Endoscopic Submucosal Dissection in Europe: Results of 1000 Neoplastic Lesions From the German Endoscopic Submucosal Dissection Registry.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) enables the curative resection of early malignant lesions and is associated with reduced recurrence risk. Due to the lack of comprehensive ESD data in the West, the German ESD registry was set up to evaluate relevant outcomes of ESD. METHODS: The German ESD registry is a prospective uncontrolled multicenter study. During a 35-month period, 20 centers included 1000 ESDs of neoplastic lesions. The results were evaluated in terms of en bloc, R0, curative resection rates, and recurrence rate after a 3-month and 12-month follow-up. Additionally, participating centers were grouped into low-volume (≤20 ESDs/y), middle-volume (20-50/y), and high-volume centers (>50/y). A multivariate analysis investigating risk factors for noncurative resection was performed. RESULTS: Overall, en bloc, R0, and curative resection rates of 92.4% (95% confidence interval [CI], 0.90-0.94), 78.8% (95% CI, 0.76-0.81), and 72.3% (95% CI, 0.69-0.75) were achieved, respectively. The overall complication rate was 8.3% (95% CI, 0.067-0.102), whereas the recurrence rate after 12 months was 2.1%. High-volume centers had significantly higher en bloc, R0, curative resection rates, and recurrence rates and lower complication rates than middle- or low-volume centers. The lesion size, hybrid ESD, age, stage T1b carcinoma, and treatment outside high-volume centers were identified as risk factors for noncurative ESD. CONCLUSION: In Germany, ESD achieves excellent en bloc resection rates but only modest curative resection rates. ESD requires a high level of expertise, and results vary significantly depending on the center's yearly case volume.

CD117 (c-kit) expression in human hepatocellular carcinoma.

AIMS: Although various methods of treatment have been tried, treatment options for advanced hepatocellular carcinoma (HCC) remain limited. Expression of the platelet-derived growth factor has been shown in HCC, which may derive from hepatic stem cells that express the c-kit proto-oncogene. Because of the promising results of imatinib and the key role played by c-kit in gastrointestinal stromal tumours and other solid tumours, the aim of this study was to determine the prevalence of c-kit (CD117) overexpression in patients with HCC. MATERIALS AND METHODS: A retrospective study of 258 archival specimens of subjects with histologically confirmed HCC was carried out. Expression of the c-kit proto-oncogene was evaluated by immunohistochemistry using rabbit anti-CD117 antibody A4502. RESULTS: The overall percentage of positive immunohistochemical staining of HCCs was 2.3% (6/258). CONCLUSIONS: Our results suggest that CD117 is not significantly overexpressed in HCC and there seems to be no role for the use of imatinib.

Ursodeoxycholic acid and/or antibiotics for prevention of biliary stent occlusion.

BACKGROUND: Malignant biliary obstruction, which requires endoscopic stenting as palliative therapy, is often complicated by clogging of the stent with subsequent jaundice and/or cholangitis. Stent clogging may be caused by microbiological adhesion and biliary stasis. Therefore, antibiotics and choleretic agents like ursodeoxycholic acid (UDCA) have been investigated to see whether they prolong stent patency. OBJECTIVES: To evaluate if UDCA and/or antibiotics may prolong stent patency and survival in patients with strictures of the biliary tract and endoscopically inserted stents. SEARCH STRATEGY: The Trials Register of The Cochrane Hepato-Biliary Group, The Cochrane Library, MEDLINE, Current Contents, EMBASE, and CancerLit were searched until June 2001. Reference lists of the identified articles were checked for further trials. SELECTION CRITERIA: All randomised or quasi-randomised clinical trials investigating UDCA and/or antibiotics in patients with biliary stents were considered for inclusion, regardless of blinding, language, and publication status. DATA COLLECTION AND ANALYSIS: Trial inclusion, quality assessment, and data extraction were performed independently by two reviewers. Principal investigators were contacted for further information. Survival data were combined by using hazard ratios (with 95% confidence interval (95% CI)). MAIN RESULTS: Five non-blinded randomised trials with 258 patients with malignant strictures treated with polyethylene stents were included. Three trials, including 152 patients, investigated a combination of UDCA and antibiotics versus no treatment. The meta-analysis of these three trials does not show a significant treatment effect on the duration of stent patency (hazard ratio (random effects model) 0.58, 95% CI 0.22 to 1.54) or mortality (hazard ratio (fixed effect model) 0.99, 95% CI 0.68 to 1.43). Two trials with 106 patients compared antibiotics with no treatment, one of these trials used a combination of antibiotics and rowachol (an 'alternative' drug of the 'mint' family). The pooled results of these two trials do not show significant effects of antibiotics on the duration of stent patency (hazard ratio (fixed effect model) 0.69 (95% CI 0.37 to 1.30)) or mortality (hazard ratio (fixed effect model) 1.23 (95% CI 0.72 to 2.08). Data concerning duration of hospital stay, frequency of cholangitis, and rate of infectious complications due to selection of antibiotic resistant bacteria strains were not available. REVIEWER'S CONCLUSIONS: Treatment with UDCA and/or antibiotics to prevent clogging of biliary stents in patients with malignant stricture of the biliary tract cannot be recommended routinely on the basis of the existing randomised clinical trials. Further trials are needed with rigorous methodology and sufficient statistical power.

[Spider naevi after discontinuation of oral contraceptives]. / Spider naevi nach Absetzen oraler Kontrazeptiva.

PIP: A 34-year-old patient has experienced spider naevus on her right arm since the age of 10. Later, when she discontinued taking the oral contraceptives (OCs) containing norgestrel and ethinyl estradiol, which she had taken for five years, suddenly several typical spider naevi appeared on her neck and both underarms. Otherwise she was free of symptoms and not abusing alcohol. Blood test showed a slight increase of gamma-GT of 41 U/l, which was still normal. The question arose whether the discontinuation of OCs caused the appearance of spider naevi, which typically is connected with acute or chronic liver disease. Typical sites are the face, the upper chest, the neck, shoulders, underarms, and the back of the hands. The most likely explanation in this case theoretically would be a hormone rebound effect after the cessation of the OC use, but there are no clinical studies available to confirm such a hypothesis. She had neither acute nor chronic liver disease. Differential diagnosis could corroborate the slightly increased, isolated value of gamma-GT due to long-term use of OCs containing estrogen because of enzyme induction. Anamnesis should also determine any occupational or external exposure to toxic substances (e.g., solvents) and other causes of liver disease should also be excluded (hemochromatosis, primary biliary cirrhosis, primary sclerosing cholangitis). In addition, the possible role of a wide variety of nonhepatological causes of the increased value should be examined (hepatobiliary illnesses and others like anorexia nervosa, alcohol abuse, and drugs). For the time being a sonographic examination is recommended within six months followed by a gamma-GT test every two months. In case the elevated value persists further examinations should verify possible causative factors.^ieng

[Diet therapy in chronic inflammatory bowel disease: results from meta-analysis and randomized controlled trials]. / Diättherapie chronisch entzündlicher Darmerkrankungen: Resultate aus Meta-Analysen und randomisierten klinischen Studien.

BACKGROUND: Crohn's disease and ulcerative colitis are chronic inflammatory bowel diseases of unknown etiology. Unspecific immunosuppressive therapy represents current standard treatment and is often associated with severe side effects. Several treatment regimens have been evaluated to identify alternative therapeutic options. Among these different diet therapies were investigated. Objective of this paper is to review the results of diet therapy in chronic inflammatory bowel disease on the basis of randomised controlled trials and meta-analysis of randomised controlled trials. METHODS: Medline and Cochrane Library were searched for meta-analysis and randomised controlled trials investigating this question. Additionally reference lists of identified articles and text books were checked for further trials. RESULTS: Four meta-analyses investigated the treatment of acute Crohn's disease with elemental-, semi-elemental-, and polymeric diets in comparison to corticosteroids or to another form of enteral diet. All meta-analyses show a superiority of corticosteroids and no difference in the effect of the compared enteral diets. Randomised controlled trials investigating diet therapy in ulcerative colitis have not been summarised in a meta-analysis yet. Eleven randomised trials were identified which evaluated diets in ulcerative colitis patients: Dietary supplementation with n-3-fatty acids (6 trials), elemental diet [2], dietary supplementation with dietary fiber [1], elimination diet [1], and dietary supplementation with olestra [1]. Only for the elimination diet a significant positive effect on the course of disease was found in one trial which investigated only 18 patients. CONCLUSIONS: Enteral nutritional therapy of acute Crohn's disease is less effective than treatment with corticosteroids. In case of severe steroid induced side effects diet treatment can present a promising alternative. Superiority of one of the investigated different formulations was not found. Meta-analyses of randomised trials provide a clear and easy to understand presentation of the effect of this intervention. Eleven published trials investigating the effect of diets in ulcerative colitis show only for elimination diet a positive treatment effect. The trials do find a positive effect of one of the other interventions but the trials are very small and cannot exclude a treatment effect. Meta-analysis of these trials would be helpful for a better presentation and understanding of these results.

[Hepatopulmonary syndrome]. / Das hepatopulmonale Syndrom.

The hepatopulmonary syndrome (HPS) is a reversible pulmonary insufficiency in association with liver disease, most frequently liver cirrhosis. The pathogenesis of HPS is poorly understood. HPS is characterized by arterial hypoxemia caused by intrapulmonary arteriovenous shunts or marked vasodilatation of the pulmonary vessels and ventilation-perfusion mismatch in the absence of intrinsic heart or lung disease. Typical clinical signs are dyspnea in the upright position which improves in supine position (platypnoe) and decrease of arterial pO2 in the upright position (orthodeoxia). The diagnosis of HPS is based on clinical features, arterial blood gas analyses in supine and upright position, contrast echocardiography and lung perfusion scanning. Arteriovenous fistula can be excluded by pulmonary angiography. There is no established medical treatment of HPS. New medical and noninvasive therapies, such as transjugular intrahepatic Stent-shunt (TIPS), lead to improvement of HPS. These treatment modalities need further elucidation. HPS was shown to be reversible after orthotopic liver transplantation (OLTx) in some cases. Severe HPS, therefore, may be an indication rather than a contraindication for OLTx.

[Prevention of hepatocellular carcinoma]. / Prävention des hepatozellulären Karzinoms.

Prevention is an increasingly important area of modern medicine. One of the foremost goals in the field of hepatology is prevention of hepatocellular carcinoma since this tumor has a poor prognosis and current therapeutic options are limited. Most hepatocellular carcinomas arise from chronic liver disease and liver cirrhosis which is considered a major risk factor for tumor development. The most common etiologic factors causing liver cirrhosis include chronic viral hepatitis, alcohol consumption, toxins and a few metabolic disorders. This review discusses current therapeutic concepts for prevention and treatment of chronic liver disease and cirrhosis.

[Nonsurgical therapy of focal liver lesions]. / Nichtchirurgische Therapie fokaler Leberläsionen.

Indications for a local non-surgical therapy of focal liver lesions are the hepatocellular carcinoma (HCC) and metastases. The HCC is one of the most frequent malignant tumors worldwide with an incidence of 1 million cases per year. The prognosis of the untreated HCC is poor. For non-surgical cases there are local and systemic therapies available. A number of studies involving thousands of patients, have used treatment by PEI. Several of these studies have shown an increased survival in the PEI-treated patients. For patients primarily not treatable with PEI transarterial chemoembolization (TACE) with lipiodol in combination with a chemotherapeutic drug and gelfoam is a possibility. Studies of patients treated with PEI or TACE show a variability in survival, however, the trend is to prolonged survival. Improvement in efficacy of treatment and decreases in toxicities could be achieved through a combination of different interventions and an optimal patient selection. Both surgical and those cases unsuitable to local therapy should be treated with tamoxifen.

[Value of manometry]. / Stellenwert der Manometrie.

Manometry of the esophagus is essential in the diagnostic workup of patients with motility disorders of the esophagus. Before manometry organic diseases causing the symptoms should be excluded by a esophago-gastroscopy and/or a barium swallow meal. Indications for manometry are noncardiac chest pain, dysphagia of unknown origin, primary or secondary motility disorders of the esophagus and preoperative assessment before antireflux surgery.

[Hepatocellular carcinoma: percutaneous ethanol injection/transarterial chemoembolization/radiofrequency thermoablation]. / Hepatozelluläres Karzinom: perkutane Ethanoinjektion/transarterielle Chemoembolisation/Radiofrequenz-Thermoablation.

In the majority of patients hepatocellular carcinoma (HCC) is associated with liver cirrhosis. Advanced or decompensated liver cirrhosis, comorbidity and multicentricity make 70-80% of HCCs inoperable at the time of diagnosis. Therefore, percutaneous ethanol injection (PEI) and radiofrequency thermal ablation (RFTA) are non-surgical therapeutic options for patients with small HCCs. In patients with advanced tumor stage transarterial chemoembolization (TACE) and its variants showed no survival benefit on the basis of randomized trials. In several studies, however, combined treatment strategies like TACE and PEI or RFTA after occlusion of tumor blood supply in the treatment of advanced HCC seems to result in a survival benefit. All HCC patients should be included in randomized treatment studies.

A sphincterotome-based technique for selective transpapillary common bile duct cannulation.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) requires selective cannulation of the common bile duct and pancreatic duct. Selective common bile and pancreatic duct cannulation with standard techniques can be achieved in most but not all cases even in experienced centers. To facilitate selective cannulation, sphincterotomes can be used. METHODS: A prospective randomized study aimed at selective deep cannulation of the common bile and pancreatic ducts comparing different ERCP procedures was performed. One hundred patients were randomly assigned to undergo cannulation with a standard catheter or with a guidewire sphincterotome (GS) without guidewire. RESULTS: The primary success rate of selective common bile duct cannulation was significantly higher in the GS group (84%) as compared with the standard catheter group (62%) (p = 0.023). In patients with primary standard catheter failure, selective common bile duct cannulation was possible in 16 patients using a GS which increased the total success rate in the standard catheter group to 94% (p < 0.001). In GS failures selective common bile duct cannulation was possible in two patients using a standard catheter and increased the total success rate from 84% to 88%. The frequency of postinterventional pancreatitis did not differ significantly between the two groups. CONCLUSIONS: ERCP using a GS without guidewire has a significantly higher primary success rate for selective common bile duct cannulation then ERCP using a standard catheter. The use of a GS should be considered to optimize selective cannulation of the common bile duct before resorting to precut techniques.

Acute liver failure due to enalapril.

This report presents a 46-year-old man who was treated for hypertension with the angiotensin-converting-enzyme (ACE) inhibitor enalapril. After 3 years of continuous treatment he presented with jaundice and progressive liver failure that continued despite withdrawal of the medication. The patient was taking no other medication. All known causes of acute liver failure could be excluded indicating a drug-induced liver damage after long-term treatment with enalapril. Analysis of liver biopsies revealed a pathomorphological pattern comparable to than observed in severe halothane hepatitis. Serological studies including T-cell stimulation with enalapril and a broad spectrum of tests for autoimmunity including autoantibodies against calreticulin, the major Ca2+ and Zn2+ binding protein of the endoplasmic reticulum and suggested to be involved in the pathogenesis of halothane hepatitis were negative. Thus, the mechanism of enalapril-induced liver injury remains obscure. Liver failure progressed and finally led to orthotopic liver transplantation. To our knowledge, this is the longest duration of chronic treatment with an ACE inhibitor before liver failure occurred. In addition, liver failure progressed despite withdrawal of the medication. It is concluded that even after long-term treatment with an ACE inhibitor liver failure may be induced. Therefore, regular monitoring of liver enzymes should be considered.

[Diagnosis of hepatocellular carcinoma]. / Diagnostik des hepatozellulären karzinoms.

Hepatocellular carcinoma (HCC) is a frequent complication of chronic liver disease. The major causes of chronic liver diseases are hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, as well as chronic alcohol misuse. The clinical presentations of HCC patients are unspecific, with signs and symptoms of chronic liver disease. Early diagnosis of HCC in an asymptomatic and potentially curable stage is of highest priority. The present strategy for the detection of early HCC in patients with chronic liver disease is 6-monthly determination of alpha-fetoprotein (AFP) and ultrasound study of the liver. If these are abnormal, further diagnostic steps include computer tomography, magnetic resonance tomography, lipiodol-angiography and histopathology. By this sequential diagnostic strategy it should be possible to identify HCC in patients with chronic liver disease at an early and potentially curable stage.

[Pancreatic and biliary tract tumors--diagnosis: ultrasonic diagnosis--endosonography]. / Pankreas- und Gallenwegstumoren--Diagnostik: Ultraschall--Endosonographie.

Pancreaticobiliary tumors are mostly adenocarcinomas with a poor 5-year survival of less than 2%. Early diagnosis of resectable tumors improves outcome. Conventional ultrasound (US) is non-invasive and is the first modality employed on suspicion of these tumors. With adequate skills and equipment, pancreatic tumors from 1.5 cm in diameter can be detected. By contrast, US is less sensitive in the detection of lymph node involvement and infiltration of blood vessels. Depending on the location tumors of the biliary tract appear as a mass lesion intrahepatically or within the gallbladder. Perihilar and extrahepatic bile duct carcinomas cause proximal duct dilatation which is readily detected by US. Again, sensitivity in the detection of lymph node metastases or portal vein invasion is limited. Endoscopic ultrasound (EUS) has emerged as the method of choice in detecting small pancreatic tumors (e.g. < 2 cm in diameter). An accuracy of over 90% in T-staging and blood vessel infiltration can be achieved whereas lymph node metastases are correctly diagnosed in only 67% of cases. EUS-guided biopsy is readily performed using a curved array scanner. This technique enables neurolysis of the coeliac plexus in patients with heavy pain. EUS adds valuable information in cases of distal extrahepatic bile duct cancer. The role of EUS is limited in perihilar and intrahepatic cholangiocarcinoma. Staging and palliative therapy of perihilar carcinoma is still a domain of endoscopic retrograde cholangiography. Intraductal EUS is restricted to specialized centers and plays no role for routine purposes.

Ampullary hamartoma: A rare cause of biliary obstruction.

Tumors of the papilla of Vater are very rare. Despite advanced imaging techniques the distinction between benign and malignant tumors remains very difficult. Because most ampullary and periampullary tumors are malignant, primary management is surgical. Here we report the case of a 65-year-old man with biliary obstruction caused by an ampullary hamartoma simulating cancer. The correct diagnosis was not established until surgery.

[Hepatocellular carcinoma: npn-surgical treatment]. / Hepatozelluläres Karzinom: Nicht-chirurgische Therapieoptionen.

The therapeutic modalities in patients with hepatocellular carcinoma (HCC) depend on the number, size and location of the lesions as well as the stage of the underlying liver disease and the physical condition of the patients. In patients with small and solitary lesions resection, liver resection and in selected cases liver transplantation can be curative. In more advanced stages of the disease with larger or multiple lesions PEI and/or transarterial chemotherapy with or without embolisation (TACE or TAC) can slow the progression of the disease. In disseminated disease, a radio-therapeutic approach can be taken in selected cases. The therapeutic strategy in patients with HCCs has to be individualized, frequently using a combination of therapeutic modalities. Different from the earlier unfavourable prognosis, today for most HCC patients a therapeutic strategy can be offered that results in a prolongation of life and in some cases even cure.

[Nonsurgical therapy of hepatocellular carcinoma]. / Nicht-chirurgische Therapie des hepatozellulären Karzinoms.

Several non-surgical local ablation methods for the treatment of hepatocellular carcinoma (HCC) have been developed. Among them, percutaneous ethanol injection is worldwide an accepted alternative to surgery in patients with small HCCs. Other local minimal-invasive treatment options, like one time radio-frequency thermal ablation seem to result in more effective tumor control. Randomized controlled trials showed no survival benefit after transarterial chemoembolization and its variants for the treatment of local advanced HCCs. Combined therapeutic strategies may play an increasing role in future in these cases. Effective chemotherapy is not available for metastasized or advanced HCCs. The role of novel techniques for the treatment of HCC has to be carefully determined in large controlled clinical studies.

Radiofrequency thermal ablation of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the major malignancies worldwide. Due to advanced or decompensated liver cirrhosis, comorbidity and multicentricity of the tumor lesions, 70-80% of HCC patients are inoperable at the time of diagnosis. Radiofrequency thermal ablation (RFTA) is a new minimally invasive and sage technique for the nonsurgical treatment of HCCs. Similar to other ablation techniques, the treatment strategy depends on several factors, including the patient's clinical status, the stage of liver cirrhosis and of the HCC. RFTA can be performed percutaneously, laparoscopically or after laparotomy. Advanced RFTA equipment, refined techniques of modifying tumor tissue response to RFTA, and combined treatment strategies should lead to better response rates even in larger HCCs.

[Recurrent bleeding from colonic varices in portal hypertension. The successful prevention of recurrence by the implantation of a transjugular intrahepatic stent-shunt (TIPS)]. / Rezidivierende Kolonvarizenblutung bei portaler Hypertonie. Erfolgreiche Rezidiv-Prophylaxe durch Implantation eines transjugulären intrahepatischen Stent-Shunts (TIPS).

HISTORY AND CLINICAL FINDINGS: Sclerotherapy was performed in a 52-year-old patient with alcoholic liver cirrhosis (Child-Pugh stage A) for recurrent bleeding from oesophageal varices. Half a year later he again was admitted to hospital because of recurrent passage of bloody stools. The cardiovascular status was stable; the liver was enlarged by 15 cm in the medioclavicular line. INVESTIGATIONS: Endoscopy revealed several varices in the colon near the right flexure. One of the varices had an ulcer of 5 mm size. Duplex sonography revealed portal hypertension with cirrhosis of the liver and partial thrombosis of the main trunk of the portal vein without any sign of cavernous transformation. TREATMENT AND COURSE: Because of the partial portal vein thrombosis it was decided to insert a transjugular intrahepatic portosystemic stent shunt. This obviated the thrombosis and lowered the portosystemic pressure gradient by 6.8%. With the shunt functioning well there were no further bleedings in the subsequent year. CONCLUSION: The only slightly invasive TIPS implantation is an effective therapeutic procedure for bleeding from colon varices caused by portal hypertension.

[Therapy of hepatocellular carcinoma]. / Therapie des hepatozellulären Karzinoms.

The therapeutic modalities in patients with hepatocellular carcinoma (HCC) depend on the number, size and location of the lesions as well as the stage of the underlying liver disease and the physical condition of the patient. In patients with small and solitary lesions, resection, liver transplantation and in some cases percutaneous ethanol injection (PEI) can be curative. In more advanced stages of the disease with larger or multiple lesions, PEI and/or transarterial chemotherapy with or without embolization (TACE or TAC) can slow the progression of the disease. In disseminated disease, a radiotherapeutic approach can be taken in selected cases. The therapeutic strategy in patients with HCCs should be individualized, frequently involving a combination of therapeutic modalities. In contrast to the earlier dismal prognosis, for most HCC patients there is today a therapeutic strategy that results in prolongation of life and in some cases even cure.