injuries were usually very severe and could be managed conservatively in only 11%. All patients with pancreatic injuries grade III, IV or V (17%) according to the American Association of Surgical Trauma Classification required surgery, endoscopic treatment or interventional radiology. The most common posttraumatic complications were necrotizing pancreatitis (15%), pseudocyst formation (9%), abscesses (6%) and fistulas (4%). CONCLUSIONS: The status of the pancreatic duct is the crucial point for management of pancreatic trauma and should be assessed as early as possible. Treatment has to be tailored to the individual situation, especially in patients with severe concomitant injuries or prolonged course.     

Gene therapy and liver diseases

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Pathogenesis and medical therapy of primary sclerosing cholangitis. Any news?

Primary sclerosing cholangitis is characterized by inflammation and fibrosis of the intra- and extrahepatic bile ducts. Medical therapy has focused on anticholestatic, antiinflammatory and immunosuppressive drugs. Although inflammation, fibrosis and cholestasis may all occur at the same time, inflammation dominates the early phase and fibrosis and cholestasis the later stages. With inflammatory bowel disease and rheumatoid arthritis as stimulants, research on anti-inflammatory drugs is in a very active stage, with an emphasis on cytokines and cytokine antagonists. For patients with primary sclerosing cholestasis to fully benefit from these developments, it is necessary to define the early disease stage that constitutes a potential therapeutic window for these agents.     

Antioxidant vitamins and lipid therapy: end of a long romance?

During the past decade, the perception flourished that lipid and antioxidant therapy were 2 independent avenues for cardiovascular protection. However, studies have shown that commonly used antioxidant vitamin regimens do not prevent cardiovascular events. We found that the addition of antioxidant vitamins to simvastatin-niacin therapy substantially blunts the expected rise in the protective high density lipoprotein (HDL)2 cholesterol and lipoprotein(A-I) subfractions of HDL, with apparent adverse effects on the progression of coronary artery disease. To better understand this effect, 12 apolipoproteins, receptors, or enzymes that contribute to reverse cholesterol transport have been examined in terms of their relationship to HDL2 and lipoprotein(A-I) levels and the potential for antioxidant modulation of their gene expression. Three plausible candidate mechanisms are identified: (1) antioxidant stimulation of cholesteryl ester transfer protein expression/activity, (2) antioxidant suppression of macrophage ATP binding cassette transmembrane transporter A1 expression, and/or (3) antioxidant suppression of hepatic or intestinal apolipoprotein A-I synthesis or increase in apolipoprotein A-I catabolism. In summary, antioxidant vitamins E and C and beta-carotene, alone or in combination, do not protect against cardiovascular disease. Their use for this purpose may create a diversion away from proven therapies. Because these vitamins blunt the protective HDL2 cholesterol response to HDL cholesterol-targeted therapy, they are potentially harmful in this setting. We conclude that they should rarely, if ever, be recommended for cardiovascular protection.     

Hepatitis C virus： Virology, diagnosis and management of antiviral therapy

Hepatitis C virus (HCV) infects approximately 170 million individuals worldwide. Prevention of HCV infection complications is based on antiviral therapy with the combination of pegylated interferon alfa and ribavirin. The use of serological and virological tests has become essential in the management of HCV infection in order to diagnose infection, guide treatment decisions and assess the virological response to antiviral therapy. Anti- HCV antibody testing and HCV RNA testing are used to diagnose acute and chronic hepatitis C. The HCV genotype should be systematically determined before treatment, as it determines the indication, the duration of treatment, the dose of ribavirin and the virological monitoring procedure. HCV RNA monitoring during therapy is used to tailor treatment duration in HCV genotype 1 infection, and molecular assays are used to assess the end-of-treatment and, most importantly the sustained virological response, i.e. the endpoint of therapy.     

Combination therapy of long-acting β agonists and inhaled corticosteroids in the management of chronic asthma

Both the Global Initiative for Asthma (GINA) and the National Heart, Lung and Blood Institute (NHLBI) Expert Panel guidelines recommend combination treatment with inhaled corticosteroids (ICSs) and inhaled longacting β-agonists (LABAs) for patients whose asthma is not adequately controlled by low doses of ICSs alone. Not only is this combination more effective than the combination of either theophylline or leukotriene modifiers with ICSs, there is suggestive evidence that the results with LABAs and ICSs may be more than additive. Through the effect of each one on the receptor for the other, they may have a synergistic action. This marked effectiveness of the combination, particularly when combined in the same device, has led to new objectives and novel applications. Therefore, for the first time, it appears that the Goals of Asthma Therapy, as outlined in the guidelines, are achievable for many patients with asthma. Also, at least for combination therapies including formoterol, adjustable dosing and perhaps even use as a rescue as well as a maintenance therapy may be possible.     

Endoscopic therapy of Barrett esophagus--a supplement to drug and surgical options?

Within the last few years intestinal metaplasia at the gastroesophageal junction (Barrett's esophagus) has turned out to be a "shooting star" in the field of gastrointestinal diseases. The detection rate of Barrett's epithelium by the endoscopists and pathologists has raised dramatically as well as the incidence of the carcinoma at the gastroesophageal junction. Furthermore the "short Barrett" was discovered as a relevant risk factor for cancer development. To date ablation techniques with thermal devices, photodynamic techniques (PDT) and the mucosal resection (EMR) compete as local endoscopic treatment methods. However to date it is still in discussion whether in case of nondysplastic Barrett's esophagus endoscopic therapy is an "overtreatment" and an "undertreatment" in case of Barrett's with high-grade dysplasia or early cancer. The currently available data are discussed.