High-dimensional profiling reveals Tc17 cell enrichment in active Crohn's disease and identifies a potentially targetable signature.

The immune-pathology in Crohn's disease is linked to dysregulated CD4+ T cell responses biased towards pathogenic TH17 cells. However, the role of CD8+ T cells able to produce IL-17 (Tc17 cells) remains unclear. Here we characterize the peripheral blood and intestinal tissue of Crohn's disease patients (n = 61) with flow and mass cytometry and reveal a strong increase of Tc17 cells in active disease, mainly due to induction of conventional T cells. Mass cytometry shows that Tc17 cells express a distinct immune signature (CD6high, CD39, CD69, PD-1, CD27low) which was validated in an independent patient cohort. This signature stratifies patients into groups with distinct flare-free survival associated with differential CD6 expression. Targeting of CD6 in vitro reduces IL-17, IFN-γ and TNF production. These results identify a distinct Tc17 cell population in Crohn's disease with proinflammatory features linked to disease activity. The Tc17 signature informs clinical outcomes and may guide personalized treatment decisions.

[Capsule endoscopy]. / Kapselendoskopie.

Video capsule endoscopy provides a noninvasive diagnostic approach to the entire small intestine. The main indications are suspected chronic or recurrent obscure intestinal bleeding, which can-not be clarified by esophago-gastro-duodenoscopy and colonoscopy. Further indications are polyposis syndromes, suspected Crohn's disease and malignomas of the small bowels. Esophago-gastroduodenoscopy and colonoscopy are essential preceding diagnostic procedures before capsule endoscopy.

[Esophageal carcinoma: non-surgical therapy]. / Osophaguskarzinom--Nicht-chirurgische Therapie.

Esophageal carcinoma is one of the most common cancers in the world. There is a rising incidence of adenocarcinoma of the esophagus in Western countries. The present standard of care of patients with early tumors (Tis-T1 N0-N1 M0) is surgery and there is no role for chemo- or radiotherapy. Surgical treatment of stage II patients with locally resectable tumors is associated with poor survival figures due to an increase of regional and distant lymph node metastases. Adjuvant chemotherapy should be used only in the setting of clinical trials. The role of neoadjuvant chemo-radiotherapy in patients with resectable tumors is controversial. There is also evidence that some patients with a complete response after chemo-radiotherapy do not have a further benefit from surgical treatment. Therefore, the appropriate application of these varied therapeutic interventions should be performed at specialized centers. The role of chemotherapy and radiation is now established in locally advanced inoperable disease. How best to deliver these modes of therapy has yet to be defined. Prospective randomised trials are the only way to define the best therapeutic strategies for the different subgroups of patients with esophageal carcinoma. Progress with newer chemotherapy agents, optimal radiotherapy protocols and innovations are likely to improve responses to combination treatments, but may more importantly limit associated toxicity. Future trials should also assess quality of life indices as end points, that are of particular importance in populations with a median survival of approx, one year. Patients with stage IVb esophageal carcinoma have a life expectancy of less than six months and palliative teatment strategies should primarily aim at the improvement of tumor related symptoms and the maintenance of nutrition.

[Sprue]. / Sprue.

Coeliac disease is an inflammatory disease of the small intestine. Coeliac disease occurs in individuals suffering from a genetically caused gluten intolerance. Mean clinical findings are malabsorption for several nutrients or steatorrhoe. Silent or latent courses are common. The diagnosis is based upon the histological finding of villous atrophy in duodenal or jejunal biopsies. Anti-endomysium-antibodies are of high sensitivity and specificity. After gluten free diet the coeliac disease improves. Gluten free diet has to be taken lifelong preventing complications i.e. osteoporosis and malignancies.

[Barrett esophagus--esophageal carcinoma: diagnosis]. / Barrett-Osophagus--Osophagus-Karzinom: Diagnostik.

The Barrett esophagus as the premalignent lesion for adenocarcinoma of the esophagus and the esophagogastric junction is of widespread interest. Endoscopy and histology are the diagnostic basis. Methylen blue staining and high-resolution endoscopes facilitate the diagnosis of Barrett esophagus. Use of a high resolution endoluminal ultrasound probe and optical coherence tomography are new methods for evaluating the local depth invasion of the Barrett mucosa. Accurate pretherapy staging for esophageal carcinoma is important for a stage--directed therapy. After endoscopy and histology the endoscopic ultrasound is the method of choice for local regional staging of esophageal carcinoma. Computed tomography and positron emission tomography were shown to be especially useful in detection of distant metastases.

Small intestinal bacterial overgrowth in patients with cirrhosis: prevalence and relation with spontaneous bacterial peritonitis.

OBJECTIVES: The significance of small intestinal bacterial overgrowth in patients with cirrhosis is not fully understood and its diagnostic criteria are not uniform. We examined the association of small intestinal bacterial overgrowth with spontaneous bacterial peritonitis and compared various microbiological criteria. METHODS: Jejunal secretions from 70 patients with cirrhosis were cultivated quantitatively and classified according to various definitions. Clinical characteristics of patients were evaluated and the incidence of spontaneous bacterial peritonitis was monitored during a 1-yr follow-up. RESULTS: Small intestinal bacterial overgrowth, defined as > or = 10(5) total colony-forming units/ml jejunal secretions, was present in 61% of patients. Small intestinal bacterial overgrowth was associated with acid-suppressive therapy (p = 0.01) and hypochlorhydria (p < 0.001). Twenty-nine patients with persistent ascites were observed. Six episodes of spontaneous bacterial peritonitis occurred after an average 12.8 wk. Occurence of spontaneous bacterial peritonitis correlated with ascitic fluid protein concentration (p = 0.01) and serum bilirubin (p = 0.04) but not with small intestinal bacterial overgrowth (p = 0.39). Its association with acid-suppressive therapy was of borderline significance (hazard ratio = 7.0, p = 0.08). CONCLUSIONS: Small intestinal bacterial overgrowth in cirrhotic patients is associated with acid-suppressive therapy and hypochlorhydria, but not with spontaneous bacterial peritonitis. The potential role of acid-suppressive therapy in the pathogenesis of spontaneous bacterial peritonitis merits further studies.

[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.

Diagnosis of small intestinal bacterial overgrowth in patients with cirrhosis of the liver: poor performance of the glucose breath hydrogen test.

BACKGROUND/AIMS: Small intestinal bacterial overgrowth is known to occur in association with cirrhosis of the liver and studies are needed to assess its pathophysiological role. The glucose breath hydrogen test as an indirect test for small intestinal bacterial overgrowth has been applied to patients with cirrhosis but has not yet been validated against quantitative culture of jejunal secretion in this particular patient population. METHODS: Forty patients with cirrhosis underwent glucose breath hydrogen test and jejunoscopy. Jejunal secretions were cultivated quantitatively for aerobe and anaerobe microorganisms. RESULTS: Small intestinal bacterial overgrowth was detected by culture of jejunal aspirates in 73% of patients, being associated with age and the administration of acid-suppressive therapy. The glucose breath hydrogen test correlated poorly with culture results, sensitivity and specificity ranging from 27%-52% and 36%-80%, respectively. CONCLUSIONS: In patients with cirrhosis, the glucose breath hydrogen test correlates poorly with the diagnostic gold standard for small intestinal bacterial overgrowth. Until other non-invasive tests have been validated, studies addressing the role of small intestinal bacterial overgrowth in patients with cirrhosis should resort to microbiological culture of jejunal secretions.

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.

[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.

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.

[Stent therapy]. / Stenttherapie.

Expandable metal stents are a significant advance in the treatment of malignant gastrointestinal tract obstruction. The devices available are not perfect in design and need further technical improvement. However they already offer advantages over conventional plastic stents. They are becoming standard for esophageal stenting. Indications for metal stents in other locations of the gastrointestinal tract have to be evaluated. Endoscopic stenting is now the method of choice in the palliative treatment of jaundice in patients with inoperable biliopancreatic neoplasias. Stent clogging as a result of biliary sludge and biofilm remains an unsolved problem of plastic stents. Expandable metal stents remain patent longer but are reserved for patients with good general health.

[Nasobiliary tube in management of postoperative bile fistulas]. / Die nasobiliäre Sonde in Management postoperative Gallefisteln.

A postoperative bile fistula is a rare but severe complication after biliary surgery. Clinical signs, laboratory findings, ultrasound and ERC lead to diagnosis. We report on 40 cases with postoperative bile leakage after cholecystectomy treated by a nasobiliary tube. In all patients the fistula healed within 7 days after placement of the tube. Two patients needed operative treatment of a subhepatic abscess, and in 2 patients drainage of a bilioma was performed. In 2 cases with biliary peritonitis, a step-by-step lavage was necessary. The nasobiliary tube for postoperative bile fistula offers regular radiological control and reduces the necessity of operative reintervention in the biliary tract.

Omeprazole in the treatment of patients with complicated gastro-oesophageal reflux disease.

Suppression of acid secretion with omeprazole is highly effective for the healing of oesophagitis. The aims of the present study were to determine whether recovery of gastro-oesophageal reflux disease in patients with stricture improves dysphagia and decreases the dilatation need and to compare the efficacy of omeprazole versus H2-receptor antagonists. Thirty-eight patients with peptic stricture (grade IV oesophagitis) and erosive oesophagitis underwent endoscopic dilatation and were randomized to omeprazole (40 mg daily; n = 20) versus ranitidine (150 mg twice daily; n = 18). Healing was proven endoscopically and patients were interviewed for dysphagia relief. Patients were assessed for relapse by endoscopy 6 months later. The follow-up period was a further 6 months. Patients received maintenance treatment with 40 mg omeprazole daily or ranitidine 150 mg twice daily and the total duration of treatment was 1 year. At 6 months, omeprazole produced a highly significant (P < 0.0001) greater rate of oesophagitis healing and highly significant (P < 0.0001) fewer dilatations compared with H2-receptor antagonists (18 (90%) patients vs five (28%) patients, respectively; 3.5 vs 9.0 dilatations/patient). At 12 months, not one of the 18 successfully treated patients from the omeprazole group had relapsed. The two remaining patients required further dilatation and 40 and 60 mg omeprazole daily for healing. In comparison, all patients on ranitidine had to undergo further bougienage. In conclusion, omeprazole is a safe and effective maintenance treatment for preventing relapse of complicated reflux oesophagitis.

[Hemosuccus pancreaticus--a rare cause of upper gastrointestinal bleeding. Successful treatment in two cases by radiologic-interventional embolization of the splenic artery]. / Haemosuccus pancreaticus--seltene Ursache einer oberen gastrointestinalen Blutung. Erfolgreiche Therapie durch radiologisch-interventionelle Embolisation der Arteria lienalis in zwei Fällen.

HISTORY AND CLINICAL FINDINGS: Two patients were admitted to hospital for diagnosis of recurrent upper gastrointestinal bleeding. Both had chronic pancreatitis with alcohol abuse. Their general condition was satisfactory. Physical examination showed no diagnostic abnormalities other than mild epigastric pain on pressure in one patient. INVESTIGATIONS: In case 1 angiography revealed pseudoaneurysm of the splenic artery as a complication of chronic pancreatitis to be the cause of the bleeding. In case 2 sonography demonstrated multiple pancreatic pseudocysts after recurrent pancreatitis. Duplex sonography revealed one of the cyst to be a partly thrombosed pseudoaneurysm of the splenic artery and the source of the bleeding. TREATMENT AND COURSE: In both cases a fistula between splenic artery and pancreatic duct having been shown to be the source of the bleeding, transcatheter embolisation of the splenic artery with platinum coils was successfully undertaken. Both patients remained symptom-free 4 and 10 months later. CONCLUSION: Although haemosuccus pancreaticus is a rare cause of upper gastrointestinal bleeding, given certain features in the patient's history and the clinical findings, it should be included in the differential diagnosis.