Anatomical analysis of gastric lymph nodes in cancer-free individuals.

Lymphadenectomy is a crucial part of the surgical therapy for gastric cancer. The number of normal lymph nodes could indicate the number of nodes that need to be retrieved during the procedure. The aim of this study is to analyze the number of lymph nodes in cadavers without gastric cancer according to the Japanese Gastric Cancer Association guidelines. Twenty fresh adult cadavers (14 males, mean age 55, range 24-93 years) were used. Abdominal lymph nodes were dissected and classified according to the Japanese Gastric Cancer Association. For total gastrectomy, the median number of lymph nodes that comprised D1 + dissection was 27 (range 15-42). The median and mean number of lymph nodes that comprised D2 dissection was 33, ranging from 18 to 50. For distal gastrectomy, the D1 + level comprised a median of 21 lymph nodes (range 11-38), and the D2 level 22 lymph nodes (range 11-39). In conclusion, considering gastrectomy + D2 lymphadenectomy as the standard treatment for gastric cancer, our results show that adequate lymphadenectomy must encompass around 30 lymph nodes. Clin. Anat., 2018. © 2018 Wiley Periodicals, Inc.

BMP8B Is a Tumor Suppressor Gene Regulated by Histone Acetylation in Gastric Cancer.

Different from genetic alterations, the reversible nature of epigenetic modifications provides an interesting opportunity for the development of clinically relevant therapeutics in different tumors. In this study, we aimed to screen and validate candidate genes regulated by the epigenetic marker associated with transcriptional activation, histone acetylation, in gastric cancer (GC). We first compared gene expression profile of trichostatin A-treated and control GC cell lines using microarray assay. Among the 55 differentially expressed genes identified in this analysis, we chose the up-regulated genes BMP8B and BAMBI for further analyses, that included mRNA and histone acetylation quantification in paired GC and nontumor tissue samples. BMP8B expression was reduced in GC compared to nontumor samples (P < 0.01). In addition, reduced BMP8B expression was associated with poorly differentiated GC (P = 0.02). No differences or histopathological associations were identified concerning BAMBI expression. Furthermore, acetylated H3K9 and H4K16 levels at BMP8B were increased in GC compared to nontumors (P < 0.05). However, reduced levels of acetylated H3K9 and H4K16 were associated with poorly differentiated GC (P < 0.05). Reduced levels of acetylated H3K9 was also associated with diffuse-type histological GC (P < 0.05). Notably, reduced BMP8B mRNA and acetylated H4K16 levels were positively correlated in poorly differentiated GC (P < 0.05). Our study demonstrated that BMP8B seems to be a tumor suppressor gene regulated by H4K16 acetylation in poorly differentiated GC. Therefore, BMP8B may be a potential target for TSA-based therapies in this GC sample subset. J. Cell. Biochem. 118: 869-877, 2017. © 2016 Wiley Periodicals, Inc.

Genetic variants in gastric cancer: Risks and clinical implications.

Cancer is a multifactorial disease that involves many molecular alterations. Gastric cancer (GC) is the third leading cause of cancer death worldwide. GC is a highly heterogeneous disease with different molecular and genetics features. Therefore, this review focuses on an overview of the genetic aspects of gastric cancer by highlighting the important impact and role of deletions and/or duplications of chromosomal segments, genomic variants, H. pylori infection and interleukin variants, as found in gene expression and newly proposed molecular classification studies. The challenge is to better understand the mechanisms and different pathways that lead to the development and progression of GC.

Optimal management of gastric cancer: results from an international RAND/UCLA expert panel.

OBJECTIVE: Defining processes of care, which are appropriate and necessary for management of gastric cancer (GC), is an important step toward improving outcomes. METHODS: Using a RAND/UCLA Appropriateness Method, an international multidisciplinary expert panel created 22 statements reflecting optimal management. All statements were scored for appropriateness and necessity. RESULTS: The following tenets were scored appropriate and necessary: (1) preoperative staging by computed tomography of abdomen/pelvis; (2) positron-emission tomographic scans not routinely indicated; (3) consideration for adjuvant therapy; (4) further clinical trials; (5) multidisciplinary decision making; (6) sufficient support at hospitals; (7) assessment of 16 or more lymph nodes (LNs); (8) in metastatic disease, surgery only for palliation of major symptoms; (9) surgeons experienced in GC management; (10) and surgeons experienced in both GC management and advanced laparoscopic surgery for laparoscopic resection. The following were scored appropriate, but of indeterminate necessity: (1) diagnostic laparoscopy before treatment; (2) a multidisciplinary approach to linitis plastica; (3) genetic assessment for diffuse GC and family history, or age less than 45 years; (4) endoscopic removal of select T1aN0 lesions; (5) D2 LN dissection in curative intent cases; (6) D1 LN dissection for early GC or patients with comorbidities; (7) frozen section analysis of margins; (8) nonemergent cases performed in a hospital with a volume of more than 15 resections per year; and (9) by a surgeon with more than 6 resection per year. CONCLUSIONS: The expert panel has created 22 statements for the perioperative management of GC patients, to provide guidance to clinicians and improve the care received by patients.

Reduced mRNA expression levels of MBD2 and MBD3 in gastric carcinogenesis.

Aberrant methylation has been reported in several neoplasias, including gastric cancer. The methyl-CpG-binding domain (MBD) family proteins have been implicated in the chromatin remodeling process, leading to the modulation of gene expression. To evaluate the role of MBD2 and MBD3 in gastric carcinogenesis and the possible association with clinicopathological characteristics, we assessed the mRNA levels and promoter methylation patterns in gastric tissues. In this study, MBD2 and MBD3 mRNA levels were determined by RT-qPCR in 28 neoplastic and adjacent nonneoplastic and 27 gastritis and non-gastritis samples. The promoter methylation status was determined by bisulfite sequencing, and we found reduced MBD2 and MBD3 levels in the neoplastic samples compared with the other groups. Moreover, a strong correlation between the MBD2 and MBD3 expression levels was observed in each set of paired samples. Our data also showed that the neoplastic tissues exhibited higher MBD2 promoter methylation than the other groups. Interestingly, the non-gastritis group was the only one with positive methylation in the MBD3 promoter region. Furthermore, a weak correlation between gene expression and methylation was observed. Therefore, our data suggest that DNA methylation plays a minor role in the regulation of MBD2 and MBD3 expression, and the presence of methylation at CpGs that interact with transcription factor complexes might also be involved in the modulation of these genes. Moreover, reduced mRNA expression of MBD2 and MBD3 is implicated in gastric carcinogenesis, and thus, further investigations about these genes should be conducted for a better understanding of the role of abnormal methylation involved in this neoplasia.

Differential expression of histone deacetylase and acetyltransferase genes in gastric cancer and their modulation by trichostatin A.

Gastric cancer is still the second leading cause of cancer-related death worldwide, even though its incidence and mortality have declined over the recent few decades. Epigenetic control using histone deacetylase inhibitors, such as trichostatin A (TSA), is a promising cancer therapy. This study aimed to assess the messenger RNA (mRNA) levels of three histone deacetylases (HDAC1, HDAC2, and HDAC3), two histone acetyltransferases (GCN5 and PCAF), and two possible targets of these histone modifiers (MYC and CDKN1A) in 50 matched pairs of gastric tumors and corresponding adjacent nontumors samples from patients with gastric adenocarcinoma, as well as their correlations and their possible associations with clinicopathological features. Additionally, we evaluated whether these genes are sensitive to TSA in gastric cancer cell lines. Our results demonstrated downregulation of HDAC1, PCAF, and CDKN1A in gastric tumors compared with adjacent nontumors (P < 0.05). On the other hand, upregulation of HDAC2, GCN5, and MYC was observed in gastric tumors compared with adjacent nontumors (P < 0.05). The mRNA level of MYC was correlated to HDAC3 and GCN5 (P < 0.05), whereas CDKN1A was correlated to HDAC1 and GCN5 (P < 0.05 and P < 0.01, respectively). In addition, the reduced expression of PCAF was associated with intestinal-type gastric cancer (P = 0.03) and TNM stages I/II (P = 0.01). The increased expression of GCN5 was associated with advanced stage gastric cancer (P = 0.02) and tumor invasion (P = 0.03). The gastric cell lines treated with TSA showed different patterns of histone deacetylase and acetyltransferase mRNA expression, downregulation of MYC, and upregulation of CDKN1A. Our findings suggest that alteration of histone modifier genes play an important role in gastric carcinogenesis, contributing to MYC and CDKN1A deregulation. In addition, all genes studied here are modulated by TSA, although this modulation appears to be dependent of the genetic background of the cell line.

Abdominal tuberculosis following kidney transplantation: clinicopathologic features and follow-up in a unique case series.

BACKGROUND: Kidney transplant recipients are at a high risk of opportunistic infection. The aims of this study were to describe the epidemiology, clinical features, and prognosis of abdominal tuberculosis (TB) in kidney transplant recipients. METHODS: All cases of abdominal TB that occurred in kidney transplant recipients at our center between 1998 and 2010 were retrospectively reviewed. Detailed demographic data, clinical profile information, and the treatment response were recorded. RESULTS: Among the 7833 kidney transplantations performed during the study period, eight patients (0.1%) developed abdominal TB. There were four men and four women in this group. The mean age of the patients was 44 ± 12 yr. The time from kidney transplantation to TB was 6.7 ± 3.4 yr. The symptoms were weight loss (87.5%), diarrhea (87.5%), fever (75%), abdominal pain (62.5%), and lower gastrointestinal bleeding (37.5%). The delay between the identification of the clinical symptoms and the diagnosis was an average of six months. The diagnosis was confirmed histopathologically for most patients. The cecum and ascending colon were the most common sites involved. Two patients required surgical intervention. Five patients received a 4-drug regimen, and three had hepatotoxicity. The median length of antituberculous therapy was nine (6-12) months. Five patients lost their graft. Overall, the hospital mortality was 12.5%. CONCLUSIONS: Kidney transplantation increases the risk of TB, particularly as an extrapulmonary disease. The symptoms of infection are often attenuated, leading to delayed diagnosis. Therefore, a careful approach to the patient and supportive data are necessary to make the final and timely diagnosis.

How useful is preoperative imaging for tumor, node, metastasis (TNM) staging of gastric cancer? A meta-analysis.

BACKGROUND: Surgery is the fundamental curative option for gastric cancer patients. Imaging scans are routinely prescribed in an attempt to stage the disease prior to surgery. Consequently, the correlation between radiology exams and pathology is crucial for appropriate treatment planning. METHODS: Systematic searches were conducted using Medline, Embase, and the Cochrane Central Register of Controlled Trials from January 1, 1998 to December 1, 2009. We calculated the accuracy, overstaging rate, understaging rate, Kappa statistic, sensitivity, and specificity for abdominal ultrasound (AUS), computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) with respect to the gold standard (pathology). We also compared the performance of CT by detector number and image type. A meta-analysis was performed. RESULTS: For pre-operative T staging MRI scans had better performance accuracy than CT and AUS; CT scanners using ≥ 4 detectors and multi-planar reformatted (MPR) images had higher staging performances than scanners with <4 detectors and axial images only. For pre-operative N staging PET had the lowest sensitivity, but the highest specificity among modalities; CT performance did not significantly differ by detector number or addition of MPR images. For pre-operative M staging performance did not significantly differ by modality, detector number, or MPR images. CONCLUSIONS: The agreement between pre-operative TNM staging by imaging scans and post-operative staging by pathology is not perfect and may affect treatment decisions. Operator dependence and heterogeneity of data may account for the variations in staging performance. Physicians should consider this discrepancy when creating their treatment plans.

A systematic review of the accuracy and indications for diagnostic laparoscopy prior to curative-intent resection of gastric cancer.

BACKGROUND: Despite improved preoperative imaging techniques, patients with incurable or unresectable gastric cancer are still subjected to non-therapeutic laparotomy. Diagnostic laparoscopy (DL) has been advocated by some to be essential in decision-making in gastric cancer. We aimed to identify and synthesize findings on the value of DL for patients with gastric cancer, in this era of improved preoperative imaging. METHODS: Electronic literature searches were conducted using Medline, EMBASE, and the Cochrane Central Register of Controlled Trials from January 1, 1998 to December 31, 2009. We calculated the change in management and avoidance of laparotomy based on the addition of DL and laparoscopic ultrasound (LUS). The accuracy, agreement (kappa), sensitivity, and specificity of DL in assessing tumor extent, nodal involvement, and the presence of metastases with respect to the gold standard (pathology) were also calculated. RESULTS: Twenty-one articles were included. DL showed moderate to substantial agreement with final pathology for T stage, but only fair agreement for N stage. For M staging, DL had an overall accuracy, sensitivity, and specificity ranging from 85-98.9%, 64.3-94%, and 80-100%, respectively. The use of DL altered treatment in 8.5-59.6% of cases, avoiding laparotomy in 8.5-43.8% of cases. LUS provided additional benefit in 5.8-7.2% of cases. CONCLUSIONS: Despite evolving preoperative imaging techniques, diagnostic laparoscopy continues to be of substantial value in staging patients with gastric cancer and in avoiding unnecessary laparotomy. The current data support DL for all patients with advanced gastric cancer.

A systematic review of the accuracy and utility of peritoneal cytology in patients with gastric cancer.

BACKGROUND: There is lack of uniformity in the utilization of peritoneal cytology in gastric cancer management. The identification of intraperitoneal free cancer cells (IFCCs) is believed to confer poor prognosis. However, while some of these patients are palliated, others may undergo more aggressive therapies. In this review, we aimed to identify and synthesize findings on the use of peritoneal cytology in predicting peritoneal recurrence and overall survival in curative gastric cancer patients. METHODS: Electronic literature searches were conducted using Medline, EMBASE, and the Cochrane Central Register of Controlled Trials from January 1, 1998 to December 31, 2009. We determined the accuracy, sensitivity, and specificity of peritoneal cytology in predicting peritoneal recurrence based on four techniques-conventional cytology, immunoassay, immunohistochemistry, and reverse transcriptase-polymerase chain reaction. Recurrence rates and overall survival rates for curative patients were determined, based on positivity or negativity for IFCCs. RESULTS: Twenty-eight articles were included. All four techniques showed wide variations in accuracy, sensitivity, and specificity in predicting peritoneal recurrence. Recurrence rates for patients positive for IFCCs ranged from 11.1 to 100%, while those negative for IFCCs had recurrence rates of 0-51%. Overall survival was significantly reduced for patients with positive IFCCs. Short follow-up periods and possible duplication of results may limit result interpretation. CONCLUSION: The presence of IFCCs appears to increase the risk of peritoneal recurrence and is associated with worse overall survival in gastric cancer patients. Further incorporation of peritoneal cytology in clinical decision-making in gastric cancer depends on the development of a consistently accurate and rapid IFCC detection method.

A systematic review and meta-analysis of the utility of EUS for preoperative staging for gastric cancer.

BACKGROUND: Accurate preoperative staging is important in determining the appropriate treatment of gastric cancer. Recently, endoscopic ultrasound (EUS) has been introduced as a staging modality. However, reported test characteristics for EUS in gastric cancer vary. Our purpose in this study was to identify, synthesize, and evaluate findings from all articles on the performance of EUS in the preoperative staging of gastric cancer. METHODS: Electronic literature searches were conducted using Medline, Embase, and the Cochrane Central Register of Controlled Trials from 1 January 1998 to 1 December 2009. All search titles and abstracts were independently rated for relevance by a minimum of two reviewers. Meta-analysis for the performance of EUS was analyzed by calculating agreement (Kappa statistic), and pooled estimates of accuracy, sensitivity, and specificity for all EUS examinations, using histopathology as the reference standard. Subgroup analyses were also performed. RESULTS: Twenty-two articles met our inclusion criteria and were included in the review. EUS pooled accuracy for T staging was 75% with a moderate Kappa (0.52). EUS was most accurate for T3 disease, followed by T4, T1, and T2. EUS pooled accuracy for N staging was 64%, sensitivity was 74%, and specificity was 80%. There was significant heterogeneity between the included studies. Subgroup analyses found that annual EUS volume was not associated with EUS T and N staging accuracy (P = 0.836, 0.99, respectively). CONCLUSION: EUS is a moderately accurate technique that seems to describe advanced T stage (T3 and T4) better than N or less advanced T stage. Stratifying by EUS annual volume did not affect EUS performance in staging gastric cancer.

Differential regulation of LRRC37A2 in gastric cancer by DNA methylation.

Gastric cancer (GC) is one of the leading types of fatal cancer worldwide. Epigenetic manipulation of cancer cells is a useful tool to better understand gene expression regulatory mechanisms and contributes to the discovery of novel biomarkers. Our research group recently reported a list of 83 genes that are potentially modulated by DNA methylation in GC cell lines. Herein, we further explored the regulation of one of these genes, LRRC37A2, in clinical samples. LRRC37A2 expression was evaluated by RT-qPCR, and DNA methylation was studied using next-generation bisulphite sequencing in 36 GC and paired adjacent nonneoplastic tissue samples. We showed that both reduced LRRC37A2 mRNA levels and increased LRRC37A2 exon methylation were associated with undifferentiated and poorly differentiated tumours. Moreover, LRRC37A2 gene expression and methylation levels were inversely correlated at the +45 exon CpG site. We suggest that DNA hypermethylation may contribute to reducing LRRC37A2 expression in undifferentiated and poorly differentiated GC. Therefore, our results show how some genes may be useful to stratify patients who are more likely to benefit from epigenetic therapy.Abbreviations: AR: androgen receptor; 5-AZAdC: 5-aza-2'-deoxycytidine; B2M: beta-2-microglobulin; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GC: gastric cancer; GLM: general linear model; LRRC37A2: leucine-rich repeat containing 37 member A2; SD: standard deviation; TFII-I: general transcription factor II-I; TSS: transcription start site; XBP1: X-box binding protein 1.

Genetic and Transcriptional Analysis of 8q24.21 Cluster in Gastric Cancer.

BACKGROUND/AIM: Previous studies from our research group have shown that trisomy 8 and the amplification of the 8q24.21 region is very frequent in gastric cancer (GC). Little is known about the role of most genes located in this region. Thus, the aim of this study was to understand the possible impact of transcriptional alterations and copy number variation (CNV) of four genes located in the 8q24.21 region - FAM49B, FAM84B, GSDMC and miR-5194 - in GC. MATERIALS AND METHODS: Fifty-one to 85 matched pairs of tumoral and adjacent non-tumoral gastric tissues, from patients with primary GC, were used to analyze gene expression and CNV of the selected genes. We also included 29 H. pylori negative and gastritis negative gastric mucosa tissues from individuals without cancer obtained by endoscopy, as control samples. RESULTS: The expression of FAM49B, GSDMC and miR-5194 was higher in both tumoral and adjacent non-tumoral samples compared to the negative control. The expression of FAM84B showed no significant difference between tumoral samples and negative controls. However, the expression of FAM84B in the adjacent non-tumoral samples was higher compared to negative control and tumoral samples. Moreover, the higher expression of GSDMC was associated with T3 and T4 tumors, with tumors on stage III and IV and with advanced tumors. Higher copy numbers of FAM49B and GSDMC were associated with intestinal tumor type and with moderately or well-differentiated tumors. Higher copy number of FAM84B was associated with moderately or well-differentiated tumors. Furthermore, the expression of all four genes was positively correlated. CONCLUSION: All four genes are upregulated in GC and may play an important role in these neoplasms. GSDMC expression was associated with more aggressive tumors.

Cholecystectomy-Associated Complications in Kidney Transplant Recipients Compared With the General Population.

Cholelithiasis is one of the most prevalent diseases in the general population. Among kidney transplant (KT) recipients, atypical clinical presentation may delay the diagnosis and proper treatment. This single-center retrospective cohort study compared cholelithiasis clinical presentation and cholecystectomy-associated complications in 230 KT recipients and in 172 members of the general population. KT recipients had a higher proportion of men, comorbidities, biliary pancreatitis, choledocholithiasis, and acute cholecystitis clinical presentations than the general population. KT recipients presented higher American Society of Anesthesiologists scores and higher rates of emergency surgeries (15.7% vs 9.9%, P = .091), conversion (5.7% vs 1.2%, P = .019), drainage (7.8% vs 2.3%, P = .016), postoperative complications (10% vs 4.7%, P = .047), and longer hospital length of stay (1 vs 1 days, interquartile range, 2 vs 0 days; P < .001). There were 5 deaths, all of which occurred in KT recipients. History of diabetes mellitus, renal function, and surgical conversion were independent risk factors associated with postoperative complications. Male sex and level of renal function were independent risk factors associated with postoperative acute cholecystitis. KT was an independent risk factor associated with postoperative choledocholithiasis (adjusted odds ratio, 5.89; 95% confidence interval, 3.03-15.66) and pancreatitis (adjusted odds ratio, 6.89; 95% confidence interval, 2.99-11.61). In conclusion, KT recipients with cholelithiasis have an increased risk for clinical and surgical complications compared with the general population.

Brazilian Group of Gastrointestinal Tumours' consensus guidelines for the management of oesophageal cancer.

Oesophageal cancer is among the ten most common types of cancer worldwide. More than 80% of the cases and deaths related to the disease occur in developing countries. Local socio-economic, epidemiologic and healthcare particularities led us to create a Brazilian guideline for the management of oesophageal and oesophagogastric junction (OGJ) carcinomas. The Brazilian Group of Gastrointestinal Tumours invited 50 physicians with different backgrounds, including radiology, pathology, endoscopy, nuclear medicine, genetics, oncological surgery, radiotherapy and clinical oncology, to collaborate. This document was prepared based on an extensive review of topics related to heredity, diagnosis, staging, pathology, endoscopy, surgery, radiation, systemic therapy (including checkpoint inhibitors) and follow-up, which was followed by presentation, discussion and voting by the panel members. It provides updated evidence-based recommendations to guide clinical management of oesophageal and OGJ carcinomas in several scenarios and clinical settings.

BRAZILIAN GASTRIC CANCER ASSOCIATION GUIDELINES (PART 2): UPDATE ON TREATMENT.

BACKGROUND: : The II Brazilian Consensus on Gastric Cancer of the Brazilian Gastric Cancer Association BGCA (Part 1) was recently published. On this occasion, countless specialists working in the treatment of this disease expressed their opinion in the face of the statements presented. AIM: : To present the BGCA Guidelines (Part 2) regarding indications for surgical treatment, operative techniques, extension of resection and multimodal treatment. METHODS: To formulate these guidelines, the authors carried out an extensive and current review regarding each declaration present in the II Consensus, using the Medline/PubMed, Cochrane Library and SciELO databases initially with the following descriptors: gastric cancer, gastrectomy, lymphadenectomy, multimodal treatment. In addition, each statement was classified according to the level of evidence and degree of recommendation. RESULTS: : Of the 43 statements present in this study, 11 (25,6%) were classified with level of evidence A, 20 (46,5%) B and 12 (27,9%) C. Regarding the degree of recommendation, 18 (41,9%) statements obtained grade of recommendation 1, 14 (32,6%) 2a, 10 (23,3%) 2b e one (2,3%) 3. CONCLUSION: : The guidelines complement of the guidelines presented here allows surgeons and oncologists who work to combat gastric cancer to offer the best possible treatment, according to the local conditions available.

Management of gastric cancer in Ontario.

OBJECTIVE: To describe the processes of care for gastric cancer in Ontario and identify areas in which care and possibly survival can be improved. SUMMARY BACKGROUND DATA: Survival in North America is poor for patients with gastric cancer, with stage-matched survival markedly worse than is seen in Asian and European series. Few Western studies have examined processes of care associated with gastric cancer. METHODS: We identified all cases of gastric cancer in Ontario, Canada from April 1, 2000 to March 31, 2005, and describe the demographics of patients, staging of the cancer, treatment, and survival. RESULTS: In this series of 3,666 patients, 81% of cases had a CT scan performed prior to resection and 90% of cases received an upper endoscopy. We found that 55% of patients were treated palliatively and only 1,645 patients underwent a curative-intent resection. Among patients who did not receive a resection over 50% of the cases appeared to have had a diagnostic laparoscopy rather than a laparotomy. Survival was related to the type of resection performed, likely reflecting the extent of disease. Higher institution volume and age were related to improved survival for curative-intent cases. CONCLUSION: In this population-based analysis, we found evidence of under-utilization of pre-operative radiology and endoscopy. Many patients were treated palliatively, reflecting presentation of the cancer at an advanced stage. For curative patients, survival was associated with age, surgical type, and resection in a higher volume institution.

II BRAZILIAN CONSENSUS ON GASTRIC CANCER BY THE BRAZILIAN GASTRIC CANCER ASSOCIATION.

BACKGROUND: Since the publication of the first Brazilian Consensus on Gastric Cancer (GC) in 2012 carried out by the Brazilian Gastric Cancer Association, new concepts on diagnosis, staging, treatment and follow-up have been incorporated. AIM: This new consensus is to promote an update to professionals working in the fight against GC and to provide guidelines for the management of patients with this condition. METHODS: Fifty-nine experts answered 67 statements regarding the diagnosis, staging, treatment and prognosis of GC with five possible alternatives: 1) fully agree; 2) partially agree; 3) undecided; 4) disagree and 5) strongly disagree A consensus was adopted when at least 80% of the sum of the answers "fully agree" and "partially agree" was reached. This article presents only the responses of the participating experts. Comments on each statement, as well as a literature review, will be presented in future publications. RESULTS: Of the 67 statements, there was consensus in 50 (74%). In 10 declarations, there was 100% agreement. CONCLUSION: The gastric cancer treatment has evolved considerably in recent years. This consensus gathers consolidated principles in the last decades, new knowledge acquired recently, as well as promising perspectives on the management of this disease.

The impact of DNA demethylation on the upregulation of the NRN1 and TNFAIP3 genes associated with advanced gastric cancer.

Gastric cancer (GC) is the third leading cause of cancer-related death worldwide. Very few therapeutic options are currently available in this neoplasia. The use of 5-Aza-2'-deoxycytidine (5-AZAdC) was approved for the treatment of myelodysplastic syndromes, and this drug can treat solid tumours at low doses. Epigenetic manipulation of GC cell lines is a useful tool to better understand gene expression regulatory mechanisms for clinical applications. Therefore, we compared the gene expression profile of 5-AZAdC-treated and untreated GC cell lines by a microarray assay. Among the genes identified in this analysis, we selected NRN1 and TNFAIP3 to be evaluated for gene expression by RT-qPCR and DNA methylation by bisulfite DNA next-generation sequencing in 43 and 52 pairs of GC and adjacent non-neoplastic tissue samples, respectively. We identified 83 candidate genes modulated by DNA methylation in GC cell lines. Increased expression of NRN1 and TNFAIP3 was associated with advanced tumours (P < 0.05). We showed that increased NRN1 and TNFAIP3 expression seems to be regulated by DNA demethylation in GC samples: inverse correlations between the mRNA and DNA methylation levels in the promoter of NRN1 (P < 0.05) and the intron of TNFAIP3 (P < 0.05) were detected. Reduced NRN1 promoter methylation was associated with III/IV TNM stage tumours (P = 0.03) and the presence of Helicobacter pylori infection (P = 0.02). The identification of demethylated activated genes in GC may be useful in clinical practice, stratifying patients who are less likely to benefit from 5-AZAdC-based therapies. KEY MESSAGES: Higher expression of NRN1 and TNFAIP3 is associated with advanced gastric cancer (GC). NRN1 promoter hypomethylation contributes to gene upregulation in advanced GC. TNFAIP3 intronic-specific CpG site demethylation contributes to gene upregulation in GC. These findings may be useful to stratify GC patients who are less likely to benefit from DNA demethylating-based therapies.

BRAZILIAN GASTRIC CANCER ASSOCIATION GUIDELINES (PART 1): AN UPDATE ON DIAGNOSIS, STAGING, ENDOSCOPIC TREATMENT AND FOLLOW-UP.

BACKGROUND: The II Brazilian Consensus on Gastric Cancer by the Brazilian Gastric Cancer Association (ABCG) was recently published. On this occasion, several experts in gastric cancer expressed their opinion before the statements presented. AIM: To present the ABCG Guidelines (part 1) regarding the diagnosis, staging, endoscopic treatment and follow-up of gastric cancer patients. METHODS: To forge these Guidelines, the authors carried out an extensive and current review regarding each statement present in the II Consensus, using the Medline/PubMed, Cochrane Library and SciELO databases with the following descriptors: gastric cancer, staging, endoscopic treatment and follow-up. In addition, each statement was classified according to the level of evidence and degree of recommendation. RESULTS: Of the 24 statements, two (8.3%) were classified with level of evidence A, 11 (45.8%) with B and 11 (45.8%) with C. As for the degree of recommendation, six (25%) statements obtained grade of recommendation 1, nine (37.5%) recommendation 2a, six (25%) 2b and three (12.5%) grade 3. CONCLUSION: The guidelines presented here are intended to assist professionals working in the fight against gastric cancer with relevant and current information, granting them to be applied in the daily medical practice.