RESUMO
BACKGROUND AND STUDY AIMS: Data from Japanese series show that surface morphology of laterally spreading tumors (LST) in the colon identifies lesions with different incidence and pattern of submucosal invasion. Such data from western countries are scarce. We compared clinical and histological features of LST in a western country and an eastern country, with special interest on mucosal invasiveness of LST, and investigated the effect of clinical factors on invasiveness in both countries. PATIENTS AND METHODS: Patients with LST lesions ≥20mm were included from a multicenter prospective registry in Spain and from a retrospective registry from the National Cancer Center Hospital East, Japan. The primary outcome was the presence of submucosal invasion in LST. The secondary outcome was the presence of high-risk histology, defined as high-grade dysplasia or submucosal invasion. RESULTS: We evaluated 1102 patients in Spain and 663 in Japan. Morphological and histological characteristics differed. The prevalence of submucosal invasion in Japan was six-fold the prevalence in Spain (Prevalence Ratio PR=5.66; 95%CI: 3.96, 8.08), and the prevalence of high-risk histology was 1.5 higher (PR=1.44; 95%CI: 1.31, 1.58). Compared to the granular homogeneous type and adjusted by clinical features, granular mixed, flat elevated, and pseudo-depressed types were associated with higher odds of submucosal invasion in Japan, whereas only the pseudo-depressed type showed higher risk in Spain. Regarding high-risk histology, both granular mixed and pseudo-depressed were associated with higher odds in Japan, compared with only the granular mixed type in Spain. CONCLUSION: This study reveals differences in location, morphology and invasiveness of LST in an eastern and a western cohort.
Assuntos
Colonoscopia , Neoplasias Colorretais , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Humanos , Mucosa Intestinal/patologia , Invasividade Neoplásica/patologia , Estudos RetrospectivosRESUMO
BACKGROUND AND AIMS: The Endoscopic Resection Group of the Spanish Society of Endoscopy (GSEED-RE) model and the Australian Colonic Endoscopic Resection (ACER) model were proposed to predict delayed bleeding (DB) after EMR of large superficial colorectal lesions, but neither has been validated. We validated and updated these models. METHODS: A multicenter cohort study was performed in patients with nonpedunculated lesions ≥20 mm removed by EMR. We assessed the discrimination and calibration of the GSEED-RE and ACER models. Difficulty performing EMR was subjectively categorized as low, medium, or high. We created a new model, including factors associated with DB in 3 cohort studies. RESULTS: DB occurred in 45 of 1034 EMRs (4.5%); it was associated with proximal location (odds ratio [OR], 2.84; 95% confidence interval [CI], 1.31-6.16), antiplatelet agents (OR, 2.51; 95% CI, .99-6.34) or anticoagulants (OR, 4.54; 95% CI, 2.14-9.63), difficulty of EMR (OR, 3.23; 95% CI, 1.41-7.40), and comorbidity (OR, 2.11; 95% CI, .99-4.47). The GSEED-RE and ACER models did not accurately predict DB. Re-estimation and recalibration yielded acceptable results (GSEED-RE area under the curve [AUC], .64 [95% CI, .54-.74]; ACER AUC, .65 [95% CI, .57-.73]). We used lesion size, proximal location, comorbidity, and antiplatelet or anticoagulant therapy to generate a new model, the GSEED-RE2, which achieved higher AUC values (.69-.73; 95% CI, .59-.80) and exhibited lower susceptibility to changes among datasets. CONCLUSIONS: The updated GSEED-RE and ACER models achieved acceptable prediction levels of DB. The GSEED-RE2 model may achieve better prediction results and could be used to guide the management of patients after validation by other external groups. (Clinical trial registration number: NCT03050333.).
Assuntos
Ressecção Endoscópica de Mucosa , Austrália , Estudos de Coortes , Colonoscopia , Neoplasias Colorretais/cirurgia , Humanos , Fatores de RiscoRESUMO
Our study aimed to evaluate the relevance of genetic susceptibility in the development of colorectal adenomas (CRA) and its relationship with the presence of family history of colorectal cancer (CRC). Genomic DNA from 750 cases (first degree relatives of patients with CRC) and 750 controls (subjects with no family history of CRC) was genotyped for 99 single nucleotide polymorphisms (SNPs) previously associated with CRC/CRA risk by GWAS and candidate gene studies by using the MassArray™ (Sequenom) platform. Cases and controls were matched by gender, age and histological lesion. Eight hundred and fifty-eight patients showed no neoplastic lesions, whereas 288 patients showed low-risk adenomas, and 354 patients presented high-risk adenomas. Two SNPs (rs10505477, rs6983267) in the CASC8 gene were associated with a reduced risk of CRA in controls (log-additive models, OR: 0.67, 95%CI:0.54-0.83, and OR:0.66, 95%CI:0.54-0.84, respectively). Stratified analysis by histological lesion revealed the association of rs10505477 and rs6983267 variants with reduced risk of low- and high-risk adenomas in controls, being this effect stronger in low-risk adenomas (log-additive models, OR:0.63, 95%CI:0.47-0.84 and OR:0.64, 95%CI:0.47-0.86, respectively). Moreover, 2 SNPs (rs10795668, rs11255841) in the noncoding LINC00709 gene were significantly associated with a reduced risk of low-risk adenomas in cases (recessive models, OR:0.22, 95%CI:0.06-0.72, and OR:0.08, 95%CI:0.03-0.61) and controls (dominant models, OR:0.50, 95%CI:0.34-0.75, and OR:0.52, 95%CI:0.35-0.78, respectively). In conclusion, some variants associated with CRC risk (rs10505477, rs6983267, rs10795668 and rs11255841) are also involved in the susceptibility to CRA and specific subtypes. These associations are influenced by the presence of family history of CRC.
Assuntos
Adenoma/genética , Neoplasias Colorretais/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Saúde da Família , Feminino , Predisposição Genética para Doença , Perfil Genético , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
OBJECTIVES: (1) To evaluate the short- and long-term clinical outcomes of patients after colorectal stent placement and (2) to assess the safety and efficacy of the stents for the resolution of colorectal obstruction according to the insertion technique. METHODS: Retrospective cohort study which included 177 patients with colonic obstruction who underwent insertion of a stent. RESULTS: A total of 196 stents were implanted in 177 patients. Overall, the most common cause of obstruction was colorectal cancer (89.3%). Ninety-two stents (47%) were placed by radiologic technique and 104 (53%) by endoscopy under fluoroscopic guidance. Technical success rates were 95% in both groups. Clinical success rates were 77% in the radiological group and 81% in the endoscopic group (p>0.05). The rate of complications was higher in the radiologic group compared with the endoscopic group (38% vs 20%, respectively; p=0.006). Among patients with colorectal cancer (158), 65 stents were placed for palliation but 30% eventually required surgery. The multivariate analysis identified three factors associated with poorer long-term survival: tumor stage IV, comorbidity and onset of complications. CONCLUSIONS: Stents may be an alternative to emergency surgery in colorectal obstruction, but the clinical outcome depends on the tumor stage, comorbidity and stent complications. The rate of definitive palliative stent placement was high; although surgery was eventually required in 30%. Our study suggests that the endoscopic method of stent placement is safer than the radiologic method.
Assuntos
Doenças do Colo/terapia , Obstrução Intestinal/terapia , Implantação de Prótese/métodos , Doenças Retais/terapia , Stents Metálicos Autoexpansíveis , Idoso , Doenças do Colo/etiologia , Doenças do Colo/mortalidade , Colonoscopia , Neoplasias Colorretais/complicações , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Constrição Patológica/complicações , Diverticulite/complicações , Feminino , Fluoroscopia , Humanos , Obstrução Intestinal/etiologia , Obstrução Intestinal/mortalidade , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos/estatística & dados numéricos , Implantação de Prótese/estatística & dados numéricos , Radiografia Intervencionista , Doenças Retais/etiologia , Doenças Retais/mortalidade , Estudos Retrospectivos , Stents Metálicos Autoexpansíveis/estatística & dados numéricos , Resultado do TratamentoRESUMO
This document summarizes the contents of the Clinical Guidelines for the Endoscopic Mucosal Resection of Non-Pedunculated Colorectal Lesions that was developed by the working group of the Spanish Society of Digestive Endoscopy (GSEED of Endoscopic Resection). This document presents recommendations for the endoscopic management of superficial colorectal neoplastic lesions.
Assuntos
Neoplasias Colorretais/cirurgia , Cirurgia Colorretal/métodos , Ressecção Endoscópica de Mucosa/métodos , Endoscopia Gastrointestinal/métodos , Mucosa Intestinal/cirurgia , Doenças do Colo/cirurgia , Cirurgia Colorretal/normas , Ressecção Endoscópica de Mucosa/normas , Endoscopia Gastrointestinal/normas , Humanos , Doenças Retais/cirurgiaRESUMO
This document summarizes the contents of the Clinical Guidelines for the Endoscopic Mucosal Resection of Non-Pedunculated Colorectal Lesions that was developed by the working group of the Spanish Society of Digestive Endoscopy (GSEED of Endoscopic Resection). This document presents recommendations for the endoscopic management of superficial colorectal neoplastic lesions.
Assuntos
Neoplasias Colorretais/cirurgia , Ressecção Endoscópica de Mucosa/normas , HumanosRESUMO
BACKGROUND: First-degree relatives (FDR) of patients with colorectal cancer have a higher risk of developing colorectal cancer than the general population. For this reason, screening guidelines recommend colonoscopy every 5 or 10 y, starting at the age of 40, depending on whether colorectal cancer in the index-case is diagnosed at <60 or ≥60 y, respectively. However, studies on the risk of neoplastic lesions are inconclusive. The aim of this study was to determine the risk of advanced neoplasia (three or more non-advanced adenomas, advanced adenoma, or invasive cancer) in FDR of patients with colorectal cancer compared to average-risk individuals (i.e., asymptomatic adults 50 to 69 y of age with no family history of colorectal cancer). METHODS AND FINDINGS: This cross-sectional analysis includes data from 8,498 individuals undergoing their first lifetime screening colonoscopy between 2006 and 2012 at six Spanish tertiary hospitals. Of these individuals, 3,015 were defined as asymptomatic FDR of patients with colorectal cancer ("familial-risk group") and 3,038 as asymptomatic with average-risk for colorectal cancer ("average-risk group"). The familial-risk group was stratified as one FDR, with one family member diagnosed with colorectal cancer at ≥60 y (n = 1,884) or at <60 y (n = 831), and as two FDR, with two family members diagnosed with colorectal cancer at any age (n = 300). Multiple logistic regression analysis was used for between-group comparisons after adjusting for potential confounders (age, gender, and center). Compared with the average-risk group, advanced neoplasia was significantly more prevalent in individuals having two FDR with colorectal cancer (odds ratio [OR] 1.90; 95% confidence interval [CI] 1.36-2.66, p < 0.001), but not in those having one FDR with colorectal cancer diagnosed at ≥60 y (OR 1.03; 95% CI 0.83-1.27, p = 0.77) and <60 y (OR 1.19; 95% CI 0.90-1.58, p = 0.20). After the age of 50 y, men developed advanced neoplasia over two times more frequently than women and advanced neoplasia appeared at least ten y earlier. Fewer colonoscopies by 2-fold were required to detect one advanced neoplasia in men than in women. Major limitations of this study were first that although average-risk individuals were consecutively included in a randomized control trial, this was not the case for all individuals in the familial-risk cohort; and second, the difference in age between the average-risk and familial-risk cohorts. CONCLUSIONS: Individuals having two FDR with colorectal cancer showed an increased risk of advanced neoplasia compared to those with average-risk for colorectal cancer. Men had over 2-fold higher risk of advanced neoplasia than women, independent of family history. These data suggest that screening colonoscopy guidelines should be revised in the familial-risk population.
Assuntos
Adenoma/epidemiologia , Neoplasias Colorretais/epidemiologia , Família , Adenoma/genética , Adulto , Fatores Etários , Idoso , Colonoscopia , Neoplasias Colorretais/genética , Estudos Transversais , Detecção Precoce de Câncer , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores Sexuais , Espanha/epidemiologiaRESUMO
BACKGROUND & AIMS: After endoscopic mucosal resection (EMR) of colorectal lesions, delayed bleeding is the most common serious complication, but there are no guidelines for its prevention. We aimed to identify risk factors associated with delayed bleeding that required medical attention after discharge until day 15 and develop a scoring system to identify patients at risk. METHODS: We performed a prospective study of 1214 consecutive patients with nonpedunculated colorectal lesions 20 mm or larger treated by EMR (n = 1255) at 23 hospitals in Spain, from February 2013 through February 2015. Patients were examined 15 days after the procedure, and medical data were collected. We used the data to create a delayed bleeding scoring system, and assigned a weight to each risk factor based on the ß parameter from multivariate logistic regression analysis. Patients were classified as being at low, average, or high risk for delayed bleeding. RESULTS: Delayed bleeding occurred in 46 cases (3.7%, 95% confidence interval, 2.7%-4.9%). In multivariate analysis, factors associated with delayed bleeding included age ≥75 years (odds ratio [OR], 2.36; P < .01), American Society of Anesthesiologist classification scores of III or IV (OR, 1.90; P ≤ .05), aspirin use during EMR (OR, 3.16; P < .05), right-sided lesions (OR, 4.86; P < .01), lesion size ≥40 mm (OR, 1.91; P ≤ .05), and a mucosal gap not closed by hemoclips (OR, 3.63; P ≤ .01). We developed a risk scoring system based on these 6 variables that assigned patients to the low-risk (score, 0-3), average-risk (score, 4-7), or high-risk (score, 8-10) categories with a receiver operating characteristic curve of 0.77 (95% confidence interval, 0.70-0.83). In these groups, the probabilities of delayed bleeding were 0.6%, 5.5%, and 40%, respectively. CONCLUSIONS: The risk of delayed bleeding after EMR of large colorectal lesions is 3.7%. We developed a risk scoring system based on 6 factors that determined the risk for delayed bleeding (receiver operating characteristic curve, 0.77). The factors most strongly associated with delayed bleeding were right-sided lesions, aspirin use, and mucosal defects not closed by hemoclips. Patients considered to be high risk (score, 8-10) had a 40% probability of delayed bleeding.
Assuntos
Técnicas de Apoio para a Decisão , Ressecção Endoscópica de Mucosa/efeitos adversos , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Espanha , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVES: Familial adenomatous polyposis is an inherited disorder characterized by the presence of multiple colorectal adenomas (more than 100 in the classic form and between 10 and 100 in the attenuated one), with a high risk of colorectal cancer development. To improve the diagnostic and therapeutic management of these patients, the Spanish Registry of Familial Adenomatous Polyposis was created in 2007.We aimed to evaluate the clinicopathological characteristics of patients with familial adenomatous polyposis in Spain. PATIENTS AND METHODS: All patients included in the Registry during one year were evaluated with respect to their demographic, clinical, pathological, and genetic characteristics. RESULTS: 243 patients of 156 unrelated families from 15 Spanish centers were included. One hundred thirty patients were male, and the mean age at diagnosis was 40 years. According to the clinical presentation, 127 corresponded to the classic form and 116 to the attenuated one. Colorectal adenoma with high-grade dysplasia was identified in 67 (28%) patients, and colorectal cancer in 42 (17%). Extracolonic manifestations were: duodenal involvement (n=46), gastric involvement (n=44), desmoid tumors (n=24), thyroid cancer (n=8), osteomas (n=6) and brain tumor (n=1). APC and/or MYH gene testing was performed in 140 (90%) families, detecting the causative mutation in 75 (54%) of them (70 in the APC gene and 5 in the MYH gene). CONCLUSIONS: During its first year of operability, a large number of patients and families were included in the Registry. The reduced prevalence of colorectal cancer as well as the large proportion of families submitted to gene testing demonstrated a high-quality clinical practice in Spain.
Assuntos
Polipose Adenomatosa do Colo , Polipose Adenomatosa do Colo/diagnóstico , Polipose Adenomatosa do Colo/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Espanha , Adulto JovemRESUMO
BACKGROUND AND AIMS: Primary sclerosing cholangitis [PSC] is usually associated with inflammatory bowel disease [IBD]. An increased risk of malignancies, mainly colorectal cancer [CRC] and cholangiocarcinoma [CCA], has been reported in PSC-IBD patients. Our aim was to determine the clinical characteristics and management of PSC in IBD patients, and the factors associated with malignancies. METHODS: PSC-IBD patients were identified from the Spanish ENEIDA registry of GETECCU. Additional data were collected using the AEG-REDCap electronic data capture tool. RESULTS: In total, 277 PSC-IBD patients were included, with an incidence rate of 61 PSC cases per 100 000 IBD patient-years, 69.7% men, 67.5% ulcerative colitis and mean age at PSC diagnosis of 40 ± 16 years. Most patients [85.2%] were treated with ursodeoxycholic acid. Liver transplantation was required in 35 patients [12.6%] after 79 months (interquartile range [IQR] 50-139). It was more common in intra- and extrahepatic PSC compared with small-duct PSC (16.3% vs 3.3%; odds ratio [OR] 5.7: 95% confidence interval [CI] = 1.7-19.3). The incidence rate of CRC since PSC diagnosis was 3.3 cases per 1000 patient-years [95% CI = 1.9-5.6]. Having symptoms of PSC at PSC diagnosis was the only factor related to an increased risk of CRC after IBD diagnosis [hazard ratio= 3.3: 95% CI = 1.1-9.9]. CCA was detected in seven patients [2.5%] with intra- and extrahepatic PSC, with median age of 42 years [IQR 39-53], and presented a lower life expectancy compared with patients without CCA and patients with or without CRC. CONCLUSIONS: PSC-IBD patients with symptoms of PSC at PSC diagnosis have an increased risk of CRC. CCA was only diagnosed in patients with intra- and extrahepatic PSC and was associated with poor survival.
Assuntos
Colangiocarcinoma , Colangite Esclerosante , Neoplasias Colorretais , Doenças Inflamatórias Intestinais , Adulto , Ductos Biliares Extra-Hepáticos/patologia , Ductos Biliares Intra-Hepáticos/patologia , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/mortalidade , Colangite Esclerosante/diagnóstico , Colangite Esclerosante/epidemiologia , Colangite Esclerosante/fisiopatologia , Colangite Esclerosante/terapia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/mortalidade , Feminino , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/fisiopatologia , Doenças Inflamatórias Intestinais/terapia , Masculino , Pessoa de Meia-Idade , Administração dos Cuidados ao Paciente/métodos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Espanha/epidemiologia , Análise de SobrevidaRESUMO
The introduction of biologic therapies has revolutionized the treatment of inflammatory bowel disease (IBD) and has significantly improved the disease course and outcomes for many patients. Biologics are the main drivers of cost in many IBD units and biosimilars, although are not better than originators, are usually cheaper and thus can increase the availability of this type of therapy. Biosimilar are highly similar to innovator but, due to the complex structures of innovators and the variability inherent in the manufacturing process, they are no identical. This fact cause concerns with respect to the efficacy and safety in medical community, especially in the medical indications in which no specific clinical trials with biosimilars have been performed as IBD. Nowadays, two biosimilars to infliximab, CT-P13 and SB2, has been approved by European Medicines Agency in all the indications of the reference product. To date, the available evidence suggests that switch from reference medicinal product (infliximab) to the biosimilar (CT-P13 or SB2) is feasible since published studies have not observed significantly difference in terms of efficacy, immunogenicity and safety. However, the experts agreed that by now there is not sufficient evidence to consider infliximab biosimilars interchangeable with the originator compound. In this manuscript, we will review the processes involved in the manufacturing and regulatory approval of biosimilars and examine the evidence presently available on approved biosimilars in Europe for IBD.
Assuntos
Medicamentos Biossimilares/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Aprovação de Drogas , Substituição de Medicamentos , Humanos , Guias de Prática Clínica como AssuntoRESUMO
Cobalamin deficiency is common in patients with Crohn's disease (CD). Intramuscular cobalamin continues to be the standard therapy for the deficiency and maintenance treatment in these patients, although oral route has been demonstrated to be effective in other pathologies with impaired absorption. Our aims were to evaluate the efficacy of oral therapy in the treatment of cobalamin deficiency and in long-term maintenance in patients with Crohn's disease. We performed a multicenter retrospective cohort study that included 94 patients with Crohn's disease and cobalamin deficiency. Seventy-six patients had B12 deficiency and 94.7% of them normalized their cobalamin levels with oral treatment. The most used dose was 1 mg/day, but there were no significant differences in treatment effectiveness depending on the dose used (≥1 mg/24 h vs. <1 mg/24 h). Eighty-two patients had previous documented B12 deficiency and were treated with oral B12 to maintain their correct cobalamin levels. After a mean follow-up of 3 years, the oral route was effective as maintenance treatment in 81.7% of patients. A lack of treatment adherence was admitted by 46.6% of patients in who the oral route failed. In conclusion, our study shows that oral cyanocobalamin provides effective acute and maintenance treatment for vitamin B12 deficiency caused by CD with or without ileum resection.
Assuntos
Doença de Crohn/tratamento farmacológico , Deficiência de Vitamina B 12/tratamento farmacológico , Vitamina B 12/administração & dosagem , Administração Oral , Adolescente , Adulto , Doença de Crohn/sangue , Doença de Crohn/complicações , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Deficiência de Vitamina B 12/sangue , Deficiência de Vitamina B 12/complicações , Adulto JovemRESUMO
Low-dose aspirin, alone or combined with other antiplatelet agents, is increasingly prescribed for cardiovascular prevention. However, the cardiovascular benefits should be evaluated together with the gastrointestinal risks. Low-dose aspirin is associated with upper and lower gastrointestinal injury, although lower gastrointestinal effects are poorly characterized. This gastrointestinal risk differs among antiplatelets drugs users. The most important risk factors are history of peptic ulcer, older age, and concomitant use of non-steroidal anti-inflammatory drugs or dual antiplatelet therapy. Effective upper gastrointestinal prevention strategies are available and should be used in at-risk patients taking low-dose aspirin or clopidogrel. Proton pump inhibitors seem to be the best gastroprotective agents, whereas the benefits of Helicobacter pylori eradication are still unclear. Low-dose aspirin has additional effects in the gastrointestinal tract. A large body of evidence indicates that it can protect against different cancers, in particular colorectal cancer. This effect could modify the future indications for use of low-dose aspirin and the risk-benefit balance.
Assuntos
Aspirina/efeitos adversos , Gastroenteropatias/prevenção & controle , Ticlopidina/análogos & derivados , Aspirina/administração & dosagem , Doenças Cardiovasculares/prevenção & controle , Clopidogrel , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Gastroenteropatias/induzido quimicamente , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Helicobacter pylori , Humanos , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Bomba de Prótons/uso terapêutico , Fatores de Risco , Ticlopidina/administração & dosagem , Ticlopidina/efeitos adversosRESUMO
OPINION STATEMENT: Nonsteroidal anti-inflammatory drug (NSAID) treatment will be necessary as part of our therapeutic armamentarium for many years to come. Therefore, safe prescription is mandatory in order to prevent adverse events. In the last two decades, new strategies and new drugs have been developed to reduce NSAID-associated upper gastrointestinal (GI) adverse events. Although the implementation of guidelines into clinical practice takes time, several studies have shown a recent and profound decrease in hospitalizations due to upper GI complications, which has been linked to widespread use of proton pump inhibitors (PPIs), better NSAID prescription, and decreased prevalence of Helicobacter pylori infection. This is encouraging.Safe NSAID prescription should be straightforward since the most relevant aspects are clinical in nature. Before issuing any prescription, three key questions should be considered:1) Is NSAID treatment necessary for this patient?2) What cardiovascular (CV) and GI risk factors does this patient have?3) What is the most suitable NSAID for this patient?GI and CV risk are easy to estimate, and we know that these risks are not the same for all NSAIDs. Selective cyclooxygenase (COX)-2 inhibitors, like celecoxib at usual doses, carry the lowest GI risk and are the best option in patients with moderate/high GI risk without high CV risk. Gastroprotective therapy (PPI as the drug of choice) should be considered if a non-selective NSAID is prescribed. For those at the highest risk, a combination of PPI plus a coxib is the best option. Also, eradication of H. pylori infection in patients with previous peptic ulcer or in NSAID-naïve users must be considered. Naproxen is the best option in patients with high CV risk and low/moderate GI risk.Patients taking aspirin represent a real challenge for treatment, since interaction with frequently prescribed NSAIDs (e.g. ibuprofen/naproxen) may alter its antiplatelet effect, representing a potential clinical problem. Switching treatment (e.g. taking aspirin before NSAID dosing) may not be an alternative since interaction may persist, especially when taking enteric-coated aspirin. Changing NSAID treatment to diclofenac/celecoxib/etoricoxib may also not be an option in patients with high or previous CV event history. Under these circumstances, careful prescription should be considered at the individual patient level.When dyspepsia develops in an NSAID user, PPI co-therapy plus reduction of the NSAID dose or a change in the type of NSAID are valid alternatives, but clinical experience shows that, for some patients, stopping NSAID therapy may be the only option. After a bleeding episode, most patients can be managed with alternative therapy to NSAIDs, but if needed, a coxib plus a PPI and H. pylori eradication is a safe alternative.
RESUMO
Previous reports clearly demonstrated that Helicobacter pylori (H. pylori) infection, nonsteroidal anti-inflammatory drugs (NSAID) or low dose aspirin (ASA) use significantly and independently increased the risk for the development of peptic ulcer disease. Today, the presence of H. pylori infection associated with low dose ASA and/or NSAID use in the same patient is becoming more frequent and therefore the potential interaction between these factors and the consequences of it has important implications. Whether NSAID intake in the presence of H. pylori infection may further increase the risk of peptic ulcer carried by the presence of only one risk factor is still a matter of debate. Studies on the interaction between the two risk factors yielded conflicting data and no consensus has been reached in the last years. In addition, the interaction between H. pylori infection and low-dose ASA remains even more controversial. In real clinical practice, we can find different clinical scenarios involving these three factors associated with the presence of different gastrointestinal and cardiovascular risk factors. These huge variety of possible combinations greatly hinder the decision making process of physicians.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Aspirina/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/microbiologia , Infecções por Helicobacter/complicações , Helicobacter pylori/patogenicidade , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/microbiologia , Animais , Doenças Cardiovasculares/mortalidade , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/mortalidade , Humanos , Úlcera Péptica/mortalidade , Prognóstico , Medição de Risco , Fatores de RiscoRESUMO
Colorectal cancer (CRC) is the third most common type of cancer worldwide. Screening measures are far from adequate and not widely available in resource-poor settings. Primary prevention strategies therefore remain necessary to reduce the risk of developing CRC. Increasing evidence from epidemiological studies, randomized clinical trials and basic science supports the effectiveness of aspirin, as well as other non-steroidal anti-inflammatory drugs, for chemoprevention of several types of cancer, including CRC. This includes the prevention of adenoma recurrence and reduction of CRC incidence and mortality. The detectable benefit of daily low-dose aspirin (at least 75 mg), as used to prevent cardiovascular disease events, strongly suggests that its antiplatelet action is central to explaining its antitumor efficacy. Daily low-dose aspirin achieves complete and persistent inhibition of cyclooxygenase (COX)-1 in platelets (in pre-systemic circulation) while causing a limited and rapidly reversible inhibitory effect on COX-2 and/or COX-1 expressed in nucleated cells. Aspirin has a short half-life in human circulation (about 20 minutes); nucleated cells have the ability to resynthesize acetylated COX isozymes within a few hours, while platelets do not. COX-independent mechanisms of aspirin have been suggested to explain its chemopreventive effects but this concept remains to be demonstrated in vivo at clinical doses.
RESUMO
Non-steroidal anti-inflammatory drugs (NSAIDs) are some of the most commonly used drugs worldwide; however, they are not innocuous. The spectrum of upper gastrointestinal (GI) tract damage caused by NSAIDs has been well established, and strategies to prevent this have been widely studied and implemented. Removing modifiable risk factors, the selection of less toxic NSAIDs and treatment with gastroprotective drugs, if necessary, are the main strategies employed. However, injury of the NSAIDs-related lower GI tract remains poorly characterized. In the last decade, there has been an increasing interest in this field and the search for effective preventive treatments is under way. Use of cyclooxygenase-2 inhibitor, prostaglandin, antibiotic or drugs that are not yet commercially available such as nitric oxide-releasing and hydrogen sulfide (H(2) S)-releasing NSAIDs compounds seem to reduce lower GI injury, but more evidence are needed before any of them are recommended in high-risk patients.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/prevenção & controle , Anti-Inflamatórios não Esteroides/administração & dosagem , Antiulcerosos/uso terapêutico , Hemorragia Gastrointestinal/induzido quimicamente , Antagonistas dos Receptores H2 da Histamina/uso terapêutico , Humanos , Misoprostol/uso terapêutico , Prostaglandinas/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêuticoRESUMO
NSAIDs are among the most commonly used drugs worldwide and their beneficial therapeutic properties are thoroughly accepted. However, they are also associated with gastrointestinal (GI) adverse events. NSAIDs can damage the whole GI tract including a wide spectrum of lesions. About 1 to 2% of NSAID users experienced a serious GI complication during treatment. The relative risk of upper GI complications among NSAID users depends on the presence of different risk factors, including older age (>65 years), history of complicated peptic ulcer, and concomitant aspirin or anticoagulant use, in addition to the type and dose of NSAID. Some authors recently reported a decreasing trend in hospitalizations due to upper GI complications and a significant increase in those from the lower GI tract, causing the rates of these two types of GI complications to converge. NSAID-induced enteropathy has gained much attention in the last few years and an increasing number of reports have been published on this issue. Current evidence suggests that NSAIDs increase the risk of lower GI bleeding and perforation to a similar extent as that seen in the upper GI tract. Selective cyclooxygenase-2 inhibitors have the same beneficial effects as nonselective NSAIDs but with less GI toxicity in the upper GI tract and probably in the lower GI tract. Overall, mortality due to these complications has also decreased, but the in-hospital case fatality for upper and lower GI complication events has remained constant despite the new therapeutic and prevention strategies.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Gastroenteropatias/induzido quimicamente , Trato Gastrointestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Celecoxib , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Trato Gastrointestinal/patologia , Humanos , Mucosa Intestinal/patologia , Pirazóis/efeitos adversos , Fatores de Risco , Sulfonamidas/efeitos adversosRESUMO
Low dose aspirin (ASA) use has been associated with a wide range of adverse side effects in the upper gastrointestinal (GI) tract, which range from troublesome symptoms without mucosal lesions to more serious toxicity, including ulcers, GI bleeding, perforation and even death. Upper GI symptoms in low dose ASA users are common but often careless or misinterpreted and they are not always related to the presence of mucosal injury. Usually, low dose ASA related ulcers are reasonably small and asymptomatic, and probably heal over a period of weeks to a few months. But, the real clinical problem occurs when the ulcer results in a GI complication (mostly bleeding). The estimated average excess risk of symptomatic or complicated ulcer related to low dose ASA is five cases per 1000 ASA users per year. Death is the worst outcome of GI complications in low dose ASA users, but data about this aspect are scarce. Current evidence indicates that low dose ASA can damage the lower GI tract also, but the real size of the problem is still unknown.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Aspirina/efeitos adversos , Gastroenteropatias/induzido quimicamente , Anti-Inflamatórios não Esteroides/administração & dosagem , Aspirina/administração & dosagem , Gastroenteropatias/complicações , Gastroenteropatias/mortalidade , Hemorragia Gastrointestinal/induzido quimicamente , Trato Gastrointestinal/efeitos dos fármacos , Humanos , Trato Gastrointestinal Inferior/efeitos dos fármacos , Úlcera Péptica/induzido quimicamente , Trato Gastrointestinal Superior/efeitos dos fármacosRESUMO
Antiplatelet agents are widely used in primary and secondary prevention of cardiovascular events. The scientific evidence has provided strong support for the benefits of aspirin in decreasing the risk of cardiovascular events in a wide range of pathologies. The relatively rare occurrence of major bleeding complications should not be underestimated, mainly due to its high morbi-mortality. The assessment of both gastrointestinal risk and cardiovascular benefits of low-dose aspirin for any individual patient may be difficult in clinical practice. In this review, we summarize the evidence supporting the efficacy of aspirin and the risks of side effects due to hemorrhagic complications. This article proposes a unifying framework for application to help the clinician in the decision making process of individuals who have different risk of cardiovascular and bleeding events with different examples. Finally, new developments in the field directed towards individualized risk assessment strategies are described.