Search

Bei gastrointestinalen Erkrankungen tritt eine Mangelernahrung haufig als Komplikation oder auch als fuhrendes Symptom auf. Die daraus entstehenden Defizite sind mit einer schlechteren Prognose, einer verminderten Leistungsfahigkeit sowie einer geringeren Lebensqualitat verbunden. Deshalb ist neben der Behandlung der Grunderkrankung eine gezielte Ernahrungstherapie erforderlich.

Die Autoimmunpankreatitis (AIP) ist eine sehr seltene Erkrankung. Die typische klinische Symptomatik besteht in extrahepatischer Cholestase, abdominellen Schmerzen und Gewichtsverlust. Berichtet wird uber einen Patienten, der unter dem Verdacht eines Pankreaskarzinoms operiert wurde. Klinisch lag ein Verschlussikterus mit „double duct sign“ in der endoskopisch-retrograden Cholangiopankreatikographie (ERCP) vor. Postoperativ (pyloruserhaltende Pankreaskopfresektion) kam es zu keinem Absinken der Cholestaseparameter. Histologisch fand sich eine AIP. Die nachtraglich durchgefuhrte Bestimmung der IgG-Subklassen zeigte eine deutliche Erhohung des IgG4. Eine begleitende Cholangitis war in der Folge unter Steroidtherapie rasch rucklaufig, die Cholestaseparameter sanken binnen 4 Wochen in den Normbereich. Die AIP sollte bei Verdacht auf Pankreaskarzinom als seltene Differentialdiagnose in Betracht gezogen werden, insbesondere dann, wenn in der bildgebenden Diagnostik kein eindeutiger Tumor abgegrenzt werden kann. Der Nachweis eines erhohten IgG4 im Serum kann in diesen Fallen der entscheidende Parameter zur Abgrenzung gegen das Pankreaskarzinom sein.

The development of an oesophageal adenocarcinoma arising in Barrett's mucosa is associated with a multistep process of genetic lesions that may be triggered by persistent oxidative damage. The glutathione peroxidase isoforms pGPx and GI-GPx, which were identified recently in the mucosa of the esophagus, may play a role as defense factors to prevent such oxidative injury. To determine alterations of the expression of pGPx and GI-GPx in Barrett's mucosa as compared to primary and regenerative squamous epithelium. Biopsy samples of oesophageal mucosa of patients with Barrett's esophagus (n = 12), patients with squamous restoration after thermal ablation (n = 10), and healthy controls (n = 5) were analyzed for pGPx and GI-GPx mRNA expression by Northern blot and for glutathione peroxidase activity by enzymatic assay. Squamous regeneration was induced by argon plasma coagulation (APC) combined with proton pump inhibitor therapy. In Barrett's epithelium mRNA levels of pGPx (the secreted isoform) were significantly reduced and of GI-GPx (the intracellular isoform) significantly increased as compared to normal squamous mucosa. In squamous mucosa that had regenerated after APC, no significant differences compared to the expression pattern of primary squamous mucosa were found. Compared to squamous mucosa, Barrett's metaplasia shows a different mRNA expression of pGPx and GI-GPx that may be associated with increased susceptibility to oxidative damage.

Atiologie: Das hereditare Non-Polyposis kolorektale Karzinom (HNPCC) ist das haufigste monogenetisch bedingte Kolonkarzinomsyndrom. Es ist gekennzeichnet durch ein autosomal-dominant vererbtes Auftreten von Karzinomen des Kolons und Rektums sowie des Endometriums, seltener auch des oberen Gastrointestinaltrakts, des hepatobiliaren Systems sowie des Urogenitalsystems. Weitere Merkmale des HNPCC sind ein fruhes Manifestationsalter, meist vor dem 50. Lebensjahr, eine Lokalisation des Kolonkarzinoms proximal der linken Flexur und haufig gering differenzierte Karzinome. Genetik: Kurzlich wurden Keimbahnmutationen in mehreren DNA-Mismatch-Reparatur-Genen als Ursache des HNPCC identifiziert. Infolge der defekten DNA-Reparatur lasst sich im Tumorgewebe eine genetische Instabilitat (Mikrosatelliteninstabilitat) nachweisen. Diagnose: Die neuen Erkenntnisse zu Pathogenese, Klinik und Diagnostik des HNPCC haben die Moglichkeiten zur Identifikation von Patienten und Risikopersonen erheblich verbessert. Die Diagnose eines HNPCC beruht derzeit in erster Linie auf der Familienanamnese und wird durch molekularbiologische Untersuchungen erganzt. Bei Mutationsnachweis in HNPCC-Familien konnen klinische Screening-Masnahmen auf die Merkmalstrager beschrankt werden. Therapie: Empfehlungen zur Therapie und Pravention sind teilweise kontrovers und werden derzeit in verschiedenen Studien untersucht.

Tolerance of interferon-α therapy for hepatitis C is often poor and medication is expensive. Compliance with diagnostic procedures and, even more important, with medical treatment is obviously critical to minimize the rate of dropouts and to maximize cost efficiency. Moreover, a good concordance with scheduled follow-ups is important for early recognition and treatment of interferon-associated side effects. Therefore, we investigated psychiatric symptoms, interpersonal problems, different modes of acquisition, and sociodemographic factors in HCV-infected patients as possible predictor variables of good versus poor compliance. In a longitudinal study, 74 patients with chronic hepatitis C (CHC) who fulfilled the criteria for treatment with interferon (IFN)-α-2b with or without ribavirin were investigated prospectively to identify those at risk for poor compliance during IFN medication. To assess predictive factors, we used both IIP-C (Inventory of Interpersonal Problems) and SCL-90-R (Symptom Check List 90 Items Revised) as psychometric instruments. Sociodemographic and somatic variables as well as compliance during IFN therapy were also evaluated. Poor compliance before or during medication was demonstrated by 23% (N = 17) of HCV patients. Sociodemographic factors and mode of acquisition, particularly former intravenous drug (IVD) abuse were not significantly linked with compliance. Logistic regression analysis demonstrated that the subgroup of patients with compliance problems was best identified by both pretherapeutic psychiatric symptoms and interpersonal problems. Predictive value was best and significant for anger-hostility (P = 0.009), intrusive (P = 0.014), depression (P = 0.015), and phobic anxiety (P = 0.049). Adopting this statistical prediction model, sensitivity was 47.1%, but specificity reached 98.3%. In total, 86.5% of cases were classified correctly. In situations of unclear indication for IFN therapy, psychological variables assessment of before the beginning of treatment may represent an additional decision-making factor.

Barrett's oesophagus is a premalignant condition. Recent reports have suggested that laser coagulation or photodynamic therapy combined with acid suppression may induce reconstitution of squamous mucosa. However, a high percentage of residual glands remain in cases treated with both techniques. Argon plasma coagulation (APC) appears to be an attractive alternative to other thermoablative techniques. The aim of this study was to investigate the reconstitution of squamous epithelium in Barrett's oesophagus after APC.Fifteen patients with histologically proven Barrett's oesophagus were included in a prospective study. After base-line documentation by videotaping and biopsies, Barrett's epithelium was treated by repeated APC at intervals of 4-6 weeks until complete squamous restoration was achieved. All patients were kept under high-dose proton pump inhibitor therapy.In 13 patients complete reconstitution of squamous epithelium was achieved. Buried glands after squamous restoration were detected transiently in only one case after the first session. As side effects seven patients had mild retrosternal discomfort. One patient reported severe retrosternal pain for 1 week. He then refused further APC sessions. Another patient was excluded because of noncompliance. During the follow-up period (6-13 months) recurrence of Barrett's epithelium was observed in one patient.APC is a suitable technique for achieving squamous restoration in Barrett's oesophagus. The rare occurrence of remaining buried glands may result from the homogeneous coagulation achieved by the ionized argon gas beam.

There is experimental and epidemiological evidence for an association between low selenium levels and gastrointestinal cancer incidence, prevalence, and mortality. To identify targets for selenium supplementation in the human digestive tract, we examined mRNA expression of various selenocysteine-containing proteins in normal mucosa biopsy specimens. Tissue samples from the esophagus and from different sites of the stomach, small bowel, and colon were obtained during endoscopies of the upper and lower gastrointestinal tract. Northern blot analyses revealed a lack of cytosolic glutathione peroxidase mRNA but a differential mRNA expression pattern of gastrointestinal and plasma glutathione peroxidase, selenoprotein P, and thioredoxin reductase. Glutathione peroxidase and thioredoxin reductase activities were detected in the mucosa of all biopsies, but the differential pattern did not reflect the differential mRNA steady-state levels. In addition to gastrointestinal glutathione peroxidase, which was found to play a role in colon cancer resistance, we identified further gastrointestinal selenoproteins, which may be involved in gastrointestinal cell defense and cell differentiation.

Primary biliary cirrhosis (PBC) is frequently associated with other autoimmune disorders. Although antibodies against gastric parietal cells are found in nearly all PBC patients, autoimmune gastritis is only very rarely associated. We describe a woman with PBC in whom chronic autoimmune gastritis complicated by a large pedunculated gastric carcinoid tumor was found. Additionally, the patient had autoimmune thyroiditis. This was interpreted as the rare association of PBC with Schmidt's syndrome type III. The carcinoid tumor was removed endoscopically. We conclude from this case that an endoscopic screening for autoimmune gastritis should at least be performed in patients with PBC and autoimmune thyroiditis, keeping in mind the possible occurrence of a polyendocrinopathy and the potentially serious complication of a gastric carcinoid tumor.

The nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPARgamma) is a key transcription factor regulating genes involved in adipogenesis, glucose homeostasis and cell differentiation. Moreover, PPARgamma has been demonstrated to control proliferation and apoptosis in various cancer cells. We investigated the biological effects of PPARgamma activation by the oral antidiabetic agent pioglitazone in Barrett's adenocarcinoma cells in vitro and in vivo.PPARgamma mRNA and protein were overexpressed in endoscopic biopsies of Barrett's epithelium and the human Barrett's adenocarcinoma cancer cell line OE33 as compared to normal esophagus and stomach and the esophageal squamous epithelium cancer cell line Kyse-180. PPARgamma activation by pioglitazone in OE33 cells in vitro led to reduced cell growth by induction of apoptosis. Effects of systemic PPARgamma activation by the thiazolidinedione pioglitazone on tumor cell proliferation and apoptosis were then assessed in vivo in nude mice bearing transplantable Barrett's adenocarcinomas derived from OE33 cells. Unexpectedly, enhanced growth of OE33 derived transplantable adenocarcinomas was observed in Balb/c nu/nu mice upon systemic pioglitazone treatment due to increased cell proliferation.These results indicate that PPARgamma is involved in the molecular pathogenesis of Barrett's adenocarcinoma formation and growth. However, activation of PPARgamma exerts differential effects on growth of Barrett's adenocarcinoma cells in vitro and in vivo emphasizing the importance of additional cell context specific factors and systemic metabolic status for the modulation of PPARgamma action in vivo.

Gastrointestinal symptoms in elderly patients are not only caused by primary diseases of the digestive organs. Even a healthy digestive tract commensurate with the age of the patient is affected by age and disease-related changes of other organs, in particular those of the cardiovascular and metabolic systems. This leads to a broad spectrum of secondary dysfunctions of the gastrointestinal tract.

Imaging of liver tumours might be improved by contrast-enhanced ultrasonography, which allows much better demonstration of the microvascular system. The aim of this study was to assess the sonographic morphology and vascularity of neuroendocrine liver metastases.Forty-eight patients with histologically proven neuroendocrine tumours (NET) and suspected liver metastases--as well as 50 consecutive patients with liver metastases of other origins--were included in a prospective study to evaluate tumour characteristics using B-mode, colour Doppler (CDI) and contrast-enhanced ultrasound (CEUS).In 4/48 patients with NET, liver biopsy revealed hemangiomas. The typical B-mode appearance was that of both echo-rich and echo-poor combined, also inhomogeneous depending on the size, and often centrally cystic. With CDI, neuroendocrine metastases appeared hypervascular (66%) or isovascular (34%). Metastases of another origin were hypovascular in 82%. With CEUS, neuroendocrine metastases showed increased arterial enhancement in 38 patients and hypoechoic appearance in the portalvenous phase in 39 patients. In liver metastases of another origin, the sensitivity for malignancy due to a hypoechoic appearance during the portalvenous phase was 100%. In liver metastases of NET origin the sensitivity for malignancy was 39/48 (82%).Neuroendocrine tumour metastases might show characteristics which are similar to hemangiomas. In patients with liver cirrhosis and severe fatty liver disease the identification of NET with CEUS as a malignant lesion is more difficult. The sensitivity of CEUS in identifying malignancy based on the lack of portalvenous enhancement is higher for metastases of other origin.

Several studies have shown that argon plasma coagulation (APC) combined with proton-pump inhibitor (PPI) therapy is a suitable procedure to eradicate Barrett's epithelium for a short-term follow-up. The real impact of this kind of management with respect to cancer risk and durability of squamous regeneration remains unclear. We present the follow-up data for up to 51 months after eradication of Barrett's mucosa.In 1998-2001, 25 patients with Barrett's esophagus were included in a prospective study. After baseline documentation, Barrett's epithelium was treated with repeated APC until complete squamous restoration was reached. Thereafter, all patients were continuously treated with high-dose PPIs.Each patient underwent a median of four APC sessions. Twenty-one (84%) of the patients had complete squamous regeneration at the end of treatment. During a follow-up of up to 51 months, Barrett's epithelium was found to have recurred in 14/21 (66%) patients. Including the patients with initially incomplete squamous restoration, a long-lasting and complete effect was achieved in only 7 patients (28%) after a mean follow-up period of 30 months.So far, it is still not proven whether coagulation-induced squamous regeneration reduces the risk of Barrett's carcinoma. Furthermore, the high relapse rate, the procedure-related risk, and the high costs incurred preclude the routine use of APC for the treatment of non-dysplastic Barrett's esophagus. The different recurrence rates between published studies may be due to technical differences and PPI schedule. We suggest that optimal conditions for the procedure must be defined before further studies are undertaken.

Autoimmune pancreatitis (AIP) is a rare disorder. Typical clinical symptoms include extrahepatic cholestasis, abdominal pain, and weight loss.The case of a patient with cholestatic icterus and double duct sign is reported, who underwent surgery (Whipple operation) because of suspected pancreatic cancer. Histology of the resected pancreas head revealed AIP. Due to this diagnosis, measurement of IgG4 showed a significantly elevated serum level. Postoperatively, cholestasis parameters remained elevated, which was interpreted as associated sclerosing cholangitis. Therapy with corticosteroids led to normalization of the cholestasis within 4 weeks.AIP should be taken into account as differential diagnosis to pancreatic cancer, especially in cases without clear demarcation of a pancreatic tumor. Measurement of IgG4 may be an important parameter to avoid unnecessary surgery.

Basis Selenium is an essential trace element, which is incorporated as selenocysteine (secys) into specific proteins in a regulated fashion. In the presence of a hairpin loop structure within the 3' untranslated region of the mRNA the opal stop codon UGA is coding for selenocysteine. Selenoprotein functions are dependent on secys incorporation. Members of the family of deiodinases as well as the family of glutathione peroxidases, selenoprotein P and thioredoxin reductase are selenoproteins. Discussion Bone, the intestine and the thyroid rely on antioxidant systems against potential cell and DNA damage through endogenous and environmental peroxides and reactive oxygen species (ROS) potentially promoting inflammation and tumorigenesis. Optimized cell defense through antioxidant selenoproteins requires optimal selenium supplementation of the organism. We have analyzed the expression of selenoproteins in these tissues, thus providing molecular tools to further elucidate optimal selenium supply on a cellular level. Conclusion Clinical intervention studies that focus on the development of disease must confirm the relevance of optimized selenium supply for the pathogenesis, prevention and therapy of metabolic bone disease as well as chronic (autoimmune) inflammation and tumorigenesis in the thyroid and intestine.

The development of an oesophageal adenocarcinoma arising in Barrett's mucosa is associated with a multistep process of genetic lesions that may be triggered by persistent oxidative damage. The glutathione peroxidase isoforms pGPx and GI-GPx, which were identified recently in the mucosa of the esophagus, may play a role as defense factors to prevent such oxidative injury. To determine alterations of the expression of pGPx and GI-GPx in Barrett's mucosa as compared to primary and regenerative squamous epithelium. Biopsy samples of oesophageal mucosa of patients with Barrett's esophagus (n = 12), patients with squamous restoration after thermal ablation (n = 10), and healthy controls (n = 5) were analyzed for pGPx and GI-GPx mRNA expression by Northern blot and for glutathione peroxidase activity by enzymatic assay. Squamous regeneration was induced by argon plasma coagulation (APC) combined with proton pump inhibitor therapy. In Barrett's epithelium mRNA levels of pGPx (the secreted isoform) were significantly reduced and of GI-GPx (the intracellular isoform) significantly increased as compared to normal squamous mucosa. In squamous mucosa that had regenerated after APC, no significant differences compared to the expression pattern of primary squamous mucosa were found. Compared to squamous mucosa, Barrett's metaplasia shows a different mRNA expression of pGPx and GI-GPx that may be associated with increased susceptibility to oxidative damage.

Four selenocysteine-containing proteins (gastrointestinal glutathione peroxidase, plasma glutathione peroxidase, selenoprotein P, and thioredoxin reductase-alpha) are expressed in the colonic mucosa. Because of their antioxidant functions, a protective role in colon carcinogenesis is discussed. The aim of this study was to elucidate an involvement of gastrointestinal selenoproteins during the adenoma-carcinoma sequence. Matched pairs of biopsies of colorectal adenomas and adjacent normal mucosa from 11 patients were analyzed for mRNA expression, protein expression, or enzyme activity of selenoproteins by Northern blot, Western blot, or enzymatic tests. All adenomas revealed a marked reduction of selenoprotein P and a variable increase of gastrointestinal glutathione peroxidase mRNA compared with adjacent tissue. Thioredoxin reductase-alpha and plasma glutathione peroxidase mRNA expression were not altered in adenomas. The Northern blot results were confirmed by Western blot analysis or enzyme activity measurement, respectively. We conclude that gastrointestinal glutathione peroxidase and selenoprotein P play a complementary role in the antioxidative cell defense along the adenoma-carcinoma sequence. It remains to be shown whether upregulation of gastrointestinal glutathione peroxidase in adenomas represents a compensatory mechanism to reduce susceptibility for oxidative damage resulting from the loss of selenoprotein P.

A patient who presented with chronic inflammation of the colon, and initially also the terminal ileum, accompanied by marked diarrhea, is described. Repeated high-dose steroid therapy was only temporarily successful, and symptoms recurred upon dose reduction. During the further course of the disease, a marked elevation of alkaline phosphatase and transaminases, as well as soft tissues swelling occurred. Clinically, the diagnosis of inflammatory bowel disease with primary sclerosing cholangitis was made. Irregularities in the walls of the common bile duct and the intrahepatic ducts seen at endoscopic retrograde cholangiopancreatography were consistent with the latter diagnosis. However, extreme eosinophilia of peripheral blood, bone marrow and bowel mucosa was present, and liver histology showed eosinophilic cholangiohepatitis. Under the diagnosis of hypereosinophilic syndrome with involvement of bowel, liver and biliary system, therapy with hydroxyurea was initiated. The patient's condition improved promptly. Eosinophil count and liver enzymes have remained normal under long-term medication with 1.0 g per day of this drug.

The trace element selenium is discussed as a chemopreventive agent in colorectal carcinogenesis. Selenocysteine-containing proteins, so-called selenoproteins, represent potential molecular targets for nutritive selenium supplementation. Due to their antioxidative potential, the selenoproteins gastrointestinal glutathione peroxidase (GI-GPx) and selenoprotein P (SePP) are considered to provide protection against reactive oxygen species (ROS), thereby reducing DNA damage and preventing development of colon cancer. GI-GPx and SePP are abundantly expressed in normal colon mucosa. Recently, we demonstrated both reduced SePP expression and increased GI-GPx expression in colorectal adenomas. In this study, we investigated the expression of SePP and GI-GPx in colorectal cancers compared with corresponding normal mucosa. Further, the occurrence of genetic alterations within the SePP and GI-GPx genes was analyzed. We observed a significant reduction or loss of SePP mRNA expression in colon cancers, whereas GI-GPx mRNA and protein expression varied between different tumor samples. In addition, we identified novel polymorphisms within the SePP and GI-GPx genes with so far unknown relevance for protein function. Our results argue against a general decrease of selenoprotein expression in colorectal carcinogenesis but imply specific differential regulation of expression of individual selenoproteins.

Selenoproteins such as glutathione peroxidases (GPx), thioredoxin reductases (TrxR), and selenoprotein P (SePP) contain molecular selenium in form of selenocysteines within their active center. They are involved in the defense of reactive oxygen species, which otherwise may cause DNA damage and alterations of protein function. Selenium intake has been linked to colon carcinogenesis in epidemiological and interventional studies. In a double-blinded, placebo-controlled trial, we demonstrate that carriers of colon adenomas present with low basal serum levels of selenium and plasma glutathione peroxidase (pGPx) activity before treatment, but both parameters can be normalized by interventional selenium supplementation. GPx activity in colon mucosa was enhanced in the verum group, albeit this had only borderline significance. No change of activity was observed for mucosal TrxR activity on selenium supplementation. In summary, our results confirm the existence of low selenium levels in patients prone to colon adenomas and show that by selenium supplementation this can be normalized. If prospective trials confirm that selenium supplementation reduces colon cancer incidence rates, it may be concluded that selenium supplementation should be recommended for patients at risk.