Prevalence of Histological Gastritis in a Community Population and Association with Epigastric Pain.

BACKGROUND AND AIMS: Gastritis is a common histological diagnosis, although the prevalence is decreasing in developed populations, alongside decreasing prevalence of H. pylori infection. We sought to determine the prevalence of the etiology of gastritis in a Swedish population sample and to analyze any associations with symptoms, an area of clinical uncertainty. METHODS: Longitudinal population-based study based in Östhammar, Sweden. A randomly sampled adult population completed a validated gastrointestinal symptom questionnaire (Abdominal Symptom Questionnaire, ASQ) in 2011 (N = 1175). Participants < 80 years of age and who were eligible were invited to undergo esophagogastroduodenoscopy (EGD) (N = 947); 402 accepted and 368 underwent EGD with antral and body biopsies (average 54.1 years, range 20-79 years; 47.8% male) with H. pylori serology. RESULTS: Gastritis was found in 40.2% (148/368; 95% CI 35.2-45.2%). By rank, the most common histological subtype was reactive (68/148; 45.9%), then H. pylori (44/148; 29.7%), chronic non-H. pylori (29/148; 19.6%), and autoimmune (4/148; 2.7%). Gastritis was significantly associated with older age and H. pylori status (p < 0.01). Gastritis subjects were divided into three histological categories: chronic inactive inflammation, autoimmune gastritis, and active inflammation; there was no difference in the presence of upper gastrointestinal symptoms when categories were compared to cases with no pathological changes. Functional dyspepsia or gastroesophageal reflux were reported in 25.7% (38/148) of those with gastritis (any type or location) versus 34.1% (75/220) with no pathological changes (p = 0.32). Epigastric pain was more common in chronic H. pylori negative gastritis in the gastric body (OR = 3.22, 95% CI 1.08-9.62). CONCLUSION: Gastritis is common in the population with a prevalence of 40% and is usually asymptomatic. Chronic body gastritis may be associated with epigastric pain, but independent validation is required to confirm these findings. Clinicians should not generally ascribe symptoms to histological gastritis.

An Interactive Web-Based Educational Tool Improves Detection and Delineation of Barrett's Esophagus-Related Neoplasia.

BACKGROUND & AIMS: Endoscopic detection of early Barrett's esophagus-related neoplasia (BORN) is a challenge. We aimed to develop a web-based teaching tool for improving detection and delineation of BORN. METHODS: We made high-definition digital videos during endoscopies of patients with BORN and non-dysplastic Barrett's esophagus. Three experts superimposed their delineations of BORN lesions on the videos using special tools. In phase one, 68 general endoscopists from 4 countries assessed 4 batches of 20 videos. After each batch, mandatory feedback compared the assessors' interpretations with those from experts. These data informed the selection of 25 videos for the phase 2 module, which was completed by 121 new assessors from 5 countries. A 5-video test batch was completed before and after scoring of the four 5-video training batches. Mandatory feedback was as in phase 1. Outcome measures were scores for detection, delineation, agreement delineation, and relative delineation of BORN. RESULTS: A linear mixed-effect model showed significant sequential improvement for all 4 outcomes over successive training batches in both phases. In phase 2, median detection rates of BORN in the test batch increased by 30% (P < .001) after training. From baseline to the end of the study, there were relative increases in scores of 46% for detection, 129% for delineation, 105% for agreement delineation, and 106% for relative delineation (all, P < .001). Scores improved independent of assessors' country of origin or level of endoscopic experience. CONCLUSIONS: We developed a web-based teaching tool for endoscopic recognition of BORN that is easily accessible, efficient, and increases detection and delineation of neoplastic lesions. Widespread use of this tool might improve management of Barrett's esophagus by general endoscopists.

Assessment of individual tumor buds using keratin immunohistochemistry: moderate interobserver agreement suggests a role for machine learning.

Tumor budding is a promising and cost-effective biomarker with strong prognostic value in colorectal cancer. However, challenges related to interobserver variability persist. Such variability may be reduced by immunohistochemistry and computer-aided tumor bud selection. Development of computer algorithms for this purpose requires unequivocal examples of individual tumor buds. As such, we undertook a large-scale, international, and digital observer study on individual tumor bud assessment. From a pool of 46 colorectal cancer cases with tumor budding, 3000 tumor bud candidates were selected, largely based on digital image analysis algorithms. For each candidate bud, an image patch (size 256 × 256 µm) was extracted from a pan cytokeratin-stained whole-slide image. Members of an International Tumor Budding Consortium (n = 7) were asked to categorize each candidate as either (1) tumor bud, (2) poorly differentiated cluster, or (3) neither, based on current definitions. Agreement was assessed with Cohen's and Fleiss Kappa statistics. Fleiss Kappa showed moderate overall agreement between observers (0.42 and 0.51), while Cohen's Kappas ranged from 0.25 to 0.63. Complete agreement by all seven observers was present for only 34% of the 3000 tumor bud candidates, while 59% of the candidates were agreed on by at least five of the seven observers. Despite reports of moderate-to-substantial agreement with respect to tumor budding grade, agreement with respect to individual pan cytokeratin-stained tumor buds is moderate at most. A machine learning approach may prove especially useful for a more robust assessment of individual tumor buds.

Correction to: Assessment of individual tumor buds using keratin immunohistochemistry: moderate interobserver agreement suggests a role for machine learning.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Relevant issues in tumor regression grading of histopathological response to neoadjuvant treatment in adenocarcinomas of the esophagus and gastroesophageal junction.

Multimodality treatment combining surgery and oncologic treatment has become widely applied in curative treatment of esophageal and gastroesophageal junction adenocarcinoma. There is a need for a standardized tumor regression grade scoring system for clinically relevant effects of neoadjuvant treatment effects. There are numerous tumor regression grading systems in use and there is no international standardization. This review has found nine different international systems currently in use. These systems all differ in detail, which inhibits valid comparisons of results between studies. Tumor regression grading in esophageal and gastroesophageal junction adenocarcinoma needs to be improved and standardized. To achieve this goal, we have invited a significant group of international esophageal and gastroesophageal junction adenocarcinoma pathology experts to perform a structured review in the form of a Delphi process. The aims of the Delphi include specifying the details for the disposal of the surgical specimen and defining the details of, and the reporting from, the agreed histological tumor regression grade system including resected lymph nodes. The second step will be to perform a validation study of the agreed tumor regression grading system to ensure a scientifically robust inter- and intra-observer variability and to incorporate the consented tumor regression grading system in clinical studies to assess its predictive and prognostic role in treatment of esophageal and gastroesophageal junction adenocarcinomas. The ultimate aim of the project is to improve survival in esophageal and gastroesophageal adenocarcinoma by increasing the quality of tumor regression grading, which is a key component in treatment evaluation and future studies of individualized treatment of esophageal cancer.

Carditis: a relevant marker of gastroesophageal reflux disease. Data from a prospective central European multicenter study on histological and endoscopic diagnosis of esophagitis (histoGERD trial).

The columnar-lined mucosa at the gastroesophageal junction may contain an inflammatory infiltrate, commonly referred to as carditis (or cardia gastritis). The etiology of carditis is not entirely clear since published data are conflicting. Some authors believe it to be secondary to gastroesophageal reflux disease (GERD) and others to Helicobacter pylori gastritis. This prospective study aims at clarifying the relationship between carditis and the histological, clinical, and endoscopic findings of GERD, in a large cohort of individuals negative for H. pylori infection. Eight hundred and seventy-three individuals (477 females and 396 males, median age 53 years) participated in this study. Biopsy material was systematically sampled from above and below the gastroesophageal junction. Reflux-associated changes of the esophageal squamous epithelium were assessed according to the Esohisto consensus guidelines. Grading of carditis was performed according to the Updated Sydney System, known from the histological evaluation of gastritis. In total, 590 individuals (67.5%) had chronic carditis. Of these, 468 (53.6%) had mild chronic inflammation, with 321 individuals (68.6%) showing no or minimal changes on endoscopic examination (Los Angeles Categories N and M). The presence of chronic carditis was associated with several GERD-related parameters of the esophageal squamous epithelium (P < 0.0001), and data retained statistical significance even when analysis was restricted to individuals with mild chronic carditis and/or endoscopically normal mucosa. Chronic carditis was also associated with the presence of intestinal metaplasia (P < 0.0001). In addition, chronic carditis had a statistically significant association with patients' symptoms of GERD (P = 0.0107). This observation remained valid for mild chronic carditis in all patients (P = 0.0038) and in those with mild chronic carditis and normal endoscopic mucosa (P = 0.0217). In conclusion, chronic carditis appears to be the immediate consequence of GERD, correlating with patients' symptoms and endoscopic diagnosis. These results are valid in individuals with nonerosive reflux disease, which indicates a higher sensitivity of histological diagnosis. Our findings may impact the routine assessment of reflux patients.

Early-stage adenocarcinoma of the esophagus with mid to deep submucosal invasion (pT1b sm2-3): the frequency of lymph-node metastasis depends on macroscopic and histological risk patterns.

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.

[Eosinophilic Esophagitis - Update - Pathogenesis, Diagnosis and Therapy]. / Eosinophile Ösophagitis ­ Neues zur Pathogenese, Diagnostik und Therapie.

Eosinophilic esophagitis (EoE) is a clinicopathological condition of the esophagus that has become increasingly recognised over the last decade. EoE represents a chronic immune-mediated inflammatory disease of the esophagus. In adults dysphagia is the predominant symptom. Upper gastrointestinal endoscopy is required in order to take biopsies from the esophagus. The diagnose is confirmed histologically by typical eosinophilic infiltration of the esophagus mucosa. Until now there is no approved therapy world-wide although we know that topic and systemic steroids are highly effective in EoE. Elimination diet is another option and in well selected patients endoscopic balloon dilation represents a therapeutic possibility.

[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.

[Small cell structured cell nests of endometrial stroma]. / Kleinzellig strukturierte Zellnester des Endometriumstromas.

Tissue from endometrial diagnostic curettage material may show small clumps of stromal cells, which are pushed together (stromal collapse) and present a picture of glandular and stromal breakdown. This can be misinterpreted as small cell structured carcinoma, possibly of neuroendocrine or basal cell origin. Immunohistochemical investigations (e.g. estrogen receptor, epithelial and neuroendocrine markers and proliferation markers) are helpful in identifying the correct differential diagnosis.

[Eosinophilic esophagitis - update - pathogenesis, diagnosis and therapy]. / Eosinophile Ösophagitis - Neues zur Pathogenese, Diagnostik und Therapie.

Eosinophilic esophagitis (EoE) is a clinicopathological condition of the esophagus that has become increasingly recognised over the last decade. EoE represents a chronic immune-mediated inflammatory disease of the esophagus. In adults dysphagia is the predominant symptom. Upper gastrointestinal endoscopy is required in order to take biopsies from the esophagus. The diagnose is confirmed histologically by typical eosinophilic infiltration of the esophagus mucosa. Until now there is no approved therapy world-wide although we know that topic and systemic steroids are highly effective in EoE. Elimination diet is another option and in well selected patients endoscopic balloon dilation represents a therapeutic possibility.

[Inflammation, malignancy and immunology in gastrointestinal spindle cell tumors: what is beyond GIST?]. / Entzündung, Malignität und Immunologie gastrointestinaler Spindelzelltumoren : Was gibt es abgesehen von GIST noch?

Many mesenchymal tumors and tumefactions associated with the gastrointestinal tract feature prominent inflammatory cells but the mechanisms for the inflammation and the processes themselves remain poorly understood. Such classic lesions include Kaposi sarcoma, inflammatory fibroid polyp, sclerosing mesenteritis and inflammatory myofibroblastic tumor but, more recently, the recognition of IgG4-related fibrosclerosing disease has resulted in modification of the views on pathogenesis and treatment of such inflammatory lesions in many anatomical sites. In some lesions the inflammation may reflect viral influences (Kaposi sarcoma) or a bacterial infectious trigger (IgG4-related fibrosclerosing disease) whereas in others such an interaction is unclear and alterations in various genes have been detected, such as anaplastic lymphoma receptor tyrosine kinase gene rearrangements in inflammatory myofibroblastic tumor and platelet-derived growth factor receptor alpha (PDGFRA) gene mutations in inflammatory fibroid polyp and some gastrointestinal stromal tumors (GIST). Even the inflammatory milieu of GISTs may have an impact on the outcome. This article discusses the practical diagnostic considerations as well as the theoretical background.

[Barrett's neoplasia: where is the problem?]. / Barrett-Neoplasie: Wo liegt eigentlich das Problem?

The Barrett mucosa is characterised by metaplastic transformation in the distal oesophagus from squamous epithelium into columnar-lined cells and shows an increased risk for progression into adenocarcinoma. Up to date an international definition of Barrett's oesophagus is still lacking and it is also difficult to separate low-grade dysplasia/intraepithelial neoplasia from high-grade dysplasia/intraepithelial neoplasia. The present review describes the criteria for the histological diagnosis, discusses the possibilities of endoscopic diagnosis and highlights the biomarkers of the Barrett mucosa.

Presence of the coxsackievirus and adenovirus receptor (CAR) in human neoplasms: a multitumour array analysis.

BACKGROUND: The Coxsackie- and Adenovirus Receptor (CAR) has been assigned two crucial attributes in carcinomas: (a) involvement in the regulation of growth and dissemination and (b) binding for potentially therapeutic adenoviruses. However, data on CAR expression in cancer types are conflicting and several entities have not been analysed to date. METHODS: The expression of CAR was assessed by immunohistochemical staining of tissue microarrays (TMA) containing 3714 specimens derived from 100 malignancies and from 273 normal control tissues. RESULTS: The expression of CAR was detected in all normal organs, except in the brain. Expression levels, however, displayed a broad range from being barely detectable (for example, in the thymus) to high abundance expression (for example, in the liver and gastric mucosa). In malignancies, a high degree of variability was notable also, ranging from significantly elevated CAR expression (for example, in early stages of malignant transformation and several tumours of the female reproductive system) to decreased CAR expression (for example, in colon and prostate cancer types). CONCLUSION: Our results provide a comprehensive insight into CAR expression in neoplasms and indicate that CAR may offer a valuable target for adenovirus-based therapy in a subset of carcinomas. Furthermore, these data suggest that CAR may contribute to carcinogenesis in an entity-dependent manner.

European guidelines for quality assurance in colorectal cancer screening and diagnosis: overview and introduction to the full supplement publication.

Population-based screening for early detection and treatment of colorectal cancer (CRC) and precursor lesions, using evidence-based methods, can be effective in populations with a significant burden of the disease provided the services are of high quality. Multidisciplinary, evidence-based guidelines for quality assurance in CRC screening and diagnosis have been developed by experts in a project co-financed by the European Union. The 450-page guidelines were published in book format by the European Commission in 2010.  They include 10 chapters and over 250 recommendations, individually graded according to the strength of the recommendation and the supporting evidence. Adoption of the recommendations can improve and maintain the quality and effectiveness of an entire screening process, including identification and invitation of the target population, diagnosis and management of the disease and appropriate surveillance in people with detected lesions. To make the principles, recommendations and standards in the guidelines known to a wider professional and scientific community and to facilitate their use in the scientific literature, the original content is presented in journal format in an open-access Supplement of Endoscopy. The editors have prepared the present overview to inform readers of the comprehensive scope and content of the guidelines.

[Chronic pancreatitis with pseudocysts?]. / Chronische Pankreatitis mit Pseudozysten?

The gross examination of cystic changes in chronic pancreatitis can cause diagnostic problems particularly in the absence of grossly detectable tumor tissue. Besides the more frequently encountered pancreatitis-associated pseudocysts, pancreatic cysts should always raise attention to the differential diagnosis of a true neoplastic process.

[Lymph node metastasis in superficial squamous carcinoma of the esophagus]. / Lymphknotenmetastasen bei Plattenepithelfrühkarzinomen des Ösophagus.

The definition of early carcinoma of the esophagus has changed with time on the basis of new data. As from 2007 an early carcinoma is defined as an intramucosal carcinoma with or without metastasis. In the subclassification based on invasion depth, m1 and m2 squamous cell carcinomas have no metastasis and are considered curable by endoscopic resection alone, whereas less than 10% of m3 carcinomas and some 20% of sm1 squamous cell carcinomas have lymph node metastasis. In this article the relationship between various histopathological findings and the incidence of lymph node metastasis is reviewed. The m3 and sm1 superficial squamous cell carcinomas showing 0-I and 0-III types, large tumors over 50 mm in size or those showing vessel permeation have higher incidences of lymph node metastasis. In the field of gastrointestinal surgical pathology pathologists are now expected to not only diagnose the presence or absence of malignancy but also to investigate in detail many of the histological factors related to the prevalence of lymph node metastasis.

[Barrett's esophagus: analyses from human and experimental animal studies]. / Barrett-Ösophagus: Erkenntnisse beim Menschen und aus experimentellen Tierstudien.

Whereas attention in the past has been focused on goblet cells as the primary marker for Barrett's esophagus (BE), the recent change in the definition now includes the non-goblet cell columnar cell-lined esophagus. In the present study the histological features of neoplasia of the lower esophagus and esophago-gastric junction in a German cohort were examined using immunohistochemical staining for MUC, CD10, intestinal and gastric type major tight junction proteins (claudins). Experimental studies using rat duodenogastric content reflux models have also been performed and data show that most neoplastic lesions of the esophageal glands in humans express gastric mucin phenotypes. Cardiac type mucosa was the main histological type in the surrounding mucosa of neoplastic lesions; however, most cardiac type mucosa has intestinal type tight junction proteins. BE with goblet cells has been reported to originate from stem cells located in the basal layer of esophageal squamous cell epithelium in previous models. However, the cardiac type mucosa seems to develop from the site of the stomach and not from the basal layer of esophageal squamous cell epithelium according to our model.

[Subjective grading of Barrett's neoplasia by pathologists: correlation with objective histomorphometric variables]. / Subjektive Graduierung von Barrett-Neoplasien durch den Pathologen: Korrelation mit objektiven histomorphometrischen Variablen.

Even though pathologists are trained to recognize the same histological features for the diagnosis and grading of different histological images, not all pathologists are influenced to a similar level of intensity by the same morphological characteristics of the tissue when scoring Barrett's dysplasia/neoplasia. The variables which most pathologists have intuitively chosen to use for scoring of the severity of Barrett's changes are mainly those related to the general tissue architecture, such as nuclear crowding, orientation and stratification. Interestingly, nuclear size is not used by most pathologists but nuclear pleomorphism and symmetry does influence a significant number of pathologists. Maybe the most difficult variables for the human eye to recognize are variables of chromatin texture (such as margination or heterogeneity), the predictive importance of which has been demonstrated in a previously published work. Textural variables may therefore remain the subject of a computerized analysis. Nevertheless, the fact that a few pathologists do actually correlate with nuclear texture in scoring, argues in favor of making further attempts to train pathologists to also rely on texture, similar to cytologists, when scoring Barrett's dysplasia.

Isolated late metastasis from testicular seminoma presenting as a parotid gland mass: case report and review of the literature.

Parotid metastases from non-head-and-neck cancers are rare and may represent a diagnostic and therapeutic challenge. A late metastasis to the parotid gland from a seminoma is an unusual manifestation of disease. A 45-year-old man with a history of testicular seminoma 5 years earlier presented with a rapidly progressing parotid mass. Ultrasonography and computed tomography showed a space-occupying lesion at the angle of the right jaw. The mass was infiltrating into the parotid gland and into the parapharyngeal space. A primary parotid neoplasm was suspected, and panendoscopy combined with open biopsy was performed. Histology examination confirmed a seminoma metastatic to the parotid gland, and comparison with the primary tumour showed identical histology. The patient received chemotherapy for recurrent seminoma in accordance with the pei (cisplatin, etoposide, ifosfamide) protocol. After 4 courses of chemotherapy, salvage radical parotidectomy with removal of all suspicious residual tumour tissue was performed. This case illustrates the difficulties that may be encountered in the differential diagnosis of parotid gland masses and underlines the necessity for a detailed clinical history and for strong interdisciplinary collaboration between oncologists and pathologists to correctly diagnose cases with such unusual presentations.