RESUMEN
BACKGROUND: Patients with primary sclerosing cholangitis (PSC) possess autoantibodies against biliary epithelial cells. However, the target molecules remain unknown. METHODS: The sera of patients with PSC and controls were subjected to enzyme-linked immunosorbent assays to detect autoantibodies using recombinant integrin proteins. Integrin αvß6 expression in the bile duct tissues was examined using immunofluorescence. The blocking activity of the autoantibodies was examined using solid-phase binding assays. RESULTS: Anti-integrin αvß6 antibodies were detected in 49/55 (89.1%) patients with PSC and 5/150 (3.3%) controls (P < 0.001), with a sensitivity and specificity of 89.1% and 96.7%, respectively, for PSC diagnosis. When focusing on the presence or absence of IBD, the proportion of the positive antibodies in PSC with IBD was 97.2% (35/36) and that in PSC alone was 73.7% (14/19) (P = 0.008). Integrin αvß6 was expressed in bile duct epithelial cells. Immunoglobulin (Ig)G from 15/33 patients with PSC blocked integrin αvß6-fibronectin binding through an RGD (Arg-Gly-Asp) tripeptide motif. CONCLUSIONS: Autoantibodies against integrin αvß6 were detected in most patients with PSC; anti-integrin αvß6 antibody may serve as a potential diagnostic biomarker for PSC.
Asunto(s)
Colangitis Esclerosante , Enfermedades Inflamatorias del Intestino , Humanos , Autoanticuerpos , Células Epiteliales/metabolismo , Ensayo de Inmunoadsorción EnzimáticaRESUMEN
BACKGROUND: Notch/Hes1 signaling has been shown to play a role in determining the fate of pancreatic progenitor cells. However, its function in postnatal pancreatic maturation is not fully elucidated. METHODS: We generated conditional Hes1 knockout and/or Notch intracellular domain (NICD) overexpression mice in Ptf1a- or Pdx1-positive pancreatic progenitor cells and analyzed pancreatic tissues. RESULTS: Both Ptf1acre/+; Hes1f/f and Ptf1acre/+; Rosa26NICD mice showed normal pancreatic development at P0. However, exocrine tissue of the pancreatic tail in Ptf1acre/+; Hes1f/f mice atrophied and was replaced by fat tissue by 4 weeks of age, with increased apoptotic cells and fewer centroacinar cells. This impaired exocrine development was completely rescued by NICD overexpression in Ptf1acre/+; Hes1f/f; Rosa26NICD mice, suggesting compensation by a Notch signaling pathway other than Hes1. Conversely, Pdx1-Cre; Hes1f/f mice showed impaired postnatal exocrine development in both the pancreatic head and tail, revealing that the timing and distribution of embryonic Hes1 expression affects postnatal exocrine tissue development. CONCLUSIONS: Notch signaling has an essential role in pancreatic progenitor cells for the postnatal maturation of exocrine tissue, partly through the formation of centroacinar cells.
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Páncreas/metabolismo , Factor de Transcripción HES-1/farmacología , Animales , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/fisiología , Modelos Animales de Enfermedad , Ratones , Transducción de Señal/fisiología , Células Madre/metabolismo , Células Madre/fisiologíaRESUMEN
BACKGROUND AND AIMS: Ulcerative colitis is the most frequent type of inflammatory bowel disease and is characterized by colonic epithelial cell damage. Although involvement of autoimmunity has been suggested in ulcerative colitis, specific autoantigens/antibodies have yet to be elucidated. METHODS: Using 23 recombinant integrin proteins, we performed enzyme-linked immunosorbent assays on sera from patients with ulcerative colitis and controls. Integrin expression and IgG binding in the colon tissues of patients with ulcerative colitis and controls were examined using immunofluorescence and coimmunoprecipitation, respectively. The blocking activity of autoantibodies was examined using solid-phase binding and cell adhesion assays. RESULTS: Screening revealed that patients with ulcerative colitis had IgG antibodies against integrin αvß6. In the training and validation groups, 103 of 112 (92.0%) patients with ulcerative colitis and only 8 of 155 (5.2%) controls had anti-integrin αvß6 antibodies (P < .001), resulting in a sensitivity of 92.0% and a specificity of 94.8% for diagnosing ulcerative colitis. Anti-integrin αvß6 antibody titers coincided with ulcerative colitis disease activity, and IgG1 was the major subclass. Patient IgG bound to the integrin αvß6 expressed on colonic epithelial cells. Moreover, IgG of patients with ulcerative colitis blocked integrin αvß6-fibronectin binding through an RGD (Arg-Gly-Asp) tripeptide motif and inhibited cell adhesion. CONCLUSIONS: A significant majority of patients with ulcerative colitis had autoantibodies against integrin αvß6, which may serve as a potential diagnostic biomarker with high sensitivity and specificity.
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Antígenos de Neoplasias/inmunología , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Colitis Ulcerosa/sangre , Colitis Ulcerosa/inmunología , Integrinas/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Estudios de Casos y Controles , Adhesión Celular/inmunología , Colon/inmunología , Ensayo de Inmunoadsorción Enzimática , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Inmunoprecipitación , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
BACKGROUND : Accurate preoperative assessment of the longitudinal extension of perihilar cholangiocarcinoma (PHCC) is essential for treatment planning. Mapping biopsies for PHCC remain challenging owing to technical difficulties and insufficient sample amounts. The aim of this study was to investigate the usefulness of a novel technique for mapping biopsies of PHCC. METHODS : Our novel method focused on a biliary stent delivery system for mapping biopsies. Fifty patients with PHCC undergoing endoscopic transpapillary mapping biopsy using the novel method were reviewed from August 2015 to June 2019. RESULTS : The median number of biopsy samples was six (range 1â-â17), and the rate of adequate sampling was 91.4â% (266â/291). Biopsy from the intrahepatic bile duct was possible in 82.0â% of patients (41â/50), and negative margins were confirmed in the resected specimens from 34â/39 patients who underwent surgery (87.2â%). None of the patients had post-endoscopic retrograde cholangiopancreatography pancreatitis. CONCLUSIONS : With our novel method, accurate assessment of the longitudinal extension of PHCC might be expected with minimal trauma to the duodenal papilla.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Tumor de Klatskin , Neoplasias de los Conductos Biliares/cirugía , Conductos Biliares Intrahepáticos , Biopsia , Colangiopancreatografia Retrógrada Endoscópica , HumanosRESUMEN
Intrahepatic cholangiocarcinoma (ICC) is frequently driven by aberrant KRAS activation and develops in the liver with chronic inflammation. Although the Notch signaling pathway is critically involved in ICC development, detailed mechanisms of Notch-driven ICC development are still unknown. Here, we use mice whose Notch signaling is genetically engineered to show that the Notch signaling pathway, specifically the Notch/Hes1 axis, plays an essential role in expanding ductular cells in the liver with chronic inflammation or oncogenic Kras activation. Activation of Notch1 enhanced the development of proliferating ductal cells (PDC) in injured livers, while depletion of Hes1 led to suppression. In correlation with PDC expansion, ICC development was also regulated by the Notch/Hes1 axis and suppressed by Hes1 depletion. Lineage-tracing experiments using EpcamcreERT2 mice further confirmed that Hes1 plays a critical role in the induction of PDC and that ICC could originate from PDC. Analysis of human ICC specimens showed PDC in nonneoplastic background tissues, confirming HES1 expression in both PDC and ICC tumor cells. Our findings provide novel direct experimental evidence that Hes1 plays an essential role in the development of ICC via PDC. SIGNIFICANCE: This study contributes to the identification of the cells of origin that initiate ICC and suggests that HES1 may represent a therapeutic target in ICC.
Asunto(s)
Neoplasias de los Conductos Biliares/patología , Conductos Biliares Intrahepáticos/patología , Colangiocarcinoma/patología , Factor de Transcripción HES-1/genética , Factor de Transcripción HES-1/metabolismo , Animales , Neoplasias de los Conductos Biliares/genética , Neoplasias de los Conductos Biliares/metabolismo , Colangiocarcinoma/genética , Colangiocarcinoma/metabolismo , Dieta/efectos adversos , Humanos , Ratones Noqueados , Ratones Transgénicos , Proteínas Proto-Oncogénicas p21(ras)/genética , Receptores Notch/metabolismoRESUMEN
Pancreatic ductal adenocarcinoma (PDAC) features abundant stromal cells with an excessive extracellular matrix (ECM), termed the desmoplastic reaction. CXCR4 is a cytokine receptor for stromal cell-derived factor-1 (CXCL12) expressed in PDAC, but its roles in PDAC and the characteristic desmoplastic reaction remain unclear. Here, we generated a mouse model of PDAC with conditional knockout of Cxcr4 (KPC-Cxcr4-KO) by crossing Cxcr4 flox mice with Pdx1-Cre;KrasLSL-G12D/+;Trp53LSL-R172H/+ (KPC-Cxcr4-WT) mice to assess the development of pancreatic intraepithelial neoplasia (PanIN) and pancreatic cancers. Tumor cell characteristics of those two types were analyzed in vitro. In addition, CXCR4 expression in human pancreatic cancer specimens was evaluated by IHC staining. In KPC-Cxcr4-KO mice, the number and pathologic grade of PanIN lesions were reduced, but the frequency of pancreatic cancers did not differ from that in KPC-Cxcr4-WT mice. The pancreatic tumor phenotype in KPC-Cxcr4-KO mice was significantly larger and undifferentiated, characterized by abundant vimentin-expressing cancer cells, significantly fewer fibroblasts, and markedly less deposition of ECM. In vitro, KPC-Cxcr4-KO tumor cells exhibited higher proliferative and migratory activity than KPC-Cxcr4-WT tumor cells. Myofibroblasts induced invasion activity in KPC-Cxcr4-WT tumor cells, showing an epithelial-mesenchymal interaction, whereas KPC-Cxcr4-KO tumor cells were unaffected by myofibroblasts, suggesting their unique nature. In human pancreatic cancer, undifferentiated carcinoma did not express CXCR4 and exhibited histologic and IHC features similar to those in KPC-Cxcr4-KO mice. In summary, the CXCL12/CXCR4 axis may play an important role in the desmoplastic reaction in PDAC, and loss of CXCR4 induces phenotype changes in undifferentiated carcinoma without a desmoplastic reaction. SIGNIFICANCE: The current study uncovers CXCR4 as a key regulator of desmoplastic reaction in PDAC and opens the way for new therapeutic approaches to overcome the chemoresistance in patients with PDAC.
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Carcinoma Ductal Pancreático/patología , Neoplasias Pancreáticas/patología , Receptores CXCR4/metabolismo , Animales , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Diferenciación Celular/genética , Movimiento Celular , Quimiocina CXCL12/metabolismo , Células Epiteliales/patología , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Hepáticas Experimentales/patología , Neoplasias Hepáticas Experimentales/secundario , Ratones Endogámicos C57BL , Ratones Noqueados , Miofibroblastos/metabolismo , Miofibroblastos/patología , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Receptores CXCR4/genéticaRESUMEN
Pancreatic neuroendocrine tumors (PanNET) were classified into grades (G) 1 to 3 by the World Health Organization in 2017, but the precise mechanisms of PanNET initiation and progression have remained unclear. In this study, we used a genetically engineered mouse model to investigate the mechanisms of PanNET formation. Although pancreas-specific deletion of the Rb gene (Pdx1-Cre;Rbf/f ) in mice did not affect pancreatic exocrine cells, the α-cell/ß-cell ratio of islet cells was decreased at 8 months of age. During long-term observation (18-20 months), mice formed well-differentiated PanNET with a Ki67-labeling index of 2.7%. In contrast, pancreas-specific induction of a p53 mutation (Pdx1-Cre;Trp53R172H ) had no effect on pancreatic exocrine and endocrine tissues, but simultaneous induction of a p53 mutation with Rb gene deletion (Pdx1-Cre;Trp53R172H;Rb f/f ) resulted in the formation of aggressive PanNET with a Ki67-labeling index of 24.7% over the short-term (4 months). In Pdx1-Cre;Trp53R172H;Rbf/f mice, mRNA expression of Pten and Tsc2, negative regulators of the mTOR pathway, significantly decreased in the islet cells, and activation of the mTOR pathway was confirmed in subsequently formed PanNET. Thus, by manipulating Rb and p53 genes, we established a multistep progression model from dysplastic islet to indolent PanNET and aggressive metastatic PanNET in mice. These observations suggest that Rb and p53 have distinct roles in the development of PanNET. SIGNIFICANCE: Pancreas-specific manipulation of Rb and p53 genes induced malignant transformation of islet cells, reproducing stepwise progression from microadenomas to indolent (grade 1) and subsequent aggressive PanNETs (grade 2-3).
Asunto(s)
Transformación Celular Neoplásica/genética , Tumores Neuroendocrinos/genética , Neoplasias Pancreáticas/genética , Proteína de Retinoblastoma/genética , Proteína p53 Supresora de Tumor/genética , Animales , Ratones , Ratones TransgénicosRESUMEN
BACKGROUND: Few reports have evaluated the effectiveness of laser-cut, covered, self-expandable metal stents (LC-CSEMS) for unresectable malignant distal biliary obstruction (MDBO) and whether reintervention is feasible after placement. We describe our experience with LC-CSEMS placement for unresectable MDBO. METHODS: Patients undergoing LC-CSEMS placement for unresectable MDBO from November 2014 to December 2018 were reviewed. Recurrent biliary obstruction (RBO), median time to RBO (TRBO), and reintervention were analyzed. RESULTS: 52 patients who underwent LC-CSEMS placement for unresectable MDBO were included in the analysis. The RBO rate was 15â% and the median TRBO was 445 days. Reintervention was attempted in nine patients and stent removal was successful in eight patients. CONCLUSIONS: Our experience suggests the effectiveness of LC-CSEMS in patients with unresectable MDBO in terms of stent patency and feasibility of reintervention.
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Colestasis , Stents Metálicos Autoexpandibles , Colestasis/etiología , Colestasis/cirugía , Remoción de Dispositivos , Humanos , Rayos Láser , Estudios Retrospectivos , StentsRESUMEN
Most pancreatic ductal adenocarcinoma (PDAC) develops from pancreatic epithelial cells bearing activating mutant KRAS genes through precancerous lesions, i.e. acinar-to-ductal metaplasia (ADM) and pancreatic intraepithelial neoplasia (PanIN). During pancreatic tumorigenesis, Hes1 expression starts with the transition from acinar cells to ADM, and continues during PanIN and PDAC formation, but the role of Hes1 in pancreatic tumorigenesis is not fully elucidated. Here we show that Hes1 plays an essential role in the initiation and progression of KRAS-driven pancreatic tumorigenesis. In vitro, activation of MAPK signaling due to EGF or mutant KRAS activation induced sustained Hes1 expression in pancreatic acinar cells. In vivo, acinar cell-specific activation of mutant KRAS by Elastase1-CreERT2;KrasG12D induced ADM/PanIN formation with Hes1 expression in mice, and genetic ablation of Hes1 in these mice dramatically suppressed PanIN formation. Gene expression analysis and lineage tracing revealed that Hes1 regulates acinar-to-ductal reprogramming-related genes and, in a Hes1-deficient state, mutant Kras-induced ADM could not progress into PanIN, but re-differentiated into acinar cells. In the Elastase1-CreERT2;KrasG12D;Trp53R172H mouse PDAC model, genetic ablation of Hes1 completely blocked PDAC formation by keeping PanIN lesions in low-grade conditions, in addition to reducing the occurrence of PanIN. Together, these findings indicate that mutant KRAS-induced Hes1 plays an essential role in PDAC initiation and progression by regulating acinar-to-ductal reprogramming-related genes.
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Carcinogénesis/genética , Carcinogénesis/patología , Páncreas/patología , Proteínas Proto-Oncogénicas p21(ras)/genética , Factor de Transcripción HES-1/genética , Células Acinares/patología , Animales , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patología , Diferenciación Celular/genética , Línea Celular , Progresión de la Enfermedad , Expresión Génica/genética , Metaplasia/genética , Metaplasia/patología , Ratones , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Lesiones Precancerosas/genética , Lesiones Precancerosas/patología , Neoplasias PancreáticasRESUMEN
The emergence of clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 technology has dramatically advanced how we manipulate the genome. Regarding in vivo experiments, Cas9-transgenic animals could provide efficient and complex genome editing. However, this potential has not been fully realized partly due to a lack of convenient platforms and limited examples of successful disease modeling. Here, we devised two doxycycline (Dox)-inducible Cas9 platforms that efficiently enable conditional genome editing at multiple loci in vitro and in vivo. In these platforms, we took advantage of a site-specific multi-segment cloning strategy for rapid and easy integration of multiple single guide (sg)RNAs. We found that a platform containing rtTA at the Rosa26 locus and TRE-Cas9 together with multiple sgRNAs at the Col1a1 locus showed higher efficiency of inducible insertions and deletions (indels) with minimal leaky editing. Using this platform, we succeeded to model Wilms' tumor and the progression of intestinal adenomas with multiple mutations including an activating mutation with a large genomic deletion. Collectively, the established platform should make complicated disease modeling in the mouse easily attainable, extending the range of in vivo experiments in various biological fields including cancer research.
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Adenoma/genética , Sistemas CRISPR-Cas/genética , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas/genética , Neoplasias Intestinales/genética , Neoplasias Renales/genética , ARN Guía de Kinetoplastida/genética , Tumor de Wilms/genética , Adenoma/patología , Animales , Femenino , Edición Génica/métodos , Neoplasias Intestinales/patología , Neoplasias Renales/patología , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos ICR , Mutación/genética , Tumor de Wilms/patologíaRESUMEN
Autoimmune pancreatitis (AIP), a major manifestation of immunoglobulin G4-related disease (IgG4-RD), is an immune-mediated disorder, but the target autoantigens are still unknown. We previously reported that IgG in patients with AIP induces pancreatic injuries in mice by binding the extracellular matrix (ECM). In the current study, we identified an autoantibody against laminin 511-E8, a truncated laminin 511, one of the ECM proteins, in patients with AIP. Anti-laminin 511-E8 IgG was present in 26 of 51 AIP patients (51.0%), but only in 2 of 122 controls (1.6%), by enzyme-linked immunosorbent assay. Because truncated forms of other laminin family members in other organs have been reported, we confirmed that truncated forms of laminin 511 also exist in human and mouse pancreas. Histologic studies with patient pancreatic tissues showed colocalization of patient IgG and laminin 511. Immunization of mice with human laminin 511-E8 induced antibodies and pancreatic injury, fulfilling the pathologic criteria for human AIP. Four of 25 AIP patients without laminin 511-E8 antibodies had antibodies against integrin α6ß1, a laminin 511 ligand. AIP patients with laminin 511-E8 antibodies exhibited distinctive clinical features, as the frequencies of malignancies or allergic diseases were significantly lower in patients with laminin 511-E8 antibodies than in those without. The discovery of these autoantibodies should aid in the understanding of AIP pathophysiology and possibly improve the diagnosis of AIP.
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Antígenos/sangre , Enfermedades Autoinmunes/sangre , Laminina/sangre , Pancreatitis/sangre , Anciano , Animales , Autoanticuerpos/sangre , Enfermedades Autoinmunes/inmunología , Femenino , Humanos , Inmunización , Inmunoglobulina G/sangre , Integrina alfa6beta1/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Persona de Mediana Edad , Pancreatitis/inmunologíaRESUMEN
Reprogramming technology has enabled the fate conversion of terminally differentiated somatic cells into pluripotent stem cells or into another differentiated state. A dynamic reorganization of epigenetic regulation takes place during cellular reprogramming. Given that reprogramming does not require changes in the underlying genome, the technology can be used to actively modify epigenetic regulation. Although reprogramming has been investigated mostly at the cellular level in vitro, studies have reported that somatic cells are reprogrammable in multicellular organisms in vivo. In vivo reprogramming provides a potential strategy for regenerative medicine. Notably, recent studies using in vivo reprogramming technology to alter epigenetic regulation at organismal levels have revealed unappreciated epigenetic mechanisms in various biological phenomena, including cancer development, tissue regeneration, aging, and rejuvenation in mammals. Moreover, in vivo reprogramming technology can be applied to abrogate epigenetic aberrations associated with aging and cancer, which raises the possibility that the technology could provide a potential strategy to control the fate of detrimental cells such as senescent cells and cancer cells in vivo. Here, we review recent progress and future perspectives of in vivo reprogramming.
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Envejecimiento/genética , Reprogramación Celular/genética , Epigénesis Genética/genética , Células Madre Pluripotentes Inducidas/fisiología , Neoplasias/genética , Regeneración/genética , Senescencia Celular/genética , Metilación de ADN/genética , Histonas/metabolismo , Humanos , Células Madre Pluripotentes Inducidas/citología , Rejuvenecimiento/fisiologíaRESUMEN
Severe acute pancreatitis is a lethal inflammatory disease frequently accompanied by pancreatic necrosis. We aimed to identify a key regulator in the development of pancreatic necrosis. A cytokine/chemokine array using sera from patients with acute pancreatitis (AP) revealed that serum CXCL16 levels were elevated according to the severity of pancreatitis. In a mouse model of AP, Cxcl16 expression was induced in pancreatic acini in the late phase with the development of pancreatic necrosis. Cxcl16-/- mice revealed similar sensitivity as wild-type (WT) mice to the onset of pancreatitis, but better resisted development of acinar cell necrosis with attenuated neutrophil infiltration. A cytokine array and immunohistochemistry revealed lower expression of Ccl9, a neutrophil chemoattractant, in the pancreatic acini of Cxcl16-/- mice than WT mice. Ccl9 mRNA expression was induced by stimulation with Cxcl16 protein in pancreatic acinar cells in vitro, suggesting a Cxcl16/Ccl9 cascade. Neutralizing antibody against Cxcl16 ameliorated pancreatic injury in the mouse AP model with decreased Ccl9 expression and less neutrophil accumulation. In conclusion, Cxcl16 expressed in pancreatic acini contributes to the development of acinar cell necrosis through the induction of Ccl9 and subsequent neutrophil infiltration. CXCL16 could be a new therapeutic target in AP.
Asunto(s)
Células Acinares/metabolismo , Células Acinares/patología , Ceruletida/toxicidad , Quimiocina CXCL16/metabolismo , Quimiocinas CC/análisis , Proteínas Inflamatorias de Macrófagos/análisis , Neutrófilos/inmunología , Pancreatitis Aguda Necrotizante/patología , Animales , Ceruletida/administración & dosificación , Quimiocina CXCL16/sangre , Quimiocina CXCL16/deficiencia , Quimiocinas CC/sangre , Modelos Animales de Enfermedad , Humanos , Inmunohistoquímica , Proteínas Inflamatorias de Macrófagos/sangre , Ratones , Ratones Noqueados , Pancreatitis Aguda Necrotizante/inducido químicamente , Suero/químicaAsunto(s)
Actinomicosis/diagnóstico por imagen , Enfermedades Pancreáticas/diagnóstico por imagen , Enfermedades Pancreáticas/microbiología , Actinomicosis/patología , Anciano , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Femenino , Humanos , Enfermedades Pancreáticas/patología , Tomografía Computarizada por Tomografía de Emisión de PositronesRESUMEN
BACKGROUND AND AIM: Cholecystitis is a major complication after self-expandable metallic stent (SEMS) placement for malignant biliary obstruction. Ischemia is one of the risk factors for cholecystitis, but little is known about the influence of tumor invasion to the feeding artery of the gallbladder on the onset of cholecystitis after SEMS placement. The aim of the present study was to identify risk factors for cholecystitis after SEMS placement. METHODS: Incidence and nine predictive factors of cholecystitis were retrospectively evaluated in 107 patients who underwent SEMS placement for unresectable distal malignant biliary obstruction at Kyoto University Hospital and Otsu Red Cross Hospital between January 2012 and June 2016. RESULTS: Cholecystitis occurred in 13 of 107 patients (12.1%) after SEMS placement during the median follow-up period of 262 days. Univariate analyses showed that tumor invasion to the feeding artery of the gallbladder and tumor involvement to the orifice of the cystic duct were significant predictors of cholecystitis (P = 0.001 and P < 0.001). Multivariate analysis confirmed that these two factors were significant and independent risks for cholecystitis with odds ratios of 22.13 (95% CI, 3.57-137.18; P = 0.001) and 25.26 (95% CI, 4.12-154.98; P < 0.001), respectively. CONCLUSIONS: This study showed for the first time that tumor invasion to the feeding artery of the gallbladder as well as tumor involvement to the orifice of the cystic duct are independent risk factors for cholecystitis after SEMS placement.
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Colecistitis/epidemiología , Colestasis/cirugía , Vesícula Biliar/irrigación sanguínea , Neoplasias Pancreáticas/patología , Complicaciones Posoperatorias/epidemiología , Stents Metálicos Autoexpandibles/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Colestasis/etiología , Femenino , Vesícula Biliar/patología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Neoplasias Pancreáticas/cirugía , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND AND AIMS: The efficacy of ERCP for histologic diagnosis of malignant biliary strictures is disappointingly low. The aim of this study was to investigate the diagnostic performance of a newly developed endoscopic device with scraping loops in combination with conventional biopsy forceps. METHODS: We performed a multicenter single-arm prospective study. Between February 2013 and December 2014, 123 patients with suspected malignant biliary strictures were enrolled in the study. The new device and conventional biopsy forceps were applied for histologic diagnosis by ERCP. The primary outcome was to evaluate cancer detectability by biopsy forceps, the new device, and their combined use. RESULTS: Of the 123 patients, 119 were diagnosed with a malignant stricture. Sufficient samples were collected in 83.7% (103/123), 93.5% (115/123), and 95.9% (118/123) of patients using biopsy forceps, the new device, and their combination, respectively. Cancer detectability of forceps biopsy, the new device, and their combination were 51.3% (61/119), 64.7% (77/119), and 74.8% (89/119), respectively. The new device had a significantly higher sample yield and cancer detectability than biopsy forceps (P < .01 and P = .018, respectively, McNemar test). Complementary use of the new device with biopsy forceps demonstrated a significantly additive effect in both sample yield and cancer detection (P < .01 each, McNemar test). The new device detected 48.3% (28/58) of cancers that were not diagnosed as malignant by biopsy forceps. CONCLUSIONS: The new endoscopic scraper demonstrated a large sample yield and high cancer detectability. It could be a first-line tissue-sampling device for biliary strictures. (University Hospital Medical Information Network Clinical Trial Registry [UMIN-CTR] (http://www.umin.ac.jp/ctr/index.htm) registration number: UMIN000009895.).
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Enfermedades de los Conductos Biliares/diagnóstico , Neoplasias de los Conductos Biliares/patología , Conductos Biliares/patología , Biopsia/instrumentación , Colangiocarcinoma/patología , Colangiopancreatografia Retrógrada Endoscópica/instrumentación , Neoplasias de la Vesícula Biliar/patología , Neoplasias Pancreáticas/patología , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades de los Conductos Biliares/etiología , Neoplasias de los Conductos Biliares/complicaciones , Neoplasias de los Conductos Biliares/diagnóstico , Colangiocarcinoma/complicaciones , Colangiocarcinoma/diagnóstico , Constricción Patológica , Femenino , Neoplasias de la Vesícula Biliar/complicaciones , Neoplasias de la Vesícula Biliar/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/complicaciones , Neoplasias Pancreáticas/diagnóstico , Estudios ProspectivosAsunto(s)
Carcinoma de Células Renales/diagnóstico por imagen , Carcinoma de Células Renales/secundario , Neoplasias Renales/patología , Neoplasias Gástricas/diagnóstico por imagen , Neoplasias Gástricas/secundario , Estudios de Seguimiento , Gastroscopios , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Crescentic glomerulonephritis (GN) is one of the common causes of rapidly progressive glomerulonephritis (RPGN). Pauci-immune crescentic GN is usually associated with anti-neutrophil cytoplasmic antibody (ANCA). However, patients with pauci-immune crescentic GN who lack ANCAs have recently been reported. Approximately 10-30 % of patients with pauci-immune crescentic GN lack ANCAs. The clinical characteristics of patients with ANCA-negative pauci-immune crescentic GN are not entirely the same as patients with ANCA-positive GN, and this suggests that ANCA-negative and ANCA-positive pauci-immune crescentic GN might be different disease entities. We report a patient with ANCA-negative crescentic GN complicated with multiple opportunistic infections (Candida albicans, herpes simplex virus, and Cytomegalovirus) in the digestive tract during the course of immunosuppressive therapy. After antifungal and antiviral therapies including itraconazole, valaciclovir, and ganciclovir, she recovered from multiple opportunistic infections. The occurrence of comorbid opportunistic infections during the course of immunosuppressive therapy may not be rare in the elderly. However, a case of multiple opportunistic infections limited to the digestive tract is very rare.
RESUMEN
A 41-year-old man was admitted to our hospital because of multiple liver tumors. Colonoscopy showed a mass lesion in the cecum. He was given a diagnosis of endocrine cell carcinoma by immunostaining technique, and received chemotherapy of CAPOX regimen for 3 courses. After that, he underwent second-line chemotherapy of EP(CDDP/VP-16)regimen due to deterioration of his performance status(PS), and his tumor marker NSE. He then showed dramatically improved PS, and improvement in the size of liver mets and NSE(4. 3mg/mL).