RESUMEN
BACKGROUND & AIMS: The fecal immunochemical test (FIT) is widely used in colorectal cancer (CRC) screening. The OC-Light FIT is 1 of 2 FITs recommended for CRC screening by the Preventive Services Task Force guidelines. However, little is known about its ability to detect CRC in large average-risk populations. METHODS: We performed a retrospective cohort study of patients (50-75 years old) in the San Francisco Health Network who were screened for CRC by OC-Light FIT from August 2010 through June 2015. Patients with a positive result were referred for colonoscopy. We used electronic health records to identify participants with positive FIT results, and collected results from subsequent colonoscopies and pathology analyses. The FIT positive rate was calculated by dividing the number of positive FIT results by the total number of FIT tests completed. The primary outcome was the positive rate from OC-Light FIT and yield of neoplasms at colonoscopy. Secondary outcomes were findings from first vs subsequent rounds of testing, and how these varied by sex and race. RESULTS: We collected result from 35,318 FITs, performed on 20,886 patients; 2930 patients (8.3%) had a positive result, and 1558 patients completed the follow-up colonoscopy. A positive result from the FIT identified patients with CRC with a positive predictive value of 3.0%, and patients with advanced adenoma with a positive predictive value of 20.8%. The FIT positive rate was higher during the first round of testing (9.4%) compared to subsequent rounds (7.4%) (P < .01). The yield of CRC in patients with a positive result from the first round of the FIT was 3.7%, and decreased to 1.8% for subsequent rounds (P = .02). CONCLUSIONS: In a retrospective analysis of patients in a diverse safety-net population who underwent OC-Light FIT for CRC screening, we found that approximately 3% of patients with a positive result from a FIT to have CRC and approximately 21% to have advanced adenoma.
Asunto(s)
Colonoscopía/métodos , Neoplasias Colorrectales/diagnóstico , Detección Precoz del Cáncer/métodos , Inmunoensayo/métodos , Anciano , Heces/química , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , San FranciscoRESUMEN
OBJECTIVES: The effectiveness of stool-based colorectal cancer (CRC) screening is contingent on colonoscopy completion in patients with an abnormal fecal immunochemical test (FIT). Understanding system and patient factors affecting follow-up of abnormal screening tests is essential to optimize care for high-risk cohorts. METHODS: This retrospective cohort study was conducted in an integrated safety-net system comprised of 11 primary-care clinics and one Gastroenterology referral unit and included patients 50-75 years, with a positive FIT between April 2012 and February 2015. RESULTS: Of the 2,238 patients identified, 1,245 (55.6%) completed their colonoscopy within 1-year of the positive FIT. The median time from positive FIT to colonoscopy was 184 days (interquartile range 140-232). Of the 13% of FIT positive patients not referred to gastroenterology, 49% lacked documentation addressing their abnormal result or counseling on the increased risk of CRC. Of the patients referred but who missed their appointments, 62% lacked documentation following up on the abnormal result in the absence of a completed colonoscopy. FIT positive patients never referred to gastroenterology or who missed their appointment after referrals were more likely to have comorbid conditions and documented illicit substance use compared with patients who completed a colonoscopy. CONCLUSIONS: Despite access to colonoscopy and a shared electronic health record system, colonoscopy completion after an abnormal FIT is inadequate within this safety-net system. Inadequate follow-up is in part explained by inappropriate screening, but there is an absence of clear documentation and systematic workflow within both primary care and GI specialty care addressing abnormal FIT results.
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Colonoscopía/estadística & datos numéricos , Neoplasias Colorrectales/diagnóstico , Heces/química , Gastroenterología , Hemoglobinas/análisis , Atención Primaria de Salud , Derivación y Consulta/estadística & datos numéricos , Negro o Afroamericano , Anciano , Atención Ambulatoria , Instituciones de Atención Ambulatoria/estadística & datos numéricos , Asiático , Estudios de Cohortes , Comorbilidad , Consejo , Documentación , Detección Precoz del Cáncer , Etnicidad/estadística & datos numéricos , Femenino , Hispánicos o Latinos , Humanos , Seguro de Salud , Lenguaje , Modelos Logísticos , Masculino , Estado Civil/estadística & datos numéricos , Persona de Mediana Edad , Análisis Multivariante , Estudios Retrospectivos , Factores de Riesgo , San Francisco/epidemiología , Factores Sexuales , Trastornos Relacionados con Sustancias/epidemiología , Factores de Tiempo , Población BlancaRESUMEN
OBJECTIVES: Secretin stimulation testing (SST) is used to evaluate patients with hypergastrinemia in the diagnosis of Zollinger-Ellison syndrome. Case series have documented false-positive SST in patients with achlorhydria. This study reviews our experience with SST in hypochlorhydric and achlorhydric patients. METHODS: We examined 27 patients with hypochlorhydria or achlorhydria based on a predefined basal acid output (BAO) measurement of less than 5.0 mEq/h who also underwent SST for diagnosis of Zollinger-Ellison syndrome. We report the frequency of false-positive SST results in this setting. RESULTS: Three hundred thirty patients underwent gastric analysis of which 27 had BAO of less than 5.0 mEq/h and SST conducted. The mean (SD) fasting gastrin level was 247 (304) pg/mL, and the mean (SD) BAO measurement was 1.6 (1.8) mEq/h. Twenty patients were off, and 7 were on antisecretory therapy at time of testing. Four patients had false-positive SST results: 3 with gastric atrophy (BAO = 0 mEq/h) and 1 with drug-induced hypochlorhydria (BAO = 0.5 mEq/hr). These false-positive test results were confirmed by structural and functional imaging studies. CONCLUSIONS: We have identified a 14.8% false-positive rate in SST in patients with hypochlorhydria or achlorhydria. Growing literature has identified severe consequences associated with discontinuing antisecretory treatment for testing; therefore, SST will require interpretation in the setting of gastric acid suppression and needs to be interpreted in this context.
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Aclorhidria/complicaciones , Secretina , Síndrome de Zollinger-Ellison/diagnóstico , Aclorhidria/metabolismo , Adolescente , Adulto , Anciano , Antiulcerosos/farmacología , Esomeprazol/farmacología , Reacciones Falso Positivas , Femenino , Ácido Gástrico/metabolismo , Mucosa Gástrica/metabolismo , Humanos , Lansoprazol/farmacología , Masculino , Persona de Mediana Edad , Omeprazol/farmacología , Rabeprazol/farmacología , Sensibilidad y Especificidad , Estómago/efectos de los fármacos , Estómago/patología , Adulto Joven , Síndrome de Zollinger-Ellison/complicaciones , Síndrome de Zollinger-Ellison/metabolismoRESUMEN
BACKGROUND & AIMS: Zollinger-Ellison syndrome (ZES) is a rare disorder characterized by gastrin-secreting tumors of the gastrointestinal tract and gastric acid hypersecretion. There is controversy over the best way to manage these patients; we investigated outcomes of patients with different forms of the disease, who did and did not undergo surgery. METHODS: We performed a retrospective chart review of patients with ZES associated with multiple endocrine neoplasia type 1 (MEN-1) (n = 16) and those with sporadic ZES (n = 33) seen at a tertiary care center from August 1994 to January 2012. Cox proportional hazards modeling was used to compare survival times among groups, based on treatment with surgery (n = 34) and the presence of MEN-1 (n = 9 with surgery; n = 7 without surgery). Differences were compared using the unpaired Student t test and the Fisher exact test. RESULTS: Patients with MEN-1 syndrome-associated ZES presented at a younger age than patients with sporadic ZES (34.9 vs 45.7 y, respectively; P < .05) and were diagnosed at a younger age (39.3 vs 49.7 y, respectively; P < .01), yet lived a similar number of years (55.9 vs 55.1 y, respectively; P = .91). None of the patients with MEN-1-associated ZES died of progressive disease, compared with 86% of deaths among patients with sporadic ZES (P < .05). Lymph node involvement, detected during surgery, increased the risk of metastasis to liver (P = .13) and lack of cure by surgery (P = .01). Surgery reduced all-cause mortality (hazard ratio, 0.11; 95% confidence interval, 0.2-0.6; P = .011) and disease-related mortality (hazard ratio, 0.14; 95% confidence interval, 0.2-0.84; P = .032) of patients with sporadic, but not MEN-1 syndrome-associated, ZES. CONCLUSIONS: The presence of MEN-1 is associated with earlier onset and diagnosis of ZES, but a benign clinical course that rarely results in disease-related death; surgery therefore can be deferred for these patients. However, 86% of deaths among patients with sporadic ZES are attributed to disease-related causes, and mortality is reduced by early surgical intervention. Patients with sporadic ZES should undergo surgery soon after diagnosis.
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Neoplasia Endocrina Múltiple Tipo 1/diagnóstico , Neoplasia Endocrina Múltiple Tipo 1/epidemiología , Síndrome de Zollinger-Ellison/complicaciones , Síndrome de Zollinger-Ellison/diagnóstico , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasia Endocrina Múltiple Tipo 1/mortalidad , Neoplasia Endocrina Múltiple Tipo 1/cirugía , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Neuronal apoptosis following ischemia can be mediated by a caspase-dependent pathway, which involves the mitochondrial release of cytochrome c that initiates a cascade of caspase activation. In addition, there is a caspase-independent pathway, which is mediated by the release of apoptosis-inducing factor (AIF). Using caspase inhibitor gene therapy, we investigated the roles of caspases on the mitochondrial release of cyt c and the release of AIF. Specifically, we used herpes simplex virus-1 amplicon vectors to ectopically express a viral caspase inhibitor (crmA or p35) in mixed cortical cultures exposed to oxygen/glucose deprivation. Overexpression of either crmA or p35 (but not the caspase-3 inhibitor DEVD) inhibited the release of AIF; this suggests that there can be cross-talk between the caspase-dependent and the ostensibly caspase-independent pathway. In addition, both crmA overexpression and DEVD inhibited cyt c release, suggesting a positive feedback loop involving activated caspases stimulating cyt c release.
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Factor Inductor de la Apoptosis/metabolismo , Isquemia Encefálica/metabolismo , Caspasas/metabolismo , Corteza Cerebral/metabolismo , Citocromos c/metabolismo , Neuronas/metabolismo , Animales , Apoptosis/fisiología , Caspasa 3/genética , Caspasa 3/metabolismo , Inhibidores de Caspasas , Caspasas/genética , Hipoxia de la Célula/fisiología , Células Cultivadas , Modelos Animales de Enfermedad , Técnicas de Transferencia de Gen , Vectores Genéticos , Glucosa/deficiencia , Herpesvirus Humano 1/genética , Mitocondrias/metabolismo , Ratas , Ratas Sprague-Dawley , Transducción de SeñalRESUMEN
Apoptosis arises from neuronal damage following an ischemic insult. Apoptosis-inducing factor (AIF) is a protein released from mitochondria in response to pro-apoptotic signals which then translocates to the nucleus and triggers DNA fragmentation. In parallel with this, pro-apoptotic signals cause the release of cytochrome c from mitochondria, activating caspase-dependent apoptosis. During post-ischemic reperfusion, reactive oxygen species (ROS) are formed in excess in mitochondria and can play a role in initiating apoptosis. In cultures, ROS are formed during post oxygen glucose deprivation (OGD) normoxia/normoglycemia that is used as a model for ischemia. In this study, we delivered viral vectors to overexpress antioxidants (GPX, catalase, CuZnSOD, or MnSOD) in mixed cortical cultures, in order to investigate the effects of ROS-reduction on the release of cytochrome c and AIF. Overexpression of MnSOD, CuZnSOD, catalase or GPX all prevented AIF translocation from mitochondria to the nucleus. Potentially, this could reflect broadly non-specific protection due to reducing ROS load. Arguing against this, overexpression of the same antioxidants did not inhibit cytochrome c release. These findings suggest a specific interaction between ROS formation and the caspase-independent route of apoptosis.