[Plasma cell myeloma in the stomach?]. / Plasmazellmyelom im Magen?

The detection of a diffuse infiltrate of heterogeneous small B-cells in the lamina propria mucosae invading the epithelium and destroying the glandular tissue by discrete aggregates of three or more marginal zone B-cells above the basal membrane (so-called lymphoepithelial lesions) is suspicious of a mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach. The demonstration of a monoclonal B-cell population by immunohistochemistry, in situ hybridization or PCR excludes a benign lymphatic lesion. In the differential diagnosis with other small B-cell lymphomas in the stomach, a panel of five different immunohistochemical markers is useful to diagnose a small lymphocytic lymphoma (CD5 and CD23 positive), a mantle cell lymphoma (CD5 and cyclin D1 positive) or a follicular lymphoma (BCL2 and CD10 positive). The presence of the translocation t(11;18)(q21;q21) or the API2/MALT1 rearrangement could give further information about the clinical course and the prognosis of a gastric MALT lymphoma.

Patients with Helicobacter pylori negative gastric marginal zone b-cell lymphoma (MZBCL) of MALT have a good prognosis.

BACKGROUND: In current guidelines H. pylori eradication is recommended as first-line therapy in patients with gastric MALT lymphoma irrespective of stage and H. pylori status. However, data on treatment and clinical course of patients with H. pylori negative MALT lymphoma are rare. AIM: To evaluate therapeutical results in patients with H. pylori negative gastric MALT lymphoma. METHODS: 21 patients (13 male and 8 female; 63.9 years, range 43 - 80) with gastric MALT lymphoma were analysed retrospectively on the basis of medical reports in all cases and repeated outpatient visits at our center in 17 cases. H. pylori infection was excluded by negative histology, rapid urease test, or C13 urease breath test, and serology in all cases. Follow-up was 56.4 (5 - 142) months. RESULTS: Ten of 21 patients were treated with H. pylori eradication, and four of them received no further therapy. The other six patients underwent surgery, chemotherapy, and radiation, after eradication therapy. Those eleven patients without H. pylori eradication received radiation (n = 3), chemotherapy (n = 1), PPIs (n = 2), no treatment (n = 4) as first-line and radiation (n = 2) as second-line therapy while initial therapy remained unknown in one case. 13 patients (61.9 %) reached complete remission of lymphoma, and seven patients (33.3 %) showed minimal histological residuals. Overall and disease-free survival was found in 95 % and 90 %, respectively. CONCLUSION: Patients with H. pylori negative gastric MALT lymphoma have a good prognosis. We favor initial H. pylori eradication therapy and a watch-and-wait strategy in case of minimal histological residuals of MALT lymphoma. Non-responders to eradication therapy can be successfully treated by radiation and chemotherapy.

Is there a role for capsule endoscopy in the staging work-up of patients with gastric marginal zone B-cell lymphoma of MALT?

INTRODUCTION: In earlier studies, involvement of the small intestine was reported in patients with gastrointestinal lymphoma. Prospective data on the involvement of the small intestine in patients suffering from gastric extranodal MZBCL of MALT do not exist so far. In this study, we investigated the frequency of the involvement of the small intestine and the role of capsule endoscopy in patients with gastrointestinal extranodal MZBCL of MALT and of follicular lymphoma. PATIENTS AND METHODS: 40 consecutive patients with gastrointestinal extranodal MZBCL of MALT (26 men, 14 women, aged 27 - 80 years), and 7 patients with known follicular lymphoma of the small intestine (5 men, 2 women, aged 34 - 63 years) underwent capsule endoscopy. RESULTS: Involvement of the small intestine was identified by capsule endoscopy in all 7 patients with known follicular lymphoma of the small intestine. In 6 of 40 patients with gastric extranodal MZBCL of MALT abnormal findings could be observed, three of these findings indicative for lymphoma involvement of the small intestine. However, in each of these 3 cases, intestinal involvement had been already diagnosed by conventional GI endoscopy before capsule endoscopy. CONCLUSIONS: Capsule endoscopy is able to detect involvement of the small intestine in patients with gastrointestinal lymphoma. However, involvement of the small intestine seems to be rare in patients with gastric extranodal MZBCL of MALT. In summary, routine diagnostic work-up of the small intestine, e. g. by capsule endoscopy seems unnecessary because of the rare involvement of the small intestine and an excellent long-term outcome irrespective of a possible intestinal manifestation.

[Severe hepatitis and subacute liver failure with "fast track" cirrhosis in an elderly lady]. / Schwere Hepatopathie und subakutes Leberversagen mit "Fast-track"-Leberzirrhose bei älterer Patientin.

We report the case of a 74-year-old lady who presented at our clinic with icterus and cholestatic hepatitis. For atrial fibrillation she had been prescribed a medication with phenprocoumone. After ruling out viral, autoimmune, and metabolic causes of hepatitis, we performed a liver biopsy which led to the diagnosis of phenprocoumone-related liver damage. The patient was discharged without phenprocoumone and completely compensated liver function. Five weeks later she returned to the hospital with encephalopathy, ascites, coagulopathy, varices, and signs of cirrhosis in abdominal ultrasound. In spite of treatment with steroids, the patient died of subacute liver failure several weeks later. This case illustrates the occasionally poor course of toxic hepatitis even after discontinuation of the responsible medication, potential treatment options are discussed.

Staging role of EUS.

Type of lymphoma and stage of disease are the two decisive prognostic factors and therapeutic determinants. For the locoregional staging, i.e. assessment of the gastric wall infiltration and perigastric lymphonodular involvement, endoscopic ultrasound (EUS) is highly useful. EUS has, therefore, to be integrated into the standard staging procedure of gastric lymphoma, although its impact on initial treatment decisions might be limited in the individual case. A benefit from the use of miniechoendoscopes, EUS elastography and EUS-guided biopsies has not yet been proven in gastric lymphoma. EUS also confers an important prognostic value regarding treatment responses to Helicobacter pylori eradication. On the contrary, EUS cannot be recommended as a regular part of follow-up investigations considering its limited value in predicting the response of the lymphoma to radiation or chemotherapy.

[Role of endoscopic ultrasound in gastrointestinal lymphomas]. / Stellenwert des endoskopischen Ultraschalls bei gastrointestinalen Lymphomen.

The majority of gastrointestinal lymphomas belongs to the group of the MALT (mucosa-associated lymphoid type) lymphomas arising in the stomach, therefore rendering them accessible to endoscopy. Staging currently follows the modified Ann Arbor classification but most likely in the future, the TNM-based Paris staging system will be applied due to its detailed description of the local spread as well as the extraintestinal dissemination. For assessment of gut wall infiltration and local lymphonodular involvement, endoscopic ultrasound currently represents the standard procedure and is an essential diagnostic tool regarding locoregional staging. Additionally, the method confers a high prognostic value regarding treatment response in MALT lymphoma. In endoscopic ultrasound stage EI 1, Helicobacter pylori eradication leads in 70 - 100 % to a complete response. However, the value of endoscopic ultrasound in the follow-up of lymphomas after chemotherapy remains elusive and controversial. There is no clear correlation between histologically proven residual disease and endosonographic results. Thus, so far, endoscopic ultrasound will not replace bioptic surveillance after MALT lymphoma treatment.

SNP-Array genotyping and spectral karyotyping reveal uniparental disomy as early mutational event in MSS- and MSI-colorectal cancer cell lines.

In this study nine colorectal cancer cell lines were analysed by 10K SNP-arrays and spectral karyotyping (SKY). Complex chromosomal alterations and breakpoints of deleted or translocated fragments found by SKY could further be characterized by SNP-array analysis. Interestingly many monoallelic regions identified by SNP-array analysis display no copy number alterations, representing uniparental disomy (UPD). It was demonstrated that UPD seems to be involved in activation of early-acting tumor suppressor genes in MSS- (APC, CDKN2A) and MSI- (MLH1, MSH2, APC, CDKN2A) colorectal cancer cell lines. Genes involved later on in the adenoma-carcinoma sequence (i.e. TP53/SMAD4) were not found to be inactivated by UPD. Furthermore, identified amplified monoallelic regions may include oncogenes activated by allele-specific-amplification (i.e. Cyclin D1). However, at present, the majority of the monoallelic regions located in the present study have not yet been associated with known tumor suppressor genes and oncogenes. Further studies are warranted to identify relevant genes in the respective regions and to further verify the results presented here.

Giant fold gastritis with consecutive gastric carcinoma in a patient with peutz-jeghers syndrome.

We describe the case of a 36-year-old patient with Peutz-Jeghers syndrome and a very unusual gastric morphology resembling giant fold gastritis. The latter lacked additional features of Menetrier's syndrome, was not influenced by eradication of Helicobacter pylori and persisted for more than ten years under regular endoscopic surveillance. Histologically, foveolar hyperplasia was found in the enlarged folds. Endoscopic ultrasound documented a hyperechoic widening of the gastric mucosa without involvement of the deeper layers. However, despite annual control gastroscopies, an adenocarcinoma developed between the folds and was in an already advanced stage at diagnosis (UICC III). We suggest that a variant of Peutz-Jeghers syndrome may be characterised by marked foveolar hyperplasia similar to Menetrier disease, and that not conventional endoscopy alone, but rather endoscopic ultrasound may be considered in such patients.

Sexual dysfunction in males with chronic hepatitis C and antiviral therapy: interferon-induced functional androgen deficiency or depression?

Decrease of libido and erectile dysfunction are reported by male patients during antiviral therapy of chronic hepatitis C, but therapy-associated underlying factors for sexual dysfunction are not well defined. To assess putative contributions of interferon-induced sex hormone changes to sexual dysfunction, we prospectively investigated changes in free testosterone, total testosterone, dehydroepiandrosterone sulfate, prolactin, sex hormone-binding globulin, FSH and LH levels and psychometric self-assessment scores in 34 male patients treated with interferon alfa-2b (5 MIU three times weekly) (n=19)+ ribavirin (n=15) for 6-12 months. Depression was measured by the Hospital Anxiety and Depression Scale. Sexual dysfunction was evaluated by the Symptom Checklist 90 Item Revised and a five-point rating scale assessing sexual arousal disorder. Free and total testosterone decreased significantly during antiviral therapy in close correlation with libido/sexual function. Depression scores increased during therapy and were also significantly associated with sexual dysfunction. However, androgen levels displayed no significant correlation with depression. These results suggest that interferon-induced decrease in sexual function is associated - but not causally related -with both androgen reduction and increased depressive symptoms. These findings may affect care for male hepatitis C patients during interferon therapy.

Prophylactic SSRI during interferon alpha re-therapy in patients with chronic hepatitis C and a history of interferon-induced depression.

Only limited data are available on selective serotonin re-uptake inhibitor (SSRI) prophylaxis for antiviral re-treatment in hepatitis C patients with previous interferon-induced major depressive episodes. Therefore, we investigated the efficacy and safety of secondary SSRI prophylaxis in these patients. In a prospective and longitudinal study, repeated psychometric testing (Hospital Anxiety and Depression Scale) was performed before, during, and after antiviral re-treatment. Chronic hepatitis C virus (HCV)-infected patients, who had been psychometrically monitored during an unsuccessful previous antiviral therapy, and had developed major depression were included. Interferon re-therapy with SSRI prophylaxis was started (n = 8). The reference group was comprised of HCV patients without a history of interferon-associated depression and also a group who were previously unsuccessfully treated with interferon and were re-treated without SSRI prophylaxis (n = 9). All patients receiving SSRI prophylaxis were able to complete interferon re-therapy as scheduled. As in the first therapeutic course, depression scores were significantly elevated during re-treatment also (P < 0.001). Depression scores were significantly lower (P =0.036) during interferon re-therapy with SSRI prophylaxis. Reference group subjects showed similar depression scores during first therapy and re-therapy (P > 0.05). In conclusion, hepatitis C patients with a history of interferon-induced major depression can be successfully re-treated with peginterferon/ribavirin and concomitant SSRI prophylaxis. In these patients, SSRI prophylaxis is safe and efficacious and should be considered, if antiviral re-therapy is indicated.

[Diagnosis and treatment of extrahepatic cholestasis]. / Diagnostik und Therapie der extrahepatischen Cholestase. Stein oder Tumor--das ist hier die Frage.

One of the most common causes of extrahepatic cholestasis is bile duct obstruction by gallstones, bile duct strictures in chronic pancreatitis involving the head of the pancreas, or tumors in the region of the pancreas, bile ducts or gallbladder. While choledocholithiasis usually gives rise to classical clinical signs (obstructive jaundice, typical pain, and fever in the case of cholangitis), tumors often become symptomatic only when far advanced. In addition to laboratory parameters, diagnostic imaging techniques, in part with a therapeutic intervention option (ERCP), are of central importance. The aim of treatment is the elimination of the obstruction and, if possible the underlying disease.

[Chronic diarrhea in malabsorption]. / Durchfall, Eisenmangel, Tetanie. So erkennen Sie eine Malassimilation.

Chronic diarrhea with malassimilation is a symptom of numerous diseases ranging from celiac disease to lactate intolerance to chronic inflammatory bowel disease. Accordingly, they require an arsenal of diagnostic options. Clarification of the situation involves history-taking, a clinical examination, orientating and specific laboratory investigations, and imaging procedures, in particular ultrasound and endoscopy. Function tests such as the xylose-tolerance test, the H2 breath test or the various pancreas function tests are available as adjunctive options where indicated.

Spectral karyotype analysis of colon cancer cell lines of the tumor suppressor and mutator pathway.

BACKGROUND AND AIMS: Microsatellite instability (MSI) is characterized by the size variation of microsatellites in tumor DNA as compared to matching normal DNA due to defects in the mismatch repair system. To examine the chromosomal differences in microsatellite-stable (MSS) and -unstable (MSI) tumors in detail, we analyzed MSS (Caco-2, Colo-205, SW948) and MSI (HCT-15, HCT-116, LoVo) cell lines by spectral karyotyping (SKY). METHODS: SKY is a sensitive method to detect chromosome aberrations by visualizing each chromosome in a different color. Metaphases were hybridized with a SKY probe mixture. Images were visualized with the SpectraCube system and analyzed with the SKYview imaging software. RESULTS: The average number of chromosomes was 49 in LoVo, 45 in HCT-116, 46 in HCT-15, 71 in Colo-205, 89 in Caco-2 and 66 in SW-948. Three aberrant chromosomes were detected in LoVo, three in HCT-116, two in HCT-15, seventeen in Colo-205, fourteen in Caco-2 and nine in SW948. CONCLUSION: The karyotypes of MSS colon cancer cells displayed complex numerical and structural aberrations. In contrast the chromosomes of MSI colon cancer cells were mostly unaltered but displayed a few isolated numerical and structural aberrations. We speculate that these isolated aberrations may be specifically involved in the pathogenesis of MSI tumors.

[Hereditary nonpolyposis colorectal carcinoma (HNPCC). Current review of etiology, clinical aspects, diagnosis and therapy]. / Hereditäres Non-Polyposis kolorektales Karzinom (HNPCC). Aktuelle Ubersicht zur Atiologie, Klinik, Diagnostik und Therapie.

ETIOLOGY: The hereditary non-polyposis colorectal carcinoma (HNPCC) is the most common monogenic colon cancer syndrome. It is characterized by autosomal dominant inherited cancers of the colon, rectum, and the endometrium. Less frequently, cancer of the upper gastrointestinal tract, the hepatobiliary system and the urogenital tract may occur. Typical characteristics are an early onset, usually before the age of 50, manifestation of colorectal cancer proximal of the splenic flexure, and often poorly differentiated carcinomas. GENETICS: Recently, germline mutations in several DNA mismatch repair genes have been identified as the molecular basis of HNPCC, resulting in deficient DNA repair and genetic instability, indicated by microsatellite instability in tumor specimens. DIAGNOSIS: New insights into pathogenesis, clinical features, and diagnosis of HNPCC have improved the identification of HNPCC patients and persons at risk. Diagnosis of HNPCC is primarily based on family history and is complemented by molecular findings. After detection of the underlying germline mutation in families with HNPCC, screening procedures can be restricted to mutation carriers. TREATMENT: Recommendations for therapy and prevention are in part controversial and are under investigation in several studies.

Inverse mRNA expression of the selenocysteine-containing proteins GI-GPx and SeP in colorectal adenomas compared with adjacent normal mucosa.

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.

Prevention of hepatitis B flare-up during chemotherapy using lamivudine: case report and review of the literature.

Reactivation of chronic hepatitis B in patients receiving cytotoxic treatment for non-Hodgkin's lymphoma is well documented. We report a case of a patient with chronic hepatitis B who was treated by chemotherapy because of non-Hodgkin's lymphoma. After the second cycle of chemotherapy she developed a severe flare-up of hepatitis B. Liver biopsy revealed highly active hepatitis and confluent necroses. Within 3 weeks, the patient recovered spontaneously. Prophylactic treatment with lamivudine (Epivir,Glaxo-Wellcome, 150 mg b.i.d.) led to a decrease of HBV-DNA below the detection limit. Further chemotherapy was administered and autologous stem cell transplantation was successfully performed without another reactivation of hepatitis B. Antiviral treatment was stopped 16 weeks after stem cell retransfusion. So far, no further flare-up of hepatitis B has occurred and the patient's lymphoma has not relapsed. Thus, the case described here indicates a possible role of lamivudine in preventing hepatitis B flare-up during antineoplastic chemotherapy. We suggest that lamivudine be considered for prophylaxis against fulminant hepatitis in patients with chronic HBV infection undergoing high-dose antineoplastic therapy.

Reconstitution of squamous epithelium in Barrett's oesophagus with endoscopic argon plasma coagulation: a prospective study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Primary biliary cirrhosis and gastric carcinoid: a rare association?

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 the 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.

[Successful therapy of persistent androgen-induced cholestasis with ursodeoxycholic acid]. / Erfolgreiche Therapie einer persistierenden androgeninduzierten Cholestase mit Ursodesoxycholsäure.

Drug-induced cholestasis can rarely persist for a considerable time period even after withdrawal of the drug. We report the case of a 55-year-old man with progressive jaundice after oral therapy with 17-alpha-methyltestosterone. Under empiric therapy with ursodeoxycholic acid the condition resolved completely. According to this observation, we suggest a therapeutic trial with ursodeoxycholic acid in cases of prolonged androgen-induced cholestasis.