Diogo Libânio

Missing rate for gastric cancer during upper gastrointestinal endoscopy: a systematic review and meta-analysis

Objectives Esophagogastroduodenoscopy (EGD) is considered a very effective method to identify gastric cancer (GC). However, the existence of missed lesions has been frequently discussed. This systematic review and meta-analysis aimed at assessing the magnitude of missing GC diagnosis with EGD and its predictive factors. Methods MEDLINE was searched to identify all studies assessing and reporting the proportion of missed GC diagnosis with EGD. Pooled proportion and negative predictive values were computed using the random-effects model and heterogeneity was assessed using the Cochrane Q-test and I2. Results The studies included (n=22) were grouped by study design. The pooled negative predictive value was 99.7% (95% confidence interval 99.6–99.9%). Missed GCs proportion was 9.4% (95% confidence interval 5.7–13.1%), being 10.0% in studies including patients with negative EGD followed over time, 8.3% in studies including patients with GC, and 23.3% in studies evaluating the proportion of missed synchronous lesions. Mainly, missed cancers were located in the gastric body both in Eastern and in Western studies (39 and 47%, respectively). The majority of missed GCs were adenocarcinomas. Younger age (<55 years), female sex, marked gastric atrophy, gastric adenoma or ulcer, and inadequate number of biopsy fragments were reported as predictive factors for diagnostic failure. Conclusion EGD is a very effective method to rule out GC. However, missing GC with EGD is not uncommon, with one out of 10 cancers being potentially missed. Interestingly, lesions were more often missed in the body and therefore a more rigorous protocol for endoscopy and biopsy should be implemented worldwide.

A multicenter prospective study of the real-time use of narrow-band imaging in the diagnosis of premalignant gastric conditions and lesions

BACKGROUND AND AIM Some studies suggest that narrow-band imaging (NBI) can be more accurate at diagnosing gastric intestinal metaplasia and dysplasia than white-light endoscopy (WLE) alone. We aimed to assess the real-time diagnostic validity of high resolution endoscopy with and without NBI in the diagnosis of gastric premalignant conditions and to derive a classification for endoscopic grading of gastric intestinal metaplasia (EGGIM). METHODS A multicenter prospective study (five centers: Portugal, Italy, Romania, UK, USA) was performed involving the systematic use of high resolution gastroscopes with image registry with and without NBI in a centralized informatics platform (available online). All users used the same NBI classification. Histologic result was considered the diagnostic gold standard. RESULTS A total of 238 patients and 1123 endoscopic biopsies were included. NBI globally increased diagnostic accuracy by 11 percentage points (NBI 94 % vs. WLE 83 %; P < 0.001) with no difference in the identification of Helicobacter pylori gastritis (73 % vs. 74 %). NBI increased sensitivity for the diagnosis of intestinal metaplasia significantly (87 % vs. 53 %; P < 0.001) and for the diagnosis of dysplasia (92 % vs. 74 %). The added benefit of NBI in terms of diagnostic accuracy was greater in OLGIM III/IV than in OLGIM I/II (25 percentage points vs. 15 percentage points, respectively; P < 0.001). The area under the curve (AUC) of the receiver operating characteristic (ROC) curve for EGGIM in the identification of extensive metaplasia was 0.98. CONCLUSIONS In a real-time scenario, NBI demonstrates a high concordance with gastric histology, superior to WLE. Diagnostic accuracy higher than 90 % suggests that routine use of NBI allows targeted instead of random biopsy samples. EGGIM also permits immediate grading of intestinal metaplasia without biopsies and merits further investigation.

Gastric Microbiota and Carcinogenesis: The Role of Non-Helicobacter Pylori Bacteria - a Systematic Review

BACKGROUND AND AIM Helicobacter pylori is the strongest risk factor for gastric cancer. However, recent advances in DNA sequencing technology have revealed a complex microbial community in the stomach that could also contribute to the development of gastric cancer. The aim of this study was to present recent scientific evidence regarding the role of non-Helicobacter pylori bacteria in gastric carcinogenesis. METHODS A systematic review of original articles published in PubMed in the last ten years related to gastric microbiota and gastric cancer in humans was performed. RESULTS Thirteen original articles were included. The constitution of gastric microbiota appears to be significantly affected by gastric cancer and premalignant lesions. In fact, differences in gastric microbiota have been documented, depending on Helicobacter pylori status and gastric conditions, such as non-atrophic gastritis, intestinal metaplasia and cancer. Gastric carcinogenesis can be associated with an increase in many bacteria (such as Lactobacillus coleohominis, Klebsiella pneumoniae or Acinetobacter baumannii) as well as decrease in others (such as Porphyromonas spp, Neisseria spp, Prevotella pallens or Streptococcus sinensis). However, there is no conclusive data that confirms if these changes in microbiota are a cause or consequence of the process of carcinogenesis. CONCLUSIONS Even though there is limited evidence in humans, microbiota differences between normal individuals, pre-malignant lesions and gastric cancer could suggest a progressive shift in the constitution of gastric microbiota in carcinogenesis, possibly resulting from a complex cross-talk between gastric microbiota and Helicobacter pylori. However, further studies are needed to elucidate the specific role (if any) of different microorganisms.

Helicobacter pylori and microRNAs: Relation with innate immunity and progression of preneoplastic conditions.

The accepted paradigm for intestinal-type gastric cancer pathogenesis is a multistep progression from chronic gastritis induced by Helicobacter pylori (H. pylori) to gastric atrophy, intestinal metaplasia, dysplasia and ultimately gastric cancer. The genetic and molecular mechanisms underlying disease progression are still not completely understood as only a fraction of colonized individuals ever develop neoplasia suggesting that bacterial, host and environmental factors are involved. MicroRNAs are noncoding RNAs that may influence H. pylori-related pathology through the regulation of the transcription and expression of various genes, playing an important role in inflammation, cell proliferation, apoptosis and differentiation. Indeed, H. pylori have been shown to modify microRNA expression in the gastric mucosa and microRNAs are involved in the immune host response to the bacteria and in the regulation of the inflammatory response. MicroRNAs have a key role in the regulation of inflammatory pathways and H. pylori may influence inflammation-mediated gastric carcinogenesis possibly through DNA methylation and epigenetic silencing of tumor suppressor microRNAs. Furthermore, microRNAs influenced by H. pylori also have been found to be involved in cell cycle regulation, apoptosis and epithelial-mesenchymal transition. Altogether, microRNAs seem to have an important role in the progression from gastritis to preneoplastic conditions and neoplastic lesions and since each microRNA can control the expression of hundreds to thousands of genes, knowledge of microRNAs target genes and their functions are of paramount importance. In this article we present a comprehensive review about the role of microRNAs in H. pylori gastric carcinogenesis, identifying the microRNAs downregulated and upregulated in the infection and clarifying their biological role in the link between immune host response, inflammation, DNA methylation and gastric carcinogenesis.

Evaluation and Management of Gastric Superficial Neoplastic Lesions

Gastric cancer is one of the most common and lethal cancers in the world. In Portugal, it is a major health problem presenting one of the highest incidence rates among European countries. In most Western countries, gastric cancer is generally diagnosed in advanced stages. Nevertheless, with the widespread use of upper endoscopy, gastric superficial neoplastic lesions are being increasingly recognized and diagnosed. However, there are no clear recommendations regarding who should be screened for its presence and only recently guidelines concerning the evaluation and management of these lesions were published. In this review, we summarize the current scientific evidence regarding diagnosis and management of gastric superficial neoplastic lesions. Topics like screening, diagnosis, endoscopic evaluation, management, treatment, pathologic evaluation and follow-up of patients with these lesions are covered and areas of future research are discussed. Whenever possible, evidence-based recommendations are made, and on the other cases expert opinion is presented.

Long-Term Outcomes of Gastric Endoscopic Submucosal Dissection: Focus on Metachronous and Non-Curative Resection Management

Introduction: Endoscopic submucosal dissection (ESD) is an effective treatment for gastric superficial neoplasms and curative in 80-85% of the patients. The aims of this study were to identify risk factors for non-curative resection and metachronous development, and to evaluate patient management and outcome after non-curative resection. Methods: In this single-centre study, the outcome of consecutive patients submitted to gastric ESD was assessed during a minimum follow-up of 18 months. Univariate analysis and multivariate logistic regression were performed to identify risk factors. Results: ESD was performed in 194 lesions (164 patients) between 2005 and 2014. The median follow-up was 40 months. En bloc and complete resection rates were 95.3 and 93.8%, respectively. Male sex, larger tumor size, longer procedural time, and more advanced histology were associated with a non-curative resection (p < 0.05), but only carcinoma detected in biopsies before resection was identified as a significant risk factor on multivariate analysis. Metachronous lesions occurred in 18.4%, and the incidence rate was 4.7 lesions/100 person-years. Older age at diagnosis was identified as the only predictor of metachronous development in logistic regression. In the non-curative resection group, survival did not differ between patients allocated to surveillance and those submitted to gastrectomy; 75% of gastrectomy specimens showed no residual lesion. Conclusions: The risk factors identified for non-curative resection help to improve patient selection and patient information. Older patients had an increased risk for the development of metachronous lesions. In patients with non-curative resections, individualized patient management and surveillance seems to be an adequate option in selected cases.

Predicting outcomes of gastric endoscopic submucosal dissection using a Bayesian approach: a step for individualized risk assessment

Background and study aims  Efficacy and adverse events probabilities influence decisions regarding the best options to manage patients with gastric superficial lesions. We aimed at developing a Bayesian model to individualize the prediction of outcomes after gastric endoscopic submucosal dissection (ESD). Patients and methods  Data from 245 gastric ESD were collected, including patient and lesion factors. The two endpoints were curative resection and post-procedural bleeding (PPB). Logistic regression and Bayesian networks were built for each outcome; their predictive value was evaluated in-sample and validated through leave-one-out and cross-validation. Clinical decision support was enhanced by the definition of risk matrices, direct use of Bayesian inference software and by a developed online platform. Results  ESD was curative in 85.3 % and PPB occurred in 7.7 % of patients. In univariate analysis, male sex, ASA status, carcinoma histology, polypoid or depressed morphology, and lesion size ≥ 20 mm were associated with non-curative resection, while ASA status, antithrombotics and lesion size ≥ 20 mm were associated with PPB. Naïve Bayesian models presented AUROCs of ~80 % in the derivation cohort and ≥ 74 % in cross-validation for both outcomes. Risk matrices were computed, showing that lesions with cancer at biopsies, ≥ 20 mm, proximal or in the middle third, and polypoid are more prone to non-curative resection. PPB risk was < 5 % in lesions < 20 mm in the absence of antithrombotics. Conclusions  The derived Bayesian model presented good discriminative power in the prediction of ESD outcomes and can be used to predict individualized probabilities, improving patient information and supporting clinical and management decisions.

Foreign body ingestion and food impaction in adults: better to scope than to wait

Background and objective To assess clinical outcomes after foreign body ingestion and food impaction; to identify predictors of foreign body presence at the time of endoscopy. Methods A prospective study including consecutive adult patients with foreign body ingestion or suspected food impaction between May 2014 and August 2016. Results In total, 521 patients were included, 320 with foreign body ingestion and 201 with suspected food impaction. Food impaction patients were significantly older and more frequently had a history of oesophageal disease. The foreign body was encountered in the upper digestive tract in 43% of the patients with foreign body ingestion, and food impaction was confirmed in 87%. Older age (odds ratio (OR)year 1.04, 95% confidence interval (CI) 1.02–1.06) and early presentation (ORfirst six hours 4.41, 95% CI 2.24–8.66) were independent predictors of foreign body presence, while a history of psychiatric disease was an independent predictor of food impaction (OR 6.69, 95% CI 1.66–26.9). Successful endoscopic treatment was achieved in more than 90% of the cases, with adverse events occurring in fewer than 5%. Foreign body forceps was the preferred device in foreign body ingestion, while retrieval basket and mobilisation were preferred in food impaction. The need to use more than one instrument was significantly higher in food impaction. Conclusion Foreign bodies are encountered at endoscopy in almost half of the cases. Older age and earlier presentation are independent predictors of its presence. Given the high proportion of patients with foreign body at endoscopy and the low risk of complications, endoscopic evaluation is probably justified in the majority of cases.

The Challenging Acute Buried Bumper Syndrome: A Case Report

Percutaneous endoscopic gastrostomy (PEG) is the preferred route of feeding and nutritional support in patients requiring long-term enteral nutrition. Major complications related to the procedure are rare. Buried bumper syndrome is a late major complication, occurring in 0.3-2.4% of patients. Although considered a late complication, it can rarely occur in an acute setting early after the procedure. We present the case of an early buried bumper syndrome, presenting 1 week after PEG tube placement, with local stoma infection associated with an infected cavity within the abdominal wall with feeding content, successfully managed with antibiotic therapy and PEG tube repositioning through the original track.

Perforated Gastric Ulcer Associated with Anti-Angiogenic Therapy

Anti-angiogenic therapy with bevacizumab, an inhibitor of vascular endothelial growth factor, is commonly used in metastatic colorectal cancer and is rarely associated with gastrointestinal perforation, perforation being more frequent in the primary tumor site or at the anastomotic level. We present the case of a 64-year-old male with stage IV rectal adenocarcinoma who was on palliative chemotherapy with FOLFOX and bevacizumab. After the 4th chemotherapy cycle, our patient started fever and epigastric pain. He was hemodynamically stable, and signs of peritoneal irritation were absent. There were no alterations in the abdominal X-ray, and C-reactive protein was markedly elevated. A CT scan revealed a de novo thickness in the gastric antrum. Upper digestive endoscopy showed an ulcerated 40-mm lesion in the angulus, with a 20-mm orifice communicating with an exsudative cavity revested by the omentum. A conservative approach was decided including fasting, broad-spectrum intravenous antibiotics, and proton-pump inhibitors. Subsequent gastroduodenal series showed no contrast extravasation, allowing the resumption of oral nutrition. Esophagogastroduodenoscopy after 8 weeks showed perforation closure. Biopsies did not show neoplastic cells or Heliobacter pylori infection. Although the success in the conservative management of perforation allowing the maintenance of palliative chemotherapy (without bevacizumab), the patient died after 4 months due to liver failure. The reported case shows an uncommon endoscopic finding due to a rare complication of anti-angiogenic therapy. Additionally, it reminds clinicians that a history of gastroduodenal ulcers should be actively sought before starting anti-angiogenic treatment and that suspicion for perforation should be high in these cases.