BackgroundIn Helicobacter pylori (H. pylori) positive stage I gastric low-grade MALT lymphoma, eradication is the accepted first-line therapy. The role of eradication therapy in lymphoma>stage IE is still unclear. However, about 20% of patients show persistent lymphoma following successful eradication or primary H. pylori-negative lymphoma. A prospective study for salvage radiation therapy with standard 36Gy in comparison to a reduced dose of 25.2Gy is still missing.MethodsA prospective, multicentre study investigated the efficacy of eradication in H. pylori-positive gastric low-grade MALT lymphoma stages IE and II1E (HELYX I). Refractory lymphoma or H. pylori-negative patients were treated in a prospective, randomised, multicentre, phase II study to receive either 25.2Gy or 36Gy radiotherapy (HELYX II).Results102 patients (3 drop outs) were included in HELYX I: 75/99 (75.8%) showed complete remission after a median of 2.8months. 18 (18.2%) had partial remission (PR) and 6 (6.0%) no change (NC). 29 patients (7 drop outs) were randomized in HELYX II (7 primarily H. pylori-negative, 15 patients from HELYX I with refractory disease after eradication). All patients achieved stable CR irrespective of radiation dose. Both presence of the t(11,18) translocation (OR 9.0, p=0.01) and monoclonality of the tumour cells (OR 6.3, p=0.006) were predictors for persistant lymphoma after eradication therapy.ConclusionsMost H. pylori-positive low grade gastric MALT lymphoma stage IE and II1E respond with stable CR after eradication therapy. In patients with refractory disease or H. pylori negative low grade gastric MALT lymphoma a dosage-reduced radiation therapy with 25.2Gy is an effective standard dose in stage IE and II1E.Trial registrationClinicalTrials.gov: NCT00154440.

The rate of lymph-node (LN) metastasis in early adenocarcinoma (EAC) of the esophagus with mid to deep submucosal invasion (pT1b sm2/3) has not yet been precisely defined. The aim of the this study was to evaluate the rate of LN metastasis in pT1b sm2/3 EAC depending on macroscopic and histological risk patterns to find out whether there may also be options for endoscopic therapy as in cancers limited to the mucosa and the upper third of the submucosa. A total of 1.718 pt with suspicion of EAC were referred for endoscopic treatment (ET) to the Dept. of Internal Medicine II at HSK Wiesbaden 1996-2010. In 230/1.718 pt, the suspicion (endoscopic ultrasound, EUS) or definitive diagnosis of pT1b EAC (ER/surgery) was made. Of these, 38 pt had sm2 lesions, and 69 sm3. Rate of LN metastasis was analyzed depending on risk patterns: histologically low-risk (hisLR): G1-2, L0, V0; histologically high-risk (hisHR): ≥1 criterion not fulfilled; macroscopically low-risk (macLR): gross tumor type I-II, tumor size ≤2 cm; macroscopically high-risk (macHR): ≥1 criterion not fulfilled; combined low-risk (combLR): hisLR+macLR; combined high-risk (combHR): at least 1 risk factor. LN rate was only evaluated in pt who had proven maximum invasion depth of sm2/sm3, and who in case of ET had a follow-up (FU) by EUS of at least 24 months. 23/38 pt with pT1b sm2 lesions and 39/69 pt with sm3 lesions fulfilled our inclusion criteria. In the pT1b sm2 group, rate of LN metastasis in the hisLR, hisHR, combLR, and combHR groups were 8.3% (1/12), 36.3% (4/11), 0% (0/5), and 27.8% (5/18). In the pT1b sm3 group, rate of LN metastasis in the hisLR, hisHR, combLR and combHR groups were 28.6% (2/7), 37.5% (12/32), 25% (1/4), and 37.1% (13/35). 30-day mortality of surgery was 1.7% (1/58 pt). In EAC with pT1b sm2/3 invasion, the frequency of LN metastasis depends on macroscopic and histological risk patterns. Surgery remains the standard treatment, because the rate of LN metastasis appears to be higher than the mortality risk of surgery. Whether a highly selected group of pT1b sm2 patients with a favourable risk pattern may be candidates for endoscopic therapy cannot be decided until the results of larger case volumes are available.

Einleitung: Mittlerweile stellen sogenannte „low-risk (LR) sm1“ Barrettkarzinome (BK) eine Option für die primäre endoskopische anstelle der chirurgischen Resektion dar. Wir analysierten daher das Lymphknoten (LK)-Metastasierungsrisiko für Patienten (Pt.) mit mittlerer Submukosainvasion (sm2) unter Einbeziehung von makroskopischen und histologischen Risikofaktoren im Hinblick auf eine mögliche endoskopische Therapie (ET).

Gastric mucosa-associated lymphoid tissue (MALT) lymphomas develop from a chronic Helicobacter infection. Phospholipase C gamma 2 (PLCG2) is important for B-cell survival and proliferation. We used BALB/c mice with a gain-of-function mutation in the Plcg2 gene (Ali5) to analyze its role in the development of gastric MALT lymphoma. Heterozygous BALB/c Plcg2(Ali5/+) and wildtype (WT) mice were infected with Helicobacter felis (H. felis) and observed up to 16 months for development of gastric MALT lymphomas. In contrast to our initial hypothesis, Plcg2(Ali5/+) mice developed MALT lymphomas less frequently than their WT littermates after long-term infection of 16 months. Infected Plcg2(Ali5/+) mice showed downregulation of proinflammatory cytokines and decreased H. felis-specific IgG1 and IgG2a antibody responses. These results suggested a blunted immune response of Plcg2(Ali5/+) mice towards H. felis infection. Intriguingly, Plcg2(Ali5/+) mice harboured higher numbers of CD73 expressing regulatory T cells (Tregs), possibly responsible for impaired immune response towards Helicobacter infection. We suggest that Plcg2(Ali5/+) mice may be protected from developing gastric MALT lymphomas as a result of elevated Treg numbers, reduced response to H. felis and decrease of proinflammatory cytokines.

Due to its rapidly increasing incidence in the last decade, esophageal adenocarcinoma has been attracting widespread interest among gastroenterologists all over the world. Advanced adenocarcinomas arising from intestinal metaplasia in the esophagus (Barrett's esophagus, BE) are associated with a poor prognosis when esophagectomy is required. In addition to high mortality rates, there is a significant morbidity rate among patients who undergo surgery. However, if cancer can be diagnosed at an early stage, the endoscopic treatment options that are available significantly reduce the mortality rates. International guidelines recommend that endoscopic treatment should be carried out in all patients with mucosal cancer and low-risk criteria, but the method of choice for resection has been a matter of continuing debate. Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection are the main techniques competing in this field. Endoscopists also have to be able to manage potential complications and need to know how to deal with recurrences. Finally, it is essential to treat nondysplastic BE as an important part of the treatment, in order to avoid metachronous neoplasia. Different methods of ablative treatment, such as argon plasma coagulation and radiofrequency ablation (RFA), have been included in the subsequent treatment after resection. This review introduces and evaluates the different resection methods and discusses ablative therapy and surveillance protocols. The major scientific databases (Medline / PubMed) were searched for diagnoses and treatment in early esophageal adenocarcinoma. The current literature and the latest national and international guidelines were also included in order to obtain a good overview of the field. In areas in which there is a low quality of evidence, such as poor healing after endoscopic treatment, the authors offer recommendations based on their own experience in this field.

Hintergrund/Einleitung: Neben der Infektion mit H. pylori spielen genetische Faktoren bei der Entstehung des Magenkarzinoms eine entscheidende Rolle. So wurde von El-Omar et al. (Nature 412: 398–402) bei erstgradigen, mit H. pylori infizierten Angehörigen und Patienten mit Magenkarzinomen eine starke Assoziation mit Polymorphismen des Interleukin-1 Genclusters beschrieben. Dabei war die Assoziation mit den Allelen IL-1B-31C und IL-1RN*2, welche für das proinflammatorische Zytokin IL-1β bzw. dessen Antagonisten IL-1ra kodieren, besonders ausgeprägt. Einen ähnlichen Befund einer Assoziation mit den Allelen IL-1–511T und IL-1RN*2 erhoben Machado et al. (Gastroenterology 121: 823–829). Die drei genannten Polymorphismen weisen ein deutliches Kopplungsungleichgewicht auf, das Magenkarzinomrisiko ist insbesondere bei für diese Allele homozygoten Individuen erhöht.

Background Preoperative chemoradiotherapy with infusional fluorouracil, total mesorectal excision surgery, and postoperative chemotherapy with fluorouracil was established by the German CAO/ARO/AIO-94 trial as a standard combined modality treatment for locally advanced rectal cancer. Here we compare the previously established regimen with an investigational regimen in which oxaliplatin was added to both preoperative chemoradiotherapy and postoperative chemotherapy.Methods In this multicentre, open-label, randomised, phase 3 study we randomly assigned patients with rectal adenocarcinoma, clinically staged as cT3-4 or any node-positive disease, to two groups: a control group receiving standard fluorouracil-based combined modality treatment, consisting of preoperative radiotherapy of 50.4 Gy in 28 fractions plus infusional fluorouracil (1000 mg/m(2) on days 1-5 and 29-33), followed by surgery and four cycles of bolus fluorouracil (500 mg/m(2) on days 1-5 and 29); or to an investigational group receiving preoperative radiotherapy of 50.4 Gy in 28 fractions plus infusional fluorouracil (250 mg/m(2) on days 1-14 and 22-35) and oxaliplatin (50 mg/m(2) on days 1, 8, 22, and 29), followed by surgery and eight cycles of oxaliplatin (100 mg/m(2) on days 1 and 15), leucovorin (400 mg/m(2) on days 1 and 15), and infusional fluorouracil (2400 mg/m(2) on days 1-2 and 15-16). Randomisation was done with computer-generated block-randomisation codes stratified by centre, clinical T category (cT1-3 vs cT4), and clinical N category (cN0 vs cN1-2) without masking. The primary endpoint was disease-free survival, defined as the time between randomisation and non-radical surgery of the primary tumour (R2 resection), locoregional recurrence after R0/1 resection, metastatic disease or progression, or death from any cause, whichever occurred first. Survival and cumulative incidence of recurrence analyses followed the intention-to-treat principle; toxicity analyses included all patients treated. Enrolment of patients in this trial is completed and follow-up is ongoing. This study is registered with ClinicalTrials.gov, number NCT00349076.Findings Of the 1265 patients initially enrolled, 1236 were assessable (613 in the investigational group and 623 in the control group). With a median follow-up of 50 months (IQR 38-61), disease-free survival at 3 years was 75.9% (95% CI 72.4-79.5) in the investigational group and 71.2% (95% CI 67.6-74.9) in the control group (hazard ratio [HR] 0.79, 95% CI 0.64-0.98; p=0.03). Preoperative grade 3-4 toxic effects occurred in 144 (24%) of 607 patients who actually received fluorouracil and oxaliplatin during chemoradiotherapy and in 128 (20%) of 625 patients who actually received fluorouracil chemoradiotherapy. Of 445 patients who actually received adjuvant fluorouracil and leucovorin and oxaliplatin, 158 (36%) had grade 3-4 toxic effects, as did 170 (36%) of 470 patients who actually received adjuvant fluorouracil. Late grade 3-4 adverse events in patients who received protocol-specified preoperative and postoperative treatment occurred in 112 (25%) of 445 patients in the investigational group, and in 100 (21%) of 470 patients in the control group.Interpretation Adding oxaliplatin to fluorouracil-based neoadjuvant chemoradiotherapy and adjuvant chemotherapy (at the doses and intensities used in this trial) significantly improved disease-free survival of patients with clinically staged cT3-4 or cN1-2 rectal cancer compared with our former fluorouracil-based combined modality regimen (based on CAO/ARO/AIO-94). The regimen established by CAO/ARO/AIO-04 can be deemed a new treatment option for patients with locally advanced rectal cancer.

ProGERD ist eine multizentrische Studie mit dem Hauptziel der Beobachtung von Patienten mit GERD in einem Zeitraum von 5 Jahren nach einer initialen Therapie mit Esomeprazol. Eine Vielzahl von Patienten mit GERD leidet zusätzlich unter Schlafstörungen. In dieser Analyse sind wir der Frage nachgegangen, wie häufig Schlafstörungen vorhanden sind und welche Veränderungen durch eine suffiziente Therapie mit Esomeprazol erreicht werden.

Einleitung: Die kollagene Kolitis (KK) gehört zur den mikroskopischen Kolitiden. Sie ist gekennzeichnet durch chronische, wässrige Diarrhoen und histologisch durch den Nachweis eines subepithelialen Kollagenbandes sowie einer lymphoplasmazellulären Infiltration der Tunica propria. Die Einfluss der KK auf die Lebensqualität ist bisher nicht untersucht worden.

Hintergrund/Einleitung: Die endoskopische Therapie ist ein vielversprechender Therapieansatz zur kurativen Therapie von prämalignen und malignen Veränderungen im Barrett (B)-ösophagus. Durch das Fortbestehen der B-schleimhaut nach einer erfolgreich durchgeführten Therapie ist das Risiko des Auftretens von Rezidiven bzw. metachronen Läsionen (mL) gegeben.

Einleitung: Das gastrale MALT Lymphom kann im Frühstadium in 75% der Fälle mittels antibiotischer Therapie in komplette Remission (CR) gebracht werden.

A prerequisite for endoscopic treatment (ET) of not only mucosal, but also submucosal early adenocarcinoma of the esophagus (EAC) would be a rate of lymph node (LN) metastasis below the mortality rate of esophagectomy (2–5 %). The aim of the present study was to evaluate the rate of LN metastasis in patients with pT1b sm1 EAC.

Einleitung: Bislang galt die radikale Ösophagusresektion als der Goldstandard für die Therapie von high-grade intraepithelialer Neoplasie (HGIN) und Adenofrühkarzinomen (FK) im Barrett-Ösophagus. Die hier präsentierten Daten sind Langzeitergebnisse einer prospektiven Beobachtungsstudie.

Einleitung: Die endoskopische Resektion von frühen plattenepithelialen Neoplasien mit kurativem Ansatz scheint eine Alternative zur radikalen Ösophagusresektion darzustellen, wenn das Malignom auf die Mukosa beschränkt ist. In diesen Fällen ist das Risiko einer lymphogenen Filialisierung sehr gering. Im Gegensatz zu Japan existiert in der westlichen Welt nur sehr limitierte Erfahrung in der endoskopischen Resektion (ER) dieser Karzinome. In der vorliegenden prospektiven Beobachtungsstudie berichten wir über die größte Serie von Patienten mit Plattenepithelfrühkarzinom (SCC) oder Carcinoma in situ (cis), die durch ER therapiert wurden.

Objective Although it is well understood that the risk of oesophageal adenocarcinoma increases with Barrett length, transition risks for cancer associated with different Barrett lengths are unknown. We aimed to estimate annual cancer transition rates for patients with long-segment (>= 3 cm), short-segment (>= 1 to <3 cm) and ultra-short-segment (<1 cm) Barrett's oesophagus.Design We used three data sources to estimate the annual cancer transition rates for each Barrett length category: (1) the distribution of long, short and ultra-short Barrett's oesophagus among a large German cohort with newly diagnosed T1 oesophageal adenocarcinoma; (2) population-based German incidence of oesophageal adenocarcinoma; and (3) published estimates of the population prevalence of Barrett's oesophagus for each Barrett length category.Results Among 1017 patients with newly diagnosed T1 oesophageal adenocarcinoma, 573 (56%) had long-segment, 240 (24%) short-segment and 204 (20%) ultra-short-segment Barrett's oesophagus. The base-case estimates for the prevalence of Barrett's oesophagus among the general population were 1.5%, 5% and 14%, respectively. The annual cancer transition rates for patients with long, short and ultra-short Barrett's oesophagus were 0.22%, 0.03% and 0.01%, respectively. To detect one cancer, 450 patients with long-segment Barrett's oesophagus would need to undergo annual surveillance endoscopy; in short segment and ultra-short segment, the corresponding numbers of patients would be 3440 and 12 364. Similar results were obtained when applying US incidence data.Conclusions The large number of patients, who need to undergo endoscopic surveillance to detect one cancer, raises questions about the value of surveillance endoscopy in patients with short segment or ultra-short segment of Barrett's oesophagus.

Background: Collagenous colitis (CC) and lymphocytic colitis (LC) are chronic disorders characterized by watery diarrhea.Aim: To evaluate prospectively the clinical features, response to treatment and outcomes in a large group of patients with CC and LC.Patients and Methods: Patients with histologically confirmed CC and LC were prospectively enrolled to complete a questionnaire on onset and duration of diarrhea, stool frequency and consistency, other gastrointestinal symptoms including weight loss, drug history, treatment success and concomitant diseases.Results: A total of 494 patients (CC, n = 287, LC, n = 207) were available for analysis. The mean age at diagnosis was 65 in CC and 61 years in LC with a identically female predominance (76 % of patients) in both groups. Prior to diagnosis the mean duration of symptoms was 37 in CC and 23 months in LC. CC and LC patients share similar pattern of clinical symptoms. Concomitant autoimmune disorders were more common in CC patients (48.4 %) than in LC patients (29.6 %). Sustained clinical remission was reported by 35.5 % of CC and 38,6 % of LC, but more CC patients (47.7 %) received medication such as corticosteroids, antibiotics, bismuth or 5-aminosalicyclic than LC patients (16.9 %). 18.6 % of CC patients and 17.6 % of LC were regularly using NSAIDs.Conclusion: Collagenous and lymphocytic colitis are frequently diagnosed in elderly female patients. CC and LC share similar symptom pattern, but concomitant autoimmune disease were more common in CC than in LC patients.

BACKGROUND:The aim of this investigation is to study the relationship between gastric morphology and serum biomarkers before and after Helicobacter pylori eradication.METHODS:First-degree relatives of gastric cancer patients underwent gastroscopy before and 2.5 years after H. pylori eradication. The morphological changes in two categories (normal to mild and moderate to severe) were compared with level of pepsinogens I and II before eradication (n = 369), after eradication (n = 115), and in those with persistent infection (n = 250).RESULTS:After eradication, pepsinogen I decreased to 70% and pepsinogen II to 45% of the previous values. Unlike pepsinogen II and pepsinogen I to II ratio that were affected by the severity of inflammation and atrophy in corpus in all groups, pepsinogen I generally did not change. After eradication, subjects with high mononuclear infiltration in corpus had lower pepsinogen I (54 versus 77.1 μ/mL), higher pepsinogen II (9.4 versus 6.9 μ/mL), and lower ratio (7.9 versus 11.6) than those without (P < 0.05).CONCLUSION:Pepsinogen II is a good marker of corpus morphological changes before and after H. pylori eradication.