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Background and Objectives: Needle-based confocal laser endomicroscopy (nCLE) is a procedure in which an AQ-Flex nCLE mini-probe is passed through an EUS-FNA needle into a pancreatic lesion to enable subsurface in vivo tissue analysis. In this study, we conducted a systematic review and meta-analysis of nCLE for the diagnosis of pancreatic lesions. Materials and Methods: We conducted a comprehensive search of several databases and conference proceedings, including PubMed, EMBASE, Google-Scholar, MEDLINE, SCOPUS, and Web of Science databases (earliest inception to March 2020). The primary outcomes assessed the pooled rate of diagnostic accuracy for nCLE and the secondary outcomes assessed the pooled rate of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and adverse events (AE) of nCLE to diagnose premalignant/malignant pancreatic lesions. Results: Eleven studies on 443 patients were included in our analysis. The pooled rate of diagnostic accuracy of EUS nCLE was 83% (95 confidence interval [CI] = 79-87; I 2 = 0). The pooled rate of sensitivity, specificity, PPV and NPV of EUS nCLE was 85.29% (95% CI = 76.9-93.68; I 2 = 85%), 90.49% (95% CI = 82.24-98.74; I 2 = 64%), 94.15% (95% CI = 88.55-99.76; I 2 = 68%), and 73.44% (95% CI = 60.16-86.72; I 2 = 93%), respectively. The total AE rate was 5.41% (±5.92) with postprocedure pancreatitis being the most common AE at 2.28% (±3.73). Conclusion: In summary, this study highlights the rate of diagnostic accuracy, sensitivity, specificity, and PPV for distinguishing premalignant/malignant lesions. Pancreatic lesions need to be further defined with more validation studies to characterize CLE diagnosis criteria and to evaluate its use as an adjunct to EUS-FNA.
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INTRODUCTION: Autoimmune hepatitis (AIH) is a cause of chronic liver disease. It is usually suspected based on clinical presentation and laboratory findings, but the diagnosis relies on the presence of specific autoantibodies and characteristic histology. Other unexplained findings should always prompt investigation for coexisting syndromes. CASE PRESENTATION: The patient is a 60-year-old Hispanic female with a history of mild asthma presented with exertional and pleuritic chest pain with weight loss, arthralgia, subjective fever, and night sweats for the last 3 months. Given the nonspecific nature of the presentation, further workup was pursued. Laboratory results indicated pancytopenia, elevated INR, and positive autoimmune panel including ANA, anti-chromatin, anti-histone, and rheumatoid factor as well as abnormal C3 and C4. Subsequent liver biopsy with interface hepatitis lead to a diagnosis of AIH with concurrent systemic lupus erythematosus suspected. CONCLUSION: The diagnostic work up for AIH is multimodal and aims to differentiate other etiologies such as congestive hepatopathy, iron overload, viral hepatitis, and other autoimmune liver diseases. In this particular case, unusual clinical and laboratory findings led to diagnosis of the overlap syndrome. Treatment for both was necessary to prevent further progression of disease.
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Autoanticorpos , Hepatite A , Hepatite Autoimune , Hidroxicloroquina/administração & dosagem , Fígado/patologia , Lúpus Eritematoso Sistêmico , Prednisona/administração & dosagem , Fator Reumatoide/sangue , Antirreumáticos/administração & dosagem , Artralgia/diagnóstico , Artralgia/etiologia , Autoanticorpos/sangue , Autoanticorpos/classificação , Biópsia/métodos , Dor no Peito/diagnóstico , Dor no Peito/etiologia , Diagnóstico Diferencial , Feminino , Hepatite A/diagnóstico , Hepatite A/imunologia , Hepatite A/fisiopatologia , Hepatite A/terapia , Hepatite Autoimune/diagnóstico , Hepatite Autoimune/imunologia , Hepatite Autoimune/fisiopatologia , Hepatite Autoimune/terapia , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/fisiopatologia , Lúpus Eritematoso Sistêmico/terapia , Pessoa de Meia-Idade , Administração dos Cuidados ao Paciente/métodos , Resultado do TratamentoRESUMO
BACKGROUND & AIMS: For 4 decades, stigmata of recent hemorrhage in patients with nonvariceal lesions have been used for risk stratification and endoscopic hemostasis. The arterial blood flow that underlies the stigmata rarely is monitored, but can be used to determine risk for rebleeding. We performed a randomized controlled trial to determine whether Doppler endoscopic probe monitoring of blood flow improves risk stratification and outcomes in patients with severe nonvariceal upper gastrointestinal hemorrhage. METHODS: In a single-blind study performed at 2 referral centers we assigned 148 patients with severe nonvariceal upper gastrointestinal bleeding (125 with ulcers, 19 with Dieulafoy's lesions, and 4 with Mallory Weiss tears) to groups that underwent standard, visually guided endoscopic hemostasis (control, n = 76), or endoscopic hemostasis assisted by Doppler monitoring of blood flow under the stigmata (n = 72). The primary outcome was the rate of rebleeding after 30 days; secondary outcomes were complications, death, and need for transfusions, surgery, or angiography. RESULTS: There was a significant difference in the rates of lesion rebleeding within 30 days of endoscopic hemostasis in the control group (26.3%) vs the Doppler group (11.1%) (P = .0214). The odds ratio for rebleeding with Doppler monitoring was 0.35 (95% confidence interval, 0.143-0.8565) and the number needed to treat was 7. CONCLUSIONS: In a randomized controlled trial of patients with severe upper gastrointestinal hemorrhage from ulcers or other lesions, Doppler probe guided endoscopic hemostasis significantly reduced 30-day rates of rebleeding compared with standard, visually guided hemostasis. Guidelines for nonvariceal gastrointestinal bleeding should incorporate these results. ClinicalTrials.gov no: NCT00732212 (CLIN-013-07F).
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Endossonografia , Hemostase Endoscópica/métodos , Síndrome de Mallory-Weiss/terapia , Úlcera Péptica Hemorrágica/terapia , Ultrassonografia Doppler , Malformações Vasculares/terapia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Síndrome de Mallory-Weiss/diagnóstico por imagem , Pessoa de Meia-Idade , Úlcera Péptica Hemorrágica/diagnóstico por imagem , Recidiva , Fluxo Sanguíneo Regional , Medição de Risco/métodos , Índice de Gravidade de Doença , Método Simples-Cego , Resultado do Tratamento , Malformações Vasculares/diagnóstico por imagemRESUMO
BACKGROUND: The sites of origin, causes and outcomes of severe hematochezia have not been compared between cirrhotics and non-cirrhotics. In cirrhotics versus non-cirrhotics presenting with severe hematochezia, we aimed at (1) identifying the site and etiology of gastro-intestinal bleeding and independent predictors of bleeding from the upper gastrointestinal tract versus small bowel or the colon, (2) comparing 30-day clinical outcomes, and (3) proposing an algorithm for management of severe hematochezia. METHODS: In this cohort study from two university-based medical centers, 860 consecutive patients with severe hematochezia admitted from 1995 to 2011 were prospectively enrolled with 160 (18.6 %) cirrhotics. We studied (a) general clinical and laboratory characteristics of cirrhotics versus non-cirrhotics, (b) predictors of bleeding sites in each patient group by multiple variable regression analysis, and compared (c) 30-day outcomes, including rebleeding, surgery and deaths. RESULTS: Cirrhosis independently predicted an upper gastrointestinal source of bleeding (OR 3.47; 95 % CI 2.01-5.96) as well as history of hematemesis, melena in the past 30 days, positive nasogastric aspirate, prior upper gastrointestinal bleeding or use of aspirin or non-steroidal anti-inflammatory. The most prevalent diagnoses were esophageal varices (20 %) in cirrhotics and colon diverticular bleeding (27.1 %) in non-cirrhotics. Thirty-day rates of rebleeding, surgical interventions and deaths were 23.1 versus 15 % (P = 0.01), 14.4 versus 6.4 % (P < 0.001), and 17.5 versus 4.1 % (P < 0.001), in cirrhotics versus non-cirrhotics, respectively. CONCLUSIONS: Cirrhosis predicted an upper gastrointestinal site of bleeding in patients presenting with severe hematochezia. The 30-day rates of rebleeding, surgery, and death were significantly higher in cirrhotics than in non-cirrhotics.
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Doenças do Colo/epidemiologia , Doenças do Esôfago/epidemiologia , Hemorragia Gastrointestinal/epidemiologia , Cirrose Hepática/epidemiologia , Úlcera Péptica Hemorrágica/epidemiologia , Gastropatias/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Angiodisplasia/complicações , Aspirina/uso terapêutico , Transfusão de Componentes Sanguíneos , California/epidemiologia , Estudos de Casos e Controles , Estudos de Coortes , Colite Isquêmica/complicações , Doenças do Colo/etiologia , Doenças do Colo/terapia , Diverticulite/complicações , Transfusão de Eritrócitos , Doenças do Esôfago/etiologia , Doenças do Esôfago/terapia , Varizes Esofágicas e Gástricas/complicações , Feminino , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/terapia , Hematemese/epidemiologia , Hematócrito , Hemorroidas/complicações , Humanos , Intestino Delgado , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Tempo de Tromboplastina Parcial , Úlcera Péptica Hemorrágica/etiologia , Úlcera Péptica Hemorrágica/terapia , Plasma , Inibidores da Agregação Plaquetária/uso terapêutico , Contagem de Plaquetas , Transfusão de Plaquetas , Estudos Retrospectivos , Fatores de Risco , Gastropatias/terapia , Úlcera/complicaçõesRESUMO
BACKGROUND AND AIMS: Few prospective reports describe the short-term natural history of colon diverticular hemorrhage based on stigmata of recent hemorrhage, and none include blood flow detection for risk stratification or as a guide to definitive hemostasis. Our purposes were to report the 30-day natural history of definitive diverticular hemorrhage based on stigmata and to describe Doppler probe blood flow detection as a guide to definitive hemostasis. METHODS: Different cohorts of patients with severe diverticular bleeding and stigmata on urgent colonoscopy are reported. For 30-day natural history, patients were treated medically. If severe rebleeding occurred, they had surgical or angiographic treatment. We report natural history with major stigmata (active bleeding, visible vessel, or adherent clot) and no stigmata or flat spots after clots were washed away. We also report Doppler probe detection of arterial blood flow underneath stigmata before and after hemostasis in a recent cohort. RESULTS: For natural history, patients with major stigmata treated medically had 65.8% (25/38) rebleeding rates, and 44.7% (17/38) had intervention for hemostasis. Patients with spots or clean bases had no rebleeding. A Doppler probe detected arterial blood flow in 92% of major stigmata--none after hemostasis--and there was no rebleeding. CONCLUSIONS: (1) Patients with major stigmata treated medically had high rates of rebleeding and intervention for hemostasis. (2) Patients with clean diverticula or only flat spots had no rebleeding. (3) High rates of arterial blood flow were detected under major stigmata with a Doppler probe, but with obliteration by hemostasis no rebleeding occurred.
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Colonoscopia/métodos , Divertículo do Colo/complicações , Endossonografia/métodos , Hemorragia Gastrointestinal/etiologia , Monitorização Fisiológica/métodos , Fluxo Sanguíneo Regional/fisiologia , Ultrassonografia Doppler em Cores/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Divertículo do Colo/diagnóstico por imagem , Divertículo do Colo/fisiopatologia , Feminino , Seguimentos , Hemorragia Gastrointestinal/diagnóstico por imagem , Hemorragia Gastrointestinal/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , RecidivaRESUMO
BACKGROUND AND AIMS: For more than 4 decades endoscopists have relied on ulcer stigmata for risk stratification and as a guide to hemostasis. None used arterial blood flow underneath stigmata to predict outcomes. For patients with severe peptic ulcer bleeding (PUB), we used a Doppler endoscopic probe (DEP) for (1) detection of blood flow underlying stigmata of recent hemorrhage (SRH), (2) quantitating rates of residual arterial blood flow under SRH after visually directed standard endoscopic treatment, and (3) comparing risks of rebleeding and actual 30-day rebleed rates for spurting arterial bleeding (Forrest [F] IA) and oozing bleeding (F IB). METHODS: Prospective cohort study of 163 consecutive patients with severe PUB and different SRH. RESULTS: All blood flow detected by the DEP was arterial. Detection rates were 87.4% in major SRH-spurting arterial bleeding (F IA), non-bleeding visible vessel (F IIA), clot (F IIB)-and were significantly lower at 42.3% (P < .0001) for an intermediate group of oozing bleeding (F IB) or flat spot (F IIC). For spurting bleeding (F IA) versus oozing (F IB), baseline DEP arterial flow was 100% versus 46.7%, residual blood flow detected after endoscopic hemostasis was 35.7% versus 0%, and 30-day rebleed rates were 28.6% versus 0% (all P < .05). CONCLUSIONS: (1) For major SRH versus oozing or spot, the arterial blood flow detection rate by the DEP was significantly higher, indicating a higher rebleed risk. (2) Before and after endoscopic treatment, spurting (F IA) PUB had significantly higher rates of blood flow detection than oozing (F IB) PUB and a significantly higher 30-day rebleed rate. (3) The DEP is recommended as a new endoscopic guide with SRH to improve risk stratification and potentially definitive hemostasis for PUB.
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Úlcera Duodenal/diagnóstico , Duodeno/irrigação sanguínea , Fluxometria por Laser-Doppler/métodos , Úlcera Péptica Hemorrágica/diagnóstico , Úlcera Gástrica/diagnóstico , Estômago/irrigação sanguínea , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Úlcera Duodenal/cirurgia , Endoscopia do Sistema Digestório/métodos , Feminino , Hemostase Endoscópica/métodos , Humanos , Pessoa de Meia-Idade , Úlcera Péptica Hemorrágica/cirurgia , Estudos Prospectivos , Recidiva , Medição de Risco , Índice de Gravidade de Doença , Úlcera Gástrica/cirurgiaRESUMO
BACKGROUND AND AIMS: Improved medical decisions by using a score at the initial patient triage level may lead to improvements in patient management, outcomes, and resource utilization. There is no validated score for management of lower gastrointestinal bleeding (LGIB) unlike for upper gastrointestinal bleeding. The aim of our study was to compare the accuracies of 3 different prognostic scores [Center for Ulcer Research and Education Hemostasis prognosis score, Charlson index, and American Society of Anesthesiologists (ASA) score] for the prediction of 30-day rebleeding, surgery, and death in severe LGIB. METHODS: Data on consecutive patients hospitalized with severe gastrointestinal bleeding from January 2006 to October 2011 in our 2 tertiary academic referral centers were prospectively collected. Sensitivities, specificities, accuracies, and area under the receiver operator characteristic curve were computed for 3 scores for predictions of rebleeding, surgery, and mortality at 30 days. RESULTS: Two hundred thirty-five consecutive patients with LGIB were included between 2006 and 2011. Twenty-three percent of patients rebled, 6% had surgery, and 7.7% of patients died. The accuracies of each score never reached 70% for predicting rebleeding or surgery in either. The ASA score had a highest accuracy for predicting mortality within 30 days (83.5%), whereas the Center for Ulcer Research and Education Hemostasis prognosis score and the Charlson index both had accuracies <75% for the prediction of death within 30 days. CONCLUSIONS: ASA score could be useful to predict death within 30 days. However, a new score is still warranted to predict all 30 days outcomes (rebleeding, surgery, and death) in LGIB.
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Hemorragia Gastrointestinal/terapia , Hospitalização , Avaliação de Resultados da Assistência ao Paciente , Idoso , Idoso de 80 Anos ou mais , Feminino , Hemorragia Gastrointestinal/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Curva ROC , Fatores de Risco , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Centros de Atenção Terciária , Resultado do TratamentoRESUMO
AIM: To describe the prevalence, diagnosis, treatment, and outcomes of end stage liver disease (ESLD) patients with severe epistaxis thought to be severe upper gastrointestinal hemorrhage (UGIH). METHODS: This observational single center study included all consecutive patients with ESLD and epistaxis identified from consecutive subjects hospitalized with suspected UGIH and prospectively enrolled in our databases of severe UGIH between 1998 and 2011. RESULTS: A total of 1249 patients were registered for severe UGIH in the data basis, 461 (36.9%) were cirrhotics. Epistaxis rather than UGIH was the bleeding source in 20 patients. All patients had severe coagulopathy. Epistaxis was initially controlled in all cases. Fifteen (75%) subjects required posterior nasal packing and 2 (10%) embolization in addition to correction of coagulopathy. Five (25%) patients died in the hospital, 12 (60%) received orthotopic liver transplantation (OLT), and 3 (15%) were discharged without OLT. The mortality rate was 63% in patients without OLT. CONCLUSION: Severe epistaxis in patients with ESLD is (1) a diagnosis of exclusion that requires upper endoscopy to exclude severe UGIH; and (2) associated with a high mortality rate in patients not receiving OLT.
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Doença Hepática Terminal/complicações , Epistaxe/etiologia , Hemorragia Gastrointestinal/etiologia , Adulto , Idoso , California/epidemiologia , Bases de Dados Factuais , Diagnóstico Diferencial , Doença Hepática Terminal/diagnóstico , Doença Hepática Terminal/mortalidade , Doença Hepática Terminal/terapia , Epistaxe/diagnóstico , Epistaxe/mortalidade , Epistaxe/terapia , Feminino , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/mortalidade , Hemorragia Gastrointestinal/terapia , Técnicas Hemostáticas , Mortalidade Hospitalar , Humanos , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/mortalidade , Valor Preditivo dos Testes , Prevalência , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to increase the histamine release from gastric enterochromaffin-like (ECL) cells and promote gastric acid secretion in rats. In contrast, in mice, PACAP has been demonstrated to induce a decrease of gastric acid secretion, an effect presumably due to somatostatin release. To more clearly define the role of PACAP in the regulation of gastric acid output, a knockout mouse model for the PACAP-specific receptor PAC1 was applied in this study. Measurements of the basal and stimulated gastric acid secretion and morphological studies on the gastric mucosa were performed in both wild-type and PAC1-deficient mice. Compared with the wild-type mice, the PAC1-deficient mice showed a nearly threefold higher basal gastric acid output, increased gastric mucosa thickness and glands height, and proportional increases in parietal and total cell counts in the gastric mucosa. The PAC1-deficient mice also showed a trend of increased plasma gastrin levels and gastrin gene expression in the gastric mucosa. This study indicates that the expression of PAC1 is clearly important for maintaining the homeostasis of gastric acid secretion. Loss of PACAP receptor during development may lead to a compensatory mechanism regulating gastric acid secretion.
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Ácido Gástrico/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Hipertrofia/patologia , Receptores de Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/deficiência , Animais , Biomarcadores/metabolismo , Gastrinas/sangue , Gastrinas/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ratos , Receptores de Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/genéticaRESUMO
CRH and 5-hydroxytryptamine (5-HT) are expressed in human colonic enterochromaffin (EC) cells, but their interactions at the cellular level remain largely unknown. The mechanistic and functional relationship between CRH and 5-HT systems in EC cells was investigated in a human carcinoid cloned BON cell line (BON-1N), widely used as an in vitro model of EC cell function. First, we identified multiple CRH(1) splice variants, including CRH(1a), CRH(1c), CRH(1f), and a novel form lacking exon 4, designated here as CRH(1i), in the BON-1N cells. The expression of CRH(1i) was also confirmed in human brain cortex, pituitary gland, and ileum. Immunocytochemistry and immunoblot analysis confirmed that BON-1N cells were CRH(1) and 5-HT positive. CRH, urocortin (Ucn)-1, and cortagine, a selective CRH(1) agonist, all increased intracellular cAMP, and this concentration-dependent response was inhibited by CRH(1)-selective antagonist NBI-35965. CRH and Ucn-1, but not Ucn-2, stimulated significant ERK1/2 phosphorylation. In transfected human embryonic kidney-293 cells, CRH(1i) isoforms produced a significant increase in pERK1/2 in response to CRH(1) agonists that was sensitive to NBI-35965. CRH and Ucn-1 stimulated 5-HT release that reached a maximal increase of 3.3- and 4-fold at 10(-8) m over the basal level, respectively. In addition, exposure to CRH for 24-h up-regulated tryptophan hydroxylase-1 mRNA levels in the BON-1N cells. These findings define the expression of EC cell-specific CRH(1) isoforms and activation of CRH(1)-dependent pathways leading to 5-HT release and synthesis; thus, providing functional evidence of a link exists between CRH and 5-HT systems, which have implications in stress-induced CRH(1) and 5-HT-mediated stimulation of lower intestinal function.
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Células Enterocromafins/metabolismo , Receptores de Hormônio Liberador da Corticotropina/metabolismo , Serotonina/metabolismo , Linhagem Celular Tumoral , Regulação da Expressão Gênica/fisiologia , Humanos , Mutação , Isoformas de Proteínas , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Hormônio Liberador da Corticotropina/genética , Transfecção , Triptofano Hidroxilase/genética , Triptofano Hidroxilase/metabolismoRESUMO
Hemorrhoids are common in Western societies. Appropriate assessment and treatment of symptomatic hemorrhoids can substantially reduce morbidity and improve patient well-being. In this article, the clinical presentation, differential diagnoses, and current treatment options, including the CRH-O'Regan banding device, an emerging technology for the anoscopic treatment of symptomatic internal hemorrhoids, are reviewed.
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Hemorroidas/diagnóstico , Hemorroidas/terapia , Diagnóstico Diferencial , Eletrocoagulação/métodos , Endoscopia Gastrointestinal , Desenho de Equipamento , Hemorroidas/complicações , Humanos , Ligadura/instrumentação , Complicações Pós-Operatórias , Escleroterapia/métodos , Instrumentos CirúrgicosRESUMO
Ghrelin is a potent orexigenic peptide principally produced in the stomach by a distinct population of neuroendocrine cells in the oxyntic mucosa of the fundus. Exogenous ghrelin given as an intravenous infusion has been shown to increase caloric intake in patients with cancer cachexia. In this study, we hypothesized that elevated endogenous ghrelin, produced by increased neuroendocrine cell tumor burden, also exerts an orexigenic effect helping to maintain body mass index. To evaluate the effect of elevated endogenous ghrelin, 35 patients with neuroendocrine tumors were enrolled, assigning them to one of two groups depending on the presence of hepatic metastases. Following an overnight fast, serum was collected and sent for ghrelin measurement by an outside laboratory. The two groups were well matched for all other relevant clinical variables including subtype of tumor, primary location of tumor and tumor treatment history. Nearly all patients with hepatic metastases had elevated levels of ghrelin compared to the standard reference range given for matched controls. The presence of hepatic metastases was associated with significantly elevated ghrelin levels (p<0.05) and a greater mean body mass index. In addition, we report a positive correlation between serum ghrelin and total tumor surface area and between serum ghrelin and body mass index, suggesting that elevated endogenous ghrelin may be sufficient to overcome any partial ghrelin resistance typically seen in cancer cachexia. These results support the possibility that ghrelin is co-released from neuroendocrine tumors and exerts an orexigenic effect in these patients, helping to maintain their body mass index despite widely disseminated disease.
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Apetite , Índice de Massa Corporal , Grelina/sangue , Tumores Neuroendócrinos/patologia , Adulto , Idoso , Biomarcadores/metabolismo , Caquexia/sangue , Cromogranina A/sangue , Feminino , Gastrinas/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estudos ProspectivosRESUMO
BACKGROUND & AIMS: To safely manage the hypersecretory state in patients with Zollinger-Ellison syndrome, both upper endoscopy and gastric analysis are required to titrate optimal medical therapy. Conventional gastric analysis requires more than 1 hour to perform and results in significant patient dissatisfaction. In this study, we have validated endoscopic gastric analysis as a novel technique that can effectively replace conventional gastric analysis. METHODS: In a prospective, cross-over study, 12 patients with Zollinger-Ellison syndrome underwent gastric analysis, first by the conventional method and then by an endoscopic technique performed on the same day. Acid concentration was determined by titration, volume output was recorded, and acid output was calculated using standard methodologies and formulas. Agreement was assessed following the Bland-Altman method. To assess repeatability, both techniques were repeated on the same day in a subset of patients. RESULTS: Excellent agreement was reported between acid output (95% limits of agreement, -1.27 to 1.61 mEq/h) and acid concentration (95% limits of agreement, -0.01 to 0.01 mEq/mL), although poor agreement was observed between volume output measured. Endoscopic gastric analysis showed greater reproducibility regarding acid and volume output measured. CONCLUSIONS: We introduce a new, rapid, reproducible, and accurate endoscopic technique to measure acid output in patients with Zollinger-Ellison syndrome who require both annual endoscopy and gastric analysis. The data presented here suggest that endoscopic gastric analysis would be equally effective in determining acid output in other hypersecretory states. Additional analysis of cost effectiveness is needed to evaluate its use as a screening tool in select populations.
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Endoscopia Gastrointestinal/métodos , Ácido Gástrico/metabolismo , Síndrome de Zollinger-Ellison/terapia , Adulto , Idoso , Estudos Cross-Over , Feminino , Seguimentos , Determinação da Acidez Gástrica , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Síndrome de Zollinger-Ellison/diagnóstico , Síndrome de Zollinger-Ellison/metabolismoRESUMO
Historically, limited trials evaluating biotherapy in treating metastatic neuroendocrine tumours have yielded mixed results. In this study, the efficacy of a novel combination therapy featuring longacting Sandostatin LAR plus alpha-interferon was evaluated. In a prospective case series, 12 patients with unresectable metastatic neuroendocrine tumours refractory to treatment initiated therapy with Infergen and Sandostatin LAR. Radiological response was followed serially at 3-month intervals. A biochemical response was considered significant if marker levels decreased by > or = 50% compared with baseline. Inhibition of tumour growth lasting for greater than 3 months (mean response 22.6+/-17.7 months) was seen in eight patients. Complete tumour regression was observed in one patient, lasting for 40 months; three patients exhibited partial tumour regression (mean response 29.3+/-24.0 months), and four patients maintained a stable tumour response (mean response 13.3+/-9.2 months). Four patients showed no response to therapy (mean response 5.0+/-6.0 months). All enrolled patients are alive currently. The biochemical response seen in seven patients did not correlate with the radiological response. These results suggest that the novel combination of longacting Sandostatin LAR with an alpha-interferon may be at least as effective as either combination therapy with short-acting octreotide or monotherapy with Sandostatin LAR.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Processos de Crescimento Celular/efeitos dos fármacos , Tumores Neuroendócrinos/tratamento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Artralgia/induzido quimicamente , Processos de Crescimento Celular/efeitos da radiação , Cromogranina A/sangue , Terapia Combinada , Diarreia/induzido quimicamente , Resistencia a Medicamentos Antineoplásicos , Feminino , Gastrinas/sangue , Cefaleia/induzido quimicamente , Humanos , Injeções Subcutâneas , Interferon Tipo I/administração & dosagem , Interferon Tipo I/efeitos adversos , Interferon-alfa , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/radioterapia , Tumores Neuroendócrinos/secundário , Octreotida/administração & dosagem , Octreotida/efeitos adversos , Pacientes Desistentes do Tratamento , Estudos Prospectivos , Radioterapia Adjuvante/métodos , Proteínas Recombinantes , Indução de Remissão , Resultado do TratamentoRESUMO
The gastric enterochromaffin-like (ECL) cell plays a major role in the regulation of gastric acid secretion. We have previously described that Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) is present on myenteric neurons in the rat and colocalizes with its high-affinity receptor, PAC1, expressed on the surface of gastric ECL cells. The study of ECL cell physiology has been hampered by the inability to isolate and purify ECL cells to homogeneity. Density gradient elutriation alone yields only 65-70% purity of ECL cells. In the present study, we used fluorescence-activated cell sorting (FACS) with a novel fluorescent ligand, Fluor-PACAP-38, for isolating pure ECL cells. FACS was used to isolate ECL cells based on their relatively small size, low density, and ability to bind the fluorescent ligand Fluor-PACAP-38. The sorted cells were unambiguously identified as ECL cells by immunohistochemical analysis using anti-PACAP type-I (PAC1), anti-histidine decarboxylase (HDC), and anti-somatostatin antibodies. Further confocal microscopy demonstrated that Fluor-PACAP-38, a ligand with a higher affinity for PAC1, bound to extracellular receptors of these FACS-purified cells. FACS yielded an average of 2 million ECL cells/4 rat stomachs, and >99% of the sorted cells were positive for PAC1 receptor and HDC expression. The absence of immunohistochemical staining for somatostatin indicated lack of contamination by gastric D cells, which are similar in size and shape to the ECL cells. Internalization of PACAP receptors and a rapid Ca2+ response in purified ECL cells were observed upon PACAP activation, suggesting that these cells are viable and biologically active. These ECL cells demonstrated a dose-dependent stimulation of proliferation in response to PACAP, with a maximum of 30% proliferation at a concentration of 10-7 M. Microarray studies were perfor med to confirm the expression of genes specific for ECL cells. These results demonstrate that rat gastric ECL cells can be isolated to homogeneity by using a combination of density gradient centrifugation, followed by cell sorting using Fluor-PACAP. These techniques now allow microarray studies to be performed in ECL cells to characterize their functional gene expression and will facilitate pharmacological, biochemical, and molecular studies on ECL cell function.
Assuntos
Divisão Celular/efeitos dos fármacos , Células Enterocromafins/metabolismo , Mucosa Gástrica/metabolismo , Fatores de Crescimento Neural/fisiologia , Neuropeptídeos/fisiologia , Neurotransmissores/fisiologia , Animais , Sinalização do Cálcio , Citometria de Fluxo , Ácido Gástrico/metabolismo , Regulação da Expressão Gênica , Fatores de Crescimento Neural/genética , Neuropeptídeos/genética , Neurotransmissores/genética , Análise de Sequência com Séries de Oligonucleotídeos , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase , Ratos , Ratos Sprague-DawleyAssuntos
Antiulcerosos/uso terapêutico , Benzimidazóis/uso terapêutico , Refluxo Gastroesofágico/tratamento farmacológico , Omeprazol/análogos & derivados , Omeprazol/uso terapêutico , 2-Piridinilmetilsulfinilbenzimidazóis , Humanos , Lansoprazol , Masculino , Pessoa de Meia-Idade , Rabeprazol , Falha de TratamentoRESUMO
The influence of central vagal stimulation induced by 2h cold exposure or intracisternal injection of thyrotropin-releasing hormone (TRH) analog, RX-77368, on gastro-duodenal enteric cholinergic neuronal activity was assessed in conscious rats with Fos and peripheral choline acetyltransferase (pChAT) immunoreactivity (IR). pChAT-IR was detected in 68%, 70% and 73% of corpus, antrum and duodenum submucosal neurons, respectively, and in 65% of gastric and 46% of duodenal myenteric neurons. Cold and RX-77368 induced Fos-IR in over 90% of gastric submucosal and myenteric neurons, while in duodenum only 25-27% of submucosal and 50-51% myenteric duodenal neurons were Fos positive. In the stomach, cold induced Fos-IR in 93% of submucosal and 97% of myenteric pChAT-IR neurons, while in the duodenum only 7% submucosal and 5% myenteric pChAT-IR neurons were Fos positive. In the duodenum, cold induced Fos in 91% of submucosal and 99% of myenteric VIP-IR neurons. RX-77368 induces similar percentages of Fos/pChAT-IR and Fos/VIP-IR neurons. These results indicate that increased central vagal outflow activates cholinergic neurons in the stomach while in the duodenum, VIP neurons are preferentially stimulated.
Assuntos
Duodeno/inervação , Mucosa Gástrica/inervação , Mucosa Intestinal/inervação , Neurônios/fisiologia , Estômago/inervação , Nervo Vago/fisiologia , Animais , Estado de Consciência , Mucosa Gástrica/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Masculino , Neurônios/efeitos dos fármacos , Estimulação Física , Ratos , Ratos Sprague-Dawley , Tireotropina/farmacologia , Nervo Vago/efeitos dos fármacosAssuntos
Fator de Crescimento Epidérmico/metabolismo , Refluxo Gastroesofágico/complicações , Laringite/complicações , Inibidores da Bomba de Prótons , Síndrome de Zollinger-Ellison/complicações , Adulto , Endossonografia/métodos , Fator de Crescimento Epidérmico/análise , Esofagoscopia/métodos , Seguimentos , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/tratamento farmacológico , Humanos , Laringite/diagnóstico , Laringite/tratamento farmacológico , Laringoscopia/métodos , Imageamento por Ressonância Magnética/métodos , Masculino , Bombas de Próton/uso terapêutico , Medição de Risco , Índice de Gravidade de Doença , Resultado do Tratamento , Síndrome de Zollinger-Ellison/diagnóstico , Síndrome de Zollinger-Ellison/tratamento farmacológicoRESUMO
Peripheral corticotropin-releasing factor (CRF) receptor ligands inhibit gastric acid secretion and emptying while stimulating gastric mucosal blood flow in rats. Endogenous CRF ligands are expressed in the upper gastrointestinal (GI) tissues pointing to local expression of CRF receptors. We mapped the distribution of CRF receptor type 1 (CRF1) and 2 (CRF2) in the rat upper GI. Polyclonal antisera directed against the C-terminus of the CRF receptor protein were generated in rabbits and characterized by western blotting and immunofluorescence using CRF1- and CRF2-transfected cell lines and in primary cultured neurons from rat brain cortex. A selective anti-CRF1 antiserum (4467a-CRF1) was identified and used in parallel with another antiserum recognizing both CRF1 and CRF2 (4392a-CRF1&2) to immunostain gastric tissue sections. Antiserum 4467a-CRF1 demonstrated specific immunostaining in a narrow zone in the upper oxyntic gland within the stomach corpus. Conversely, 4392a-CRF1&2 labeled cells throughout the oxyntic gland and submucosal blood vessels. Pre-absorption with the specific antigen peptide blocked immunostaining in all experiments. Doublestaining showed co-localization of 4392a-CRF1&2 but not 4467a-CRF1 immunoreactivity with H/K-ATPase and somatostatin immunostaining in parietal and endocrine cells of the oxyntic gland. No specific staining was observed in the antrum with either antisera, whereas only antiserum 4392a-CRF1&2 showed modest immunoreactivity in the duodenal mucosa. Finally, co-localization of CRF2 and urocortin immunoreactivity was found in the gastric glands. These results indicate that both CRF receptor subtypes are expressed in the rat upper GI tissues with a distinct pattern and regional differences suggesting differential function.