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INTRODUCTION: The incremental yield of I-Scan virtual chromoendoscopy compared to high-definition white light endoscopy (HD-WLE) in detection of colorectal adenomas has not been thoroughly elucidated. METHODS: A systematic search from inception to April 2023 was conducted to identify randomized controlled trials (RCTs) comparing I-Scan to HD-WLE for detection of adenomas. A random effects model was used to compute risk difference (RD) with corresponding 95% confidence intervals in adenoma detection rate (ADR). Influence analysis was done to assess robustness of findings. The number needed to diagnose was computed. Heterogeneity was assessed using the I2 statistic and explored further by subgroup analyses defined a priori. Certainty in effect estimates was assessed using the GRADE approach. RESULTS: We identified four studies (I-Scan n = 730, HD-WLE n = 765). I-Scan increased adenoma detection by 9% (risk difference (RD), 0.09; 0.04, 0.14; I2 02%; certainty, low). Influence analysis revealed that the gain in yield remained statistically significant with exclusion of all but one study. The number needed to capture one additional adenomatous polyp with I-Scan use was 11.2. I-Scan 1 use was associated with a statistically significant gain in ADR, whereas no significant difference in ADR was noted with I-Scan use on subgroup analysis. DISCUSSION: In conclusion, I-Scan increases the yield of adenoma detection by 9% compared to HD-WLE, with low certainty in the estimate of this effect. Data on the gain in yield of detecting large polyps, sessile serrated lesions, and on the impact of formally training endoscopists and trainees in I-Scan use and similar technology on adenoma detection rate are needed.
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Adenoma , Neoplasias Colorretais , Pólipos , Humanos , Colonoscopia , Adenoma/diagnóstico por imagem , Neoplasias Colorretais/diagnóstico , LuzRESUMO
BACKGROUND AND AIMS: EUS, MRCP, and intraoperative cholangiogram (IOC) are the recommended diagnostic modalities for patients with intermediate probability for choledocholithiasis (IPC). The relative cost-effectiveness of these modalities in patients with cholelithiasis and IPC is understudied. METHODS: We developed a decision tree for diagnosing IPC (base-case probability, 50%; range, 10%-70%); patients with a positive test were modeled to undergo therapeutic ERCP. The strategies tested were laparoscopic cholecystectomy with IOC (LC-IOC), MRCP, single-session EUS + ERCP, and separate-session EUS + ERCP. Costs and probabilities were extracted from the published literature. Effectiveness was assessed by assigning utility scores to health states, average proportion of true-positive diagnosis of IPC, and the mean length of stay (LOS) per strategy. Cost-effectiveness was assessed by extrapolating a net-monetary benefit (NMB) and average cost per true-positive diagnosis. RESULTS: LC-IOC was the most cost-effective strategy to diagnose IPC (base-case probability of 50%) among patients with cholelithiasis in health state-based effectiveness analysis (NMB of $34,612), diagnostic test accuracy-based effectiveness analysis (average cost of $13,260 per true-positive diagnosis), and LOS-based effectiveness analysis (mean LOS of 4.13) compared with strategies 2 (MRCP), 3 (single-session EUS + ERCP), and 4 (separate-session EUS + ERCP). These findings were robust on deterministic and probabilistic sensitivity analyses. CONCLUSIONS: For patients with cholelithiasis with IPC, LC-IOC is a cost-effective approach that should limit preoperative testing and may shorten hospital LOS. Our findings may be used to design institutional and organizational management protocols.
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Colecistectomia Laparoscópica , Coledocolitíase , Colangiografia , Colangiopancreatografia Retrógrada Endoscópica/métodos , Colecistectomia Laparoscópica/métodos , Coledocolitíase/diagnóstico por imagem , Análise Custo-Benefício , Humanos , ProbabilidadeRESUMO
INTRODUCTION: Antithrombotic therapy is often interrupted before the placement of a percutaneous endoscopic gastrostomy (PEG) tube because of potentially increased risk of hemorrhagic events. The aim of our study was to evaluate the risk of bleeding events and overall complication rates after PEG in patients on uninterrupted antiplatelet and anticoagulation therapy in a high-volume center. METHODS: Data regarding demographics, diagnoses, comorbidities, and clinical outcomes pertinent to PEG were collected from 2010 to 2016. Furthermore, data regarding antithrombotic therapy along with the rate of minor or major complications including bleeding associated with this procedure were analyzed. Significant bleeding was defined as postprocedure bleeding from PEG site requiring a blood transfusion and/or surgical/endoscopic intervention. RESULTS: We included 1,613 consecutive PEG procedures in this study, of which 1,540 patients (95.5%) received some form of uninterrupted antithrombotic therapy. Of those patients, 535 (34.7%) were on aspirin, 256 (16.6%) on clopidogrel, and 119 (7.7%) on both aspirin and clopidogrel. Subcutaneous heparin was uninterrupted in 980 (63.6%), intravenous heparin in 34 (2.1%), warfarin in 168 (10.9%), and direct-acting oral anticoagulation in 82 (5.3%) patients who overlapped on multiple drugs. We observed 6 significant bleeding events in the entire cohort (0.39%), and all were in subcutaneous heparin groups either alone or in combination with aspirin. No clinically significant bleeding was noted in patients on uninterrupted aspirin, warfarin, clopidogrel, or direct-acting oral anticoagulation groups. Only 5 patients (0.31%) had PEG-related mortality. DISCUSSION: The risk of significant bleeding associated with the PEG placement was minimal in patients on uninterrupted periprocedural antithrombotic therapy.
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Fibrinolíticos/efeitos adversos , Gastrostomia/efeitos adversos , Hemorragia/etiologia , Hemorragia/mortalidade , Idoso , Idoso de 80 Anos ou mais , Aspirina/efeitos adversos , Clopidogrel/efeitos adversos , Feminino , Gastrostomia/métodos , Humanos , Intubação Gastrointestinal , Masculino , Pessoa de Meia-Idade , RiscoRESUMO
BACKGROUND AND AIMS: The American Society for Gastrointestinal Endoscopy (ASGE) 2010 guidelines for suspected choledocholithiasis were recently updated by proposing more specific criteria for selection of high-risk patients to undergo direct ERCP while advocating the use of additional imaging studies for intermediate- and low-risk individuals. We aim to compare the performance and diagnostic accuracy of 2019 versus 2010 ASGE criteria for suspected choledocholithiasis. METHODS: We performed a retrospective chart review of a prospectively maintained database (2013-2019) of over 10,000 ERCPs performed by 70 gastroenterologists in our 14-hospital system. We randomly selected 744 ERCPs in which the primary indication was suspected choledocholithiasis. Patients with a history of cholecystectomy or prior sphincterotomy were excluded. The same patient cohort was assigned as low, intermediate, or high risk according to the 2010 and 2019 guideline criteria. Overall accuracy of both guidelines was compared against the presence of stones and/or sludge on ERCP. RESULTS: Of 744 patients who underwent ERCP, 544 patients (73.1%) had definite stones during ERCP and 696 patients (93.5%) had stones and/or sludge during ERCP. When classified according to the 2019 guidelines, fewer patients were high risk (274/744, 36.8%) compared with 2010 guidelines (449/744, 60.4%; P < .001). Within the high-risk group per both guidelines, definitive stone was found during ERCP more frequently in the 2019 guideline cohort (226/274, 82.5%) compared with the 2010 guideline cohort (342/449, 76.2%; P < .001). In our patient cohort, overall specificity of the 2010 guideline was 46.5%, which improved to 76.0% as per 2019 guideline criteria (P < .001). However, no significant change was noted for either positive predictive value or negative predictive value between 2019 and 2010 guidelines. CONCLUSIONS: The 2019 ASGE guidelines are more specific for detection of choledocholithiasis during ERCP when compared with the 2010 guidelines. However, a large number of patients are categorized as intermediate risk per 2019 guidelines and will require an additional confirmatory imaging study.
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Coledocolitíase , Colangiopancreatografia Retrógrada Endoscópica , Coledocolitíase/diagnóstico por imagem , Atenção à Saúde , Endoscopia Gastrointestinal , Humanos , Estudos RetrospectivosRESUMO
Background: The American Society of Gastrointestinal Endoscopy (ASGE) has proposed practice guidelines for evaluating patients with suspected choledocholithiasis. This study aims to assess and compare practice patterns for following ASGE guidelines for choledocholithiasis in a large academic vs. community hospital setting. Methods: A total of one thousand ER indicated for choledocholithiasis were randomly selected. Patients' demographics, total bilirubin, imaging studies including magnetic resonance cholangiopancreatography (MRCP), intraoperative cholangiogram (IOC), endoscopic ultrasound (EUS), and ERCP results were retrospectively collected. Patients with prior sphincterotomy were excluded. We examined the following practice deviations from the current ASGE guidelines; (1) ERCP was potentially delayed in high probability cases while awaiting additional imaging studies, (2) ERCP was performed without additional imaging studies in cases of low/intermediate-risk, or (3) ERCP was performed in low/intermediate-risk cases when additional imaging studies were negative. Results: A total of 640 patients with native papilla who underwent ERCP were included in the final analysis. Overall, the management of 43% (275) of patients was deviated from the applicable ASGE guidelines. Academic and community provider rates of non-adherence were 32 vs. 45%, respectively (p-value: < 0.01). Of 381 high-risk cases, 54.1% had additional imaging before ERCP. (Academic vs. community; 11.7 vs. 88.3%, p-value: < 0.01). In 26.7% (69/258) of low/intermediate risk cases, ERCP was performed without additional studies; academic (14.5%) vs. community (85.5%) (p-value: < 0.01). Finally, in 11.2% (19/170) of patients, ERCP was performed despite intermediate/low probability and negative imaging; academic (26.3%) vs. community (73.7%) (p-value: 0.02). Conclusion: Our study results show that providers do not adhere to ASGE practice guidelines in 43% of suspected choledocholithiasis cases. The rate of non-adherence was significantly higher in community settings. It could be due to various reasons, including lack/delays for alternate studies (i.e., MRCP, EUS), concern regarding the length of stay, patient preference, or lack of awareness/understanding of the guidelines. Increased availability of alternate imaging and educational strategies may be needed to increase the adoption of practice guidelines across academic and community settings to improve patient outcomes and save healthcare dollars.
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Kruppel-like factor (KLF) proteins are emerging as key regulators of lipid metabolism, diabetes, and the biosynthesis of immunological cytokines. However, their role in the synthesis of prostaglandins, widely known biochemical mediators that act in a myriad of cell biological processes remain poorly understood. Consequently, in this study a comprehensive investigation at the cellular, biochemical, and molecular levels reveal that KLF11 inhibits prostaglandin E(2) synthesis via transcriptional silencing of the promoter of its biosynthetic enzyme, cytosolic phospholipase A2alpha. Mechanistically, KLF11 accomplishes this function by binding to the promoter via specific GC-rich sites and recruiting the Sin3-histone deacetylase chromatin remodeling complex. Further functional characterization reveals that this function of KLF11 can be reversed by epidermal growth factor receptor-AKT-mediated post-translational modification of threonine 56, a residue within its Sin3-binding domain. This is the first evidence supporting a relevant role for any KLF protein in doing both: transcriptionally inhibiting prostaglandin biosynthesis and its reversibility by an epidermal growth factor receptor-AKT signaling-mediated posttranslational mechanisms.
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Proteínas de Ciclo Celular/fisiologia , Dinoprostona/metabolismo , Proteínas Repressoras/fisiologia , Animais , Proteínas Reguladoras de Apoptose , Células CHO , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular , Proliferação de Células , Cromatina/química , Cricetinae , Cricetulus , Epigênese Genética , Humanos , Lipídeos/química , Modelos Biológicos , Modelos Genéticos , Fosfolipases A2/metabolismo , Regiões Promotoras Genéticas , Processamento de Proteína Pós-Traducional , Proteínas Repressoras/metabolismo , Dedos de ZincoRESUMO
OBJECTIVES: The prevalence of diagnosed celiac disease is <1 in 2,000 in the United States, but screening studies undertaken in European and other populations have revealed a much higher prevalence. The objective of this study was to determine the prevalence of celiac disease and the utility of screening in the general adult population of a geographically isolated area. METHODS: Serum tissue transglutaminase antibodies (tTG-IgA) were measured in volunteer health-care participants aged ≥ 18 years at the annual Casper, Wyoming, Blue Envelope Health Fair blood draw. Subjects with positive tTG-IgA tests had their endomysial IgA antibodies checked. Double positives were offered endoscopy with small bowel biopsy. All subjects completed a short gastrointestinal (GI) symptom questionnaire. RESULTS: A total of 3,850 residents of the Natrona County had serologic evaluation for celiac disease, 34 of whom tested positive for both tTG and endomysial antibody (EMA) IgA. Excluding three individuals with previous diagnosis of celiac disease, the overall prevalence of positive celiac serology in this community sample was 0.8%. All 31 subjects were offered a small bowel biopsy. Of the 18 biopsied subjects, 17 (94%) had at least partial villous atrophy. Symptoms that were reported by the fair attendees did not predict positivity. CONCLUSIONS: Screening for celiac disease was widely accepted in this preventative health-care setting. Undiagnosed celiac disease affects 1 in 126 individuals in this Wyoming community. Most were asymptomatic or had atypical presentations. Serologic testing can readily detect this disease in a general population.
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Anticorpos Anti-Idiotípicos/sangue , Doença Celíaca/epidemiologia , Imunoglobulina A/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Anti-Idiotípicos/imunologia , Doença Celíaca/sangue , Feminino , Ferritinas/sangue , Hemoglobinas/metabolismo , Humanos , Imunoglobulina A/imunologia , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Prevalência , Inquéritos e Questionários , Transglutaminases/imunologia , Wyoming/epidemiologia , Adulto JovemRESUMO
BACKGROUND/AIMS: Crohn's disease frequency has increased in recent years in Iran. Genetic and environmental factors predispose people to this disease. Mutation in Caspase Recruitment Domain 15 (CARD15) gene is the most well known genetic predisposing factor to this disease. Frequency of three common CARD15 mutations has been studied in different ethnic groups. We aimed to study the frequency of these mutations in Iranian patients affected with Crohn's Disease. METHODOLOGY: One hundred fifteen proved cases of Crohn Disease and 115 age and sex matched normal controls were recruited in this study. Lf1007fs, R702W and G908R mutations were studied by Polymerase Chain Reaction-Restriction Fragment Length Polymorphims (PCR-RFLP) followed by sequencing the positive cases. RESULTS: Lf1007fs and G908R mutations were not found in either patients or age-sex matched controls. Just in two patients, R702W mutation was proved by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) and sequencing. None of these patients had illeal or fibrostenotic type of disease while 14.7% of total patients had stricturing type of disease. No complication was seen in these two patients while 50.4% of patients had acquired complications during the course of disease. CONCLUSION: The three mutations described are not responsible for the pathogenesis of Crohn's Disease in Iranians. The results are in accordance with other Asian nations' studies on IBD Patients.
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Doença de Crohn/genética , Mutação , Proteína Adaptadora de Sinalização NOD2/genética , Adulto , Estudos de Casos e Controles , Análise Mutacional de DNA , Feminino , Predisposição Genética para Doença , Humanos , Irã (Geográfico) , Masculino , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de RestriçãoRESUMO
AIM: To determine the frequency and risk factors for colorectal cancer (CRC) development among individuals with resected advanced adenoma (AA)/traditional serrated adenoma (TSA)/advanced sessile serrated adenoma (ASSA). METHODS: Data was collected from medical records of 14663 subjects found to have AA, TSA, or ASSA at screening or surveillance colonoscopy. Patients with inflammatory bowel disease or known genetic predisposition for CRC were excluded from the study. Factors associated with CRC developing after endoscopic management of high risk polyps were calculated in 4610 such patients who had at least one surveillance colonoscopy within 10 years following the original polypectomy of the incident advanced polyp. RESULTS: 84/4610 (1.8%) patients developed CRC at the polypectomy site within a median of 4.2 years (mean 4.89 years), and 1.2% (54/4610) developed CRC in a region distinct from the AA/TSA/ASSA resection site within a median of 5.1 years (mean 6.67 years). Approximately, 30% (25/84) of patients who developed CRC at the AA/TSA/ASSA site and 27.8% (15/54) of patients who developed CRC at another site had colonoscopy at recommended surveillance intervals. Increasing age; polyp size; male sex; right-sided location; high degree of dysplasia; higher number of polyps resected; and piecemeal removal were associated with an increased risk for CRC development at the same site as the index polyp. Increasing age; right-sided location; higher number of polyps resected and sessile endoscopic appearance of the index AA/TSA/ASSA were significantly associated with an increased risk for CRC development at a different site. CONCLUSION: Recognition that CRC may develop following AA/TSA/ASSA removal is one step toward improving our practice efficiency and preventing a portion of CRC related morbidity and mortality.
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Pólipos do Colo/diagnóstico por imagem , Colonoscopia/normas , Neoplasias Colorretais/epidemiologia , Detecção Precoce de Câncer/normas , Adulto , Fatores Etários , Idoso , Colo/diagnóstico por imagem , Colo/patologia , Pólipos do Colo/cirurgia , Colonoscopia/estatística & dados numéricos , Neoplasias Colorretais/prevenção & controle , Detecção Precoce de Câncer/métodos , Detecção Precoce de Câncer/estatística & dados numéricos , Reações Falso-Negativas , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Fatores de Tempo , Adulto JovemRESUMO
Evidence suggests that up to one fifth of colorectal carcinomas develop from serrated polyps, named for their pattern of colonic crypts, and include the sessile serrated adenoma/polyp (SSA/P) that has malignant potential. SSA/Ps are typically located in the proximal colon and have molecular features of hypermethylation of CpG islands in gene promoters and activating point mutations (V600E) in the BRAF oncogene. Both of these features are seen in sporadic colorectal carcinomas with microsatellite instability (MSI) which is potentially consistent with an origin of these cancers from precursor SSA/Ps. Dysplasia is detected in a subset of SSA/Ps with a high risk of progression to carcinoma. An uncommon serrated polyp is the traditional serrated adenoma that is typically found in the left colon, has a tubulovillous architecture, and frequently harbors mutant KRAS To date, the epidemiology of these serrated lesions is poorly understood, and limited observational data suggest a potential chemopreventive benefit of nonsteroidal anti-inflammatory drugs. The current primary strategy to reduce the risk of colorectal carcinoma from serrated polyps is to enhance their detection at colonoscopy and to ensure their complete removal. This review provides insight into the epidemiologic, clinical, histopathologic, and molecular features of serrated polyps and includes data on their endoscopic detection and chemoprevention. Cancer Prev Res; 10(5); 270-8. ©2017 AACR.
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Pólipos Adenomatosos/patologia , Neoplasias do Colo/prevenção & controle , Pólipos do Colo/patologia , Neoplasias do Colo/patologia , HumanosRESUMO
BACKGROUND: We studied the role of peripheral neutrophil to lymphocyte ratio (NLR) on survival outcomes in colon and rectal cancer to determine if its inclusion improved prognostication within existing staging systems. PATIENTS AND METHODS: Disease-free (DFS) and overall survival (OS) hazard ratios (HRs) of pretreatment NLR were calculated for 2536 patients with stage I to III colon or rectal cancer and adjusted for age, positive/total number of nodes, T stage, and grade. The association of NLR with clinicopathologic features and survival was evaluated and compared with the American Joint Committee on cancer (AJCC) TNM staging and Memorial Sloan Kettering Cancer Center (MSKCC) models. RESULTS: High NLR was significantly associated with worse DFS (HR, 1.36; 95% confidence interval [CI], 1.08-1.70; P = .009) and OS (HR, 1.65; 95% CI, 1.29-2.10; P < .0005) in all stages for patients with colon, but not rectal, cancer. High NLR was significantly associated with site-specific worse prognosis, which was stronger in the left versus right colon; an inverse relationship with grade was found. The impact of high NLR on DFS and OS occurred early, with the majority of deaths within 2 years following surgery. Adjusted HRs for 5-year and 2-year outcomes in colon cancer per each additional 2-unit increase in NLR were 1.15 (95% CI, 1.08-1.23) and 1.20 (95% CI, 1.10-1.30), respectively. The addition of NLR enhanced the prognostic utility of TNM (TNM alone vs. TNM + NLR: concordance index, 0.60 vs. 0.68), and MSKCC (MSKCC alone vs. MSKCC + NLR: concordance index, 0.71 vs. 0.73) models for colon cancer patients. CONCLUSION: NLR is an independent prognostic variable for nonmetastatic colon cancer that enhances existing clinical staging systems.
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Neoplasias do Colo/patologia , Linfócitos/metabolismo , Neutrófilos/metabolismo , Neoplasias Retais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Neoplasias do Colo/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias Retais/cirurgia , Taxa de Sobrevida , Adulto JovemRESUMO
Colorectal cancer (CRC) is one of the leading causes of cancer related mortality worldwide. Although young-onset CRC raises the possibility of a hereditary component, hereditary CRC syndromes only explain a minority of young-onset CRC cases. There is evidence to suggest that young-onset CRC have a different molecular profile than late-onset CRC. While the pathogenesis of young-onset CRC is well characterized in individuals with an inherited CRC syndrome, knowledge regarding the molecular features of sporadic young-onset CRC is limited. Understanding the molecular mechanisms of young-onset CRC can help us tailor specific screening and management strategies. While the incidence of late-onset CRC has been decreasing, mainly attributed to an increase in CRC screening, the incidence of young-onset CRC is increasing. Differences in the molecular biology of these tumors and low suspicion of CRC in young symptomatic individuals, may be possible explanations. Currently there is no evidence that supports that screening of average risk individuals less than 50 years of age will translate into early detection or increased survival. However, increasing understanding of the underlying molecular mechanisms of young-onset CRC could help us tailor specific screening and management strategies. The purpose of this review is to evaluate the current knowledge about young-onset CRC, its clinicopathologic features, and the newly recognized molecular alterations involved in tumor progression.
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Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Polipose Adenomatosa do Colo/genética , Polipose Adenomatosa do Colo/patologia , Adulto , Idade de Início , Animais , Biomarcadores Tumorais/metabolismo , Instabilidade Cromossômica , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Ilhas de CpG , Metilação de DNA , Predisposição Genética para Doença , Síndrome do Hamartoma Múltiplo/genética , Síndrome do Hamartoma Múltiplo/patologia , Hereditariedade , Humanos , Polipose Intestinal/congênito , Polipose Intestinal/genética , Polipose Intestinal/patologia , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Síndromes Neoplásicas Hereditárias/genética , Síndromes Neoplásicas Hereditárias/patologia , Síndrome de Peutz-Jeghers/genética , Síndrome de Peutz-Jeghers/patologia , Fenótipo , Prognóstico , Fatores de RiscoRESUMO
BACKGROUND: Iron is not routinely added to parenteral nutrition (PN) formulations in the United States because of the risk of anaphylaxis and concerns about incompatibilities. Studies have shown that iron dextran in non-lipid-containing PN solutions is safe. Data are limited on iron status, prevalence of iron deficiency anemia (IDA), and efficacy of intravenous iron infusion in long-term home PN (HPN). We aimed to determine the incidence of IDA and to examine the effectiveness of parenteral iron replacement in patients receiving HPN. METHODS: Medical records of patients receiving HPN at the Mayo Clinic from 1977 to 2010 were reviewed. Diagnoses, time to IDA development, and hemoglobin, ferritin, and mean corpuscular volume (MCV) values were extracted. Response of iron indices to intravenous iron replacement was investigated. RESULTS: Of 185 patients (122 women), 60 (32.4%) were iron deficient. Five patients were iron deficient, and 18 had unknown iron status before HPN. Of 93 patients who had sufficient iron storage, 37 had IDA development after a mean of 27.2 months (range, 2-149 months) of therapy. Iron was replaced by adding maintenance iron dextran to PN or by therapeutic iron infusion. Patients with both replacement methods had significant improvement in iron status. With intravenous iron replacement, mean ferritin increased from 10.9 to 107.6 mcg/L (P < .0001); mean hemoglobin increased from 11.0 to 12.5 g/dL (P = .0001); and mean MCV increased from 84.5 to 89.0 fL (P = .007). CONCLUSIONS: Patients receiving HPN are susceptible to IDA. Iron supplementation should be addressed for patients who rely on PN.
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Deficiências de Ferro , Nutrição Parenteral , Anemia Ferropriva/epidemiologia , Suplementos Nutricionais , Índices de Eritrócitos , Feminino , Ferritinas/sangue , Hemoglobinas/análise , Humanos , Enteropatias/terapia , Ferro/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Nutrição Parenteral no Domicílio/métodos , Fatores de TempoRESUMO
The majority of colorectal cancers (CRCs) arise from adenomatous polyps. In this study, we sought to present the underrecognized CRC with the residual polyp of origin (CRC RPO+) as an entity to be utilized as a model to study colorectal carcinogenesis. We identified all subjects with biopsy-proven CRC RPO+ that were evaluated over 10 years at Mayo Clinic, Rochester, MN, and compared their clinical and pathologic characteristics to CRC without remnant polyps (CRC RPO-). Overall survival and disease-free survival overlap with an equivalent hazard ratio between CRC RPO+ and RPO- cases when age, stage, and grade are adjusted. The somatic genomic profile obtained by whole genome sequencing and the gene expression profiles by RNA-seq for CRC RPO+ tumors were compared with that of age -and gender-matched CRC RPO- evaluated by The Cancer Genome Atlas. CRC RPO+ cases were more commonly found with lower-grade, earlier-stage disease than CRC RPO-. However, within the same disease stage and grade, their clinical course is very similar to that of CRC RPO-. The mutation frequencies of commonly mutated genes in CRC are similar between CRC RPO+ and RPO- cases. Likewise, gene expression patterns are indistinguishable between the RPO+ and RPO- cases. We have confirmed that CRC RPO+ is clinically and biologically similar to CRC RPO- and may be utilized as a model of the adenoma to carcinoma transition.
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OBJECTIVE: Whereas few adenomas become cancer, most colorectal cancers arise from adenomas. Telomere length is a recognized biomarker in multiple cancers, and telomere maintenance mechanisms (TMM) are exploited by malignant cells. We sought to determine whether telomere length and TMM distinguish cancer-associated adenomas from those that are cancer-free. METHODS: Tissues were identified as cancer-adjacent polyp (CAP)-residual adenoma contiguous with cancer-and cancer-free polyp (CFP)-adenomas without malignancy. Telomere length, TMM, and expression were measured in 102 tissues including peripheral blood leukocytes (PBLs), normal colon epithelium, adenoma, and cancer (in CAP cases) from 31 patients. Telomere length was measured in a separate cohort of 342 PBL from CAP and CFP patients. RESULTS: The mean differences in telomere length between normal and adenoma were greater in CAP than in CFP cases, P=0.001; telomere length in PBL was 91.7 bp greater in CAP than in CFP, P=0.007. Each 100 bp telomere increase was associated with a 1.14 (1.04-1.26) increased odds of being a CAP, P=0.0063. The polyp tissue from CAP patients had shorter telomeres and higher Telomerase reverse transcriptase (hTERT) expression compared with polyps from CFP patients, P=0.05. There was a greater degree of alternative lengthening of telomere (ALT) level difference in CFP polyps than in CAP polyps. The polyp telomere lengths of aggressive CAPs were significantly different from the polyps of non-aggressive CAPs, P=0.01. CONCLUSIONS: Adenomas that progress to cancer exhibit distinct telomere length and TMM profiles. We report for the first time that PBL telomeres differ in patients with polyps that become malignant, and therefore may have clinical value in adenoma risk assessment and management.
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The role and relevance of deamidated gliadin antibodies specific for celiac disease in gluten-sensitive ataxia/neuropathy is unknown. We investigated the association of celiac-specific serology with gluten-sensitive ataxia/neuropathy, in patients with and without gliadin-induced enteropathy. 51 patients with unexplained ataxia/neuropathy suspected to have gluten sensitivity were included in the study and their serum celiac-specific markers were measured. Deamidated gliadin-IgA (83% vs. 22%), deamidated gliadin-IgG (50% vs. 3%), tissue transglutaminase-IgA (78% vs. 11%), and anti-endomysial-IgA (70% vs. 0%), were significantly more positive in ataxia/neuropathy patients with celiac disease versus those without enteropathy (P<0.001). Our findings suggest that the serological profile of gluten-sensitive ataxia/neuropathy without intestinal involvement lacks the recognition of deamidated gliadin and tissue transglutaminase epitopes.
Assuntos
Autoanticorpos/sangue , Doença Celíaca/sangue , Ataxia Cerebelar/imunologia , Gliadina/imunologia , Doenças do Sistema Nervoso Periférico/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/imunologia , Autoantígenos/sangue , Autoantígenos/imunologia , Doença Celíaca/imunologia , Doença Celíaca/patologia , Ataxia Cerebelar/sangue , Desaminação , Ensaio de Imunoadsorção Enzimática , Feminino , Genótipo , Antígenos HLA/genética , Humanos , Imunoglobulina A/sangue , Imunoglobulina A/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso Periférico/sangue , Transglutaminases/imunologiaRESUMO
BACKGROUND: Environmental risk factors playing a causative role in Crohn's Disease (CD) remain largely unknown. Recently, it has been suggested that refrigerated food could be involved in disease development. We thus conducted a pilot case control study to explore the association of CD with the exposure to domestic refrigeration in childhood. METHODOLOGY/PRINCIPAL FINDINGS: Using a standard questionnaire we interviewed 199 CD cases and 207 age-matched patients with irritable bowel syndrome (IBS) as controls. Cases and controls were followed by the same gastroenterologists of tertiary referral clinics in Tehran, Iran. The questionnaire focused on the date of the first acquisition of home refrigerator and freezer. Data were analysed by a multivariate logistic model. The current age was in average 34 years in CD cases and the percentage of females in the case and control groups were respectively 48.3% and 63.7%. Patients were exposed earlier than controls to the refrigerator (X2 = 9.9, df = 3, P = 0.04) and refrigerator exposure at birth was found to be a risk factor for CD (OR = 2.08 (95% CI: 1.01-4.29), P = 0.05). Comparable results were obtained looking for the exposure to freezer at home. Finally, among the other recorded items reflecting the hygiene and comfort at home, we also found personal television, car and washing machine associated with CD. CONCLUSION: This study supports the opinion that CD is associated with exposure to domestic refrigeration, among other household factors, during childhood.
Assuntos
Doença de Crohn/etiologia , Habitação , Refrigeração , Adulto , Distribuição por Idade , Estudos de Casos e Controles , Doença de Crohn/diagnóstico , Doença de Crohn/epidemiologia , Feminino , Humanos , Incidência , Irã (Geográfico)/epidemiologia , MasculinoRESUMO
BACKGROUND: Despite claims of rarity, some studies indicate that the prevalence of inflammatory bowel disease has increased in Iran during the past decades. Establishment of a registry and the clinical characteristics are presented in this study. METHODS: Two hundred ninety-three patients with ulcerative colitis and 207 with Crohn's disease, referred to tertiary referral gastrointestinal centers in Tehran from 2004 through 2007, were assessed. Demographic and clinical features, intestinal and extraintestinal manifestations, inflammatory bowel disease in relatives, measles infection and vaccination, nutrition during infancy, and drugs and surgical interventions were assessed. RESULTS: The mean+/-SD age at the diagnosis was 33.8+/-12.9 years in Crohn's disease and 37.1+/-13.7 years in ulcerative colitis. Male:female ratio was 0.9:1.0 for Crohn's disease and 0.7:1.0 for ulcerative colitis. A total of 177 (85.5%) patients with Crohn's disease, and 254 (86.7%) patients with ulcerative colitis had never smoked. Measles vaccination was mentioned in 150 (72.5%) of Crohn's disease and 214 (73%) of ulcerative colitis patients. Breastfeeding during infancy was reported in 178 (86%) and 257 (87.7%) of Crohn's disease and ulcerative colitis patients, respectively. Appendectomy was reported in 37 (17.9%) of Crohn's disease and 16 (5.5%) of ulcerative colitis patients, whereas tonsillectomy was reported in 11.6% of each group. CONCLUSION: Demographic and clinical characteristics of inflammatory bowel disease patients are similar to that of other developing countries, in this study, more inflammatory bowel disease cases have been assessed in comparison with previous studies, which may be due to different time scales of socioeconomic evolution and environmental factors in Iran.