Mismatch repair deficiency, chemotherapy and survival for resectable gastric cancer: an observational study from the German staR cohort and a meta-analysis.

PURPOSE: In a post hoc analysis of the MAGIC trial, patients with curatively resected gastric cancer (GC) and mismatch repair (MMR) deficiency (MMRd) had better median overall survival (OS) when treated with surgery alone but worse median OS when treated with additional chemotherapy. Further data are required to corroborate these findings. METHODS: Between April 2013 and December 2018, 458 patients with curatively resected GC, including cancers of the esophagogastric junction Siewert type II and III, were identified in the German centers of the staR consortium. Tumor sections were assessed for expression of MLH1, MSH2, MSH6 and PMS2 by immunohistochemistry. The association between MMR status and survival was assessed. Similar studies published up to January 2021 were then identified in a MEDLINE search for a meta-analysis. RESULTS: MMR-status and survival data were available for 223 patients (median age 66 years, 62.8% male), 23 patients were MMRd (10.3%). After matching for baseline clinical characteristics, median OS was not reached in any subgroup. Compared to perioperative chemotherapy, patients receiving surgery alone with MMRd and MMRp had a HR of 0.67 (95% CI 0.13-3.37, P = 0.63) and 1.44 (95% CI 0.66-3.13, P = 0.36), respectively. The meta-analysis included pooled data from 385 patients. Compared to perioperative chemotherapy, patients receiving surgery alone with MMRd had an improved OS with a HR of 0.36 (95% CI 0.14-0.91, P = 0.03), whereas those with MMRp had a HR of 1.18 (95% CI 0.89-1.58, P = 0.26). CONCLUSION: Our data support a positive prognostic effect for MMRd in GC patients treated with surgery only and a differentially negative prognostic effect in patients treated with perioperative chemotherapy. MMR status determined by preoperative biopsies may be used as a predictive biomarker to select patients for perioperative chemotherapy in curatively resectable GC.

[Acute pancreatitis : Typical findings in computed tomography and magnetic resonance imaging]. / Akute Pankreatitis : Typische Befunde in Computer- und Magnetresonanztomographie.

CLINICAL PROBLEM: Imaging plays a major role to differentiate interstitial edematous from necrotic pancreatitis and to describe relevant local complications for proper patient management and decision-making in acute pancreatitis. STANDARD RADIOLOGICAL PROCEDURES: The revised Atlanta classification 2012 of acute pancreatitis divides patients into mild, moderately severe and severe groups. Computed tomography (CT) and magnetic resonance imaging (MRI) are well established for diagnosis and follow-up of acute pancreatitis and its complications METHODOLOGICAL INNOVATIONS AND ASSESSMENT: Based on the revised Atlanta classification, CT and MRI allow for adequate categorization of interstitial edematous and necrotic pancreatitis. Imaging and standardized reporting nomenclature enable confident differentiation of early and late complications in acute pancreatitis. RECOMMENDATIONS: The aim of this review article is to present an image-rich overview of different morphologic characteristics of acute pancreatitis and associated local complications by CT or MRI using case examples.

[S2k-guideline Helicobacter pylori and gastroduodenal ulcer disease]. / S2k-Leitlinie Helicobacter pylori und gastroduodenale Ulkuskrankheit.

In the line "bismuth-containing quadruple therapy" of Table 7 (p 342), in the column "dosage" incorrectly at the three antibiotics respectively 1-1-1-1. The correct is: 3-3-3-3.

[Surgical management of a retrorectal tumor with consideration of a rare differential diagnosis]. / Management eines retrorektalen Tumors unter Berücksichtigung einer seltenen Differenzialdiagnose.

We present a case of a retrorectal space occupying lesion diagnosed as an adenocarcinoma of unknown primary origin by preoperative histopathology. Localization slightly above the anal sphincter would have required extirpation of the rectum. Rectal palpation, endosonography and radiological imaging, however, suggested a retrorectal tumor or a metastasis of an adenocarcinoma. Both entities would have required local resection. We applied a surgical algorithm including frozen biopsy allowing a stepwise choice of operative procedure from the spectrum in question. The operation performed was thus tailored to the entity of the tumor.

Colonic ischaemia as a severe Shiga toxin/verotoxin producing Escherichia coli O104:H4 complication in a patient without haemolytic uraemic syndrome, Germany, June 2011.

An increasing rate of infections with Shiga toxin/verotoxin-producing Escherichia coli (STEC/VTEC) O104:H4 has been observed in Germany since May 2011, with unusually high numbers of patients suffering from haemolytic uraemic syndrome (HUS). We report a STEC/VTEC O104:H4 case without HUS, presenting with colonic ischaemia demanding surgery. This atypical clinical presentation of STEC O104:H4 infection might indicate new severe complications associated with this uncommon strain, and highlights the importance of immediate interdisciplinary assessment of STEC/VTEC patients.

S3-guideline "helicobacter pylori and gastroduodenal ulcer disease" of the German society for digestive and metabolic diseases (DGVS) in cooperation with the German society for hygiene and microbiology, society for pediatric gastroenterology and nutrition e. V., German society for rheumatology, AWMF-registration-no. 021 / 001.

This guideline updates a prior consensus recommendation of the German Society for Digestive and Metabolic Diseases (DGVS) from 1996. It was developed by an interdisciplinary cooperation with representatives of the German Society for Hygiene and Microbiology, the Society for Pediatric Gastroenterology and Nutrition (GPGE), and the German Society for Rheumatology. The guideline is methodologically based on recommendations of the Association of the Scientific Medical Societies in Germany (AWMF) for providing a systematic evidence-based S 3 level consensus guideline and has also implemented grading criteria according to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) process. Clinical applicability of study results as well as specifics for Germany in terms of epidemiology, antibiotic resistance status, diagnostics, and therapy were taken into account.

The combined presence of H pylori infection and gastro-oesophageal reflux disease leads to an up-regulation of CDX2 gene expression in antrum and cardia.

BACKGROUND: CDX2 is an epithelial transcription factor that regulates intestinal differentiation and is involved in the development of intestinal metaplasia (IM). AIM: To analyse the expression of CDX2 in the gastric mucosa in various locations and its relationship to Helicobacter pylori infection and gastro-oesophageal reflux disease (GORD). METHODS: 69 patients with upper gastrointestinal symptoms were stratified into four groups according to their H pylori and GORD status. Patients without infection and without GORD were the reference group (H pylori(-)/GORD(-)). Biopsies from the antrum, corpus and cardia were assessed by histopathology according to the updated Sydney System. CDX2 transcription levels were determined by quantitative RT-PCR and immunohistochemistry. RESULTS: CDX2 gene expression was significantly up-regulated in antral and cardia mucosa of patients with both H pylori infection and GORD (26- and 100-fold, respectively; p<0.05), but remained unchanged in corpus mucosa. If only H pylori infection or GORD was present, CDX2 expression levels were 6- to 11-fold increased in the antrum, but without reaching statistical significance. CDX2 expression correlated positively with the degree of IM (p<0.01) and the degree of H pylori induced inflammation (p<0.05). Gene expression data were confirmed immunohistochemically by the detection of CDX2 in areas of IM and in focally distributed CDX2-expressing cells in non-metaplastic gastric mucosa. CONCLUSIONS: The combined presence of H pylori infection and GORD leads to an up-regulation of CDX2 gene expression in cardia and antral mucosa, but not in the corpus.

[S3-guideline "Helicobacter pylori and gastroduodenal ulcer disease"]. / S3-Leitlinie "Helicobacter pylori und gastroduodenale Ulkuskrankheit" der Deutschen Gesellschaft für Verdauungs- und Stoffwechselkrankheiten (DGVS).

This guideline updates a prior concensus recommendation of the German Society for Digestive and Metabolic Diseases (DGVS) from 1996. It was developed by an interdisciplinary cooperation with representatives of the German Society for Microbiology, the Society for Pediatric Gastroenterology and Nutrition (GPGE) and the German Society for Rheumatology. The guideline is methodologically based on recommendations of the Association of the Scientific Medical Societies in Germany (AWMF) for providing a systematic evidence-based consensus guideline of S 3 level and has also implemented grading criteria according to GRADE (Grading of Recommendations Assessment, Development and Evaluation). Clinical applicability of study results as well as specifics for Germany in terms of epidemiology, antibiotic resistance status, diagnostics and therapy were taken into account.

[Barrett carcinoma--diagnosis, screening, surveillance, endoscopic treatment, prevention]. / Barrett-Karzinom--Diagnose, Screening, Surveillance, endoskopische Therapie, Prävention.

An adenocarcinoma of the distal esophagus may also be designated as Barrett's carcinoma as it evolves from Barrett's esophagus. Barrett's esophagus currently is defined as a columnar metaplasia of the distal esophagus, as identified by endoscopy, that, upon histopathology, is confirmed to contain intestinal metaplasia. A different histological entity of columnar metaplasia of the distal esophagus is cardia-type mucosa which probably precedes intestinal metaplasia, but lacks goblet cells typical for the latter. The conversion rate from Barrett's esophagus to Barrett's carcinoma amounts to 0.5 to 1 % per year. Patients with reflux symptoms should undergo early endoscopy in order to search for Barrett's esophagus (screening). In those cases where Barrett's esophagus is identified, regular endoscopic controls should be scheduled (surveillance). The intervals for this have been defined by recent consented guidelines. The aim is to detect neoplasia early. Neoplasia confined to the epithelium or mucosal layer can mostly be treated by endoscopic resection. The depth of infiltration, as determined by histopathology of the resected specimen, allows one to estimate the risk of lymph node metastasis, and therefore is crucial for the final judgment as to whether the endoscopic intervention may be considered curative. Individually, the risk of metastasis has to be weighed against the risk of morbidity and mortality conferred by the alternative surgical resection. The rapid increase of the incidence of Barrett's carcinoma in Western countries suggests that life style factors, in particular overweight, having a causal role. Data from interventional trials on prevention are, however, pending.

Multichannel intraluminal impedance and pH-metry for investigation of symptomatic gastroesophageal reflux disease.

BACKGROUND: Combined multichannel intraluminal impedance and pH-metry (MII-pH) is a technique that enables monitoring of gastroesophageal reflux independent of its acidity. AIM: To investigate the utility of MII-pH in the clinical investigation of patients with gastroesophageal reflux disease (GERD) symptoms. METHODS: 32 consecutive patients underwent 24-hour ambulatory MII-pH. 16 patients were on PPI (PPI+) therapy and 16 were taking no acid-suppressive medication (PPI-). We investigated the pattern of reflux by means of acid and nonacid reflux and the relation to typical and atypical symptoms. In addition, we investigated the symptom association by using the symptom index. RESULTS: Symptom-related acid reflux was higher in the PPI+ group (33 vs. 25%) and symptom-related nonacid reflux was higher in the PPI- group (36 vs. 21%). The association between type of symptoms and the association to reflux is highly significant (p < 0.001) in the PPI- group. In this group the association of acid reflux is more likely to correlate with typical symptoms and the association of nonacid reflux is more likely to be associated with atypical symptoms. CONCLUSIONS: These data show that nonacid reflux can be associated with symptoms in patients with GERD symptoms. The diagnostic value of MII-pH is independent of PPI therapy.

[Sonographic diagnosis of a liver abscess caused by an enterohepatic fistula in a patient with Crohn's disease]. / Sonographische Diagnose eines Leberabszesses infolge einer enterohepatischen Fistel bei einem Patienten mit Morbus Crohn.

Liver abscesses in patients with Crohn's disease are rare. We report on a patient with Crohn's disease and a liver abscess of the left lobe caused by an enterohepatic fistula. With treatment of antibiotics and Infliximab the abscess showed complete regression. Percutaneous drainage of the liver abscess was not performed because the abscess was shown not to be completely liquefied at echo-enhanced ultrasound. This case report demonstrates the usefulness of percutaneous conventional and echo-enhanced ultrasound for the diagnosis of liver abscesses. Furthermore, this case also shows that enterohepatic fistulas can be diagnosed precisely with percutaneous ultrasound.

Missing gastric cancer in dyspepsia.

BACKGROUND: Dyspepsia is common in gastric cancer, but also in many benign conditions. European Helicobacter pylori Study Group and American Gastroenterological Association guidelines recommend endoscopy in dyspepsia for patients with alarm symptoms or at age >45 years. However, recommendations are controversial. AIM: To investigate whether criteria for endoscopy in patients with dyspepsia are adequate to detect gastric cancer. METHODS: In 215 patients at initial diagnosis of gastric adenocarcinoma, symptoms were classified as alarm and non-alarm. Cases were staged according to the TNM system. Stages T(1)-T(3)N(x)M(0) were defined as potentially curable. RESULTS: Dyspepsia was present in 128 patients. Among patients with dyspepsia, 15 were < or =45 years and 41 denied alarm symptoms. The combination of both criteria excluded only three (2.3%) patients from endoscopy, but increasing the threshold to >50 and >55 years would have raised the rate of excluded patients to seven (5.5%) and 11 (8.6%). Only 53 potentially curable stages and 18 early gastric cancers occurred, but the tumour stage was not associated with dyspepsia duration, age threshold of 45 years, or alarm symptoms. CONCLUSIONS: Our results support current European Helicobacter Study Group and American Gastroenterological Association criteria for endoscopy in patients with dyspepsia to detect gastric cancer. Regardless, most cancers are advanced at detection.

The interplay between Helicobacter pylori, gastro-oesophageal reflux disease, and intestinal metaplasia.

Helicobacter pylori infection and gastro-oesophageal reflux disease (GERD) account for most upper gastrointestinal pathologies with a wide spectrum of clinical manifestations. The interplay of both conditions is complex, in part intriguing, and has become a matter of debate because of conflicting results. The cardia is an area where both H pylori and abnormal GERD exert their damaging potential, inducing inflammation and its consequences, such as intestinal metaplasia. While the role of intestinal metaplasia within columnar lined epithelium (Barrett's oesophagus) in the context of GERD is well established as a risk for neoplasia development, the role of intestinal metaplasia at the cardia in the context of H pylori infection is unclear. A particular challenge is the distinction of intestinal metaplasia as a consequence of GERD or H pylori if both conditions are concomitant. Available data on this issue, including follow up of a small patient series, are presented, but more studies are required to shed light on this issue because they will help to identify those patients that need surveillance.

Carditis at the interface between GERD and Helicobacter pylori infection.

Inflammation of the gastric cardia ('carditis') is a histological diagnosis. It seems reasonable to transfer histological criteria of the updated Sydney classification from the distal stomach to the cardia as long as a special classification of inflammation of the esophagogastric junction is lacking. The two best characterized causes of carditis are Helicobacter pylori infection and gastroesophageal reflux disease (GERD). However, the causal contribution and interference of these two factors are highly controversial, as is the clinical relevance of carditis in terms of eliciting symptoms or conferring an increased cancer risk. Variability of studies on carditis is based on conflicting concepts of the normal anatomy of the esophagogastric junction. Cardia-type mucosa (CM) apparently exists at birth as a tiny circular area, and extends to a larger area in adulthood. This implies that cardia-type mucosa is largely metaplastic. Metaplastic CM may evolve in the lower esophagus as a consequence of GERD. It is a general phenomenon that H. pylori-induced gastritis also involves the gastric cardia, irrespective whether the cardia is lined by fundus-type mucosa or CM. The contribution of GERD to inflammation of CM in H. pylori-negative individuals is, however, highly controversial. Prevalence of carditis in GERD patients fluctuates between 10 and 97%. Hence, because of its high frequency and low specificity, carditis can currently not be considered as a clinical entity. The role of carditis for the increasing incidence of cancer of the esophagogastric junction requires careful studies that include accurate description of the area with adequate biopsy protocols.

Ablative procedures for prevention and treatment of esophageal adenocarcinoma.

Ablation of Barrett's mucosa by endoscopic resection, photodynamic therapy or thermoablative methods in combination with adequate acid suppression leads to mucosal replacement largely by squamous epithelium. In appropriately selected cases, these methods have the potential to cure superficial Barrett's neoplasia. Endoscopic resection is an alternative to surgical resection of high-grade intraepithelial neoplasia or early esophageal adenocarcinoma, if the tumor is less than 20 mm in size, is not ulcerated, and does not exhibit differentiation grade 3 or lymph vessel infiltration on histological examination. In the presence of submucosal infiltration, the likelihood of lymph node infiltration is related to the infiltration depth. The risk of a noncurative endoscopic ablative approach has to be weighted against the general risk of surgery. With photodynamic or thermoablative treatment, the completeness of destruction of neoplastic tissue can only be judged at follow-up. These methods are therefore restricted to cases that have an increased surgical risk. Ablation of non-neoplastic Barrett's mucosa is currently not indicated.