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Gastrointestinal endoscopy 09/2012; · 6.71 Impact Factor
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ABSTRACT: BACKGROUND: Toll-like receptors (TLR) are essential for Helicobacter pylori (HP) recognition. Their role in the progression of gastric lesions leading to cancer is not established. AIM: To evaluate for the first time in humans the expression of TLR2, TLR4, and TLR5, as well as the expression of other related molecules in the entire sequence of gastric lesions. METHODS: Biopsy samples (n = 80, 48% HP+) from normal mucosa, HP gastritis, metaplasia, dysplasia or adenocarcinoma were obtained from 44 patients. mRNA quantification of TLR2, TLR4, TLR5, Toll-interacting protein (TOLLIP), PPAR-γ, NF-κB, TNF-α, COX-1, COX-2, and CDX-2 was performed by real-time RT-PCR. TLR2, TLR4, and TLR5 protein expression was quantified by immunohistochemistry. RESULTS: When compared to normal mucosa (1.0 arbitrary unit (AU)), HP gastritis presented higher expression of TLR2 (2.23 ± 0.36 AU), TLR4 (1.92 ± 0.40 AU) and TNF-α (2.14 ± 0.50 AU) and lower TOLLIP and PPARγ expression (0.72 ± 0.12 AU, p < .05 all genes). Metaplasia and dysplasia/carcinoma presented higher expression of TLR2 (1.66 ± 0.46 and 1.48 ± 0.20 AU, respectively, p < .05), lower expression of TOLLIP (0.66 ± 0.09 and 0.52 ± 0.04 AU, p < .05) and PPARγ (0.73 ± 0.12 and 0.63 ± 0.10 AU, p < .05). The significant trend for decrease in TOLLIP and PPARγ was associated with increasing levels of CDX-2 from normal mucosa to carcinoma (p < .05), translating that in diffuse and higher TLRs protein expression (p < .05). CONCLUSION: Gastric carcinogenesis is associated with decreasing levels of TLRs inhibitors and elevated TLRs levels throughout all the spectrum of lesions. Future studies should investigate if modulation of these receptors activity may influence gastric carcinogenesis and tumor progression.
Helicobacter 09/2012; · 3.15 Impact Factor
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ABSTRACT: To describe a modified technique for placement of a tracheobronchial self-expanding plastic stent (SEPS) in patients with benign refractory hypopharyngeal strictures in order to improve dysphagia and allow stricture remodeling.
A case series of four consecutive patients with complex hypopharyngeal strictures after combined therapy for laryngeal cancer, previously submitted to multiple sessions of dilation without lasting improvement, is presented. All patients underwent placement of a small diameter and unflared tracheobronchial SEPS. Main outcome measurements were improvement of dysphagia and avoiding of repeated dilation.
The modified introducer system allowed an easy and technically successful deployment of the tracheobronchial Polyflex stent through the stricture. All four patients developed complications related to stent placement. Two patients had stent migration (one proximal and one distal), two patients developed phanryngocutaneous fistulas and all patients with stents in situ for more than 8 wk had hyperplastic tissue growth at the upper end of the stent. Stricture recurrence was observed at 4 wk follow-up after stent removal in all patients.
Although technically feasible, placement of a tracheobronchial SEPS is associated with a high risk of complications. Small diameter stents must be kept in place for longer than 3 mo to allow adequate time for stricture remodeling.
World Journal of Gastroenterology 02/2012; 18(6):551-6. · 2.47 Impact Factor
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João-Bruno Soares,
Pedro Pimentel-Nunes,
Luís Afonso,
Carla Rolanda,
Paula Lopes,
Roberto Roncon-Albuquerque,
Nádia Gonçalves,
Inês Boal-Carvalho,
Fernando Pardal,
Susana Lopes,
Guilherme Macedo,
Lúcio Lara-Santos,
Rui Henrique, Luís Moreira-Dias,
Raquel Gonçalves,
Mário Dinis-Ribeiro,
Adelino F Leite-Moreira
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ABSTRACT: We evaluated expression of TLR2, TLR4 and proinflammatory genes [NF-κB, TNF-α, cyclooxygenase-2 (COX-2)] in liver samples of patients in different stages of liver disease. Fifteen patients with unexplained transaminases elevation (reference group), 22 with viral chronic hepatitis (hepatitis group), 14 with virus-induced severe fibrosis/cirrhosis (cirrhosis group) and 10 with hepatocarcinoma (hepatocarcinoma group) were consecutively included in the study. Quantification of TLR2, TLR4, NF-κB, TNF-α and COX-2 mRNA was done by real-time RT-PCR and TLR2 and TLR4 protein expression was evaluated by immunohistochemistry. Compared with reference, TLR2 and TLR4 mRNA was increased in hepatitis (TLR2: 2.66 ± 0.69; TLR4: 3.11 ± 0.79; P < 0.05) and cirrhosis (TLR2: 2.14 ± 0.5; TLR4: 1.74 ± 0.27; P < 0.05) and decreased in hepatocarcinoma (TLR2: 0.48 ± 0.15; TLR4: 0.54 ± 0.10; P < 0.05). This associated with increased TNF-α and COX-2 mRNA in hepatitis (TNF-α: 3.24 ± 0.79; COX-2: 2.47 ± 0.36; P < 0.05) and cirrhosis (TNF-α: 1.73 ± 0.28; COX-2: 1.8 ± 0.35, P < 0.05), whereas NF-κB mRNA was increased in hepatitis (2.42 ± 0.31; P < 0.05) and unchanged in cirrhosis (1.34 ± 0.17; P = 0.3). Hepatocarcinoma presented increased COX-2 mRNA (1.63 ± 0.15; P < 0.05) and maintained (at decreased levels) mRNA of NF-κB (0.52 ± 0.12) and TNF-α (0.52 ± 0.12; P < 0.05, all genes). Immunohistochemistry confirmed increased expression of TLR2 and TLR4 in hepatitis and cirrhosis and maintained expression in hepatocarcinoma. Upregulation of TLR2, TLR4 and their proinflammatory mediators is associated with virus-induced hepatic IFC sequence.
Innate Immunity 02/2012; 18(5):700-8. · 4.00 Impact Factor
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Pedro Pimentel-Nunes,
Nádia Gonçalves,
Inês Boal-Carvalho,
Luís Afonso,
Paula Lopes,
Roberto Roncon-Albuquerque,
João-Bruno Soares,
Elisabete Cardoso,
Rui Henrique, Luís Moreira-Dias,
Mário Dinis-Ribeiro,
Adelino F Leite-Moreira
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ABSTRACT: Animal data suggest that Toll-like receptors (TLR) may play an important role in colon carcinogenesis. Studies in humans to support that hypothesis are scarce.
To evaluate the expression of TLR2, TLR4 and TLR5, and the expression of several other related molecules, in different human colonic lesions.
Colon biopsy samples from normal mucosa, normal mucosa adjacent to lesion, adenoma or sporadic carcinoma were obtained from 35 consecutive patients undergoing colonoscopy. Quantification of TLR2, TLR4, TLR5, Toll-interacting protein (TOLLIP), peroxisome proliferator-activated receptor γ (PPAR-γ), nuclear factor κB, tumour necrosis factor (TNF) α, cyclooxygenase (COX) 1 and 2 mRNA was performed by real-time reverse transcription PCR. TLR2, TLR4 and TLR5 protein expression was quantified by immunohistochemistry.
When compared with normal mucosa (1.0 arbitrary unit (AU)), adjacent normal mucosa presented higher expression of COX-2 (1.86±0.3 AU, p=0.01) and TNFα (1.44±0.18 AU, p=0.04) and lower TOLLIP expression (0.75±0.05 AU, p=0.004). Adenomas and carcinomas presented higher expression of COX-2 (1.63±0.27 and 1.38±0.14 AU, p=0.03 and p=0.05, respectively) and lower expression of TOLLIP (0.44±0.04 AU, p<0.001), with diffuse and higher TLR protein expression (p<0.001). Carcinomas also expressed higher TLR2 (2.31±0.32 AU, p=0.006) and lower PPAR-γ (0.56±0.12 AU, p=0.003). There was a trend towards decreased TOLLIP (p<0.001) and PPAR-γ (p=0.05) from normal mucosa to adenoma/carcinoma.
Persistently positive TLR expression and lower expression of TLR inhibitors was associated with higher TLR protein levels throughout the spectrum of lesions of colon carcinogenesis. Increasing activation of these receptors by bacteria may play a crucial role in colon carcinogenesis and tumour progression.
Journal of clinical pathology 01/2012; 65(4):302-8. · 2.43 Impact Factor
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ABSTRACT: TLRs are important innate immunity receptors. Even though TLR2, 4 and 5 appear to be important for Helicobacter pylori (HP) recognition, their role in the evolution of gastritis to more advanced lesions is still unknown. To compare the expression of TLR2, 4 and 5 in normal gastric mucosa, HP+ gastritis, intestinal metaplasia, dysplasia and adenocarcinoma. Immunohistochemistry for TLR2, 4 and 5 was performed with anti-TLR2-TLR4-TLR5 antibodies in 117 histological samples of normal gastric mucosa (n = 22), HP+ gastritis (n = 20), intestinal metaplasia (n = 33), dysplasia (mucosectomy specimens, n = 20) and intestinal type adenocarcinoma (surgery specimens,n = 22); quantification of expression was performed independently by two pathologists taking into account the percentage of positive epithelial cells and the degree of expression (zero to three score). A statistically significant trend for progressive increase of TLRs expression from normal mucosa to gastric dysplasia was found (mean expression: normal mucosa 0.1; gastritis 1.0; metaplasia 2.2; dysplasia 2.8, p < 0.01). All dysplasia samples presented more than 90% positive epithelial cells with strong expression (2.8;95%CI2.7-3). There was less TLRs expression in carcinomas (TLR2:1.0; TLR4:2.0 and TLR5:1.2, p < 0.05) when compared with dysplasia, with TLR4 being more expressed than TLR2 and 5 in these lesions (p = 0.03). A score of all markers' expression of eight leads to a low (4%) false positive rate in patients with precancerous conditions. Progression of gastric lesions associated with gastric carcinogenesis is associated with increased TLRs expression. Gastric dysplasia presents a high level of TLRs expression, suggesting that these receptors may play a role in adenocarcinoma development.
Pathology & Oncology Research 04/2011; 17(3):677-83. · 1.37 Impact Factor
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ABSTRACT: COX-2, the inducible isoenzyme, was found to be overexpressed in approximately 85% of colorectal adenocarcinomas, contributing to key steps in tumor development. COX-2 polymorphisms that might modify the levels of protein expression would be anticipated to have a substantial influence on disease phenotype. Therefore, we sought to understand the role of three COX-2 polymorphisms (-1195A>G, -765G>C, and 8473T>C) in colorectal cancer (CRC) onset.
We conducted a hospital-based case-control study involving 117 consecutively enrolled CRC patients and 256 healthy individuals without any clinical evidence of cancer. The COX-2 polymorphisms' genotypes were characterized by PCR-restriction fragment length polymorphism or real-time PCR techniques.
The -1195A>G polymorphism was associated with a 1.73-fold increased predisposition to CRC onset. In a stratified analysis, men and ever-smokers carrying -1195G allele (AG+GG) had an increased risk for CRC development (odds ratio: 2.58; 95% confidence intraval: 1.29-5.15 and odds ratio: 10.3; 95% confidence intraval: 3.37-31.2, respectively). More interestingly, men ever-smokers carrying -1195G allele appeared to have a nine-fold increased risk for CRC onset (95% CI: 2.94-27.6). No difference in the genotype's distribution was noticed between cases and controls for the remaining two polymorphisms.
The -1195A>G COX-2 polymorphism seems to modulate the genetic susceptibility for CRC onset, especially in men ever-smokers. This genetically based higher-risk group definition may help shift the balance between risk and benefits for the use of COX-2 inhibitors in chemoprevention that is currently hampered by the adverse gastrointestinal and cardiovascular side-effects.
European journal of gastroenterology & hepatology 05/2010; 22(5):607-13. · 1.66 Impact Factor
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European Journal of Gastroenterology & Hepatology - EUR J GASTROENTEROL HEPATOL. 01/2010; 22(5):607-613.
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European Journal of Gastroenterology & Hepatology 10/2008; 20(9):939-40. · 1.76 Impact Factor
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Miguel Areia,
Pedro Amaro,
Mário Dinis-Ribeiro,
Maria Augusta Cipriano,
Carol Marinho,
Altamiro Costa-Pereira,
Carlos Lopes, Luís Moreira-Dias,
José Manuel Romãozinho,
Hermano Gouveia,
Diniz Freitas,
Maximino Correia Leitão
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ABSTRACT: Conventional endoscopy has low sensitivity, specificity, and interobserver agreement for the diagnosis of gastric atrophy, intestinal metaplasia, and dysplasia. Magnification chromoendoscopy (ME) may optimize the evaluation of premalignant gastric lesions.
As part of a multicenter trial, we aimed at validating a previously proposed classification for gastric methylene blue ME at a different center. SETTING, PATIENTS, AND INTERVENTIONS: A sample of patients (n = 42) with previously diagnosed chronic atrophic gastritis with or without intestinal metaplasia underwent ME (Pentax EG-3430Z) with 1% methylene blue by 2 endoscopists.
A simplified version of a previously published ME classification (group I, group II [further divided into subgroups IIE and IIF], and group III) was used for macroscopic lesions (n = 203) with Sydney-Houston and Vienna classifications being used for histologic analysis (n = 479 biopsy specimens).
Excellent reproducibility (wK = 0.92 [95% CI, 0.88-0.96]) was observed for classification in groups and substantial reproducibility (wK = 0.78 [95% CI, 0.72-0.84]) was found for classification in subgroups. Global validity was 82% (range 78%-86%), showing no false negatives (sensitivity of 100% [1/1 biopsy]) and a very low rate of false positives (specificity 99% [297/299 biopsies]) for dysplasia detection.
This classification for methylene blue ME was highly reproducible and valid for the diagnosis of premalignant gastric lesions when used in a center different from that involved in its conception. Despite requiring an unconventional endoscope and a longer procedure, these results could reinforce ME as a valuable technique in the surveillance of patients at risk for gastric cancer.
Gastrointestinal endoscopy 07/2008; 67(7):1011-8. · 6.71 Impact Factor
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Helicobacter 03/2008; 13(1):75-6. · 3.15 Impact Factor
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ABSTRACT: The follow-up of patients with atrophic chronic gastritis or intestinal metaplasia may lead to early diagnosis of gastric cancer. However, to-date no cost-effective model has been proposed. Improved endoscopic examination using magnification chromoendoscopy together with non-invasive functional assessment with pepsinogen serum levels are accurate in the diagnosis of intestinal metaplasia (extension) and minute dysplastic lesions. The aim of this study was to assess the feasibility and cost-effectiveness of a follow-up model for patients with atrophic chronic gastritis and intestinal metaplasia based on gastric mucosal status using magnification chromoendoscopy and pepsinogen.
A cohort of patients with lesions as severe as atrophic chronic gastritis were followed-up according to a standardized protocol using magnification chromoendoscopy with methylene blue and measurement of serum pepsinogen I and II levels. A single node decision tree and Markov chain modeling were used to define cost-effectiveness of this follow-up model versus its absence. Transition rates were considered time-independent and calculated using primary data following cohort data analysis. Costs, quality of life and survival were estimated based on published data and extensive sensitivity analysis was performed.
A total of 100 patients were successfully followed-up over 3 years. Seven cases of dysplasia were diagnosed during follow-up, all among patients with incomplete intestinal metaplasia at baseline, six of whom had extensive (pepsinogen I to II ratio <3) incomplete intestinal metaplasia. For those individuals with atrophic chronic gastritis or complete intestinal metaplasia, a yearly measurement of pepsinogen levels or an endoscopic examination on a 3-yearly basis would cost 455 euros per quality-adjusted life year (QALY) gain. Endoscopic examination and pepsinogen serum level measurement on a yearly basis would cost 1868 euros per QALY for patients with extensive intestinal metaplasia.
The follow-up of patients with atrophic chronic gastritis or intestinal metaplasia is both feasible and cost-effective if improved accurate endoscopic examination of gastric mucosa together with non-invasive assessment of gastric mucosal status are used to identify individuals at high-risk for development of gastric cancer.
Journal of Gastroenterology and Hepatology 10/2007; 22(10):1594-604. · 2.87 Impact Factor
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ABSTRACT: To study the role of an insertion/deletion polymorphism in the pepsinogen C (PGC) gene, an effective marker for terminal differentiation of the stomach mucosa, in the susceptibility to the development of gastric lesions.
The study was performed with 99 samples of known gastric lesions and 127 samples without evidence of neoplastic disease. PCR was employed and the 6 polymorphic alleles were amplified: Allele 1 (510 bp), Allele 2 (480 bp), Allele 3/4 (450/460 bp), Allele 5 (400 bp) and Allele 6 (310 bp).
Our results revealed that Allele 6 carriers seemed to have protection against the development of any gastric lesion (OR = 0.34; P<0.001), non-dysplastic lesions associated with gastric adenocarcinoma such as atrophy or intestinal metaplasia (OR = 0.28; P<0.001) or invasive GC (OR = 0.39; P = 0.004).
Our study reveals that the Allele 6 carrier status has a protective role in the development of gastric lesions, probably due to its association with higher expression of PGC. Moreover, the frequency of Allele 6 carriers in the control group is far higher than that obtained in Asian populations, which might represent a genetic gap between Caucasian and Asian populations.
World Journal of Gastroenterology 09/2006; 12(31):5033-6. · 2.47 Impact Factor
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ABSTRACT: To investigate the relationship between the -765G > C COX-2 polymorphism and the development of different gastric lesions: atrophy or intestinal metaplasia and gastric adenocarcinoma.
A cross-sectional study was performed involving 320 Portuguese individuals (210 without evidence of neoplastic disease, 73 patients with gastric adenocarcinomas and 37 with atrophy or intestinal metaplasia) using a PCR-RFLP method.
-765C allele was overrepresented in the patients with gastric adenocarcinoma (51%) when compared either with the control group (38%) or patients with atrophy or intestinal metaplasia (27%). Callele was found to be very common in our population (0.22), and a multivariate logistic regression analysis revealed nearly 3-fold increased risk for the progression to gastric adenocarcinoma in patients with atrophy or intestinal metaplasia carrying the -765C allele (OR = 2.67, 95% CI = 1.03-6.93; P = 0.04).
-765C carrier status should be considered as another susceptibility marker for gastric adenocarcinoma development in patients with atrophy or intestinal metaplasia.
World Journal of Gastroenterology 09/2006; 12(34):5473-8. · 2.47 Impact Factor
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Acta Dermato Venereologica 02/2005; 85(5):446. · 3.18 Impact Factor
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ABSTRACT: Mucosa-associated lymphoid tissue (MALT) lymphoma is the most frequent non-Hodgkin lymphoma in the gastrointestinal tract, but colon involvement has only been reported in multiorgan lymphoma. We present a rare case of a woman with MALT involvement of eye conjunctiva, tonsils, stomach, duodenum and colon. In selected cases like this, with multiorgan involvement, we recommend performing colonoscopy, with biopsies for immunohistochemistry with CD10 and cyclin D1 for differential diagnosis with other entities with different prognosis, such as follicular lymphoma, and mantle cell lymphoma, respectively.
Digestive Endoscopy 07/2003; 15(3):232 - 234. · 1.19 Impact Factor
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Mário Dinis-Ribeiro,
Altamiro da Costa-Pereira,
Carlos Lopes,
Lúcio Lara-Santos,
Mateus Guilherme, Luís Moreira-Dias,
Helena Lomba-Viana,
Armando Ribeiro,
Costa Santos,
José Soares,
Nuno Mesquita,
Rui Silva,
Rafael Lomba-Viana
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ABSTRACT: The aim of this study was to define the reproducibility and accuracy of magnification chromoendoscopy for the diagnosis of lesions associated with gastric cancer (intestinal metaplasia and dysplasia).
A total of 136 patients with previously diagnosed lesions and 5 gastrectomy specimens were studied. Endoscopic examination was performed with a magnification endoscope after methylene blue (1%) spraying. According to differences in color and mucosal pattern, groups and subgroups of endoscopic images were defined, and biopsies taken (n = 462). Five endoscopists were asked to classify individually 2 endoscopic images per subgroup on 2 separate occasions.
Three groups of endoscopic images were defined: nonmetaplastic, nondysplastic mucosa (I); metaplastic mucosa (II); and dysplastic mucosa (III). Ten subgroups were defined according to pit pattern: round small (IA), round and tubular small (IB), coarse round (IC), and course round pits with a straight pit (ID); blue irregular marks (IIA), blue round and tubular pits (IIB), blue villi (IIC), and blue small pits (IID); and loss of clear pattern, with depression (IIIA) or with slight elevation (IIIB). The kappa statistic for intraobserver agreement on the classification of endoscopic images in groups was 0.86; for interobserver agreement, it was 0.74. For classification into subgroups, kappa values ranged from 0.48 to 0.78. For 85% of the areas classified endoscopically as Group I (n = 146), no mucosal lesions or gastritis was described at histologic examination; for 83% of those in Group II (n = 198), intestinal metaplasia was found. Subgroups IIA and IIB were more often associated with complete intestinal metaplasia (62%), and IIC and IID with incomplete metaplasia (67%); in Group III (n = 118), dysplasia was diagnosed histopathologically in 33%. For the diagnosis of dysplasia, specificity was 81% (95% CI [77%, 85%]) and negative predictive value 99% (95% CI [99%, 100%]). Conclusions: Gastric endoscopic patterns with chromoendoscopy and magnification seem reproducible and valid for the diagnosis of lesions associated with gastric cancer. This procedure may improve the follow-up of individuals at high-risk of gastric cancer, at least for the exclusion of severe lesions.
Gastrointestinal Endoscopy 05/2003; 57(4):498-504. · 4.88 Impact Factor
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ABSTRACT: A cohort of individuals (n = 136) with lesions as severe as atrophic chronic gastritis (ACG) was cross-sectionally evaluated for the validity assessment of pepsinogen I (PGI) and pepsinogen II (PGII) serum levels for the diagnosis of intestinal metaplasia (IM) and gastric dysplasia. PGI/PGII ratio [median (range)] was 4 (0.5-7.5) in patients with ACG (n = 35); 4.6 (1.9-6.8) in type I IM (n = 18); 4.2 (1.4-5.9) in type II or type III IM limited to the antrum and incisura (n = 20); 2.4 (0.4-5.6) in extensive incomplete IM (n = 38); and 1.3 (0.4-6.4) in low-grade dysplasia (n = 23) (P = .002). Using histopathologic data as a reference test, the area under the receiver operating characteristic curves (CI 95%) was 0.73 (0.64-0.82) for extensive IM, 0.72 (0.58-0.85) for the diagnosis of dysplasia, and 0.81 (0.66-0.95) for the diagnosis of high-grade dysplasia. Using a PGI/PGII ratio of < or =3 as the cutoff for dysplasia diagnosis, the sensitivity was 70% (62-78%), the specificity was 65% (57-73%), and the negative predictive value estimates were over 90%. No differences in PG levels according to age or gender were observed. Helicobacter pylori did not significantly influence validity measurement estimates. PGI/PGII serum level ratio can be used even in the management of patients with a high a priori probability for a positive test. It may be useful for the exclusion of more advanced lesions (extensive IM and neoplastic lesions).
Neoplasia 6(5):449-56. · 5.95 Impact Factor
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ABSTRACT: To determine the prevalence of associated primary tumors in patients with gastric cancer.
Retrospective study of 2,668 patients with gastric cancer observed at our department between July 1974 and December 1999. Associated tumors were diagnosed using Warren and Gates criteria, and included tumors that were not considered to be a metastasis, invasion, or recurrence of gastric cancer.
Of all, 3.4% (n = 78) had primary tumors other than gastric cancer, 27% of which were synchronous (n = 21) and 73%, metachronous (n = 57). The mean follow-up time was 4 years (range, 1-13 years), and the male-to-female ratio was 1:1. The median age at diagnosis of gastric cancer was 67 years (range, 37-84 years), 69 years for patients with synchronous tumors versus 60 years for those with metachronous (p = 0.050). For at least half the patients the median time interval to metachronous cancer was 3 years (range, 1-22 years). Seventy-eight percent (n = 61) had two cancers; most were colonic (19%), uterine and ovarian (16%), and breast tumors (13%). Seventeen percent (n = 13) had three tumors: colon (46%), breast (23%), and skin (23%). Four percent (n = 3) had four tumors. One case with seven tumors was also observed [colon, breast (two tumors), uterus, skin, and stomach (two tumors)]. No statistically significant differences were found between synchronous and metachronous with regard to sex, gastric cancer location, and staging (TNM). Sixty-three percent (n = 49) died while under observation.
We found associated tumors in 3.4% of patients with gastric cancer. The most frequent associated tumors were breast and colon cancer. Surveillance for these tumors would be appropriate, at least in first years, after diagnosis of gastric cancer.
Journal of Clinical Gastroenterology 34(5):533-5. · 3.16 Impact Factor
