Abstract: The present review summarizes the clinically relevant effects of acute and chronic alcohol consumption on motility, mucosal inflammation and cancer of the esophagus and the stomach. Alcohol consumption results in a significant increase in the morbidity of these two organs, the most important probably being the significant increase in the development of esophageal cancer. This review refers to epidemiologic and systematic experimental data to elucidate the clinical impact of alcohol consumption as well as the underlying alcohol-induced pathophysiologic mechanisms for these esophageal and gastric diseases. Much research is still needed to clarify the effects of alcohol itself and the byproducts that result during the production of the different types of alcoholic beverages on dismotility and mucosal injury to the esophagus and stomach.

Abstract: Spontaneous bacterial peritonitis (SBP) is a bacterial infection of ascitic fluid in patients with decompensated cirrhosis. The modifier ‘spontaneous’ distinguishes this from surgical peritonitis. The

Abstract: Background and Aims: Alcoholic liver disease continues to be a major health problem with respect to both morbidity and mortality. To understand the clinical syndromes of alcoholic liver disease, this review highlights the papers on both clinical and basic research of alcoholic liver disease, especially on steatosis, alcoholic hepatitis and fibrosis. Methods: The various forms of alcoholic liver disease are described, and knowledge about the clinical and pathophysiological features of different stages of alcoholic liver disease are summarized. Results: Clinical studies combined with basic research have established a spectrum of alcoholic liver disease from steatosis to steatohepatitis, fibrosis, and cirrhosis. New insights into the pathogenesis of alcoholic liver disease include the key roles of the excess production of cytokines, reactive oxygen species, and the shortage of protective mediators, including adiponectin. Conclusion: These new insights will lead to new specific therapies for the treatment of alcoholic hepatitis and alcoholic liver fibrosis.

Abstract: Alcohol abuse is a major cause of liver fibrosis and cirrhosis in developed countries. Before alcoholic liver fibrosis becomes evident, the liver undergoes several stages of alcoholic liver disease including steatosis and steatohepatitis. Although the main mechanisms of fibrogenesis are independent of the etiology of liver injury, alcoholic liver fibrosis is distinctively characterized by a pronounced inflammatory response due to elevated gut-derived endotoxin plasma levels, an augmented generation of oxidative stress with pericentral hepatic hypoxia and the formation of cell-toxic and profibrogenic ethanol metabolites (e.g. acetaldehyde or lipid oxidation products). These factors, based on a complex network of cytokine actions, together result in increased hepatocellular damage and activation of hepatic stellate cells, the key cell type of liver fibrogenesis. Although to date removal of the causative agent, i.e. alcohol, still represents the most effective intervention to prevent the manifestation of alcoholic liver disease, sophisticated molecular approaches are underway, aiming to specifically blunt profibrogenic signaling pathways in liver cells or specifically induce cell death in activated hepatic stellate cells to decrease the scarring of the liver.

Abstract: Alcoholic pancreatitis is a major complication of alcohol abuse. Since only a minority of alcoholics develop pancreatitis, there has been a keen interest in identifying the factors that may confer individual susceptibility to the disease. Numerous possibilities have been evaluated including diet, drinking patterns and a range of inherited factors. However, at the present time, no susceptibility factor has been unequivocally identified. In contrast, considerable progress has been made with respect to the constant effects of alcohol on the pancreas. The molecular mechanisms of alcohol-induced pancreatic injury are being increasingly defined with an emphasis, in recent years, on the acinar cell itself as the principal site on ethanol-related damage. It has now been established that the acinar cell is capable of metabolizing alcohol and that the direct toxic effects of alcohol and/or its metabolites on acinar cells may predispose the gland to autodigestive injury in the presence of an appropriate triggering factor. A significant recent development relates to the characterization of pancreatic stellate cells, increasingly implicated in alcoholic pancreatic fibrosis. Here the current concepts regarding the mechanisms/pathways mediating alcohol-induced pancreatic injury are outlined.

Abstract: Background: Chronic, excessive alcohol consumption is clearly associated with acute and chronic pancreatitis. However, both clinical and laboratory studies demonstrate that alcohol consumption alone does not directly cause alcoholic chronic pancreatitis. Growing evidence suggests that environmental and possibly genetic cofactors must also be present to overcome the redundant mechanisms protecting the pancreas from pancreatitis and facilitating complete recovery. Methods: The SAPE hypothesis model was used to organize potential triggering factors, susceptibility factors and disease-modifying factors based on insights from animal studies. A systematic review of genetic studies on alcoholic pancreatitis was conducted and the results were analyzed in the context of animal studies. Results: To date, no major genetic cofactors for susceptibility or progression have been identified in ∼90% of cases of human alcoholic chronic pancreatitis. Mutations have been identified in the pancreatic secretory trypsin inhibitor gene (SPINK1) in about 8% of cases, and an excess in cystic fibrosis transmembrane conductance inhibitor (CFTR) gene variants have been reported, but the details of the complex genetics with CFTR have not been clarified. None of the polymorphisms in alcohol-metabolizing genes or detoxifying genes appear to explain pancreatic susceptibility. Conclusions: New, adequately powered genetic studies are needed. Several major genetic epidemiology studies are underway in both Europe and the United States to help determine why only a subset of alcoholics develop alcoholic chronic pancreatitis.

Abstract: Chronic consumption of alcoholic beverages is an accepted social custom worldwide. In the upper aerodigestive tract, local morphologic, metabolic and functional alterations are present due to alcohol consumption. A clinical link between the chronic consumption of alcohol and head and neck cancer has been observed for decades. While alcohol was described initially as a risk enhancer only in smokers, a number of epidemiological studies have now provided sufficient evidence that chronic alcohol consumption increases the risk of head and neck cancer independent of exposure to tobacco smoke. The systemic effects of alcohol interact with local changes in the morphology and function of the salivary glands. In addition, alcohol leads to accumulation of pathologic microbes within the mucosa, leading to chronic infection. Susceptibility to carcinogens and cell proliferation in the mucosa are increased, resulting in genetic changes with the development of dysplasia, leukoplacia and carcinoma. Chronic alcohol consumption is correlated with an increased risk of cancer and an increased mortality in a dose-effect relationship. A number of biologically plausible mechanisms exist by which alcohol may cause cancer. These mechanisms are discussed in this article.

Abstract: The introduction of total mesorectal excision in the early 1980s has improved local control and survival in patients with rectal cancer. Laparoscopic resections for colonic malignancies are gaining acceptance in the light of the recent evidence of oncologic adequacy from randomized clinical trials. Technical difficulties and the difference in the natural history of the disease have excluded rectal cancer from major clinical trials comparing laparoscopic to conventional rectal surgery. This review examined the feasibility, safety and oncologic outcomes of reported laparoscopic total mesorectal excision for surgical treatment of operable rectal cancer.

Abstract: The transjugular intrahepatic portosystemic shunt (TIPS) is an interventional treatment resulting in decompression of the portal system by creation of a side-to-side portosystemic anastomosis. Since its introduction 16 years ago, more than 1,000 publications have appeared demonstrating broad acceptance and increasing clinical use. This review summarizes our present knowledge about technical aspects and complications, follow-up of patients and indications. A technical success rate near 100% and a low occurrence of complications clearly depend on the skills of the operator. The follow-up of the TIPS patient has to assess shunt patency, liver function, hepatic encephalopathy and the possible development of hepatocellular carcinoma. Shunt patency can best be monitored by duplex sonography and can avoid routine radiological revision. Short-term patency may be improved by anticoagulation, while such a treatment does not influence long-term patency. Stent grafts covered with expanded polytetrafluoroethylene show promising long-term patency comparable with that of surgical shunts. With respect to the indications of TIPS, much is known about treatment of variceal bleeding and refractory ascites. The thirteen randomized studies that are available to date show that survival is comparable in patients receiving TIPS or endoscopic treatment for acute or recurrent variceal bleeding. Another group comprises patients with refractory ascites and related complications, such as hepatorenal syndrome and hepatic hydrothorax. It has been demonstrated that TIPS improves these complications. Five randomized studies comparing TIPS with paracentesis and one study comparing TIPS with the peritoneo-venous shunt showed good response of ascites but controversial results on survival. In addition, TIPS has been successfully applied to patients with Budd-Chiari syndrome, portal vein thrombosis, before liver transplantation, and for the treatment of ectopic variceal bleeding.

Abstract: Background: Laparoscopic cholecystectomy (LC) is the standard operation for gallstone disease. The aim of this review was to scrutinize the advantages and benefi ts of this minimal invasive technique compared to the conventional operation according to the available literature. Regarding the evidence-based medicine criteria, the current status of laparoscopy in the treatment of cholecystolithiasis, cholecystitis and common bile duct stones has been worked out. Methods: A Medline, PubMed, Cochrane search. Results: Ten randomized controlled trials (RCTs) are available comparing laparoscopic versus open cholecystectomy. The superiority of LC in less postoperative pain, shorter recovery and hospital stay is stated. Operation time was longer in the fi rst years of LC. 3 RCTs deal with acute cholecystitis: one paper could not fi nd any signifi cant advantage of LC over conventional cholecystectomy, the other two found benefi ts in recovery, hospital stay and postoperative pain. The range of conversion is between 5 and 7% in elective cases and increases up to 27% for acute cholecystitis. With a rate of more than 90% in Europe, the standard procedure for common bile duct stones is ‘therapeutic splitting’ with

Abstract: There are three procedures for the management of early gastric cancer (EGC): laparoscopic wedge resection (LWR), intragastric mucosal resection (IGMR), and laparoscopic gastrectomy. LWR or IGMR can be applied to treat EGC without the risk of lymph node metastasis. However, owing to the recent technical advances in endoscopic mucosal resection for EGC, the use of laparoscopic local resection for these lesions has gradually decreased. On the other hand, laparoscopic gastrectomy with lymph node dissection, such as laparoscopy-assisted distal gastrectomy, is widely accepted for the treatment of EGC with the risk of lymph node metastasis. To establish the acceptability of laparoscopic gastrectomy with D2 lymph node dissection against advanced gastric cancers, safe techniques and new instruments must be developed. The following advantages of laparoscopic surgery for the treatment of gastric cancer have been well demonstrated: clinical course after operation, pulmonary function, immune response. In the future, laparoscopic surgeons have to design and implement education and training systems for standard laparoscopic procedures, evaluate clinical outcomes by multicentric randomized control trial studies, and clarify the oncological aspects of laparoscopic surgery in basic studies.

Abstract: Background/Aims: Alcohol drinking is responsible for a number of gastrointestinal diseases and cancers. Although heavy drinking episodes and chronic drinking are well linked to mech

Abstract: Portal hypertension is defined by an elevation in blood pressure in the portal system Different causes are known and include a pre-, intra-, or posthepatic block Portal hypertension is also classified according to the sinusoidal system Portal pressure becomes elevated by either an increase in blood flow (Q), an increase in resistance (R), or both Regulation of the vascular tone in the splanchnic system includes intrinsic and extrinsic aspects A variety of metabolic end-products (eg adenosine), endothelium-derived substances (eg nitric oxide), and certain neurotransmitters (eg acetylcholine) are known to relax the tone and thus produce vasodilation Important vasoconstrictor influences on splanchnic arterioles include circulating agents (eg angiotensin), endothelium-derived substances (eg endothelin), and again neurotransmitters (norepinephrine) Besides vascular tone, structural changes (thrombosis, fibrosis, shear stress, and cell regeneration) add to overall hepatic resistance Further consequences of portal hypertension include an increase in blood flow which leads to a hyperdynamic state with fluid retention, leading to secondary involvement of other organs, such as cirrhotic cardiomyopathy, hepatopulmonary syndrome and hepatorenal syndrome Finally, portal hypertension will end up in the formation of collateral vessels Varices can involve the whole gastrointestinal tract and are a frequent source of bleeding

Abstract: Background: The current experience of laparoscopic liver resection is reviewed focusing on the role and limitations of resection of colorectal metastases Surgical technique, outcom

Abstract: Portal hypertension is a complication of liver cirrhosis that may itself cause complications such as variceal bleeding, ascites and hepatorenal syndrome. There are several options for symptomatic treatment including drug therapy, endoscopy, transjugular intrahepatic portosystemic shunt (TIPS), and various surgical procedures, notably liver transplantation, the only causal treatment. The indication for liver transplantation has to be defined carefully. Progression of the primary disease, evaluation of comorbidity and overall prognosis have to be considered. Conservative symptomatic treatment is used for bridging purposes until liver transplantation can be provided to cure portal hypertension and the underlying primary disease. Careful timing of the transplantation is necessary as well as reorganization of the waiting lists by introducing new priority systems as the Model for End-Stage Liver Disease (MELD) in order to reduce mortality. Furthermore, living donor liver transplantation and split liver transplantation are methods to enlarge the donor pool, and thus accessibility of transplantation to a greater number of patients. This review evaluates the indication of liver transplantation in the treatment of portal hypertension.

Abstract: Background/Aims: Alcohol use and hepatitis C are prominent risk factors for liver injury and this review offers the current understanding of each factor’s effects on liver disease. Methods: A Medline database search was preformed for English articles with a focus on alcohol, hepatitis C and liver disease. Article citations were also considered for further applicable articles, and the strongest studies were included in our review. Results: Up to 60% of patients with hepatitis C have a past history of alcohol use. In patients with hepatitis C, chronic alcohol consumption of more than 5 drinks/day increases the rate of liver fibrosis, risk for cirrhosis, hepatocellular carcinoma, and, possibly, death from liver disease. Numerous studies have further found that even moderate amounts of alcohol can be detrimental to hepatitis C patients. The prevalence of hepatitis C is higher in alcoholics with advanced liver disease than in alcoholics without liver disease. Also, recent alcohol use decreases the response rate to interferon treatment. Conclusions: Hepatitis C and alcohol use are often co-occurring risk factors for liver disease, and though their interaction is not clear, it is known that heavy drinking significantly promotes liver disease progression.

Abstract: Alcohol-induced diseases of the gastrointestinal tract play an important role in clinical gastroenterology. However, the precise pathophysiological mechanisms are still largely unknown. Alcohol research depends essentially on animal models due to the fact that controlled experimental studies of ethanol-induced diseases in humans are unethical. Animal models have already been successfully applied to disclose and analyze molecular mechanisms in alcohol-induced diseases, partially by using knockout technology. Because of a lack of transferability of some animal models to the human condition, results have to be interpreted cautiously. For some alcohol-related diseases like chronic alcoholic pancreatitis, the ideal animal model does not yet exist. Here we provide an overview of the most commonly used animal models in gastrointestinal alcohol research. We will also briefly discuss the findings based on animal models as well as the current concepts of pathophysiological mechanisms involved in acute and chronic alcoholic damage of the esophagus, stomach, small and large intestine, pancreas and liver.

Abstract: Laparoscopic colorectal resections offer several benefits postoperatively, including minimal impairment of gastrointestinal and pulmonary function, less immunosuppression, shorter hospital stay and improved reconvalescence. Since the introduction of laparoscopic surgery for the therapy of curable colorectal cancer, some concern was voiced in terms of oncologic radicality, the issue of port-site metastases and tumor cell distribution. However, the clinical reality has demonstrated that oncologic radicality is equivalent to open surgery, and the incidence of port-site metastases is not increased when compared to wound recurrence at the laparotomy site. Focusing on colon and rectum, various indications of laparoscopic-endoscopic 'rendezvous' procedures exist including laparoscopic-assisted endoscopic transluminal resection, endoscopic-assisted wedge or anatomical resections, and, finally, intraoperative tumor location by colonoscopy to achieve oncologic resection margins in laparoscopic curative resections. In terms of colorectal curative resections, long-term results provide level I evidence that laparoscopic surgery for colon cancer is oncologically adequate and can be performed with equivalent morbidity and mortality rates when compared to conventional surgery. In terms of rectal cancer, no level I evidence is available. However, short-term data from experienced centers do not report inferior oncologic outcome particularly related to laparoscopic total mesorectal excision.

Abstract: The complications of portal hypertension are totally prevented if hepatic venous pressure gradient is decreased below 12 mm Hg. Besides, if this target is not achieved, a 20% decrease in portal pressu

Abstract: Background: Methylation of the CpG islands in the p16 gene promoter region is an important transcription repression mechanism that has been identified as an alternative mechanism for inactivating specific genes in cancer. Given that, DNA methylation is a common event in colorectal cancer. Materials and Methods: The aim of this study was to establish the methylation status of the p16 gene in 104 patients with colorectal carcinoma and evaluate its prognostic value. DNA was bisulfite-modified and analyzed for p16 promoter methylation by methylation-specific PCR. Results: Methylation of thep16 gene was determined in 18.3% of our patient population (19/104). The methylated state did not correlate with any clinicopathological factors. During a median follow-up period of 72 months, the overall survival rate for patients with gene methylation was 75% and without gene methylation it was 61% (p = 0.09). Conclusions: Although not statistically significant, this difference indicates a clinically valuable tendency.

Abstract: Few data exist about the incidence of drug-induced pancreatitis in the general population. Drugs are related to the etiology of pancreatitis in about 1.4-2% of cases. Although statins are generally well tolerated, acute pancreatitis has been reported in a few cases treated with atorvastatin, fluvastatin and simvastatin. A 86-year-old man with long-standing history of hypertension and hyperlipidemia, who was treated with lisinopril 10 mg and atorvastatin 20 mg once daily presented with acute pancreatitis. Other causes of the disease were ruled out. After cessation of the drugs, his physical condition improved and the amylase level decreased. To our knowledge, pancreatitis induced by a combination of atorvastatin together with lisinopril has never been reported in the literature.

Abstract: Chronic pancreatitis is characterized by progressive and irreversible loss of pancreatic exocrine and endocrine function. The majority of cases in the Western world are related to alcohol consumption. Treatment of alcoholic chronic pancreatitis has been difficult, since the mechanisms of disease progression and the causes of pain are poorly understood. The conservative management of chronic pancreatitis focuses on (a) avoidance of precipitating factors such as alcohol and smoking; (b) treatment of pain, and (c) replacement of exocrine and endocrine function. There is a lack of good controlled, randomized treatment trials in alcoholic pancreatitis. However, there is good evidence that lifestyle changes, such as alcohol cessation, hamper progression of the disease. Conservative treatment of pain should be based on a stepwise approach; however, underlying causes such as pseudocysts may require endoscopic or surgical therapy. Treatment of exocrine insufficiency requires pancreatic enzyme supplementation and adjustment to several smaller meals per day, while treatment of endocrine insufficiency requires insulin treatment.

Abstract: Endoscopy plays a major role in the management of gastrointestinal varices in portal hypertension. It is used for the prophylaxis of the first bleeding episode, therapy of active bleeding and prophylaxis of recurrent bleeding. Today not only nonselective betablockers, but also endoscopic band ligation is an option in the primary prophylaxis of the first bleeding episode in patients with large esophageal varices. Acutely bleeding varices should be treated by ligation, pharmacological and antibiotic therapy. Prophylaxis of recurrent bleeding despite endoscopic and pharmacologic treatment is patient dependent: shunt surgery is an option in young patients in a good medical condition (Child-Pugh class A). In patients with refractory ascites and a bilirubin level below 3 mg/dl, TIPS is a good option. Nevertheless, the first-line treatment in most patients in Germany is endoscopic band ligation. Bleeding from ectopic varices and due to hypertensive gastropathy should be treated individually either by endoscopy, TIPS or drug therapy.

Abstract: Background/Aims: Alcoholism is a widespread disorder in our societies. However, only a small percentage of alcoholics appear in specific psychotherapeutic treatment programs. The va

Abstract: Background: Palliation of pancreatic cancer remains the only option for the majority of patients. Palliative techniques such as surgical bypass and endoscopic retrograde cholangiopancreatography (ERCP) with stenting are not ideal. The ‘ideal’ palliative technique would combine the efficacy of surgery with the minimal complications of an endoscopic procedure. Endoscopically delivered perductal electrolytic ablation of pancreatic lesions has the potential to meet these criteria. Methods: Fifteen pigs were used. The pancreatic duct was cannulated with an electrolysis catheter. Animals were randomised to either: controls, treatment 2-week survivor or treatment 8-week survivor. An electrolytic dose was administered to the treatment animals. Post-operatively, serum amylase and leucocyte count were assessed. Pancreata were histologically examined to detect evidence of acute pancreatitis. Results: Electrolysis was well tolerated. There was no difference in post-operative hyperamylasaemia and leucocyte count between the groups. Histological examination showed inflammation at the ablation site at 2 weeks, by 8 weeks this was replaced by scarring. Conclusion: The results of this study suggest that endoscopic perductal electrolytic ablation of the pancreas is feasible and safe. Biochemical and histological findings indicate self-limiting localised inflammation of the pancreas. This technique may have a role in the palliation of pancreatic cancer and warrants further investigation.

Abstract: Transthoracic surgery for oesophageal cancer is associated with a high incidence of respiratory complications. Recent development of minimally invasive oesophagectomy by the use of video-assisted thoracoscopic approach may have a potential to minimize morbidity and mortality. While results from earlier series were equivocal, recent reports have shown an encouraging trend. This article serves to review the recent literature evidence in relation to the surgical approach, safety, efficacy and potential problems of such a highly complex minimally invasive operation.

Abstract: In recent years we have witnessed a wide range of innovations and new developments in gastrointestinal endoscopy. New technical devices based on high magnifi cation have further progressed to the dimension of microscopic endoscopy. Moreover, the visual assessment of the entire small bowel and the biliary/pancreatic system has become possible. These developments have revolutionized our approach to diseases of the gastrointestinal tract. The borders between traditional medical and surgical endoscopy are beginning to disappear, making room for more interaction across medical and surgical disciplines. In this issue of Digestive Diseases we are introduced to the latest innovations in endoscopy and laparoscopy in gastrointestinal diseases. An international panel of highly skilled and renown surgical experts shares with us the advances in surgical endoscopy and laparoscopy in the major diseases of the gastrointestinal tract. Integrating gastroenterological and surgical points of view on these modern technologies will greatly benefi t the treatment of our patients. In the end, we believe it really does not matter whether you are a gastroenterological surgeon or a surgical gastroenterologist, there is more common ground than we may believe today. M.P. Ebert, Magdeburg P. Malfertheiner, Magdeburg

Abstract: Background: Endoscopic and laparoscopic local resection of gastric tumors has increasingly been performed in recent years. This article describes the technical considerations and ea

Abstract: Alcoholic liver disease (ALD) remains a major cause of morbidity and mortality worldwide. For example, the Veterans Administration Cooperative Studies reported that patients with cirrhosis and superimposed alcoholic hepatitis had a 4-year mortality of >60% (worse than many common cancers such as breast and prostate). The cornerstone for therapy for ALD is lifestyle modification, including drinking cessation and treatment of decompensation, if appropriate. Nutrition intervention has been shown to play a positive role on both an in-patient and out-patient basis. Corticosteroids are effective in selected patients with alcoholic hepatitis, and treatment with pentoxifylline appears to be a promising anti-inflammatory therapy. Recent studies have indicated anti-TNFα therapy, at least for alcoholic hepatitis. Some complementary and alternative medicinal agents, such as milk thistle and S-adenosylmethionine, may be effective in alcoholic cirrhosis. Treatment of the complications of ALD can improve the quality of life and, in some cases, decrease short-term mortality.