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BACKGROUND AND AIM: Current diagnostic modalities for indeterminate biliary strictures offer low accuracy. Probe-based confocal laser endomicroscopy (pCLE) permits microscopic assessment of mucosal structures by obtaining real-time high-resolution images of the mucosal layers of the gastrointestinal tract. Previously, an interobserver study demonstrated poor to fair agreement even among experienced confocal endomicroscopy operators. Our objective was to assess interobserver agreement and diagnostic accuracy upon completion of a pCLE training session. METHODS: Forty de-identified pCLE video clips of indeterminate biliary strictures were sent to five endoscopists at four tertiary care centers for scoring. Observers subsequently attended a teaching session by an expert pCLE user that included 20 training clips and rescored the same pCLE video clips, which were randomized and renumbered. RESULTS: Pre-training interobserver agreement for all observers was 'fair' (Κ: 0.31, P-value: <0.0001) and diagnostic accuracy was 72% (55-80%). Post-training interobserver agreement for all observers was 'substantial' (Κ: 0.74, P-value: <0.0001) and diagnostic accuracy was 89% (80-95%). Using a paired t-test, we observed an increase of 17% (95% CI 7.6-26.4) in post-training diagnostic accuracy (t = 5.01, df = 4, P-value 0.007). CONCLUSIONS: Interobserver agreement and diagnostic accuracy improved after observers underwent training by an expert pCLE user with a specific sequence set. Users should participate in such training programs to maximize diagnostic accuracy of pCLE evaluation.
Assuntos
Colestase/terapia , Competência Clínica , Endoscopia Gastrointestinal/educação , Endoscopia Gastrointestinal/métodos , Microscopia Confocal/métodos , Colestase/patologia , Humanos , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Gravação em VídeoRESUMO
Titin is an extremely large protein found in highest concentrations in heart and skeletal muscle. The single mammalian gene is expressed in multiple isoforms as a result of alternative splicing. Although titin isoform expression is controlled developmentally and in a tissue specific manner, the vast number of potential splicing pathways far exceeds those described in any other alternatively spliced gene. Over 1 million human splice pathways for a single individual can be potentially derived from the PEVK region alone. A new splicing pattern for the human cardiac N2BA isoform type has been found in which the PEVK region includes only the N2B type exons. The alterations in splicing and titin isoform expression in human heart disease provide impetus for future detailed study of the splicing mechanisms for this giant protein.
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Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Processamento Alternativo , Animais , Conectina , Humanos , Proteínas Musculares/química , Proteínas Quinases/química , Sarcômeros/genética , Sarcômeros/metabolismoRESUMO
Intrahepatic cholestasis of pregnancy (ICP) is an incompletely understood liver disease which results in systemic accumulation of bile acids, associated with maternal pruritus and increased risk of intrauterine fetal death. Onset is typically in the third trimester; however, rare cases have been reported early in the first trimester. We present a case of severe, early onset ICP at five weeks gestation in a spontaneous pregnancy. The patient was treated successfully with ursodeoxycholic acid and, after close obstetrical surveillance, delivered a healthy female infant via induced delivery at 34 weeks six days.
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Pancreatic cystic lesions can be benign, premalignant or malignant. The recent increase in detection and tremendous clinical variability of pancreatic cysts has presented a significant therapeutic challenge to physicians. Mucinous cystic neoplasms are of particular interest given their known malignant potential. This review article provides a brief but comprehensive review of premalignant pancreatic cystic lesions with advanced endoscopic ultrasound (EUS) management approaches. A comprehensive literature search was performed using PubMed, Cochrane, OVID and EMBASE databases. Preneoplastic pancreatic cystic lesions include mucinous cystadenoma and intraductal papillary mucinous neoplasm. The 2012 International Sendai Guidelines guide physicians in their management of pancreatic cystic lesions. Some of the advanced EUS management techniques include ethanol ablation, chemotherapeutic (paclitaxel) ablation, radiofrequency ablation and cryotherapy. In future, EUS-guided injections of drug-eluting beads and neodymium:yttrium aluminum agent laser ablation is predicted to be an integral part of EUS-guided management techniques. In summary, International Sendai Consensus Guidelines should be used to make a decision regarding management of pancreatic cystic lesions. Advanced EUS techniques are proving extremely beneficial in management, especially in those patients who are at high surgical risk.
Assuntos
Endossonografia , Cisto Pancreático/diagnóstico por imagem , Lesões Pré-Cancerosas/diagnóstico por imagem , Antineoplásicos/uso terapêutico , Humanos , Cisto Pancreático/diagnóstico , Cisto Pancreático/tratamento farmacológico , Cisto Pancreático/patologia , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/tratamento farmacológico , Lesões Pré-Cancerosas/patologiaRESUMO
BACKGROUND: Endoscopic ultrasound (EUS) is a resource-intensive endoscopic procedure, but may result in high downstream health resource utilization and multispecialty impact. Our aim was to examine the downstream impact of EUS by specialty and by indication. METHODS: A retrospective chart review was performed at an academic medical center for patients for whom EUS represented the first point of contact at the study institution within a 20-month period. RESULTS: A total of 552 EUS procedures were reviewed and 208 represented the first point of contact. The most common principle indication involved the pancreas (n = 117, 56%). Downstream health utilization was calculated for an average of 313 days postprocedure (range: 35-632 days). Following unique referral for endoscopic ultrasound, 52% of the patients in the study were retained within the institution for further management and, of these, 34% had a major intervention in the form of surgery or chemoradiotherapy. Compared with other indications, patients presenting with a pancreatic mass were significantly more likely to remain in the study institution for further management (62% versus 39%, p = 0.005), were more likely to have a downstream surgery (29% versus 14%, p = 0.020) and were more likely to have downstream chemo-radiotherapy (11% versus 3%, p = 0.012). CONCLUSIONS: EUS represents a unique portal of entry into tertiary referral medical centers. First point of contact EUS referrals are associated with major downstream health resource utilization and significantly increased utilization for mass lesions of the pancreas.
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Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is the most sensitive and specific test for establishing a tissue diagnosis for many gastrointestinal malignancies; however, cytologic morphology alone may not be definitive for subsets of tumors. Our aim was to quantify the impact of the broad application of flow cytometry (FC) and immunohistochemistry (IHC) on EUS-FNA diagnostic yield. A retrospective chart review was performed on EUS procedures at a tertiary referral, academic medical center. All EUS-FNA cases performed over a 21-month period were examined. Of 606 EUS procedures reviewed during the period of study, 264 utilized FNA. After pancreatic cyst cases were excluded, 235 EUS-FNA cases for 221 patients were selected for analysis. For cases with subsequent histological evaluation, including the subset utilizing FC/IHC, the sensitivity of EUS-FNA was 89%, specificity was 100%, and accuracy was 91%. One quarter (58/235, 25%) of the tissue specimens underwent further testing by FC/IHC. There were 48 definitive diagnoses made in the subset utilizing FC/IHC. In 20 of the 48 diagnoses (42%), FC/IHC was deemed critical to the diagnosis, and without FC/IHC testing in those cases, the overall sensitivity and accuracy of EUS-FNA would be reduced to 74 and 77%, respectively. FC/IHC allowed for six diagnoses rarely or not previously described by EUS-FNA. Application of FC/IHC improves characterization predominantly for nonadenocarcinoma tumor subtypes and may lead to a diagnostic result for tumors not previously characterized by EUS-FNA. With an adequate tissue sample, broad application of FC/IHC increases the diagnostic yield of EUS-FNA.
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Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/estatística & dados numéricos , Citometria de Fluxo , Imuno-Histoquímica , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Melanoma/diagnóstico por imagem , Melanoma/patologia , Melanoma/secundário , Pessoa de Meia-Idade , Cisto Pancreático/diagnóstico por imagem , Cisto Pancreático/patologia , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
Systemic corticosteroids represent the standard treatment for autoimmune pancreatitis with IgG4-associated cholangitis. For steroid-dependent disease, azathioprine has been used for maintenance of remission. Mycophenolate mofetil has been used for transplant immunosuppression and more recently for autoimmune hepatitis; however, there are no case reports to date on the use of mycophenolate mofetil in adult patients with autoimmune pancreatitis. A patient with IgG4-mediated autoimmune pancreatitis and IgG4-associated cholangitis refractory to steroids and intolerant of azathioprine was treated with mycophenolate mofetil, which inhibits de novo guanosine synthesis and blockade of both B and T lymphocyte production. Introduction of mycophenolate mofetil and uptitration to 1000 mg by mouth twice daily over a treatment period of 4 mo was associated with improvement in the patient's energy level and blood glucose control and was not associated with any adverse events. The patient was managed without a biliary stent. However, there was a return of symptoms, jaundice, increase in transaminases, and hyperbilirubinemia when the prednisone dose reached 11 mg per day. In the first report of mycophenolate mofetil use in an adult patient with IgG4-associated autoimmune pancreatitis and IgG4-associated cholangitis, the introduction of mycophenolate mofetil was safe and well-tolerated without adverse events, but it did not enable discontinuation of the steroids. Mycophenolate mofetil and other immunomodulatory therapies should continue to be studied for maintenance of remission in the large subset of patients with refractory or recurrent autoimmune pancreatitis.