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Background: Since 2010, combination therapy with gemcitabine and cisplatin is the standard treatment for patients with biliary tract cancer (BTC) based on the ABC-02 trial. However, treatment after first-line progression is less clearly defined. We therefore retrospectively analyzed the efficacy of a 3-drug chemotherapy regimen in patients with advanced BTC. Methods: Patients with advanced BTC treated with palliative chemotherapy between April 2000 and October 2005 at Regensburg University Hospital were reviewed retrospectively. We analyzed the efficacy and safety of an institutional standard 3-drug regimen consisting of irinotecan, gemcitabine and 5-FU (IGF). One cycle, lasting 21 days, included applications on days 1 and 8 consisting of 75 mg/m2 irinotecan i.v. for 90 min, 1,000 mg/m2 gemcitabine i.v. for 30 min and 2,000 mg/m2 fluorouracil (5-FU) for 24 h. Results: A total of 12 histologically confirmed cases with gallbladder cancer and intrahepatic BTC were reviewed. Fifty percent of the patients (6/12) had been pretreated with other chemotherapies. Median progression-free survival was 9.4 months (1.5-21.5) and median overall survival was 17.2 months (2.5-24.3). Only neutropenia (8%) was observed as an NCI-CTC grade 3 toxicity. Anemia and leucopenia grades 1 and 2 were the most common side effects. Conclusions: The combination of IGF shows a promising survival benefit with manageable toxicity in patients with advanced BTC. Therefore, this regimen seems to be a feasible second-line treatment option for patients with rapid progression under first-line therapy with gemcitabine and cisplatin and with a good performance status.

The immune system and the hypothalamic-pituitary-adrenal axis are linked by several mechanisms. Intracellular glucocorticoid receptors represent one important connection. The aim of this study was to examine the coherence between the number of glucocorticoid receptors, activation of the hypothalamic-pituitary-adrenal axis, inflammatory cytokine levels and the severity of illness in critically ill patients. In a prospective study, blood was collected from 20 healthy members of the hospital staff (control group) and 50 ventilated patients (sample group) within the first 24 hours after intubation and within three days of extubation. 5H-dexamethasone-binding assay was used to assess cytoplasmatic free glucocorticoid receptors levels. ACTH, cortisol, IL-6 and TNFα. levels were measured by ELISA. In the sample group, specific binding of 5H-dexamethasone was significantly decreased compared to the control group. Glucocorticoid receptor levels tended to be lower in more severely ill patients. Plasma cortisol and ACTH levels were significantly different from the control group after extubation but not at intubation. Severe illness is associated with rapid down-regulation of 5H-dexamethasone binding. This decrease occurs before elevation of plasma cortisol. Therefore, down-regulation of cortisol binding may be directly associated with the stress response and not due to feedback regulation following increase in plasma cortisol levels.

The time required for a colonoscopy must be justified under economic aspects. The objective of this study was to analyze patient- and staff-related factors influencing the time for cecal and ileal intubation. A prospective study was performed on 500 consecutive patients undergoing colonoscopy in 2005. The authors analyzed patient age, gender, height, weight, surgical history, the presence of liver cirrhosis and splenomegaly, the number of children given birth, the presence of colorectal cancer and inflammatory bowel disease, the quality of bowel preparation, sedation, and the experience of the attending colonoscopist, the nurse and the team as factors of possible relevance to cecal and ileal intubation time. The cecum was reached in 495/500 examinations (99%). Intubation of terminal ileum was possible in 477/500 patients (96%). Mean cecal and ileal intubation times were 10.5 ± 10.2 min and 6.4 ± 7.9 min, respectively. Time to cecal intubation was related to the experience of the endoscopist (p = 0.009), the nurse (p = 0.04) and the whole team (p = 0.002), as well as to an adequate cleaning of the bowel (p = 0.01). A short intubation time requires experienced staff in combination with an adequate cleaning of the bowel without reference to biological or pathologic factors except for colon-shortening surgery. The gain in examination quality by inspecting the terminal ileum comes to the cost of a prolongation of insertion time of 25–30% in experienced hands.

BACKGROUND AND STUDY AIMS Extensive anastomotic leaks after esophageal resection and esophageal perforations are a therapeutic challenge. The aim of the present study was to assess the potential of the self-expandable Polyflex plastic stent for the treatment of these conditions. PATIENTS AND METHODS Between January 2002 and March 2003, nine patients were treated with a self-expandable Polyflex plastic stent for sealing of thoracic esophagoenteric anastomotic leaks following surgical resection (n = 5) or esophageal perforation (n = 4). RESULTS In all patients the stents were inserted successfully without technical problems. In all but two patients complete sealing of the leak was achieved as demonstrated by radiography with water-soluble contrast media. The stent migration rate was 30 % and repositioning of the migrated stents was possible in all cases. Complete mucosal healing of the esophageal leaks and stent extraction was achieved in six patients. The stents were in situ for an average period of 135 +/- 78 days. Two critically ill patients with anastomotic leaks died in spite of stent insertion due to sepsis and one patient with esophageal perforation died due to the underlying malignant disease. CONCLUSIONS Our preliminary experience with the self-expanding and removable Polyflex plastic stent for the sealing of anastomotic leaks and esophageal perforations suggests that this stent is a feasible treatment option, in particular, for more extensive esophageal defects, patients with co-morbid conditions, and critically ill patients.

Squamous cell carcinomas account for more than 80 % of esophageal malignancies in Germany. Alcohol and tobacco smoke are two of the most important risk factors. In superficial esophageal squamous cell carcinoma, endoscopic mucosal resection (EMR) is a very useful and effective treatment modality. However, in patients with submucosal esophageal cancer, radical esophageal resection is regarded as the gold standard for treatment at present. We report the case of a 71-year-old female patient with alcohol-induced liver cirrhosis with esophageal varices and a - therefore inoperable - early esophageal squamous cell carcinoma. Photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA) seemed not to be an effective treatment modality due to its limited penetration depth (< 2 mm) and the liver toxicity of 5-ALA. PDT using Photofrin(R) with a higher penetration depth seemed to be associated with a high risk of bleeding due to the esophageal varices. Furthermore, this sensitizer is associated with a high rate of strictures and a long-lasting skin sensitivity. In contrast, arguments against an endoscopic mucosal resection (EMR) were endosonographically suspected submucosal tumor growth and a high risk of bleeding. Nevertheless, with respect to the lack alternatives we decided to perform an EMR after ligation of esophageal varices. The tumor could be resected in sano without major bleeding complication. Histology demonstrated a carcinoma in situ without submucosal invasion. After 3 months a second EMR was necessary due to recurrence. Meanwhile after a follow-up period of 18 months only low grade intraepithelial neoplasia without macroscopically suspicious lesions was observed.

Die Detektion von Metastasen beim malignen Melanom ist therapeutisch relevant. Ziel der Arbeit ist der Vergleich der Palpation mit der Sonographie zur Lymphknotenbeurteilung beim lokal fortgeschrittenen malignen Melanom. 83 Patienten mit malignem Melanom (Clark-Level IV oder V) wurden sowohl palpatorisch als auch sonographisch auf suspekte Lymphknoten untersucht. Bei positiven Lymphknoten wurde das Untersuchungsergebnis mit dem histopathologischen Befund oder aber dem Befund bei der nachsten Visite verglichen. Lymphknotenmetastasen wurden histopathologisch bei 14 Patienten nach der ersten Studienuntersuchung, bei drei weiteren Patienten nach der Kontrolluntersuchung nachgewiesen. Sensitivitat, Spezifitat, positiver und negativer Vorhersagewert fur den Nachweis von Filiae oder von grosenprogredienten und verdachtigen Lymphknoten bei der nachsten Untersuchung lagen fur die Palpation bei 65%, 81%, 48% bzw. 89%, fur die Lymphknotensonographie bei 100%, 66%, 45% bzw. 100%. Die Lymphknotensonographie sollte integraler Bestandteil bei der Detektion von Lymphknotenmetastasen beim lokal fortgeschrittenen malignen Melanom sein.

Percutaneous gastrostomies (PG) are nowadays usually placed endoscopically (PEG). Due to stenoses in the pharynx or the esophagus or in case of a lack of diaphany, other methods for the placement of PG such as computed tomography (CT-) guided or ultrasound-guided PG (PUG) are performed. We present a case of a 63-year old male patient with a retroperitoneal liposarcoma and multivisceral resection who presented with the symptoms and signs of an ileus due to metastatic occlusion of the small bowel. The placement of a decompression-PEG was impossible due to interposition of colon between the stomach and the abdominal wall. After filling the stomach with water via a naso-gastral decompression tube, the stomach could be visualized at the left thoracic wall, since the spleen and the left kidney had been removed at prior surgery. A transcostal decompression-PUG was inserted. The intervention described is the first published ultrasound guided transcostal decompression gastrostomy and is an example for the growing significance of interventional ultrasound.

Hintergrund und Ziel: Die Indikation zur Therapie der HCV-RNA-positiven chronischen Hepatitis C ergibt sich nach den derzeitigen deutschen Leitlinien nicht aus der Histologie, sondern durch das Vorliegen erhohter Transaminasen. Die Indikation zur Gewinnung einer Leberhistologie vor Therapiebeginn wird kontrovers diskutiert. Ziel dieser Studie war die Untersuchung der Korrelation verschiedener biochemischer und virologischer Parameter mit dem histologischen Entzundungs- und Fibrosegrad bei chronischer Hepatitis C. Patienten und Methodik: In einer retrospektiven Untersuchung wurden die Daten von 126 Patienten analysiert, bei denen zwischen Januar 1994 und Marz 1998 bei chronischer Hepatitis C eine Leberpunktion durchgefuhrt worden war. Die Histologien wurden einheitlich von einem Pathologen nach einem numerischen Entzundungs- und Fibrosegrad analysiert. Entzundungs- und Fibrosegrade wurden korreliert mit biochemischen und virologischen Parametern. Ergebnisse: Der Entzundungsgrad korrelierte mit der Hohe der GPT (r = 0,33; p < 0,001) nicht aber das Fibrosestadiulm (r = 0,15). Weder Entzundungs- noch Fibrosegrad zeigten eine signifikante Korrelation mit dem HCV-Genotype (n = 110) oder der HCV-RNA-Kopienzahl im Serum (n = 57). Entzundungs- und Fibrosegrad waren hochsignifikant miteinander assoziiert (p < 0,0001). Schlusfolgerung: Transaminasen spiegeln als “Surrogatmarker” in etwa die histologische Entzundungsaktivitat wider, erlauben jedoch keine Ruckschlusse auf das Fibrosestadium. Bei einem Teil der Patienten konnen jedoch durchaus eine hohe Entzundungsaktivitat bei niedrigen Transaminasen oder hohe Transaminasen bei niedriger histologischer Entzundungsaktivitat vorliegen. Virologische Parameter wie HCV-Genotyp oder HCV-RNA-Kopienzahl im Serum lassen keine Ruckschlusse auf den Entzundungsgrad oder das Fibrosestadium zu. Der Verzicht auf eine Leberhistologie vor Einleitung der Therapie einer Hepatitis C und die ausschliesliche Bestimmung von “Surrogatmarkern” konnen zu einer deutlichen Fehleinschatzung der tatsachlichen Entzundungs- und Umbauvorgange in der Leber fuhren.

Treatment refractoriness is a severe problem in the management of patients with ulcerative colitis and Crohn's disease. Despite some promising new therapeutic approaches, corticosteroids are still the preferential primary treatment for moderate to severe Crohn's disease and of severe ulcerative colitis. However, clinical response to corticosteroids varies, and many patients are resistant to such treatment. Since corticosteroids have frequent and even severe side effects, and toxicity increases with chronic steroid intake, factors predictive of response to such treatment would be very helpful for decisions on further management of these patients. At least in severe attacks of ulcerative colitis, the consensus seems to be that a high frequency of bowel movements as well as a high C-reactive protein and low serum albumin recorded after a few days of intensive medical treatment are important signs for early prediction of treatment failure in the majority of the patients. In Crohn's disease thus far, data on predictive factors are conflicting. No reliable marker with sufficient predictive value for treatment refractoriness could be identified. This might be due to the tremendous heterogeneity of Crohn's disease with many clinical phenotypes, which requires subgroup analysis with sufficient numbers of patients. Corticosteroids as well as other immunomodulating and immunosuppressive medications interfere with the immune system, which plays a central role in the mediation of intestinal inflammation. Treatment refractoriness might have its origin in specific immunological peculiarities eventually reflected in abnormal immunological, biochemical, and clinical parameters. Further exploration of those parameters to predict treatment refractoriness in patients with ulcerative colitis or Crohn's disease is of great clinical importance for safe and efficient management of patients.

Chronic hepatitis C patients are advised not to share toothbrushes, razors, nail-scissors or other personal articles that potentially may have been in contact with blood, with others. This study examines the contamination of toothbrushes in patients with chronic hepatitis C as a model for a possible unconventional way of transmission. In 30 patients with chronic hepatitis C, 2 mL of saliva (before and after toothbrushing) and the toothbrush rinsing water after toothbrushing were tested for HCV-RNA. Saliva before and after toothbrushing was positive for HCV-RNA in nine (30%) and 11 patients (36.7%), respectively. Twelve of the toothbrush rinsing water specimens (40%) tested HCV-RNA-positive. In six of these 12 patients, the 'native' saliva had been negative for HCV-RNA. Patients with HCV-RNA-positive toothbrush rinsing water showed no significant differences from those with negative rinsing water with respect to certain clinical, biochemical and virological parameters. In conclusion, our study demonstrates a contamination with HCV-RNA of a considerable portion of toothbrushes used by hepatitis C patients, suggesting at least a theoretical risk of infection by sharing these objects and strengthening the recommendations to take care of a clear separation of these personal care objects between patients and their household members.

Ehlers-Danlos syndrome (EDS) type IV is an autosomal dominant connective tissue disease caused by mutations in the type III collagen gene resulting in extreme tissue fragility. Affected individuals are at risk of dramatic and often fatal complications, mostly spontaneous arterial, uterine, or colonic ruptures. Phenotypic expression of EDS type IV is variable and clinical signs are generally quite subtle, thus making a prompt diagnosis difficult. The case of a 33-year-old woman is described who presented with a wide range of clinical features and sequelae that eventually led to the diagnosis of EDS type IV. She presented with spontaneous liver rupture, renal infarction, and pneumothorax, all representing rare complications of EDS type IV. Prior history revealed a uterine rupture in advanced pregnancy associated with ischemic necrosis of the descending and sigmoid colon. EDS type IV should be suspected in young individuals who present with such unusual complications. Early diagnosis is essential if severe or even lethal complications are to be avoided in the diagnostic and therapeutic management of such patients.

Fistulae or leakages of anastomotic junctions of the gastrointestinal tract used to be an indication for surgery. However, patients often are severely ill and endoscopic therapeutic options have been suggested to avoid surgical intervention. This is a retrospective analysis of fibrin glue application in the treatment of gastrointestinal fistulae or anastomotic leakages. The aim of this study was to investigate the value of fibrin glue in the treatment of gastrointestinal fistulae and leakages. From September 1996 to November 2002, 52 patients with gastrointestinal fistulae or insufficiencies have been treated endoscopically including the use of fibrin glue (Tissucol Duo S®, Baxter, Unterschleissheim, Germany). Clinical data comprising concomitant therapies and results were analysed by chart review. Twenty-six lesions were located in the oesophagus or gastroesophageal junction, 4 in the stomach, 7 in the small intestine, 13 colorectal and 2 in the pancreas. The duration of treatment ranged from 12 to 1,765 days. Two to 81 ml fibrin glue (median 8.5) was used in 1–40 sessions (median 4). All patients received antibiotics; additional endoscopic options were frequently applied. Endoscopic therapy cured 55.7% patients (n = 29); 36.5% (n = 19) were cured with fibrin glue as sole endoscopic option. In 23.1% (n = 12), surgical intervention became necessary. Patients without major infectious complications tended to have a higher cure rate without surgery (87.5% vs. 50%). Eleven patients died (21.1%). Endoscopic therapy is a valuable option in the treatment of fistulae and anastomotic insufficiencies of the gastrointestinal tract. It usually is applied repeatedly. Fibrin glue is a mainstay of this procedure. Major infectious complications seem to define a subgroup of patients with poorer outcome.

Sclerosing cholangitis in critically ill patients (SC-CIP) with sepsis and acute respiratory distress syndrome (ARDS) is a cholestatic liver disease with a rapid progression to liver cirrhosis and hepatic failure. Data on outcome of these patients after liver transplantation (LT) are sparse.Eleven patients (46 ± 12 years; mean labMELD-score: 27 ± 7) with SC-CIP underwent LT. Six patients had severe polytrauma with multiple bone fractures, sepsis and ARDS. Five non-traumatic patients acquired SC-CIP during long-term intensive-care-unit stays due to sepsis and ARDS. Time to diagnosis, the microbiologic results and the survival rates after LT were evaluated.SC-CIP was diagnosed by endoscopic retrograde cholangiopancreatography (ERCP) within 3 ± 1 months after manifestation of cholestasis and histologically confirmed in explanted livers. The predominant microorganisms isolated in bile were: Enterococcus and Candida albicans. Mean follow-up after LT was 28 ± 20 months. One female patient (non-traumatic) died due to sepsis 26 days after LT. All other patients left the hospital alive, but two (non-traumatic) patients died from sepsis, and one (traumatic) patient died in a hemorrhagic shock, thereafter. Seven of 11 patients (5 with polytrauma) are still alive and have a good quality of life. The survival of the SC-CIP patients after LT was comparable with that of patients transplanted due to alcoholic liver cirrhosis.SC-CIP develops rapidly within several months. Enterococcus and C. albicans were the main isolated microorganisms in the bile. Sepsis was the main cause of death after LT. Overall, SC-CIP is a good indication for LT in selected patients.

Bolus impaction in the esophagus is a common indication for emergency endoscopy. The aim of this study was to determine the most common causes of esophageal bolus impaction. In this retrospective study, data of 54 patients (41 male, 13 female) with bolus impaction in the esophagus were analyzed. Type and localization of the bolus and the endoscopic extraction tool used were evaluated. In 48 of 54 patients (89%), biopsy samples were taken of the esophagus for histological examination. Mean age of the patients was 53 ± 20 years. Fourteen of 54 patients (26%) had experienced bolus impaction previously. Meat bolus (n = 35, 65%) was the most common cause of esophageal obstruction. In most cases, boluses were found in either the distal (n = 31) or the proximal (n = 18) esophagus. In 22 patients (41%), the bolus was pushed into the stomach by the endoscope. In most other cases the bolus, including foreign bodies, could be removed with the 5-arm polyp grasper or alligator forceps. Main causes of bolus impaction were eosinophilic esophagitis (n = 10) or reflux disease with or without peptic stenosis (n = 10), respectively. Bolus impaction is frequently correlated with eosinophilic esophagitis and reflux esophagitis; therefore, diagnostic workup should include esophageal biopsy sampling.

Objective. Gastrointestinal (GI) tract involvement has been observed in the majority of patients with SSc. This has been attributed to an accumulation of extracellular matrix within the GI walls. We visualized the walls of the oesophagus, stomach and duodenum with its layers and measured the thickness in SSc patients and control patients utilizing endoscopic ultrasound (EUS). Methods. Twenty-five SSc patients and 25 controls were evaluated. In addition to analysis of clinical symptoms, endoscopy and EUS (20-MHz miniprobe) were performed. The thickness of the complete wall was measured, and the mucosa, submucosa and muscularis were evaluated separately. Results. Clinical symptoms of SSc patients were dysphagia (14/25) and heartburn (19/25). Endoscopic findings were hiatal hernia (16/25), oesophagitis (6/25), amotility (19/25) and a dehiscent pylorus (15/25). In comparison with controls, SSc patients had significantly thicker oesophageal [SSc 1.619 (0.454) mm, control 1.392 (0.333) mm; P = 0.025], antral [SSc 1.876 (0.635) mm, control 1.599 (0.291) mm; P = 0.029] and duodenal [SSc 1.730 (0.522) mm, control 1.525 (0.222) mm; P = 0.039] walls. Predominantly, submucosa and muscularis were significantly thicker in SSc patients. The presence of dysphagia or amotility was significantly associated with the thickening of the GI walls. Conclusions. The EUS revealed a significant thickening of the walls of the upper GI tract in SSc patients. Predominantly, the submucosa and muscularis are enlarged. These results strengthen the hypothesis that increased matrix deposition is an important aspect in the pathogenesis of GI involvement in SSc.

Secondary sclerosing cholangitis (SSC) is a chronic cholestatic biliary disease, characterized by inflammation, obliterative fibrosis of the bile ducts, stricture formation and progressive destruction of the biliary tree that leads to biliary cirrhosis. SSC is thought to develop as a consequence of known injuries or secondary to pathological processes of the biliary tree. The most frequently described causes of SSC are longstanding biliary obstruction, surgical trauma to the bile duct and ischemic injury to the biliary tree in liver allografts. SSC may also follow intra-arterial chemotherapy. Sclerosing cholangitis in critically ill patients is a largely unrecognized new form of SSC, and is associated with rapid progression to liver cirrhosis. The mechanisms leading to cholangiopathy in critically ill patients are widely unknown; however, the available clinical data indicate that ischemic injury to the intrahepatic biliary tree may be one of the earliest events in the development of this severe form of sclerosing cholangitis. Therapeutic options for most forms of SSC are limited, and patients with SSC who do not undergo transplantation have significantly reduced survival compared with patients with primary sclerosing cholangitis. Sclerosing cholangitis in critically ill patients, in particular, is associated with rapid disease progression and poor outcome.

An 18-year-old male experienced a first episode of Crohn's disease with inflammation of the colon, stenosis of small intestine and a fistula of the anal sphincter. After resection of the fistula and 30 cm of proximal ileum the patient remained free of symptoms under medication with azathioprine and mesalazine for 6 years. Then, blood in the stool occurred. Diagnostic work-up - gastroscopy and colonoscopy 2004 and 2006, magnetic resonance enteroclysis 2004 and 2006 and wireless capsule enteroscopy 2006 - revealed slight inflammation in the ileum but no bleeding source. The bleeding ceased, but after 2 uneventful years abdominal cramps appeared and diagnostic work-up (magnetic resonance enteroclysis, radiograph) located the capsule still in the terminal ileum proximal to an inflamed stenosis. Corticosteroids were subscribed for 4 weeks, but the capsule stayed in place. Surgery was discussed, but denied by the patient. Finally, the capsule could be taken out by double balloon enteroscopy.

Studies of the prevalence of gastroesophageal reflux disease (GERD) have reported that male gender is an independent risk factor especially for erosive reflux disease (ERD). Non erosive GERD (NERD) is more common in females. The rate of prevalence and severity of reflux symptoms increase in females with age, while among men it peaked between 50 and 70 years and thereafter declined. The gender effect may be caused by differences in parietal cell mass between males and females. Barrett's esophagus is a major complication of gastroesophageal reflux disease and is associated with 30-125 times increased risk of developing carcinoma. Most studies have found gender differences with females significantly less likely to have Barrett's esophagus with a 20-yr age shift between the parallel age specific prevalence curves, for males between the ages of 20 and 59 yr and for females between the ages of 20 and 79 yr. Male predominance for ERD as a precursor to Barrett's esophagus may be partly explain the greater male/female sex ratio for Barrett's esophagus. Female sex hormones may play a protective role. Knowledge of gender-specific differences of reflux disease and Barrett's esophagus may be helpful to improve surveillance and screening strategies, although distinct recommendations are lacking so far .

Sclerosing cholangitis in critically ill patients (SC-CIP) is a newly described entity of severe biliary disease with progression to liver cirrhosis. The mechanisms leading to this form of cholangiopathy with stricture formation and complete obliteration of bile ducts are unknown.In the last 2 yr, sclerosing cholangitis was diagnosed in 26 patients during or after their stay on the intensive care unit by ERCP and/or liver histology. Complete patient records were available for 17 patients. Histological evaluations of liver biopsies and of four explanted livers, parameters of cardiovascular and respiratory conditions, treatment modalities, and accompanying infections were analyzed to find further hints for the pathomechanisms leading to SC-CIP.With the beginning of cholestasis, the earliest endoscopic findings were intrahepatic biliary casts with impairment of the biliary flow and subsequent biliary infection, in most cases with Enterococcus faecium. Liver biopsy confirmed cholangitis and histology of explanted livers revealed ulcerated biliary epithelium with hemorrhagic exudates in the bile ducts. In the further course, progressive sclerosis with formation of multiple strictures of the bile ducts was observed. All patients suffered severe respiratory insufficiency with the need for mechanical ventilation (40.7+/-32.9 days). The PaO2/FiO2 ratio until beginning of cholestasis was 150.5+/-43.1. Half of the patients (9/17) were treated with high-frequency oscillatory ventilation and 12/17 patients by intermittent prone positioning. All patients required catecholamines for hemodynamic stabilization.SC-CIP is a severe and in most cases rapidly progressive complication of intensive care patients. Ischemic injury of the biliary tree with the formation of biliary casts and subsequent ongoing biliary infection due to multiresistant bacteria seem to be major pathogenic mechanisms in the development of this new entity of sclerosing cholangitis.

Esophageal stenting has become an important technique in the treatment of different clincal problems such as malignant or benign stenosis, anastomotic leaks after surgery, or fistulas. In this study we present our experience with the self-expanding Polyflex plastic stent in various indications, arising complications, and patient’s outcomes. Over a three-year period, 35 patients underwent self-expanding Polyflex plastic stent placement for esophageal stenosis (n = 23) with 22 malignant, and for perforations, fistulas, or anastomotic leaks after surgery (n = 12). The short-term efficacy and long-term outcomes were analyzed. In patients with stenosis, implantation was performed without any complications in 91% (21/23). In one patient perforation occurred while passing the stenosis; in another patient the stent dislocated during the insertion procedure. Dysphagia score improved from 3.0 to 1.0 after stenting. In all patients with perforations, fistulas, or anastomotic leaks (n = 12), stents were placed successfully without any complication. Complete sealing of the mucosal defect was proven by radiography in 92% (n = 11) and healing was seen in 42% (n = 5). If indicated, stent removal was performed without any complications. Stent migration (n = 13; 37%) was the most common long-term complication. The placement of self-expanding Polyflex plastic stents is a highly sufficient and cost-effective treatment for malignant and benign esophageal disorders. Because the long-term results were highly favorable, self-expanding plastic stent placement could be used as the initial treatment for various conditions.

Esophageal involvement in Crohn's disease is very rare. In only a small subgroup of these patients -- up to date fourteen cases have been described in the literature -- the course of the illness may be complicated by esophageal fistula formation. The therapy for fistulizing esophageal Crohn's disease so far has been disappointing, recurrence and progression are likely, and surgery still is the primary treatment modality for refractory patients. We here present a case of severe Crohn's disease with an esophagobronchial fistula and the successful closure of the fistula tract with the novel liquid polymer sealant "Onyx". This approach offers a new option for the treatment of this rare complication of Crohn's disease and should be considered if surgery is not possible.

Early treatment of acute hepatitis C with interferon alpha-2b for 24 weeks prevents chronic infection in almost all patients. Because pegylated interferons have replaced conventional interferon in the therapy of chronic hepatitis C, the aim of this study was to analyze the efficacy of an early treatment of acute hepatitis C with peginterferon alpha-2b. Between February 2001 and February 2004, 89 individuals with acute HCV infection were recruited at 53 different centers in Germany. Patients received 1.5 microg/kg peginterferon alpha-2b for 24 weeks; treatment was initiated after a median of 76 days after infection (range 14-150). End-of-treatment response and sustained virological response were defined as undetectable HCV RNA at the end of therapy and after 24 weeks of follow-up, respectively. In the total study population, virological response was 82% at the end of treatment and 71% at the end of follow-up. Of 89 individuals, 65 (73%) were adherent to therapy, receiving 80% of the interferon dosage within 80% of the scheduled treatment duration. End-of-treatment and sustained virological response rates in this subpopulation were 94% and 89%, respectively. A maximum alanine aminotransferase level of more than 500 U/L prior to therapy was the only factor associated with successful treatment. In conclusion, in acute HCV infection, early treatment with peginterferon alpha-2b leads to high virological response rates in individuals who are adherent to treatment. The high number of dropouts underlines the importance of thorough patient selection and close monitoring during therapy. Thus, future studies should identify factors predicting spontaneous viral clearance to avoid unnecessary therapy.

Background Fluorescence endoscopy is a promising new method for detection and treatment of premalignant and malignant lesions. The aim of this pilot study was to investigate the feasibility of hexaminolevulinate-based photodetection of rectal adenoma and cancer, including safety, dose finding, and efficacy. Methods Ten patients with known rectal adenoma or cancer were sensitized by instillation of 3.2 mM of hexaminolevulinate as an enema. Fluorescence endoscopy was performed after retention of the enema for 30 to 60 minutes, followed by a rest time of up to 30 minutes before endoscopy. Biopsy specimens were taken from fluorescent and non-fluorescent areas and fluorescence microscopy studies were performed to assess the distribution of protoporphyrin IX fluorescence in different tissue layers. Adverse events were reported by direct questioning of all patients; skin photosensitivity, changes in biochemical tests of liver function, blood pressure and heart rate, and the occurrence of GI symptoms (nausea, vomiting) were recorded for 5 patients. Observations Hexaminolevulinate-induced fluorescence endoscopy produced selective fluorescence of all rectal adenomas with intraepithelial neoplasia. For rectal cancer, there was only weak fluorescence or none at all. No hexaminolevulinate-induced side effect was observed. In two patients, fluorescence differentiated adenomas and hyperplastic polyps. Conclusions Hexaminolevulinate-based fluorescence endoscopy (3.2 mM administered as an enema) in patients with rectal cancer and adenoma was well tolerated and produced no significant skin sensitivity or other side effects. The optimal duration of application is 30 to 45 minutes, with a rest time of 30 minutes. Selective fluorescence of adenoma with intraepithelial neoplasia suggests that hexaminolevulinate-based fluorescence endoscopy may be useful for detection of premalignant lesions.

Some patients with Crohn's disease (CD) do not respond to corticosteroid therapy. Furthermore, corticosteroids frequently cause side effects. Thus, predictive parameters for treatment refractoriness would be helpful for treatment decisions.A total of 300 patients with active CD (i.e., with a Crohn's Disease Activity Index [CDAI]200) entered the study. Treatment started with 60-100 mg/day prednisolone equivalent, which was then tapered to 10-15 mg/day within 6 wk and maintained at that dose for another 4 wk. After 10 wk of treatment, response to steroids was defined by a CDAI150, steroid resistance by a CDAI alwaysor =150 and steroid dependency by a relapse after dose reduction. Of 239 eligible patients, 196 were responders, 26 were steroid resistant, and 17 were steroid dependent.Prior bowel resections, a high initial CDAI, and perianal disease were associated with steroid resistance. Of the steroid resistant patients 53.9% were bowel-resected compared to 20.4% of the responders (relative risk = 3.63; 95% CI = 1.79-7.36). Perianal disease was observed in 42.3% of steroid resistant patients versus 21.9% of responders (relative risk = 2.28; 95% CI = 1.12-4.66) and initial CDAI was 347+/-91 in resistant patients versus 301+/-81 in responders (p0.05). Parameters for steroid dependent patients were not significantly different from those of responders.In this study (thus far the largest study for the evaluation of predictive factors for treatment refractoriness to corticosteroids in CD), only prior bowel resection, perianal disease, and a high initial CDAI were found to be predictive of resistance to steroid treatment.

Fluorescence endoscopy is a new technique which allows a better detection of non-visible malignant or premalignant lesions or, those which are difficult to detect. Exogenously applied sensitisers accumulate selectively in malignant lesions and induce fluorescence after illumination with light of adequate wavelength. However, also endogenous fluorophores, different located in malignant or benign lesions, induce a different autofluorescence in these lesions. Tissue fluorescence can be detected by optical sampling of the mucosa using fluorescence spectroscopy or by generating real time fluorescence images with specialised camera systems. Compared to point fluorescence spectroscopy the latter technique enables the screening of large surface areas of mucosa. Meanwhile, fluorescence endoscopy is a widely used technique in urology employing 5-aminolaevulinic acid sensitisation. In gastroenterology, this technique seems promising for the detection of early cancers or dysplasia in patients with Barrett's oesophagus or ulcerative colitis. Using different sensitisers, photodynamic therapy seems to be a promising option for patients with advanced oesophageal cancer and in the palliative treatment of non-resectable bile duct cancer, furthermore for patients with early gastric cancer and dysplasia in Barrett's oesophagus. Probably, by laser light fractionation or a combination of different sensitisers, an enhanced effect can be expected.

OBJECTIVE Associations between HLA-DR genotypes and susceptibility to Crohn's disease (CD) have been reported. However, it is not known whether certain HLA-DR genotypes or IL-1ra gene polymorphism are associated with responsiveness to treatment or different clinical patterns of disease. DESIGN/SETTING In a large, randomized, controlled multicentre trial, 318 patients with CD were treated with daily doses of 6, 9 or 18 mg budesonide. Patients were stratified into two groups: patients without steroid pretreatment and with active CD (CDAI > 150) and patients with conventional steroid pretreatment of < or= 30 mg prednisolone per day, which was replaced by oral budesonide within 3 weeks. MAIN OUTCOME MEASURES The HLA-DRB1 genotypes 1-16 and the IL-1ra gene polymorphism were examined for an association with budesonide treatment failure. RESULTS Only HLA-DR 8 was associated with treatment failure of budesonide. HLA-DR 8 is not very common. Only 17/243 patients who could be evaluated expressed this genotype, and 13 of these 17 patients did not respond to budesonide (P < 0.00067). Neither the other HLA-DR genotypes nor the IL-1ra gene polymorphism had an influence on treatment outcome of budesonide therapy. No significant association of fistulas, perianal disease, need for bowel resections, and disease localization with certain HLA-DRB1 genotypes or the IL-1ra gene polymorphism were found. CONCLUSIONS This is the first description of an association of a certain HLA-DR genotype (HLA-DR 8) with treatment failure in inflammatory bowel disease (IBD).

Objectives Currently, the (13)C-urea breath test is the reference method for non-invasive diagnosis of Helicobacter pylori infection and therapy control. Therefore, new technologies have been developed to measure the ratio of (13)CO(2)/(12)CO(2) in breath. The laser-assisted ratio analyser (LARA) device is based on optogalvanic effects of the stimulated CO(2) molecules. Design In this study, the LARA system is prospectively compared to conventional isotope ratio mass spectrometry (IRMS) analysis of (13)C-urea breath tests. Methods The (13)C-urea breath test was used to screen 103 patients for H. pylori infection. Breath samples were analysed by LARA and IRMS techniques. Results Seven breath tests could not be analysed by the LARA system, one by IRMS. Out of the remaining 95 breath tests, 13 were positive for H. pylori infection (13.7%). In reference to IRMS analysis (with a cut-off of > 5 delta per thousand at 30 min), LARA produced one false positive and one false negative breath test result giving a sensitivity of 92.3% and a specificity of 98.8%. The mean difference in delta over baseline values between IRMS and LARA measurements was 2.02 delta per thousand +/- 5.48 delta per thousand. Conclusion LARA allows the reliable qualitative evaluation of 13C-urea breath tests, but the quantitative results differ from IRMS findings.

We describe the first case of sirolimus-induced drug fever in a female liver transplant recipient, with a history of hepatitis C-induced end-stage liver cirrhosis in 1999. In 2005, six years after transplantation, she developed calcineurin inhibitor-induced renal function impairment. Immunosuppression was switched from tacrolimus to sirolimus. Two days after the intake of sirolimus, she developed daily fever spikes, but no infectious focus was found. Antibiotic therapy had no influence on the fever. After fourteen days, sirolimus was switched back to tacrolimus and the fever disappeared. In history, the patient developed ciclosporin-induced generalized seizures eleven days after liver transplantation, followed by the development of a motoric speech disorder. Magnetic resonance imaging (MRI) findings were consistent with leucoencephalopathy, therefore immunosuppressive therapy was changed from ciclosporin to tacrolimus and the neurologic symptoms improved significantly. Our case is the first reported case of sirolimus-induced drug fever. In addition, the patient showed the rare occurrence of ciclosporin-induced leukencephalopathy with seizures.

patients with colorectal polyps$2 cm resected in a general hospital from january 2001 to august 2003. Results: 118 large polyps were resected in 67 men and 39 women. 78 patients had an ER and 28 a SR. 43% of the ER were performed using endoscopic mucosal resection. An endoloop was necessary in 8% of cases, Argon plasma coagulation in 17% and clipping in 9%. 14% of SR were transanal, 14% laparoscopic and 71% open resections. A colectomy was necessary in 82% of SR. Polyp histology was similar in both groups. One perforation and one bleeding occurred in the ER group which required a surgical treatment and one of them died. No complication occurred in the SR group. 2 patients in the ER group had to be referred to surgery because a T1 carcinoma was diagnosed. A follow-up colonoscopy was performed in 26 patients of the ER group after a mean follow-up time of 6.5 months. Recurrence was detected in 9 patients : 6 had repeat ER and 3 were referred to surgery. Altogether 7 patients in the ER group had to be referred to surgery so that 33% of all patients had to be operated on. Whereas 14.6% of patients with pedunculated polyps had to be operated on, 45.2% of patients with sessile or flat polyps had to (p= 0.002). 44% of patients with polyps located in the right colon had to be operated on, whereas 24.1% of those with polyps in the left and transverse colon had to (p > 0.05). 24% of patients who had their colonoscopy performed by an expert endoscopist had to be operated on (20.7% of patients with benign polyps). 20 patients were referred to an expert endoscopist for a second attempt of ER and 75%were successful. 50% of patients in the SR group had not had an ER attempt by an expert endoscopist. Conclusions : one in three patients with a large colorectal polyp has to be operated on. The rate of referral to surgery may be decreased to one in five for benign polyps if an expert endoscopist gets involved. Referral to surgery is related to the size of polyps, their sessile or flat shape, their location in the right colon, their malignancy and to the lack of attempt of ER by an expert endoscopist. HexaminolevulinateInduced Fluorescence Endoscopy in Patients with Rectal Adenoma and Cancer Esther Endlicher, Cornelia Gelbmann, Ruth Knuechel, Alois Fuerst, Rolf-Marcus Szeimies, Stefan Goelder, Juergen Schoelmerich, Helmut Messmann Background and Aims: Fluorescence endoscopy is a promising new method for detection and therapy of premalignant and malignant lesions. The aim of the present pilot study was to investigate the feasibility of hexaminolevulinate based photodetection in patients with rectal adenoma and cancer, including safety, dosefinding and efficacy. Methods: 10 patients with known rectal adenoma and cancer were sensitised with 3.2 mM hexaminolevulinate (Photocure, Oslo, Norway). Fluorescence endoscopy was performed after an enema lasting for 30-60 minutes and a resting time of 0-30 minutes before endoscopy. Biopsies were taken from fluorescent and non-fluorescent areas and fluorescence microscopy studies were performed to investigate distribution of protoporphyrin IX (PPIX) fluorescence in different tissue layers. Adverse events were reported by open questioning in all patients while skin photosensitivity, serum transaminases, blood pressure, heart rate and gastric discomfort were recorded actively in 5 patients. Results: Hexaminolevulinate-induced fluorescence endoscopy led to selective fluorescence of all rectal adenoma containing intraepithelial neoplasia. In rectal cancer only a weak or even no fluorescence could be detected. No side effects related to hexaminolevulinatewere observed. In twopatients differentiation of adenoma and hyperplastic polyps was possible due to fluorescence. Conclusion: Hexaminolevulinate based fluorescence endoscopy using a 3.2 mM enema in patients with rectal cancer and adenoma was well tolerated and showed no significant skin sensitivity and other side effects. The optimal time of administration seems to be 30-45 minutes with a resting time of 30 minutes. Selective fluorescence of intraepithelial neoplasia containing adenoma indicates that hexaminolevulinatebased fluorescence endoscopy has the potential for the detection of premalignant lesions. Partially ulcerated surface, tumour necrosis and moderate differentiation are probably the reasons for lacking fluorescence in complete cancer after local sensitisation with hexaminolevulinate.